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{{displayTitle}} READ
Irritable bowel syndrome sounds like what you might call those fits your cranky boss has when she doesn't have her morning mocha latte. (“Watch out, Charlotte's in full irritable bowel syndrome mode. She just went off on Sam for typing too loudly.”) But it's no joke for those who suffer from IBS.
The thing is, not many know the difference between the occasional upset stomach and all-out IBS, which is a chronic condition. And if you don't know, you can't get help to manage the pain, discomfort, and sometimes embarrassment that can accompany it. Since some experts say the condition tends to pop up when you're in your 20s and 30s, it's time to clear up the BS so you can address the symptoms and never miss another party because you're gassy.
What Is IBS?
Woman Using Toilet Irritable bowel syndrome affects the large intestine and is basically a collection of symptoms you may be familiar with: abdominal pain or cramping, bloating, diarrhea or constipation, and/or mucus in your stool. While this condition can be chronic, symptoms are often inconsistent (with either diarrhea or constipation being more predominant) and don’t always appear at the same time, which can make it tricky to know something is up in the first place, says Stephen Wangen, a naturopathic doctor and medical director of the IBS Treatment Center in Seattle. No wonder the number of people with symptoms outnumbers the number of people who get professional help.
IBS affects people of all ages, although it tends to start before 35, perhaps due to the lifestyle shifts that occur as you transition into college and your first jobs, says Mark Larson, M.D., a gastroenterologist at the Mayo Clinic. “In your 20s and 30s, so many things are changing. The anxiety about the future and relationships is much more intense, and your gut takes a hit from all that stress.”
The root causes of IBS, however, are somewhat of a mystery. In addition to stress and other factors that can cause the balance of good and bad gut bacteria to get out of whack, experts believe there may be a connection between IBS and unknown food allergies or intolerances, as some people have more severe symptoms when they eat certain foods.
How to Treat IBS
If you’ve been battling digestive issues at all for three to six months—you don't need to experience symptoms daily or even the same ones—it's time to see a doctor, Larson says. He or she will ask about your woes and may perform some tests such as an endoscopy, an x-ray to look at your intestines, or blood work to figure out if you're dealing with other possible health issues such as ulcertive colitis, Chron's disease, and celiac disease.
While IBS treatment is specific to each individual, experts generally agree on an overall healthy lifestyle with a balanced diet, exercise, proper hydration, and stress management.
Yogurt Larson recommends yogurt for probiotics (or supplements for those who avoid dairy) to repopulate your gut with “healthy” bacteria. Those suffering from constipation may benefit from eating more fiber, which can help improve bowel function and keep things moving. Exercise of any kind also encourages better circulation and decreases the chances of getting backed up, he says.
Some experts advise going on the FODMAPS diet, which eliminates most fruit, dairy, wheat, beans, and several other foods, but many other experts say the science doesn't justify going on such a restrictive plan. Talk to your doctor to decide what is best for you.
Be sure to drink plenty of water, and if diarrhea is a problem, you may want to avoid excessive alcohol and caffeinate, which can exacerbate the issue.
Finally, stress management is huge, Larson says. Try relaxation or deep-breathing techniques, meditation, boxing class—whatever helps you chill.
The Bottom Line
Because IBS shows up in so many different forms, there’s really no one-size-fits all answer for treatment. But that's no reason to stay silent (and gassy, if that's the case—nobody likes SBDs). See a doctor who can help you determine if it's just IBS or something bigger, and from there you can learn how to adapt your diet and lifestyle so you can manage your symptoms.
Expert-approved
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Lower Blepharoplasty or Hyaluronic Acid/Restylane For Puffiness and Prominent Tear Troughs? (photo)
Hi, I'm 24 years old but I've had quite prominent puffiness and tear troughs around the eyes for about 2 years (they are much worse in the morning but don't go away.) I have consulted a plastic surgeon who immediately suggested a lower transconjunctival blepharoplasty but he doesn't know if a blepharoplasty will fix the dark line (tear trough). I've heard a could actually make them prominent. Please let me know what you think!
Doctor Answers (13)
Fillers or blepharoplasty for bags and tear trough.
+2
If a 24 year old has bags it is not from aging! It is usually congenital and/or for to allergies. You need removal of fat where the is too much and placing in the tear trough where there is too little. This can be done transconjunctivally.
Beverly Hills Facial Plastic Surgeon
5.0 out of 5 stars 14 reviews
Best Treatment for Dark Circles and Hollow Lower Eye Lids in 24 Year Old Itallian Woman
+2
Hi Valentina,
I would treat you with Ulthera (ultrasound tightening of your lower eyelid), followed by the injection of Restylane to fill any remaining lower eyelid hollow. I would wait at least 3 months after the Ulthera before filling, as you will likely require much less. The dark circles under your eyes should improve as the trough is filled. Transconjunctival blepharoplasty (surgery) should be a last resort in a 24 year old Italian women. Ciao bella. Good luck and be well.
Dr. P
Michael A. Persky, MD
Los Angeles Facial Plastic Surgeon
5.0 out of 5 stars 23 reviews
Lower eyelid procedures
+2
The dark circles may be related to shadowing or discoloration. If shadowing, fillers such as restylane may help. Conservative fat removal may be beneficial as well but an exam is essential. In addition during sugary, release of the arcs marginalis may help soften that depression
Steven Wallach, MD
Manhattan Plastic Surgeon
4.5 out of 5 stars 16 reviews
You might also like...
Lower Eyelid Bags with deep circles
+2
Judging from your photo, I would not recommend surgery for several reasons. The appearance of bags in your case is not due to oversized fat bags but rather by a hollowed tear trough (the groove under the "bags". Performing surgery to remove the normal amount of fat you have would simply lead to hollowing rather than an improvement. In addition, because your young age, your face will change, particularly the skin and subcutaneous fat in this area.
The option with best results and lowest risks is filler injections, usually Restylane. As mentioned, the injections need to be performed by an experienced physician as this is a delicate area with a high risk of lumpiness in inexperienced hands.
Mark Samaha, MD
Montreal Facial Plastic Surgeon
5.0 out of 5 stars 8 reviews
Tear Troughs in the Lower Eyelids
+2
The wrong thing for you to do would be to let someone take the fat out of your lower eyelids. The bags will improve, but you will have an aged, hollow, long lower eyelid.
The best result would be possible only with surgery. While many surgeons advocate fat grafting this process is fraught with problems. Particularly the fact that fat survival is un-predictable, prone to future fluctuation and the procedure is not reversible. Furthermore the added soft tissue volume tends to be too full when smiling. It is my preference to use a tear-trough implant and based on your photograph you would be a very good candidate. This can be thought of as reshaping the skeleton of the lower orbital rim/upper cheek area to bring the soft tissues of the cheek, the orbital fat, and the bony rim into proper alignment. The goal is a soft round cheek blending seamlessly into the lower eyelid. The implant feels like bone once in place, does not bunch up/move with smiling, and does not change over time.
Injectable fillers such as Restylane can provide descent correction of the problem temporarily. I would suggest this if your budget doesn't allow for surgery, if you are just not mentally ready for surgery, or if you don't have any time for surgery. Restylane into the lower eyelids should only be done by an experienced physician injector, preferable a surgeon. A very thorough knowledge of the anatomy is necessary here. Generally the procedure results in only mild swelling and slight or no bruising. The correction will not be as complete as surgery but it can be very satisfying. I would suggest using 1/2 cc on each side. The product needs to be kept very deep (against the bone) to avoid bruising, lumps, and a bluish tinge to the skin. An additional 1/2 cc per side may be beneficial but I would suggest waiting a few weeks after the first treatment before adding more (if at all). When done with a proper nerve block, it is essentially painless. I would say that Juvederm is acceptable but not as asspropriate as Restylane. I would also tell you to absolutely avoid Radiesse or Sculptra in this area.
Louis W. Apostolakis, MD
Austin Facial Plastic Surgeon
4.5 out of 5 stars 15 reviews
Fillers would be a better option
+2
With your age, and the appearance of good skin elasticity, I would not normally recommend surgery. Properly placed filler in that area can help reduce the "dark" circle look and is very safe. Taking fat out now would only to later "hollow" out your eye and actually make you look older. Filler in this area last a very long time, often 1-2 years and usually does not require a large amount of filler.
Samson Lee, MD
Seattle Facial Plastic Surgeon
5.0 out of 5 stars 4 reviews
Transconjunctival lower blepharoplasty would classically be offered.
+2
However, removing the lower eyelid fullness will leave you a bit hollow under the eyes. The state the art treatment for this would be under eye fillers with Restylane. It is essential that you find a cosmetic surgeon who regularly performs this treatment and understands how to shape and adjust this product with enzyme when necessary. This type of treatment typically last about a year or more and it is likely that you can continue to have these treatment for a very long time, making surgery unnecessary for the foreseeable future.
Kenneth D. Steinsapir, MD
Los Angeles Oculoplastic Surgeon
5.0 out of 5 stars 15 reviews
Lower eyelid bags and tear trough options.
+2
At 24 years old the lower eyelid area should just be beginning to show early signs of aging. In some cases, the lower lids area can appear more aged due to a genetic preponderance of volume loss over the inferior orbital rim. This leads to tear trough deformity and accentuates the early appearance of "eyelid bags" in this area. Volume addition using injectable fillers or fat grafting can help to refill thehollowing tear trough area. Often this your of treatment yields more natural looking results than traditional blepharoplasty techniques that rely on removal or repositioning of fat. My recommendation would be to consider fillers or fat graft at this time. There are examples in the photos section of my profile for your review. Good luck! Dr. Torkian
Behrooz Torkian, MD
Beverly Hills Facial Plastic Surgeon
4.0 out of 5 stars 8 reviews
Lower Eyelid Surgery or Filler for Young Patient
+1
Thank you for sharing your photographs.
Generally, there are a few options to improve the appearance of the lower eyelids, eye bags, or dark circles. First option includes basic skin care, tretinoin, and/or chemical peels. This nonsurgical method helps improve the skin quality, reduce pigmentary changes, and improves overall appearance of the lower eyelid & cheek areas.
Second more advanced option is an injectable filler or fat to plump up the area. Fillers are made of material that is slowly removed over time, such as Restylane. Facial fillers treatment is quick and performed in the office with minimal recovery.
The last option, and also the most aggressive, is eyelid plastic surgery (blepharoplasty). Cosmetic surgery of the lower eyelid may remove or reposition fat in the eye bag area, and possible remove some sagging skin. Plastic surgeons typically don't recommend cosmetic eyelid surgery in young patients. However, each patient is unique and circumstances may vary. Age alone is not a determining factor if a person is a cosmetic surgery candidate.
Only after a comprehensive evaluation can a specialist help determine appropriate options for you. Best of luck.
Dr. Chaboki
Houtan Chaboki, MD
Washington DC Facial Plastic Surgeon
5.0 out of 5 stars 46 reviews
Blepharoplasty in 24year old
+1
You have prominent fat in your lower lids. this is unusual in someone you age. Assuming no medical issues for your problem I would address the 'puffyness" under your eyes. The treatment for the fat would be a re-positioning of the herniated fat and possibly a resection of a portion of the fat. The discoloration is a difficult problem that is rarely totally corrected. the discoloration can be improved with a combination of bleaching agents and laser in my experience. The tear trough regionis improved by re-positioning a portion of the fat.
Jay M. Pensler, MD
Chicago Plastic Surgeon
4.5 out of 5 stars 10 reviews
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.
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Patents
1. Advanced Patent Search
Publication numberUS5052391 A
Publication typeGrant
Application numberUS 07/601,150
Publication date1 Oct 1991
Filing date22 Oct 1990
Priority date22 Oct 1990
Fee statusPaid
Also published asWO1992006737A1
Publication number07601150, 601150, US 5052391 A, US 5052391A, US-A-5052391, US5052391 A, US5052391A
InventorsLeon M. Silberstone, Michael E. Halleck
Original AssigneeR.F.P., Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
High frequency high intensity transcutaneous electrical nerve stimulator and method of treatment
US 5052391 A
Abstract
A transcutaneous electrical nerve stimulation (TENS) device provides significantly improved patient results by supplying high frequency electrical pulses at frequencies in a range of 2.5 to 60 kilohertz. The frequency and intensity of the pulses can be adjusted, to treat the patient at the optimal frequency and amplitude in order to treat chronic or acute pain or to block the pain caused by a traumatic or medical procedure. Starting at a mid-level of intensity where no stimulation occurs, the frequency is adjusted downwardly until there is some nerse sensation. At this point, the procedure may be performed while the frequency is adjusted downwardly as needed to maintain nerve sansation. The wave form characteristic of the pulses is an AC wave form with a square wave portion with rapid rise time and slower fall time followed by a pulse portion of the opposite polarity compared to the square wave portion.
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Claims(20)
The invention claimed is:
1. A method for blocking the pain caused by a traumatic or medical procedure on a patient with the use of transcutaneous electrical nerve stimulation, comprising the steps of:
(a) generating a series of electrical pulses at a frequency in the range of 2.5 to 60 kilohertz;
(b) applying said generated electrical pulses to a desired area on a patient's body;
(c) electrically conducting the applied electrical pulses through the patient's body to stimulate selected nerves; and
(d) performing the procedure.
2. A method as defined in claim 1 wherein generating the series of electrical pulses includes:
generating the electrical pulses with an electrically powered stimulator; and
electrically isolating the patient from the stimulator.
3. A method as defined in claim 2 wherein electrically isolating the patient from the stimulator comprises coupling a signal generated by the stimulator through a transformer to the patient.
4. A method as defined in claim 1 wherein the generating step further comprises adjusting the frequency of the electrical pulses within said range.
5. A method as defined in claim 4 further comprising adjusting the high frequency electrical pulses to 60 kilohertz.
6. A method as defined in claim 4 wherein generating the series of electrical impulses further comprises adjusting the intensity of the electrical pulses.
7. A method as defined in claim 6, further comprising the additional steps of:
(e) adjusting the frequency to the highest frequency within the frequency adjustment range;
(f) adjusting the intensity to the lowest intensity within the intensity adjustment range; then
(g) adjusting the intensity to a level which is slightly below that level which achieves perceptible nerve sensation to the patient;
(h) adjusting the frequency downward from the highest frequency to a relatively lower frequency until the patient begins to perceive a nerve sensation; and
(i) continuing to adjust the frequency downwardly as necessary throughout the procedure to maintain the nerve sensation.
8. A method as defined in claim 1 further including forming the high frequency electrical pulses to include a square wave portion and an opposite polarity pulse centered about a zero reference potential.
9. A method as defined in claim 8 further comprising forming the square wave portion with a leading edge having a relatively rapid rise time and with a trailing edge having a relatively slower fall time.
10. An apparatus for blocking the pain caused by a traumatic or medical procedure on a patient with the use of transcutaneous electrical nerve stimulation, comprising:
source means for supplying a source of relatively high DC voltage;
voltage control means connected to said source means and receptive of the relatively high DC voltage and operative for supplying a controllable level of the DC voltage;
an output transformer means having a primary and a secondary winding, the primary winding connected to said voltage control means and receptive of the controlled DC voltage level supplied by said voltage control means, the transformer means operatively inducing in the secondary winding an electrically isolated output signal of approximately the same frequency as the signal in the primary winding and with an amplitude characteristic proportional t the amplitude characteristic of the signal in the primary winding;
oscillator means operative for generating a square wave oscillator signal;
power driver means connected to the other end of said primary winding of said output transformer means, the power driver means receptive of said square wave oscillator signal and operative for switching current through the primary winding at a frequency related to the frequency of the oscillator square wave signal;
the secondary winding of said transformer means supplying an output signal in response to the conduction of the power driver means, the output signal being a wave form which includes a square wave portion of one polarity having a leading edge with a relatively rapid rise time and a trailing edge with a relatively slower fall time and a pulse portion of the opposite polarity; and
a pair of electrodes connected to the secondary winding of said output transformer means for conducting the output signal to the skin of a patient.
11. Apparatus as defined in claim 10, further comprising:
adjustment means connected to said oscillator means and operative for adjusting the frequency of the oscillator square wave signal.
12. Apparatus as defined in claim 11, further comprising:
adjustment means connected to said voltage control means and operative for adjusting the level of the controlled voltage.
13. Apparatus as defined in claim 11 wherein said square wave oscillator signal is adjustable within a range of 2.5 kilohertz to 60 kilohertz.
14. Apparatus as defined in claim 10 wherein the power driver means conducts current through the primary winding during one state of the square wave oscillator signal and does not conduct current through the primary winding during the other state of the square wave oscillator signal, and said square wave signal has a predetermined frequency within the range of 2.5 kilohertz to 60 kilohertz.
15. Apparatus as defined in claim 14 further comprising:
a second pair of electrodes connected in parallel with said first electrodes.
16. Apparatus as defined in claim 14 further comprising:
a first output channel comprising the source means, the voltage control means, the output transformer means, the oscillator means, the power driver means, and the pair of electrodes, all as first aforesaid; and
a second output channel comprising the first said source means, a second said voltage control means, a second said output transformer means, a second said oscillator means, a second said power driver means, and a second pair of electrodes.
17. A method for blocking the pain caused by a traumatic or medical procedure on a patient with the use of transcutaneous electrical nerve stimulation, comprising the steps of:
(a) generating a high frequency series of electrical pulses;
(b) adjusting the frequency of the pulses to a relatively high rate;
(c) adjusting the intensity of the pulses to a relatively low level;
(d) applying said generated pulses to a desired area on a patient's body;
(e) adjusting the intensity of the pulses to a desired level;
(f) adjusting the frequency of the pulses to a relatively lower frequency until the patient begins to perceive a nerve sensation; and
(g) continuing to adjust the frequency downwardly as necessary throughout the procedure to maintain the nerve sensation.
18. A method as defined in claim 17 wherein the high frequency electrical pulses can be adjusted within the frequency range of 2.5 to 60 kilohertz.
19. A method as defined in claim 17 further including forming the high frequency electrical pulses to include a square wave portion and an opposite polarity pulse centered about a zero reference potential.
20. A method as defined in claim 19 further comprising forming the square wave portion with a leading edge having a relatively rapid rise time and with a trailing edge having a relatively slower fall time.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to transcutaneous electrical nerve stimulation and more particularly to a new and improved apparatus and process of applying relatively high frequency and high intensity pulses of electrical energy to the skin of a patient in order to obtain improved medical results such as blocking pain for a traumatic or medical procedure.
2. Description of the Prior Art
Transcutaneous electrical nerve stimulation (TENS) is a well known medical treatment used for symptomatic relief and management of chronic intractable pain, and as an adjunctive treatment in the management of post surgical and post traumatic acute pain. TENS involves the application of electrical pulses to the skin of a patient. Electrodes are located at selected locations on the patient's skin and the electrical energy is transferred between the two electrodes. The electrical energy is usually applied in the form of mild, electrical impulses. The impulses pass through the skin and interact with the nerves that lie underneath the skin. The electrical impulses act on the nervous system in such a way as to suppress the sensation of pain that would otherwise serve as a protective mechanism. As a symptomatic treatment, TENS has proven to effectively reduce pain for patients suffering from chronic or acute pain. TENS has no capacity for curing the cause of the pain, but simply interacts with the nervous system to suppress or relieve the pain.
The typical TENS system includes the TENS stimulator, lead wires and electrodes which are connected to the skin of the patient. The TENS stimulator is, in effect, an electrical pulse generator which delivers the electrical pulses or impulses at a predetermined fixed or selectable frequency. Typical prior TENS frequency treatment ranges have been in terms of hundreds of pulses per second. In many cases, the treatment frequency is fixed by the design of the electrical pulse generator, or is established as a preselected, generally arbitrary rate at the time of treatment. Most typical TENS pulse generators allow adjustment of the intensity or amplitude of the pulses delivered. The typical intensity ranges in the neighborhood of less than 100 volts peak to peak. The electrical impulses applied have taken a variety of different forms. For example, symmetrical sinusoidal wave forms, symmetrical biphasic wave forms and DC needle spikes have all been applied in various TENS treatments. Each of the wave forms are believed to offer some advantage, although there has been no clear previous consensus that any particular type of wave form is more advantageous than another type.
Furthermore, the prior TENS has typically been used for pain reduction rather than as an analgesic or painblocker in order to allow the performance of a traumatic or medical procedure upon a patient and there has been a long felt need for an analgesic or pain-blocker for certain medical procedures. For example, the use of electrolysis to remove hair from a patient's upper lip typically is painful to a patient and causes swelling. It is typical for a patient to only be able to tolerate from a few seconds to several minutes of electrolysis. Similarly, pain, discomfort and anxiety are common in electrolysis for hair removal in many anatomical sites in the human body.
It is against this background information, and other information, that the present invention has resulted.
SUMMARY OF THE INVENTION
A number of significant improvements and advancements in the field of electrolysis and surgery are available as a result of the present invention. Many traumatic or medical procedures which would typically produce pain and swelling in the skin of a patient can be performed with the use of the TENS device of the present invention. These significantly improved medical results are obtained by applying the TENS electrical impulses at substantially higher frequencies than have previously been used or recognized. In addition, the high frequency of the TENS impulses is adjusted or selected for optimal medical results. Further, each electrical impulse is preferably of a predetermined wave form characteristic which is believed to substantially increase and enhance the TENS effect and reduce swelling. Many other improvements will be apparent and discovered upon full comprehension and application of the aspects of this invention.
In accordance with one of its aspects, the present invention pertains to a method of TENS stimulation in which a relatively high frequency, preferably in the neighborhood of between 2.5 kilohertz and 60 kilohertz, is applied to the patient. For reasons not fully understood at the present time, the relatively higher frequency seems to stimulate an increased TENS effect with reduced swelling.
In accordance with another of its aspects, the present invention allows the relatively high frequency of impulses to be selected to optimize the relief obtained by the patient. The method involved is to initially apply the impulses at the high end of the high frequency range and at the low end of the amplitude or intensity range. The amplitude of the electrical impulses is adjusted to a level for the particular TENS treatment session, preferably at a mid-level. The frequency is then selectively decreased in order to maximize the stimulation effect until the patient senses a motor nerve response or "tingling". By adjusting both the intensity and the frequency in this manner, the treatment is optimized for each patient.
According to a further aspect of the present invention, the electrical impulse to the patient is preferably an AC wave form which includes a square wave portion forming the first positive half cycle of the AC wave form followed by a generally negative rounded pulse portion forming the negative half cycle of the AC wave form. The square wave portion is characterized by a relatively fast rise time, a sustained or slightly decreasing amplitude level over the majority of the time of the square wave portion and a slower fall time. The fall time slope generally characterizes the initial significant portion of the negative rounded pulse portion. The negative portion thereafter returns to the baseline to commence another AC wave form repetition. The energy within the positive going square wave and the negative rounded wave is generally equal, thereby transferring a zero net DC charge to the patient.
A more complete understanding and appreciation of the present invention can be obtained by reference to the accompanying drawings, which are briefly described below and from the detailed description of a presently preferred embodiment, and from the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a generalized illustration of the method of treating a patient with TENS, using a TENS stimulator connected to at least one pair of electrodes attached to the skin of the patient.
FIG. 2 is a block diagram of one embodiment of the TENS stimulator which may be used as shown in FIG. 1.
FIG. 3 is a block diagram of an output portion of the TENS stimulator shown in FIG. 2, illustrating an alternative embodiment providing two output channels driven by a single power driver.
FIG. 4 is a block diagram of another embodiment of the TENS stimulator, providing two separate output channels, each of which is driven by its own power driver.
FIG. 5 is a schematic circuit diagram of the stimulator in FIG. 2, which is duplicated for each output channel of the TENS stimulator shown in FIG. 4.
FIGS. 6A and 6B are diagrams of a single pulse of a repetitive AC output wave form supplied by the TENS stimulator shown in FIGS. 2 and 4.
DETAILED DESCRIPTION
The treatment of a human patient 10 with a TENS unit in accordance with the present invention is illustrated in FIG. 1. Lacerations 11 requiring sutures are shown on the patient 10. A pair of conventional electrodes 12 and 14 are attached to the patient's skin in a predetermined location adjacent one of the lacerations 11 to alleviate or block pain so that sutures may be applied with little or no pain to close the laceration. The electrodes 12 and 14 are respectively connected by conductors 16 and 18 to a TENS stimulator 20. Pulses of electrical energy are delivered through the conductors 16 and 18 to the electrodes 1 and 14, where they are conducted into the skin to stimulate the nerves and achieve a TENS medical effect.
Preferably the TENS stimulator of the present invention provides two output channels for stimulating two separate areas of the patient 10. For example, the TENS stimulator 20 has one output channel to which the electrodes 12 and 14 and the conductors 16 and 18 are connected. A second output channel connects electrodes 22 and 24 by conductors 26 and 28, respectively, to the TENS stimulator. It has been determined that in some acute pain situations, the application of two separate TENS impulses between two pairs of electrodes is very effective in stimulating favorable patient treatment.
A single channel TENS stimulator 30 is illustrated in FIG. 2. The stimulator 30 includes a power supply 32 which preferably takes the form of a rechargeable battery. The battery is connected by a switch 34 to a DC inverter 36. The DC inverter converts the relatively lower DC voltage level of the battery power supply 32 to a relatively higher DC level and applies that higher DC level at 38 to a voltage control 40. A potentiometer 42 controls the voltage control 40 to adjust the output voltage at 44 between ground reference and the maximum voltage at 38 The voltage at 44 is applied to a primary winding 46 of an output transformer 48. Current is conducted through the primary winding 46 by a power driver 50 connected to the other terminal of the primary winding 46. Signals 52 from an oscillator 54 control the power driver 50. Preferably the signals are square wave signals supplied by the oscillator 54, and the power driver 50 responds to the square wave signals by conducting current through the primary winding 46 in relation to the on times of the square wave signal 52. A potentiometer 56 adjusts the frequency of the oscillator 54.
Output signals are derived by the secondary winding 58 of the transformer 48. The output signals are supplied on the electrodes 16 and 18, for example, to the patient electrodes 12 and 14 (FIG. 1). Use of the output transformer 48 effectively supplies the output pulses centered relative to ground level, and thereby transfers a zero net DC charge to the patient.
Use of the voltage control 40 to control the level of DC voltage at 44, by use of the potentiometer 42, establishes the intensity or amplitude of the output signal applied from the secondary winding 58 of the transformer 48. The power driver 50, as will be explained in greater detail below, essentially conducts the amount of current established by the potential at 44 through the primary winding. The potentiometer 56 controls the frequency of the oscillator 54 to thereby control the frequency of pulses delivered from the output transformer 48. Of course, in place of the potentiometers 42 (intensity) and 56 (frequency) any other suitable means for control may be substituted, such as digitally controlled potentiometers working in conjunction with a microprocessor. A microprocessor might further be utilized in the present invention to drive displays of the frequency and intensity information.
The relative size of the battery of the present invention is significantly larger than most batteries of TENS devices which are adapted to be worn by the patient Due to the relatively high electrical power requirements which have been determined to be desirable for TENS treatment, the power supply 32 should be a relatively large battery capable of being recharged. Considerable electrical power is consumed by the relatively high energy pulses created by the voltage level at 44 and switched through the primary winding 46 by the power driver 50.
In another embodiment of the TENS stimulator, a single output transformer 48 and power driver 50 are used in a TENS stimulator to obtain two output channels, as is shown in FIG. 3. The remainder of the circuit not shown in FIG. 3 is the same as that described in conjunction with FIG. 2. As can be appreciated, two conductors 16 and 26 are connected to one end of the secondary winding 58 and another pair of conductors 18 and 28 are connected to the other end of the secondary winding 58 of the output transformer 48. The single output signal developed across the output winding 58 is thus applied to each separate pair of conductors 16, 18 and 26, 28. While the arrangement shown in FIG. 3 has the advantage of cost reduction, it does reduce the magnitude of the signals applied on the conductor pairs 16, 18 and 26, 28 by an equal amount, since the conductor pairs are connected in parallel to separate parallel impedances through the patient Thus, equal intensities or voltages of output signals are applied on both of the conductor pairs 16, 18 and 26, 28.
A third embodiment 60 of the TENS stimulator, which allows true independent control over the output signal pulses delivered over two separate output channels, is illustrated in FIG. 4. A single power supply and DC inverter 36 are used, and the remainder of the components are essentially duplications of those described in conjunction with the TENS stimulator 30 shown in FIG. 2. As such, the duplicated components for one channel are labeled with reference numerals ending in a subscript a, and those duplicated components used in the second channel are labeled with reference numbers ending in a subscript b. In all regards, each of the channels in the TENS stimulator 60 operate similarly and in the manner previously described in conjunction with the TENS stimulator 30 shown in FIG. 2.
It should be noted that the magnitude of the output signal pulses from secondary windings 58a and 58b of transformers 48a and 48b are separately and independently adjustable by the potentiometers 42a and 42b, respectively. Similarly, the frequency of application of the output pulses from the two channels are separately and independently adjustable by the potentiometers 56a and 56b. Thus, the output signal pulses supplied by each channel are separately controllable and adjustable in frequency and amplitude for each channel.
The TENS stimulator 30, and the essential portions duplicated to obtain the TENS stimulator 60 shown in FIG. 4, are shown in greater detail in schematic form in FIG. 5.
The power supply 32 includes a conventional rechargeable battery 62. In addition, charging jacks 64 are connected by diode 66 across the battery 62. The charging jacks 64 will be utilized either to power the TENS stimulator 30 from a conventional DC power supply which may be driven by AC power, or to charge the rechargeable battery 62. An LED 68 is also provided to indicate the application of power at the charging jacks 64. Power from the power supply 32 is connected by the switch 34 to the DC inverter 36. Another LED 70 is provided to signal the operation of the TENS device when the switch 34 is closed A variety of different circuits for the power supply can be employed.
The DC inverter 36 utilizes a conventional DC inverter integrated circuit (IC) 72. The IC 72 is connected in the conventional manner illustrated. An inductor 74 is connected between two terminals of the IC 72, and switching currents therethrough develop relatively high voltage spikes. The resulting high voltage spikes are rectified by a diode 76. The rectified spikes charge a relatively high capacity filter capacitor 78. The maximum DC voltage level signal 38 is available between the terminals of the filter capacitor 78. Feedback resistors 80 and 82 supply a feedback signal to the IC 72 for the purpose of regulating the output voltage to the fixed maximum level. Preferably the ICU 72 is a commercial part, Motorola No. MC34063P1. Preferably the inductor 74 is a 200 microhenry, 1.5 amp component. A variety of different circuits for the inverter 36 can be employed.
The voltage control 40 receives the maximum DC output signal 38. The voltage control 40 includes a biasing transistor 84 and a regulating transistor 86. The base of the biasing transistor 84 is connected to the potentiometer 2. The voltage level from the potentiometer 42 establishes the conductivity of the biasing transistor 84. The level of conductivity of the biasing transistor 84 establishes the signal applied to the base of the regulating transistor 86, thereby causing transistor 86 to regulate the output voltage at 44 to a predetermined level established by the potentiometer 42. A resistor 88 in series with the emitter of the regulating transistor 86 further limits the amount of current drawn from the filter capacitor 78 through the primary winding 46 of the output transformer 48. A number of alternative circuits for the voltage control can be employed.
The oscillator 54 is of a conventional configuration which utilizes an operational amplifier 90 in conjunction with a feedback network which includes the potentiometer 56 and a capacitor 92 connected to its input terminal. The output signal 52 from the oscillator 54 is substantially a square wave having a frequency established by the resistance of the potentiometer 56 in the feedback network connected to the input terminal of the operational amplifier 90. A variety of other conventional square wave oscillator circuits can be employed
The square wave signal 52 is applied to the power driver 50. The power driver 50 includes a first switching transistor 94 which receives the square wave signal 52 at its base terminal. When the square wave signal 52 is high, the switching transistor 94 is conductive and a positive signal is developed across resistor 96. The positive signal across resistor 96 is applied to the base terminal of a power switching transistor 98 to render it conductive. When conductive, the power switching transistor 98 conducts current through the primary winding 46 of the output transformer 48. When the square wave signal at 54 is low, the transistors 94 and 98 are non-conductive. A number of different types of power driver circuits 50 could be employed, but, as will be described below, the power driver circuit 50 should preferably retain the capability to achieve the desirable characteristics of the output wave form.
The amount of energy conducted through the primary winding 46 is determined in large measure by the voltage level at 44, which is developed by the regulating transistor 86, and by the magnitude of the current conducted through the primary winding as controlled by the regulating transistor 86. Thus, the voltage control essentially controls the intensity of the treatment the patient receives, while the power driver actually develops the signals applied to the patient by switching signals through the primary winding 46 of the transformer 48. The signal in the primary winding 46 establishes the maximum intensity or amplitude of the output signal induced in the secondary winding 56 of the output transformer 48. Of course, increasing the frequency of the square wave pulses 52 from the oscillator 54 thereby controls the frequency of the electrical impulses delivered from the TENS stimulator 30. Changing the frequency of the output pulses does not significantly change the magnitude of the energy delivered to the patient.
FIGS. 6A and 6B illustrate the signal characteristics of an output pulse wave form 100 provided at the secondary winding 56 of the output transformer 48. FIG. 6A exemplifies the output pulse wave form delivered into a 500 ohm resistive load, while FIG. 6B exemplifies the output wave form delivered to a 10,000 ohm resistive load.
The wave form 100 shown in FIG. 6A is centered about a zero reference potential or base line. Centering the wave form 100 is attained by the inherent functionality of the output transformer 48. As a result of this centering, the amount of charge transferred during a first half cycle, represented by that square wave portion above the zero reference, and the amount of charge transferred during a second half cycle portion, represented by the negative rounded pulse portion below the reference line, are equal. Therefore, a zero net charge transfer to the patient occurs.
As will be noted by comparing FIG. 6A and 6B, the first positive square wave portion of each wave form is essentially the same. This positive portion is characterized generally as a square wave having a relatively rapid rise time, or leading edge, shown at 102, a relatively constant or slightly decreasing maximum value at 104 which is sustained during the majority of the time that the positive portion occurs, and by a relatively slower fall time, or trailing edge, shown at 106. The amount of decrease at 104 depends substantially on the resistive component of the load between the electrodes (FIG. 1) attached to the patient's body, with greater resistances achieving lesser reductions or decreases.
The slope of the trailing edge 106 continues into the negative portion and may continue to curve in various configurations shown at 108 when another output pulse 100 is generated by the TENS stimulator 30. The ending curve of the negative portion is characterized by a relatively rapid rise time of the same slope as the leading edge 102 of the positive square wave portion.
The relatively rapid rise time and relatively slower fall time of the output wave form are achieved as a result of the inherent collector to base capacitance in the power switching transistor 98, shown in FIG. 5. This capacitance allows the collector voltage of the power switching transistor 98 to rapidly change, thereby inducing a high charging current in the primary winding. However, after this inherent base to collector capacitance has been charged during the time that the power switching transistor 98 is conductive, the current flow through the secondary winding is relatively more slowly terminated when the power switching transistor 98 becomes nonconductive. Thus, the relatively slower fall time (106, FIGS. 6A and 6B) is created in the output pulse. During the mid-region -04 of the square wave portion, the current flow through the primary winding increases at a relatively uniform rate to obtain the sustained output voltage at 104.
For reasons which are not readily understood at the present time, a square wave portion having the relatively rapid rise time and the relatively slower fall time seems to provide an additional beneficial effect in patient treatment using TENS. It appears as though the significant aspects of the square wave which give rise to this improvement are the relatively rapid rise time and the relatively slower fall time.
To utilize the TENS stimulator of the present invention on a patient, the electrodes are attached to the patient and the conductors connect the output terminals of the output transformer 48 to the electrodes. Prior to turning the power on, the frequency potentiometer 56 is manually preset to provide the maximum output pulse delivery frequency upon energization, which is preferably about 60 kilohertz. The intensity potentiometer 42 is also manually preset to provide a relatively low amplitude or intensity for the output signal pulse upon energization. The switch 34 is then closed to energize the circuit and the intensity potentiometer 42 is adjusted to increase the amplitude or intensity of the output signal pulses to a mid-level, or until the patient begins to receive a sensation or tingling. Thereafter the frequency is adjusted downwardly with the frequency potentiometer 56 from its maximum level until the patient begins to sense a stimulation caused by a lower frequency of application of electrical impulses. Generally speaking the frequency at which the patient begins to sense the application of electrical impulses is an optimum one for that particular patient, and it will generally fall within the range of 2.5 kilohertz to 60 kilohertz. The amount of the stimulation should not be such as to induce pain, but should be a relatively comfortable sensation.
At this time, the medical procedure, such as applying sutures or performing electrolysis, may be performed. With time, the patient may need to adjust the frequency downwardly from the previous level to maintain the tingling sensation whereby there is an increase in the level of analgesia produced. These rises in analgesia continue throughout treatment in response to slight decreases in frequency. This constant adjustment in frequency may be carried out by the patient, by means of a hand-held remote control device (not shown) that includes a button for easily decreasing the frequency as the clinical sensation of tingling decreases. This control of pain reduction by the patient is one of the theories proposed for the efficacy of the present invention, since it removes the feeling of "lack of control" in an environment associated with pain, discomfort and anxiety.
By providing the independent adjustment of frequency, relatively high frequency application of TENS to a patient is possible. Furthermore, by adjusting the frequency of the TENS application separately and particularly for each patient, the optimum TENS treatment frequency for the patient may be obtained. However, the frequency level is slowly and gradually adjusted throughout the whole treatment session resulting in increased analgesia. The application of the output pulse wave form having a square wave positive portion with a relatively rapid rise time leading edge and relatively longer fall time trailing edge, increases the effective stimulation and treatment of the patient.
It is believed that the present invention obtains the desired results due to the fact that the electrical impulses generated thereby influence the nerve cells to produce natural substances such as Beta-endorphins, GABA, norepinephrine, dopamine, enkephalin, substance P and somatostatin, which produce analgesia and inhibitory action on nociceptive dorsal horn neurons and trigger reactions such as the secretion of serotonin, a naturally occurring neurotransmitter which controls and raises the pain threshold level. In addition, the electrical impulses may act to block the natural nerve pain impulses travelling along A delta and C delta nociceptive fine afferent nerve fibers. Thus, the treatment of the present invention appears to be effective as a result of the combination of blocking the pain impulses, triggering the reaction of various naturally occurring body elements to increase analgesia as well as raising the pain threshold and inhibiting cells in important pain pathways in the spinal cord to the brian. Although these are theories based on actual observations, the present invention has proved effective in relief of chronic and acute pain far in excess of prior TENS devices.
In an experimental treatment with the present invention used in conjunction with electrolysis to remove facial hair on forty-two patients, the following results were shown, as evaluated by the patients themselves after orientation sessions describing how to relay pain reduction during treatment. The patients had pain reduction during treatment that ranged from fifty to one hundred percent. Of the forty-two patients treated, only one had any signs of slight swelling as a result of treatment which normally would have resulted in swelling for all forty-two patients. Furthermore, among patients too sensitive to tolerate more than a few minutes of electrolysis without the present invention, it was possible to use the TENS stimulator of the present invention for up to one hour of electrolysis without pain, discomfort and anxiety, yet with a feeling of complete relaxation for the patient. This lack of pain, anxiety and adverse skin reaction continues for several hours after the patient leaves the professional's office. Therefore, there is no post operative pain, discomfort or swelling.
Presently preferred embodiments of the invention have been described above with a degree of specificity. It should be understood, however, that this description has been made by way of preferred example and that the invention itself is defined by the scope of the appended claims.
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Classifications
U.S. Classification607/46, 607/66, 607/76
International ClassificationA61N1/36
Cooperative ClassificationA61N1/36021, A61N1/06
European ClassificationA61N1/36E2
Legal Events
DateCodeEventDescription
4 Apr 2003FPAYFee payment
Year of fee payment: 12
4 Apr 2003SULPSurcharge for late payment
Year of fee payment: 11
31 Mar 1999FPAYFee payment
Year of fee payment: 8
18 Aug 1995FPAYFee payment
Year of fee payment: 4
18 Aug 1995SULPSurcharge for late payment
9 May 1995REMIMaintenance fee reminder mailed
2 Mar 1993CCCertificate of correction
6 Nov 1990ASAssignment
Owner name: R.F.P., INC., COLORADO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:SILVERSTONE, LEON M.;HALLECK, MICHAEL E.;REEL/FRAME:005510/0096;SIGNING DATES FROM 19901025 TO 19901030
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1. Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer
Steroids 2011;76(9):910-920.
Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogenous and exogenous female sex hormones, have a role in stimulating NSCLC progression. Aromatase, a key enzyme for estrogen biosynthesis, is expressed in NSCLC. Clinical data show that women with high levels of tumor aromatase (and high intratumoral estrogen) have worse survival than those with low aromatase. The present and previous studies also reveal significant expression and activity of estrogen receptors (ERα, ERβ) in both extranuclear and nuclear sites in most NSCLC. We now report further on the expression of progesterone receptor (PR) transcripts and protein in NSCLC. PR transcripts were significantly lower in cancerous as compared to non-malignant tissue. Using immunohistochemistry, expression of PR was observed in the nucleus and/or extranuclear compartments in the majority of human tumor specimens examined. Combinations of estrogen and progestins administered in vitro cooperate in promoting tumor secretion of vascular endothelial growth factor and, consequently, support tumor-associated angiogenesis. Further, dual treatment with estradiol and progestin increased the numbers of putative tumor stem/progenitor cells. Thus, ER- and/or PR-targeted therapies may offer new approaches to manage NSCLC.
doi:10.1016/j.steroids.2011.04.015
PMCID: PMC3129425 PMID: 21600232
Progesterone; Estrogen; Steroid hormone receptor; Non-small cell lung cancer; VEGF; Progenitor cells; Cancer stem cells; Angiogenesis
2. LUNG CANCER IN NEVER SMOKERS: MOLECULAR PROFILES AND THERAPEUTIC IMPLICATIONS
The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. While a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years demonstrates that lung cancers in never smokers are much more likely to carry activating mutations of the Epidermal Growth Factor Receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anti-cancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers.
doi:10.1158/1078-0432.CCR-09-0377
PMCID: PMC2950319 PMID: 19755392
3. Lung cancer and occupation: results of a multicentre case-control study.
The objective of the current study was to estimate the risk of lung cancer attributable to occupational factors and not due to tobacco. At 24 hospitals in nine metropolitan areas in the United States, 1793 male lung cancer cases were matched for race, age, hospital, year of interview, and cigarette smoking (never smoker, ex-smoker, smoker (1-19 and > or = 20 cigarettes per day)) to two types of controls (cancer and non-cancer hospital patients). Information on usual occupation, exposure to specific potential carcinogens, and cigarette smoking was obtained by interview. Risk of lung cancer was increased significantly for electricians; sheetmetal workers and tinsmiths; bookbinders and related printing trade workers; cranemen, derrickmen, and hoistmen; moulders, heat treaters, annealers and other heated metal workers; and construction labourers. All of these occupations are potentially exposed to known carcinogens. Odds ratios (ORs) were increased for exposure to coal dust (adjusted OR = 1.5; 95% confidence interval (95% CI) 1.1-2.1). After stratification, this association was statistically significant only after 10 or more years of exposure. Lung cancer was also related to exposure to asbestos (adjusted OR = 1.8; 95% CI 1.5-2.2). The ORs increased with increasing duration of exposure to asbestos for all smoking categories except for current smokers of 1-19 cigarettes per day. The statistical power to detect ORs among occupations that were previously reported to be at increased risk of lung cancer but that failed to show an OR of at least 1.5 in the current study was small. The cumulative population attributable risk (PAR) of lung cancer due to occupation was 9.2%. It is concluded that occupational factors play an important part in the development of lung cancer independently of cigarette smoking. Because occupations at high risk of lung cancer were under-represented, the cumulative PAR of the present study is likely to be an underestimate of the true contribution of occupation to risk of lung cancer.
PMCID: PMC1012148 PMID: 1419861
4. Relation between smoking history and gene expression profiles in lung adenocarcinomas
BMC Medical Genomics 2012;5:22.
Background
Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers’ lung carcinomas remain to a large extent unclear.
Methods
Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets.
Results
Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking.
Conclusions
Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
doi:10.1186/1755-8794-5-22
PMCID: PMC3447685 PMID: 22676229
Lung cancer; Smoking; Gene expression analysis; Adenocarcinoma; EGFR; Never-smokers; Immune response
5. Promoter methylation of RASSF1A and DAPK and mutations of K-ras, p53, and EGFR in lung tumors from smokers and never-smokers
BMC Cancer 2007;7:74.
Background
Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the ras-association domain isoform A (RASSF1A) and the death-associated protein kinase (DAPK) genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-ras, p53, and EGFR genes determined previously on these same lung tumors.
Methods
Promoter methylation of the RASSF1A and DAPK genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-ras, p53, and EGFR were obtained from our previous studies.
Results
The RASSF1A gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The DAPK gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the RASSF1A or DAPK genes did not correlate with the frequency of mutations of the K-ras, p53, and EGFR gene.
Conclusion
Our results showed that RASSF1A and DAPK genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-ras, p53 and EGFR genes, suggesting each of these events may represent independent event in non-small lung tumorigenesis.
doi:10.1186/1471-2407-7-74
PMCID: PMC1877812 PMID: 17477876
6. Tobacco Smoking and Lung Cancer
Tobacco smoking remains the most established cause of lung carcinogenesis and other disease processes. Over the last 50 years, tobacco refinement and the introduction of filters have brought a change in histology, and now adenocarcinoma has become the most prevalent subtype. Over the last decade, smoking also has emerged as a strong prognostic and predictive patient characteristic along with other variables. This article briefly reviews scientific facts about tobacco, and the process and molecular pathways involved in lung carcinogenesis in smokers and never-smokers. The evidence from randomised trials about tobacco smoking’s impact on lung cancer outcomes is also reviewed.
PMCID: PMC3749017 PMID: 23984018
Tobacco Smoking; Lung Neoplasms; Nicotine; EML4 ALK fusion protein, human; K-Ras Gene; Receptor, Epidermal Growth Factor; Carcinogens
7. Arsenic, asbestos and radon: emerging players in lung tumorigenesis
Environmental Health 2012;11:89.
The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards.
doi:10.1186/1476-069X-11-89
PMCID: PMC3534001 PMID: 23173984
8. COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma
Thorax 2004;59(8):679-681.
Background: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC.
Methods: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell.
Results: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype.
Conclusions: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype.
doi:10.1136/thx.2003.018291
PMCID: PMC1747095 PMID: 15282388
9. TP53 Mutations in Korean Patients with Non-small Cell Lung Cancer
Journal of Korean Medical Science 2010;25(5):698-705.
Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.
doi:10.3346/jkms.2010.25.5.698
PMCID: PMC2858827 PMID: 20436704
Lung Neoplasms; Mutation; Genes, p53
10. The Natural Tumor Suppressor Protein Maspin and Potential Application in Non Small Cell Lung Cancer
Current pharmaceutical design 2010;16(16):1877-1881.
The grim prognosis of lung cancer, that has an overall 10–15% survival at 5 years, remains in the US the leading cause of cancer mortality, providing a compelling rationale for studying the molecular basis of this malignancy. Surmising the common, general association with smoking, lung cancers differ at the microscopic, anatomical, epidemiological and clinical level and harbor complex genetic and epigenetic alterations. Currently, lung cancer is divided into small cell lung carcinoma (SCLC) and non small cell lung carcinoma (NSCLC) for the purpose of clinical management. NSCLC constitutes 80–85% of lung cancers and is further divided into histological subtypes such as adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, etc.
The ultimate goal for lung cancer research is to develop a strategy to block the tumor progression and improve the prognosis of lung cancer. This goal can realistically be achieved only when the biological complexity of this disease is taken into account. To this end, identification and understanding of molecular markers that are mechanistically involved in tumor progression are needed. Our recent studies suggest histological subtype-dependent distinct correlations between the expression and/or subcellular localization of tumor suppressive maspin with the progression and prognosis of NSCLC. Maspin is an epithelial specific member of the serine protease inhibitor (serpin) superfamily but recently identified as an endogenous inhibitor of histone deacetylase 1 (HDAC1). This novel biochemical activity coincides with a consensus emerged recently from the evidence that nuclear maspin confers better differentiated epithelial phenotypes, decreased tumor angiogenesis, increased tumor sensitivity to drug-induced apoptosis, and a more favorable prognosis. In the current review, we discuss the evidence that maspin may be a marker that stratifies the progression and prognosis of different subtypes of NSCLC.
PMCID: PMC2908495 PMID: 20337574
lung cancer; molecular marker; prognosis; histological subtypes; histone deacetylase 1; natural HDAC inhibitor; subcellular localization; differential expression; drug discovery
11. Update on anti-angiogenic therapy in non-small cell lung cancer: Are we making progress?
Journal of Thoracic Disease 2011;3(1):19-29.
Non-small cell lung cancer (NSCLC) remains a leading cause of death worldwide among patients diagnosed with malignancy. Despite new chemotherapy regimens and new cytotoxic combinations investigated in multiple clinical trials in recent years, no significant improvement in the prognosis of patients with lung cancer was achieved. The five-year survival rate for all patients diagnosed with NSCLC is about 15%, only 5% better than that of more than 40 years ago. New therapeutic approaches that target various different aspects of tumor progression and metastasis are of particular interest in to NSCLC patients. Drugs that block tumor vascularization (angiogenesis) or interfere with the activity of growth factor receptors and molecular pathways that are triggered by activation of these receptors are already used in clinical practice. In this review we will briefly discuss briefly the basic mechanisms of lung cancer angiogenesis, rationale for using drugs that block this process and present the most current recent data on their clinical efficacy.
doi:10.3978/j.issn.2072-1439.2010.11.11
PMCID: PMC3256499 PMID: 22263059
lung cancer; VEGF; angiogenesis; antiangiogenesis
12. A susceptibility locus on chromosome 6q greatly increases risk lung cancer risk among light and never smokers
Cancer research 2010;70(6):2359-2367.
Cigarette smoking is the major cause for lung cancer but genetic factors also affect susceptibility. We studied families that included multiple relatives affected by lung cancer. Results from linkage analysis showed strong evidence that a region of chromosome 6q affects lung cancer risk. To characterize the effects that this region of chromosome 6q region has on lung cancer risk we identified a haplotype that segregated with lung cancer. We then performed Cox regression analysis to estimate the differential effects that smoking behaviors have upon lung cancer risk according to whether each individual carried a risk-associated haplotype or could not be classified and was assigned unknown haplotypic status. We divided smoking exposures into never smokers, light smokers (<20 pack years), moderate smokers (20-<40 pack years) and heavy smokers (40 or more pack years). Comparing results according to smoking behavior stratified by carrier status, compared to never smokers, there was weakly increasing risk for increasing smoking behaviors, with the hazards ratios being 3.44, 4.91, and 5.18 respectively for light, moderate or heavy smokers, while among the individuals from families without the risk haplotype, the risks associated with smoking increased strongly with exposure, the hazards ratios being respectively 4.25, 9.17 and 11.89 for light, moderate and heavy smokers. The never smoking carriers had a 4.71 fold higher risk than the never smoking individuals without known risk haplotypes. These results identify a region of chromosome 6q that increases risk for lung cancer and that confers particularly higher risks to never and light smokers.
doi:10.1158/0008-5472.CAN-09-3096
PMCID: PMC2855643 PMID: 20215501
13. Progress and Challenges in Selected Areas of Tobacco Carcinogenesis
Chemical research in toxicology 2007;21(1):160-171.
Tobacco use continues to be a major cause of cancer in the developed world and, despite significant progress in this country in tobacco control which is driving a decrease in cancer mortality, there are still over one billion smokers in the world. This perspective discusses some selected issues in tobacco carcinogenesis focusing on progress during the 20 years of publication of Chemical Research in Toxicology. The topics covered include metabolism and DNA modification by tobacco-specific nitrosamines, tobacco carcinogen biomarkers, an unidentified DNA ethylating agent in cigarette smoke, mutations in the K-RAS and p53 gene in tobacco-induced lung cancer and their possible relationship to specific carcinogens, secondhand smoke and lung cancer, emerging issues in smokeless tobacco use, and a conceptual model for understanding tobacco carcinogenesis. It is hoped that a better understanding of mechanisms of tobacco-induced cancer will lead to new and useful approaches for prevention of lung cancer and other cancers caused by tobacco use.
doi:10.1021/tx7002068
PMCID: PMC2556958 PMID: 18052103
tobacco specific nitrosamines; secondhand smoke; smokeless tobacco; tobacco carcinogen biomarkers
14. Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases.
BMJ : British Medical Journal 1997;314(7098):1860-1863.
OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.
PMCID: PMC2126967 PMID: 9224127
15. Smoking-related Genomic Signatures in Non–Small Cell Lung Cancer
Rationale: Tobacco smoking is responsible for 85% of all lung cancers. To further our understanding of the molecular pathogenesis of lung cancer, we determined whether smoking history leads to the emergence of specific genomic alterations found in non–small cell lung cancer (NSCLC).
Objectives: To identify gene copy number alterations in NSCLCs associated with smoking history or DNA repair capacity.
Methods: Seventy-five NSCLCs were selected for this study from patients with current, none, or past smoking history, including pack year information. Tissue sections were microdissected, and DNA was extracted, purified, and labeled by random priming before hybridization onto bacterial artificial chromosome (BAC) arrays. Normalized ratios were correlated with smoking history and DNA repair capacity was measured by an in vitro lymphocyte assay in the same patients.
Measurements and Main Results: We identified smoking-related genomic signatures in NSCLCs that could be predicted with an overall 74% accuracy. Lung tumors arising from current-smokers had the greatest number of copy number alterations. The genomic regions most significantly associated with smoking were located within 60 regions and were functionally associated with genes controlling the M phase of the cell cycle, the segregation of chromosomes, and the methylation of DNA. Verification of the data is provided from data in the public domain and by quantitative real-time polymerase chain reaction. The associations between genomic abnormalities and DNA repair capacity did not reach statistical significance.
Conclusions: These findings indicate that smoking history leaves a specific genomic signature in the DNA of lung tumors and suggest that these alterations may reflect new molecular pathways to cancer development.
doi:10.1164/rccm.200801-142OC
PMCID: PMC2720147 PMID: 18776155
array comparative genomic hybridization; tobacco; profile; microarray
16. LUNG CANCER IN NEVER SMOKERS: CLINICAL EPIDEMIOLOGY AND ENVIRONMENTAL RISK FACTORS
More than 161,000 lung cancer deaths are projected to occur in the U.S. in 2008. Of these, an estimated 10–15% will be caused by factors other than active smoking, corresponding to 16,000–24,000 deaths annually. Thus lung cancer in never smokers would rank among the most common causes of cancer mortality in the U.S. if considered to be a separate category. Slightly more than half of the lung cancers caused by factors other than active smoking occur in never smokers. As summarized in the accompanying article, lung cancers that occur in never smokers differ from those that occur in smokers in their molecular profile and response to targeted therapy. These recent laboratory and clinical observations highlight the importance of defining the genetic and environmental factors responsible for the development of lung cancer in never-smokers. This article summarizes available data on the clinical epidemiology of lung cancer in never smokers, and the several environmental risk factors that population-based research has implicated in the etiology of these cancers. Primary factors closely tied to lung cancer in never smokers include exposure to known and suspected carcinogens including radon, second-hand tobacco smoke, and other indoor air pollutants. Several other exposures have been implicated. However, a large fraction of lung cancers occurring in never-smokers cannot be definitively associated with established environmental risk factors, highlighting the need for additional epidemiologic research in this area.
doi:10.1158/1078-0432.CCR-09-0376
PMCID: PMC3170525 PMID: 19755391
17. Lung cancer in never smokers Epidemiology and risk prediction models
In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/ nonsmokers and describe the never smoker lung cancer risk models used by CISNET modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model.
doi:10.1111/j.1539-6924.2012.01768.x
PMCID: PMC3485693 PMID: 22882894
18. Occupation, Gender, Race, and Lung Cancer
Objective
To examine associations between occupation and lung cancer by gender and race.
Methods
We used data from the Maryland Lung Cancer Study of nonsmall cell lung carcinoma (NSCLC), a multicenter case control study, to estimate odds ratios (ORs) of NSCLC in different occupations.
Results
After adjusting for smoking, environmental tobacco smoke, and other covariates, NSCLC ORs among women but not men were elevated in clerical-sales, service, and transportation-material handling occupations; ORs were significantly increased in all three categories (OR [95% confidence interval]: 4.07 [1.44 to 11.48]; 5.15 [1.62 to 16.34]; 7.82 [1.08 to 56.25], respectively), among black women, but only in transportation-material handling occupations (OR [95% confidence interval[: 3.43 [1.02 to 11.50]) among white women.
Conclusions
Women, especially black women, in certain occupations had increased NSCLC ORs.
doi:10.1097/JOM.0b013e31817d3639
PMCID: PMC2585362 PMID: 18849762
19. Regular Adult Aspirin Use Decreases the Risk of Non-Small Cell Lung Cancer among Women
Background
Prior studies indicate that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of non-small cell lung cancer (NSCLC); however, results have been contradictory in part because of variation in study design. Few studies have examined the use of aspirin or other NSAIDs on risk of NSCLC in women.
Methods
Through a case-control study of African American and Caucasian women with and without NSCLC, we examined the relationship between use of aspirin, NSAIDs, and acetaminophen and risk of NSCLC. Risk was estimated by calculating odds ratios and 95% confidence intervals for ever/never use, duration of use, and duration of use category (never, 1–5 years, >5 years) after adjusting for major risk factors for lung cancer. Risk estimates were stratified by race, age, smoking history, and body mass index.
Results
Ever use of adult-strength aspirin was associated with a significant reduction in risk of NSCLC (odds ratio, 0.66; 95% confidence interval, 0.46–0.94). Additionally, there was a significant trend toward a reduced risk of NSCLC in adult-strength aspirin users with increasing duration of use (Ptrend = 0.02). In stratified analyses, aspirin use was associated with a significantly reduced risk of lung cancer among Caucasians and 55- to 64-year-olds. Baby aspirin and NSAID use was associated with a significant reduction in risk of NSCLC only among 65- to 74-year-olds.
Conclusion
Our results suggest that long-term use of adult-strength aspirin may reduce the risk of NSCLC in women.
doi:10.1158/1055-9965.EPI-07-0517
PMCID: PMC3771076 PMID: 18187393
20. WHAT PROPORTION OF LUNG CANCER IN NEVER-SMOKERS CAN BE ATTRIBUTED TO KNOWN RISK FACTORS?
Though tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime non-smokers. In this paper, we calculate the burden of lung cancer in never-smokers attributable to previously identified risk factors in North America, Europe, and China, using population-based estimates of exposure prevalence and estimates of relative risk derived from recently published meta-analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40% to 19.93%. Due to differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never-smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never-smokers, and highlight the need for further research in this area, particularly in Europe and North America.
doi:10.1002/ijc.27477
PMCID: PMC3359408 PMID: 22322343
lung cancer; population attributable fraction; non-smokers
21. The accumulated evidence on lung cancer and environmental tobacco smoke.
BMJ : British Medical Journal 1997;315(7114):980-988.
OBJECTIVE: To estimate the risk of lung cancer in lifelong non-smokers exposed to environmental tobacco smoke. DESIGN: Analysis of 37 published epidemiological studies of the risk of lung cancer (4626 cases) in non-smokers who did and did not live with a smoker. The risk estimate was compared with that from linear extrapolation of the risk in smokers using seven studies of biochemical markers of tobacco smoke intake. MAIN OUTCOME MEASURE: Relative risk of lung cancer in lifelong non-smokers according to whether the spouse currently smoked or had never smoked. RESULTS: The excess risk of lung cancer was 24% (95% confidence interval 13% to 36%) in non-smokers who lived with a smoker (P < 0.001). Adjustment for the effects of bias (positive and negative) and dietary confounding had little overall effect; the adjusted excess risk was 26% (7% to 47%). The dose-response relation of the risk of lung cancer with both the number of cigarettes smoked by the spouse and the duration of exposure was significant. The excess risk derived by linear extrapolation from that in smokers was 19%, similar to the direct estimate of 26%. CONCLUSION: The epidemiological and biochemical evidence on exposure to environmental tobacco smoke, with the supporting evidence of tobacco specific carcinogens in the blood and urine of non-smokers exposed to environmental tobacco smoke, provides compelling confirmation that breathing other people's tobacco smoke is a cause of lung cancer.
PMCID: PMC2127653 PMID: 9365295
22. Regional, disease specific patterns of smoking-attributable mortality in 2000
Tobacco Control 2004;13(4):388-395.
Background: Smoking has been causally associated with increased mortality from several diseases, and has increased considerably in many developing countries in the past few decades. Mortality attributable to smoking in the year 2000 was estimated for adult males and females, including estimates by age and for specific diseases in 14 epidemiological subregions of the world.
Methods: Lung cancer mortality was used as an indirect marker of the accumulated hazard of smoking. Never-smoker lung cancer mortality was estimated based on the household use of coal with poor ventilation. Estimates of mortality caused by smoking were made for lung cancer, upper aerodigestive cancer, all other cancers, chronic obstructive pulmonary disease (COPD), other respiratory diseases, cardiovascular diseases, and selected other medical causes. Estimates were limited to ages 30 years and above.
Results: In 2000, an estimated 4.83 million premature deaths in the world were attributable to smoking, 2.41 million in developing countries and 2.43 million in industrialised countries. There were 3.84 million male deaths and 1.00 million female deaths attributable to smoking. 2.69 million smoking attributable deaths were between the ages of 30–69 years, and 2.14 million were 70 years of age and above. The leading causes of death from smoking in industrialised regions were cardiovascular diseases (1.02 million deaths), lung cancer (0.52 million deaths), and COPD (0.31 million deaths), and in the developing world cardiovascular diseases (0.67 million deaths), COPD (0.65 million deaths), and lung cancer (0.33 million deaths). The share of male and female deaths and younger and older adult deaths, and of various diseases in total smoking attributable deaths exhibited large inter-regional heterogeneity, especially in the developing world.
Conclusions: Smoking was an important cause of global mortality in 2000, affecting a large number of diseases. Age, sex, and disease patterns of smoking-caused mortality varied greatly across regions, due to both historical and current smoking patterns, and the presence of other risk factors that affect background mortality from specific diseases.
doi:10.1136/tc.2003.005215
PMCID: PMC1747946 PMID: 15564623
23. Teen smoking, field cancerization, and a "critical period" hypothesis for lung cancer susceptibility.
Environmental Health Perspectives 2002;110(6):555-558.
Cigarette smoking by children and adolescents continues to be prevalent, and this fact represents a major public health problem and challenge. Epidemiologic work has previously suggested that exposure of the lung to tobacco carcinogens at an early age may be an independent risk factor for lung cancer. Recent studies at the molecular and cellular levels are consistent with this, now suggesting that early exposure enhances DNA damage and is associated with the induction of DNA alterations in specific chromosomal regions. In this paper we hypothesize that adolescence, which is known to be the period of greatest development for the lung, may constitute a "critical period" in which tobacco carcinogens can induce fields of genetic alterations that make the early smoker more susceptible to the damaging effects of continued smoking. The fact that lung development differs by sex might also contribute to apparent gender differences in lung cancer susceptibility. Because this hypothesis has important implications for health policy and tobacco control, additional resources need to be devoted to its further evaluation. Targeted intervention in adolescent smoking may yield even greater reductions in lung cancer occurrence than otherwise anticipated.
PMCID: PMC1240869 PMID: 12055044
24. Randomized Phase II Trial of Erlotinib Alone or With Carboplatin and Paclitaxel in Patients Who Were Never or Light Former Smokers With Advanced Lung Adenocarcinoma: CALGB 30406 Trial
Journal of Clinical Oncology 2012;30(17):2063-2069.
Purpose
Erlotinib is clinically effective in patients with non–small-cell lung cancer (NSCLC) who have adenocarcinoma, are never or limited former smokers, or have EGFR mutant tumors. We investigated the efficacy of erlotinib alone or in combination with chemotherapy in patients with these characteristics.
Patients and Methods
Patients with advanced NSCLC (adenocarcinoma) who were epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy naive never or light former smokers (smokers of > 100 cigarettes and ≤ 10 pack years and quit ≥ 1 year ago) were randomly assigned to continuous erlotinib or in combination with carboplatin and paclitaxel (ECP) for six cycles followed by erlotinib alone. The primary end point was progression-free survival (PFS). Tissue collection was mandatory.
Results
PFS was similar (5.0 v 6.6 months; P = .1988) in patients randomly assigned to erlotinib alone (arm A; n = 81) or to ECP (arm B; n = 100). EGFR mutation analysis was possible in 91% (164 of 181) of patients, and EGFR mutations were detected in 40% (51 of 128) of never smokers and in 42% (15 of 36) of light former smokers. In arm A, response rate (70% v 9%), PFS (14.1 v 2.6 months), and overall survival (OS; 31.3 v 18.1 month) favored EGFR-mutant patients. In arm B, response rate (73% v 30%), PFS (17.2 v 4.8 months), and OS (38.1 v 14.4 months) favored EGFR-mutant patients. Incidence of grades 3 to 4 hematologic (2% v 49%; P < .001) and nonhematologic (24% v 52%; P < .001) toxicity was greater in patients treated with ECP.
Conclusion
Erlotinib and erlotinib plus chemotherapy have similar efficacy in clinically selected populations of patients with advanced NSCLC. EGFR mutations identify patients most likely to benefit.
doi:10.1200/JCO.2011.40.1315
PMCID: PMC3397694 PMID: 22547605
25. Phase II study of erlotinib as a salvage treatment for non-small-cell lung cancer patients after failure of gefitinib treatment
Annals of Oncology 2008;19(12):2039-2042.
Background: Both gefitinib and erlotinib are reversible epidermal growth factor receptor tyrosine kinase inhibitors, but they have somewhat different pharmacological properties. We conducted a phase II study of erlotinib after failure of gefitinib treatment in patients with non-small-cell lung cancer (NSCLC).
Patients and methods: Patients with advanced/metastatic NSCLC who had shown disease progression on gefitinib treatment were treated with erlotinib 150 mg/day until disease progression or intolerable toxicity.
Results: Between September 2006 and January 2008, a total of 23 patients were enrolled and all were assessable for response and toxicity. All patients were never smokers and all but one had adenocarcinoma. Of these 23 patients, one had a partial response and one stable disease, resulting in an objective response rate of 4.3% and a disease control rate of 8.7%. These two patients benefited from erlotinib for 6.2 months and 7.8 months, respectively; both had also benefited from prior gefitinib therapy. The most common toxic effects were skin rash and diarrhea.
Conclusion: Erlotinib should not be given routinely after failure of gefitinib treatment, but can be an option for more highly selected subsets, especially those who had benefited from prior gefitinib treatment. Identification of molecular markers in tumors is important to understand and overcome acquired resistance to gefitinib.
doi:10.1093/annonc/mdn423
PMCID: PMC2733114 PMID: 18644828
erlotinib; gefitinib; non-small cell lung cancer
Results 1-25 (655765)
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• Writer's pictureTerri Gilmore
So, I Think I Need Hearing Aids…Now What?
Step 1: Hearing Aid Consultation: If you have a hearing loss and it is determined that you could benefit from hearing aids, an audiologist can help you through the process of choosing what is most appropriate for you. There are hundreds of hearing aids available, so the audiologist narrows down the choices to those hearing aids that are most likely to meet your needs. Although the audiologist is there to provide guidance, you are the one who will ultimately make the decision about what type of hearing aid is right for you.If you are not satisfied with your choice, don’t worry, you have at least 90-days in which you can exchange or return the hearing aids. If returned, we will refund your money, minus a $100 service fee per hearing aid.
Step 2: Hearing Aid Ordering and Delivery: After you have decided about the style and technology that best suits your hearing needs, hearing aids can be ordered. Depending on the hearing aid model, a cast of the inside of your ear, which is called an “ear impression”, may need to be taken. These custom-fit hearing aids will arrive in about one week. Other types of hearing aids can be fit the very same day!Once you have your hearing aids, we ensure that the hearing aids feel and sound comfortable. We demonstrate how the hearing aids work and provide instructions on how to care for them.
Step 3: Follow-up: Hearing aids are not like glasses—we don’t “pop” them into your ears and off you go. You may need to return several times to have your hearing aids fine-tuned. Once you leave the office, we ask that you write down your hearing aid experiences so that, we can more specifically address your unique listening needs during your follow-up appointments.
Step 4: Maintenance: Following the 90-day trial period, our relationship with you and your hearing aids doesn’t end. We recommend that you return for periodic hearing aid checks to keep your hearing aids functioning to peak performance.Any hearing aid purchased from us also comes with a manufacturer’s 2- 3 year repair and 2- 3 year loss and damage warranty. You will be provided with information on an optional warranty program before the manufacturer’s warranty expires. This would give you the opportunity renew the repair and/or loss and damage warranty. Even if your hearing aids are out of warranty, all in-house repairs and hearing aid maintenance checks are free of charge for the lifetime of your hearing aids.
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CKDdb-logoCKDdb - Molecule ID A0631
geneC1QBP, GC1QBP, HABP1
nameComplement component 1
speciesHomo sapiens
Molecule reference
SwissProtUniProtEnsEMBLGeneIDUniGeneOMIM
C1QBP_HUMANQ07021ENSG00000108561708Hs.555866601269
Functions and classifications
GOC:cell surface, C:cytosol, C:extracellular space, C:mitochondrial matrix, C:mitochondrion, C:nucleolus, C:nucleus, C:plasma membrane, F:adrenergic receptor binding, F:complement component C1q binding, F:hyaluronic acid binding, F:kininogen binding, F:mitochondrial ribosome binding, F:mRNA binding, F:transcription corepressor activity, F:transcription factor binding, P:apoptotic process, P:blood coagulation, intrinsic pathway, P:complement activation, classical pathway, P:immune response, P:innate immune response, P:mature ribosome assembly, P:mRNA processing, P:negative regulation of defense response to virus, P:negative regulation of interferon-gamma production, P:negative regulation of interleukin-12 production, P:negative regulation of MDA-5 signaling pathway, P:negative regulation of mRNA splicing, via spliceosome, P:negative regulation of RIG-I signaling pathway, P:negative regulation of transcription from RNA polymerase II promoter, P:phosphatidylinositol 3-kinase signaling, P:positive regulation of apoptotic process, P:positive regulation of dendritic cell chemotaxis, P:positive regulation of mitochondrial translation, P:positive regulation of neutrophil chemotaxis, P:positive regulation of protein kinase B signaling, P:positive regulation of substrate adhesion-dependent cell spreading, P:positive regulation of trophoblast cell migration, P:regulation of complement activation, P:RNA splicing, P:transcription, DNA-templated, P:viral process, P:phosphatidylinositol 3-kinase cascade, P:positive regulation of protein kinase B signaling cascade, P:virus-host interaction
UniProt3D-structure, Acetylation, Adaptive immunity, Apoptosis, Cell membrane, Complement pathway, Complete proteome, Cytoplasm, Direct protein sequencing, Host-virus interaction, Immunity, Innate immunity, Membrane, Mitochondrion, mRNA processing, mRNA splicing, Nucleus, Phosphoprotein, Reference proteome, Ribosome biogenesis, Secreted, Transcription, Transcription regulation, Transit peptide
PADBribosome
Studies, tissues and diseases
Study IDSpeciesNTissue / SourceCompartmentDiseaseFold change in diseaseP-valueDetectionValidationPubMed/DOI
Exp19369687Mus musculus kidneyproximal tubule cellsCyclosporine_A_induced (Ciclosporine A in vitro model)0.58< 0.02MALDI TOF/TOFWestern blot19369687
Exp19698090bHomo sapiens25bloodmononuclear cellsDialysis (hemodialysis)2.30.00000335RNA microarray 19698090
Exp19698090bHomo sapiens25bloodmononuclear cellsDialysis (hemodialysis)2.470.00000127RNA microarray 19698090
Exp19836472Mus musculus kidneytubule cellsDiabetes (Diabetic Nephropathy)0.16 LC-MS/MS 19836472
Exp20093355Homo sapiens33kidney Fibrosis (Interstitial fibrosis and tubular atrophy)down MS/MS, LTQ LX linear ion trap 20093355
Exp25667632Homo sapiens10kidneybiopsy sectionGlomerulonephritis (membranous nephropathy)0.65< 0.05MALDI-TOF/TOF 25667632
Exp26317775aHomo sapiens53kidneybiopsy specimensChronic_Renal_Insufficiency (CKD)0.473.78E-03RNA microarray 26317775
Compile date 08-10-2018© iMODE-CKD consortium
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\
Observation and the Senses
the roots of knowledge remain obscure
rule
OBSERVATION: The fundamental basis of all science is observation. And ALL observation is made with the senses. Instruments (such as meter sticks, thermometers, Voltmeters, and Geiger counters) are often used to augment the senses.
Traditionally there are five senses:
But despite the importance of the senses for life, science, and knowledge of all variety, much about the senses remains obscure. For example, touch may actually be several distinct senses.
eye SIGHT: Even the most important sense, vision, is only partly understood. It has been long understood that light, diverging from its point of origin (or reflection), is focused by the convex lense at the front of the eye forming a real image on the light sensitive back surface of the transparent spherical eye. This retina is densely populated with several distinct kinds of nerve sensors: Most abundant by far, the long, slender rods are (therefore?) very sensitive to dim light (coupled together, they may detect single photons) and are responsible for black and white night vision; it is generally believed that three pigmented variations of shorter, larger diameter cones results in sensitivity to different color ranges, thereby provide information for color vision. Gerald Huth has noted that the rods and cones form a detector array. Huth proposes that rather than each rod or cone being an isolated detector, they work together as a spatial array to detect light with the spacing between rod-rod, cone-cone, and rod-cone being responsible for the three different color detection ranges. Whether distinguishing color is a matter of pigments or spacing, the traditional notion of three primary colors is a certainly a simplified description of color processing by human eyes and brains rather than a description of fundamental aspects of color or light. (See a dialog on colored vision and Primary colors: No for a further explanations of color vision and color printing.) The retina consists of 5 layers of cells with extensive interconnections between each layer. There are about 125 times as many receptors in the retina as there are ganglion cells in the optic nerve. So some processing must occur in the eye prior to transmitting the information to the brain. The signals from different cone types are segregated in opponent pairs during this processing so that ganglion cells have specific receptive fields that are excited by one cone type in the center and inhibited by those further away. This organization has been extensively investigated but the perception of color does not relate easily with this organization.
retina Only the front part of human eyes have similarity to cameras that use film. More similar are digital cameras using CCDs (charge coupling devices) containing millions of distinct pixel light detectors, each of which sends electronic signals to a computer chip for processing such as color correction and jpeg compression. Rods and cones use spatial, molecular, and electrical processes to detect the light. 11-cis-retinal (an aldehyde) is an oxidized form of Vitamin A (an alcohol often derived from half of a β-carotene molecule). Absorbed light partially dissociates electrons in the cis double bond (in middle of a series of resonating double bonds), allowing the normally stiff 11-cis-retinal molecule to briefly rotate. The bond reforms 50% cis and 50% trans isomers. The differently shaped trans-retinal forces a shape change in the larger enclosing protein, rhodopsin, releasing an electron signal. Nearby proteins called transducin amplify the electric signal. Recent experiments with rodents suggest that when light is brighter the transducin move away from the rhodopsin reducing the signal amplification. Transparent ganglions pre-process information from clusters of cones and rods, perhaps distinguishing color, pattern, and motion before transmission to the brain for further processing. Despite the pre-processing, vision is data intense, requiring the largest nerve bundle in the body to transport electrical information to the brain. Much about the recognition of patterns (such as with letters and faces) and motion remains less than completely understood. Conceivably there may be other aspects of vision beyond color, pattern, and motion.
HEARING: Like vision, the initial mechanism of hearing is understood. Sound vibrations cause the membrane in the ear (ear drum) to push on a series of three bony levers (hammer, anvil, stirrup) transferring vibrations through an inner membrane to a liquid in the Cochlea, the snail shaped inner ear. The motion of the liquid causes the sway of a series of hairs. The motion of hairs is detected by nerves much like nerves can feel the motion of hairs on other body surfaces. (A similar system of fluid moving hairs is used in the nearby semicircular canals to maintain balance by detecting head motions.) The detection of tones, rhythms, and harmonies are presumably functions of the brain. Like motion and patterns in vision, they remain shrouded in mystery.
TASTE: Classically the tongue detects four flavors: sweet, salty, sour and its chemical opposite, bitter. Recently a fifth taste of glutamate (msg) has been proposed. There are proposals for the mechanism of taste involving a chemical lock and key process where there is a match of molecular shape and functional groups with larger receptor molecules. Taste buds mostly located along the edges of the tongue (from front to back in the order listed above) contain taste pores which house taste cells attached to nerves.
SMELL: The detection of odors is done by a series of nerve cells at the top most part of the nasal passage. Tiny nerves fibers lead directly from this olfactory bulb into the central part of the brain. The sense of smell may use similar chemical lock and key mechanisms to those of taste; if that is true, there may need to be as many as 1000 distinct nerve receptors. Apparently a single substance at different concentrations causes different combinations of receptors to report detection; the result is perception of distinct odors from different concentrations of the same substance. Perception also varies with time. Attempts to classify odors into primary smells has generally been unsatisfactory.
The taste of a particular food is typically a combination of information from the taste buds and the olfactory bulb. The possibility of patterns and motions in tastes and odors similar to visual and sound harmonies and time rhythms remains beyond current investigation.
TOUCH: The sense of touch seems to involve several types of sensors, or perhaps sensors that can report differing types of information. The skin can report temperature (or at least warmth or cold), pressure (such as touch), the motion of skin hairs and perhaps even their position as when they are more erect when cold, and pain of excess heat, cold, pressure, cut, or puncture. Possible connections between temperature, pressure, pain and pleasure remain nearly at the level of cult!
Some areas of the body are more heavily populated with nerves: at other locations the body is unable to distinguish two touches some distance apart. A kiss is thought to create much pleasure because the face and lips are very sensitive and seem to involve many nerves. Other sexual pleasures are probably similar.
Much of the time the senses report monotonously duplicate information that the nervous system generally ignores. Small background sounds, peripheral vision where little changes, and constant reports of the pressure of clothes and moderate temperatures generally go unnoticed. But at any moment a person can usually choose to monitor information from a given sensor. A person can feel their shirt collar, the motion of a toe, and sometimes even hear their heart beat. But usually a person's brain takes note of only the most interesting of the thousands of bits of information from their senses. A study of fruit fly photoreceptors may reveal part of the mechanism used to discount nerve signals. Fruit fly detectors involves a protein channel that regulates the flow of ions through cells. The protein is abundant when there has been no stimulation. But after stimulation 70% of the protein is moved to a storage compartment reducing the signals.
Internal organs also contain nerves that typically are continually ignored unless a problem occurs. But any person who has ever experienced pressure caused by child birth, appendicitis, a gall stone, or kidney stone knows how intense that pain can be. Sometimes it is as if those nerves have never been calibrated and their location mapped so that the pain seems to originate some distance from the actual source.
(to Part 2: speculation on consciousness, pleasure, pain and drugs)
References:
rule
to main menu
Color Vision
created 4/17/99
to ccs/xhtml 3/18/2002
last revised 2/16/2006
by D Trapp
Mac made
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5eff3d1f6f98e57329caed0ceb9053d3
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4,313,417,797,626,862,000
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Galician (Galego)Español (spanish formal Internacional)PortuguésEnglish (United Kingdom)
Home Plenaria
Datas importantes
Plenária Correo-e
Abstract.
Rubin (1976) classified missing data as MCAR, MAR, and MNAR. Given that models for missing data often make unverifiable assumptions about the missing value mechanism, sensitivity analysis is needed. In joint modeling of time-to-event and longitudinal data, similar issues arise. The longitudinal covariate may be measured with error, its values are likewise only available at the specific time points at that the patient appears at the clinic for longitudinal measurements, and the time-to-event may also be censored.
Undeniably, there is a strong connection between the missing data and the joint longitudinal and time-to-event settings, the theme of this work. We build an extended shared random effects joint model, similar in spirit to that of Creemers et al (2011). An added layer of complexity is that data can be coarsened in various ways: the longitudinal sequence can be incomplete; the time-to-event outcome can be censored; both of these can occur simultaneously. Within the extended framework, we provide a characterization of MAR, consistent to the one in the missing data setting, and juxtapose it with more conventional joint models. This opens routes for sensitivity analysis.
Reference:
Njeru Njagi, E., Molenberghs, G., Kenward, M.G., Verbeke, G., and Rizopoulos, D. (2014). A Characterization of Missingness at Random in a Generalized Shared-parameter Joint modelling Framework for Longitudinal and Time-to-Event Data, and Sensitivity Analysis. Biometrical Journal, 56, 1001-1015.
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4,940,722,401,609,818,000
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Hidenori Ohnishi
Gifu University, Gifu-shi, Gifu-ken, Japan
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Publications (31)64.02 Total impact
• Article: Hypothermia augments NF-kappaB activity and the production of IL-12 and IFN-gamma.
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ABSTRACT: The differentiation of Th1 and Th2 is strictly regulated by humoral and cellular factors. The imbalance between Th1 and Th2 is considered to be the pathogenesis of allergic and autoimmune disorders. It is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of Th1 and Th2. We investigated the expression of IFN-gamma, IL-4, IL-5, IL-10 and IL-12 from LPS- or PHA-stimulated PBMCs at 30 degrees C or 37 degrees C using ELISA and Real-time PCR. We measured the change of NF-kappaB activity at 30 degrees C or 37 degrees C with LPS stimulation using the reporter gene assay. IFN-gamma production from LPS-stimulated PBMCs at 30 degrees C was up-regulated compared with 37 degrees C. IL-5 and IL-10 production from PHA-stimulated PBMCs at 30 degrees C were down-regulated compared with 37 degrees C. This augmented IFN-gamma production was caused by the up-regulation of IL-12 production from CD14+ blood monocytes. Both IL-12 mRNA and IL12 protein at 30 degrees C were up-regulated compared with 37 degrees C. NF-kappaB, the key molecule for the expression of IL-12, was also augmented at 30 degrees C compared with 37 degrees C. Hypothermia up-regulated the expression of IL-12 and IFN-gamma due to the augmented NF-kappaB activity. It is suggested that hypothermia modifies the pattern of cytokine gene expression.
Allergology International 10/2008; 57(4):331-8.
• Article: [QOL questionnaire for pediatric patients with bronchial asthma and their parents or caregivers. Preparation and evaluation of the short form version 2008 (Gifu)].
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ABSTRACT: The QOL questionnaire version 2001 for pediatric patients with bronchial asthma and their parents or caregivers includes 15 questions for patients under the age of 4 years and 20 questions for patients over the age of 4 years. We have already reported that the QOL questionnaire version 2001 reflects reliability (including reproducibility), factorial validity, and changes in paroxysmal attacks of asthma. In this study, we revised the questionnaire for use in routine medical practice. In this study, based on the data of a previous report, the number of questions was reduced further and it was revised to the questionnaire the short form by integrated data. The revised version 2008 (Gifu) consisted of emotional burden, asthma attack, instability of symptoms and proper acceptance of asthma as a common factor, moreover 4 or more years old added load of exercise factor which consisted of two questions in each factor. This QOL short form questionnaire version 2008 (Gifu) is a disease specific questionnaire in comparison with health control, bronchial asthma and non-asthmatic patients, such as atopic dermatitis and allergic rhinitis. Although Cronbach's alpha fell with reduction of the number of questions, we conclude that it was acceptable in the clinical practice.
Arerugī = [Allergy] 09/2008; 57(8):1022-33.
• Article: A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma.
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ABSTRACT: Cysteinyl-leukotrienes are important pro-inflammatory mediators in bronchial asthma (BA) and are derived from arachidonic acid by the action of 5-lipoxygenase. We identified a novel polymorphism, c.760 G>A (E254K), in exon 6 of the 5-lipoxygenase gene (5-LO). This substitution was detected in 11 out of 180 patients with BA, but not in any of the 150 non-allergic subjects. The frequency of c.760 G>A showed a significant difference between BA and non-allergic subjects (P=0.0007). The c.760 G>A polymorphism existed at the surface edge of the C-terminal catalytic domain, and the E-to-K substitution changed the charge of the side chain from negative to positive. Thus, our results suggest that E254K in the 5-LO might be associated with BA.
International Journal of Molecular Medicine 03/2008; 21(2):139-44. · 1.98 Impact Factor
• Article: Development of fluorescence-linked immunosorbent assay for high throughput screening of interferon-gamma.
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ABSTRACT: Human interferon-gamma (hIFN-gamma) is produced by lymphocytes and has a variety of biological properties. Measurement of hIFN-gamma is widely used for various immunological responses for allergic or autoimmune diseases. Enzyme-linked immunosorbent assay (ELISA) is an established immunoassay used to quantify cellular metabolites or cytokines. ELISA requires many incubation and wash steps and is not practically suitable for screening large numbers of samples. We have developed a fluorescence-linked immunosorbent assay (FLISA) method for the detection of hIFN-gamma. We measured the 50% inhibitory concentration (IC50) value of the hIFN-gamma production by interleukin (IL)-18 binding protein and anti-IL-18 monoclonal antibody. The IC50 described by FLISA was compared with that by ELISA. We developed a new system for measuring hIFN-gamma using Allophycocyanine (APC) fluorescent protein and compared it with the previous method using Cy5.5. The proposed FLISA had a smaller coefficient of variation than ELISA, and the means of coefficient of variation using the same samples measured by ELISA and FLISA were, respectively, 11.1% and 3.8%, suggesting that the edge effect often giving non-specific results may be smaller in FLISA than in ELISA. The improved FLISA system proposed is ideally suited for efficient measurements of hIFN-gamma. This homogeneous and multiplex method will be a powerful tool for high throughput screening for drug discovery research.
Allergology International 04/2006; 55(1):49-54.
• Article: Molecular mechanism of a temperature-sensitive phenotype in peroxisomal biogenesis disorder.
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ABSTRACT: Peroxisomal biogenesis disorders include Zellweger syndrome and milder phenotypes, such as neonatal adrenoleukodystrophy (NALD). Our previous study of a NALD patient with a marked deterioration by a fever revealed a mutation (Ile326Thr) within a SH3 domain of PEX13 protein (Pex13p), showing a temperature-sensitive (TS) phenotype in peroxisomal biogenesis. Clinical TS phenotypes also have been reported in several genetic diseases, but the molecular mechanisms still remain to be clarified. The immunofluorescent staining with anti-Pex13p antibody also revealed TS phenotype of the I326T mutant protein itself in the patient cells. Protease digestion of the recombinant Pex13p-SH3 domain showed an increase of protease susceptibility, suggesting a problem of mutant protein fold. Conformational analyses against urea denaturation using urea gradient gel electrophoresis or fluorescence emission from tryptophan residue revealed that the mutant protein should be easily unfolded. Far-UV circular dichroism (CD) spectra demonstrated that both wild-type and the mutant protein have antiparallel beta-sheets as their secondary structure with slightly different extent. The thermal unfolding profiles measured by CD showed a marked lower melting temperature for I326T protein compared with that of wild-type protein. Analysis of the protein 3D-structure indicated that the Ile326 should be a core residue for folding kinetics and the substitution of Ile326 by threonine should directly alter the kinetic equilibrium, suggesting a marked increase of the unfolded molecules when the patient had a high fever. Structural analyses of the protein in the other genetic diseases could provide an avenue for better understanding of genotype-phenotype correlations.
Pediatric Research 09/2005; 58(2):263-9. · 2.70 Impact Factor
• Article: Systematic optimization of active protein expression using GFP as a folding reporter.
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ABSTRACT: Many recombinant proteins have been used as drugs; however, human proteins expressed using heterologous hosts are often insoluble. To obtain correctly folded active proteins, many optimizations of expression have been attempted but usually are found to be applicable only for specific targets. Interleukin-18 (IL-18) has a key role in many severe disorders including autoimmune diseases, and therapeutic approaches using IL-18 have been reported. However, production of IL-18 in Escherichia coli resulted in extensive inclusion body formation and previous conventional screenings of expression conditions could obtain only a condition with a low yield. To address the problem, we applied a folding reporter system using green fluorescent protein (GFP) for screening of the expression conditions for hIL-18. The established system efficiently screened many conditions, and optimized conditions for the expression of hIL-18 significantly enhanced the final yield of the active protein. Systematic screening using a GFP reporter system could be applied for the production of other proteins and in other organisms.
Protein Expression and Purification 09/2004; 36(2):327-32. · 1.59 Impact Factor
• Article: Generation of highly stable IL-18 based on a ligand-receptor complex structure.
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ABSTRACT: Human interleukin-18 (hIL-18), initially cloned as an IFN-gamma-inducing factor, has a key role in many inflammatory diseases. We have previously developed a high production system for correctly folded active hIL-18 protein, leading to the revelation of the 3D-structure and the receptor binding mode. These findings can strongly indicate the experimental and medical applications of IL-18; however, the recombinant protein is prone to be inactivated forming multimers. Recently, therapeutic approaches using recombinant IL-18 have shown the effectiveness for treatment of cancer; indicating the necessity of a more stable protein for therapy with intertrial reliability. Here we have generated a highly stable hIL-18 with replacement of cysteine by serine based on the tertiary structure and the binding mechanism, retaining the biological activity. Similar rational designs can be applied to develop new therapeutic molecules of other cytokines.
Biochemical and Biophysical Research Communications 05/2004; 317(1):181-6. · 2.48 Impact Factor
• Article: Optimized gene synthesis and high expression of human interleukin-18.
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ABSTRACT: Human interleukin-18 (hIL-18), originally known as an IFN-gamma-inducing factor, is a recently cloned cytokine that is secreted by Kupffer cells of the liver and by stimulated macrophages. We have previously established a method of expression and purification of IL-18. The yield however remains low and the insufficient expression of a heterologous protein could be due to skewed codon usage between the expression host and the cDNA donor. The sequence of mature hIL-18 has 37 a.a. rare codons for Escherichia coli in a total of 157 a.a. To overcome this problem, gene synthesis was performed with optimized codons for the expression host E. coli. The final yield of the hIL-18 protein with optimized codons was about five times higher than the yield with the native sequence. Using a minimal medium, this system produces large quantities of labeled proteins that can be used in NMR analysis. Our simple and efficient production system can be applied to the production of other cytokines for new structural and therapeutic use.
Protein Expression and Purification 12/2003; 32(1):110-8. · 1.59 Impact Factor
• Article: The structure and binding mode of interleukin-18.
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ABSTRACT: Interleukin-18 (IL-18), a cytokine formerly known as interferon-gamma- (IFN-gamma-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-gamma production, Fas-mediated cytotoxicity and developmental regulation of T-lymphocyte helper type I. We determined the solution structure of IL-18 as a first step toward understanding its receptor activation mechanism. It folds into a beta-trefoil structure that resembles that of IL-1. Extensive mutagenesis revealed the presence of three sites that are important for receptor activation: two serve as binding sites for IL-18 receptor alpha (IL-18Ralpha), located at positions similar to those of IL-1 for IL-1 receptor type I (IL-1RI), whereas the third site may be involved in IL-18 receptor beta (IL-18Rbeta) binding. The structure and mutagenesis data provide a basis for understanding the IL-18-induced heterodimerization of receptor subunits, which is necessary for receptor activation.
Natural Structural Biology 12/2003; 10(11):966-71.
• Article: Interleukin‐18 is associated with the severity of atopic dermatitis
[show abstract] [hide abstract]
ABSTRACT: Background: Interleukin (IL)-18 acts as both a Th1 and Th2 cytokine, but its association with allergic diseases remains unclear. The aim of the present study was to measured plasma IL-18 and serum IgE levels in atopic children to evaluate how IL-18 is associated with allergic diseases.Methods: The plasma IL-18 and serum IgE levels in 51 atopic children, 28 healthy control children and 14 healthy control adults were measured by enzyme-linked immunosorbent assay (ELISA). The 5′ end of the IL-18 gene of 48 atopic children and 20 healthy control children was sequenced.Results: The plasma IL-18 level was significantly elevated in children with bronchial asthma and/or atopic dermatitis. Plasma IL-18 levels in the moderate or severe atopic dermatitis group were significantly higher than those in either the control group or the mild atopic dermatitis group. There was a positive correlation between plasma IL-18 and serum IgE levels. Three allelic combinations of polymorphisms in the IL-18 gene promoter region were observed. There was no significant difference in the plasma IL-18 levels between groups carrying these genotypes. However, bronchial asthma patients had significantly higher frequencies of the −137 G/G genotype than did control children.Conclusions: The plasma IL-18 level was elevated, particularly in patients with atopic dermatitis. As the clinical severity of atopic dermatitis increased, the plasma IL-18 level also tended to increase. These findings suggest that IL-18 may be associated with the severity of atopic dermatitis.
Allergology International 08/2003; 52(3):123 - 130.
• Article: [Evaluation before and after pranlukast administration with the QOL questionnaire (revised version 2001) for pediatric patients with bronchial asthma and their parents or caregivers].
[show abstract] [hide abstract]
ABSTRACT: We conducted a longitudinal investigation with the QOL questionnaire (revised version 2001) before and after the 4-week-administration of a leukotriene receptor antagonist pranlukast. A significant improvement in the < 4 yrs group was observed at week 1, and that in > or = 4 yrs group at week 2. Under these conditions, the overall QOL score, physical domains and mental domains, significantly improved in both the < 4 yrs group and the > or = 4 yrs group. Overall, a slight correlation was observed between ratio changes in QOL scores and differences in symptom scores. However, no correlation was found in part of patients, suggesting that the QOL questionnaire allows measurement of mental changes in the patients themselves and their parents or caregivers for therapeutic effects which cannot be determined with ordinary physical findings only. In "event present" group, a significant difference in physical and mental domains was revealed by the comparison of QOL scores before and after administration. And furthermore in "event absence" group, the p-value for physical domain and mental domain was 0.0505 and 0.0912 in the < 4 yrs group, respectively, 0.0101 and 0.0446 in the > or = 4 yrs group, respectively. The above results led us to consider the QOL questionnaire (revised version 2001) useful for routine medical care. Furthermore, pranlukast was considered useful for improvement not only of physical symptoms of bronchial asthma but also of the patient's QOL, although the placebo effects in this open trial must be considered.
Arerugī = [Allergy] 06/2002; 51(5):421-9.
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Thalassemia
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Thalassemia
Topic Overview
Red blood cells
What is thalassemia?
Thalassemia (say "thal-uh-SEE-mee-uh") is an inherited blood disorder that causes your body to make less hemoglobin or abnormal hemoglobin. Hemoglobin helps red blood cells spread oxygen through your body. Low levels of hemoglobin may cause anemia, an illness that makes you feel weak and tired. Severe anemia can damage organs and lead to death.
What are the types of thalassemia?
There are two main types: alpha and beta. Beta thalassemia is the most common.
Beta thalassemia
You need both alpha- and beta-globin to make hemoglobin. Beta thalassemia occurs when one or both of the two genes that make beta-globin don't work or only partly work as they should.
• If you have one damaged gene, you may have mild anemia and probably won't need treatment. This is called beta thalassemia minor or beta thalassemia trait. It happens when you get a normal gene from one parent and a thalassemia gene from the other.
• When both genes are damaged, it means you got a thalassemia gene from each parent. You may have moderate or severe anemia.
• If you have moderate anemia (beta thalassemia intermedia), you may need blood transfusions.
• People with severe anemia (called beta thalassemia major or Cooley's anemia) need blood transfusions throughout life. Symptoms of anemia usually begin within a few months after birth.
Alpha thalassemia
This type occurs when one or more of the four alpha-globin genes that make hemoglobin are missing or damaged.
• If one gene is missing or damaged: Your red blood cells might be smaller than normal. You will have no symptoms and you will not need treatment. But you are a silent carrier. This means you don't have the disease but can pass the defective gene to your child.
• If two genes are missing or damaged: You will have very mild anemia that will typically not need treatment. This is called alpha thalassemia minor or alpha thalassemia trait.
• If three genes are missing: You will have mild to moderately severe anemia. This is sometimes called hemoglobin H disease. If it is severe, you may need blood transfusions.
• If all four genes are missing: This is called alpha thalassemia major or hydrops fetalis. The fetus will be stillborn, or the child will die soon after birth.
What causes thalassemia?
A defect in one or more genes causes thalassemia.
If you, either parent, or any of your siblings have thalassemia or carry a gene for thalassemia and you're thinking about having a child, you may want to talk to a genetic counselor before you get pregnant. A genetic counselor can tell you how likely it is that your child will have the disease and how severe it might be.
What are the symptoms?
Mild thalassemia usually doesn't cause any symptoms.
Moderate or severe disease may cause symptoms of anemia. For example, you may feel weak, tire out more easily, and feel short of breath. Other symptoms also can occur depending on how severe your disease is and what problems it causes.
Children with severe thalassemia may grow slowly (failure to thrive), have skull bones that are not shaped normally, and have problems with feeding, frequent fevers, and diarrhea.
How is thalassemia diagnosed?
Your doctor will do an exam and ask about your health history. Tests you may need include:
• A complete blood count (CBC).
• A gene test to see if you have the genes that cause thalassemia.
• An iron level test.
• A blood test that measures the amounts of different types of hemoglobin, to help find out which type of thalassemia you have.
If you learn that you have thalassemia, your family members should to talk to their doctors about testing.
How is it treated?
Treatment depends on how severe your condition is.
Most large medical centers have treatment centers for blood disorders. They are an excellent resource to help you and your family get the best care.
• Mild thalassemia, the most common form, does not need treatment.
• Moderate thalassemia may be treated with blood transfusions and folic acid supplements. Folic acid is a vitamin that your body needs to produce red blood cells.
• Severe thalassemia may be treated with:
• Blood transfusions.
• Folic acid.
If you have repeated blood transfusions, it's possible for your body to get too much iron. This can damage your heart and other organs. Make sure to avoid vitamins that contain iron, and don't take extra vitamin C, which can increase how much iron you absorb from food. If you have too much iron, your doctor may give you chelation therapy. This is a medicine that helps remove iron from your body.
Less common treatments for severe thalassemia include:
Get a flu vaccine each year. Also talk to your doctor about getting a pneumococcal vaccine. These vaccines may protect you from severe infections, which can make anemia worse and cause severe illness in people who have thalassemia.
Other Places To Get Help
Organization
Centers for Disease Control and Prevention (CDC): Blood Disorders
www.cdc.gov/ncbddd/blooddisorders/index.html
References
Other Works Consulted
• Borgna-Pignatti C, Galanello R (2009). Thalassemias and related disorders: Quantitative disorders of hemoglobin synthesis. In JP Greer et al., eds., Wintrobe's Clinical Hematology, 12th ed., vol. 1, pp. 1083–1131. Philadelphia: Lippincott Williams and Wilkins.
• Hillman R, et al. (2011). Thalassemia. In Hematology in Clinical Practice, 5th ed., pp. 65–78. New York: McGraw-Hill.
• Pennell DJ, et al. (2013). Cardiovascular function and treatment in ß-thalassemia major: A consensus statement from the American Heart Association. Circulation, 128(3): 281–308.
• Weatherall DJ (2010). The thalassemias: Disorders of globin synthesis. In K Kaushansky et al., eds., Williams Hematology, 8th ed., pp. 675–707. New York: McGraw-Hill.
Credits
ByHealthwise Staff
Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine
Specialist Medical Reviewer Brian Leber, MDCM, FRCPC - Hematology
Current as ofMarch 12, 2014
This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.
© 1995-2014 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.
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Family Dentistry
Family dentistry deals with maintaining oral health of the entire family. Family dentists diagnose, treat and prevent various dental conditions in all members of the family. Family dentistry overlaps with a number of other fields in a number of ways. For example, family dentistry and general dentistry have a lot in common, but they differs from other fields in a number of ways too. Most notably, they deal with providing dental services to anyone in the family whereas other fields deal with a specialized procedure or age group. Family dentist plays an important role in maintaining the overall health of our society.
What are the responsibilities of the family dentist?
Family dentist performs a number of procedures to diagnose, treat and prevent the various diseases and conditions that affect the teeth of the family members. He is also responsible for providing proper information and guidance to maintain oral health.
Here are some of the most common procedures performed by family dentists:
• Cleanings: To prevent conditions such as dental caries and bacterial infections, it is essential to clean your teeth periodically. Brushing twice a day helps, but some food particles may still get trapped in between the teeth and sometimes can only be removed by the dentist. The family dentist uses various instruments such as dental picks, elevators and drill instruments to clean the teeth. Ideally, cleaning procedures should be performed once in every four months. This way, any infections or dental caries can be detected early on and appropriate measures taken to stop it from progressing and causing any significant damage.
• Dental fillings: Dental fillings are performed to rectify holes in the teeth, which are usually due to bacterial infections or dental caries. Bacteria emits harmful chemical substances which attack the surface of the teeth and causes holes to develop. Food particles may get stuck in these holes and lead to further infection. Dental caries is an infectious disease, it damages the structure of the tooth and if not treated on time can lead to teeth having holes. Dental fillings are done to cover these holes and improve the functionality of teeth. Most common types of dental fillings are amalgam, gold and metal alloys, or porcelain/composite filling (matches your tooth color).
Family dentists also provide information on various dentistry related topics. If you have any doubts or wish to know more about a specific dental procedure, the best way to start would be to contact your dentist.
Find Family Dentistry
Search our dental directory to find a local dentist to give you a happier, healthier smile.
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Family Dentistry Blog
• Finding a Reputable Family Dentistry Practice
August 31, 2012
Everyone wants to have healthy and perfect teeth. Those who want to avoid having oral and dental problems must find a family dentistry practice that helps one have spectacular looking teeth for them and their family. When it comes to the dental care of dental care of the entire family, one must not look for [...]
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5eff3d1f6f98e57329caed0ceb9053d3
|
7,874,687,211,089,543,000
|
Burdock Tea for Strengthening Hair
The use of burdock tea is becoming increasingly popular as more people realize the many cosmetic and remedial benefits it can offer. One thing that is not as commonly known about burdock tea is that it can be great for promoting the growth of strong, healthy hair. People that have trouble with hair loss, breaking or splitting ends, or weak hair growth in general should consider burdock tea as a helpful and natural herbal remedy.
What Causes Weak and Damaged Hair?
What many people fail to realize is that those luxurious locks are not actually alive. Apart from the root, where hair is grown, everything beyond the hair follicles no longer receives any nutrients from the body (or from your fancy shampoo). While this makes it easy to cut and style as you choose, it does make hair maintenance more challenging.
There are many things that can cause hair and scalp problems such as dandruff and weak, damaged hair. Some of the most common causes for these problems are stress, lack of vitamins and nutrients, and the application of harsh chemicals such as dyes and bleaches. Other reasons that your hair may be suffering can be attributed to environmental situations or heated tools such as blow dryers, curlers, and straightening irons.
A Healthy Scalp for Healthy Hair
A healthy scalp is much more important to overall hair care than simply reducing dandruff. Because the roots and follicles are found in the scalp, the health of the scalp itself is a huge factor in determining growth, shine and strength of your hair. You can promote the health of the scalp by making sure to get a healthy amount of certain vitamins and nutrients. These can be acquired through foods, or by applying directly to the scalp in certain shampoos, rinses and various natural products. Certain herbal teas can also be used as a scalp rinse to cleanse the scalp of oils and dirt while replenishing its essential nutrients.
The Benefits of Burdock Tea
Natural compounds and benefits found in burdock tea such as tannins, vitamin A, and fatty acids which are all beneficial toward strengthening hair growth. Drinking burdock tea can also help cleanse the body and the bloodstream of harmful toxins. A healthier body can decrease problems such as dandruff and hair loss which also make it highly beneficial. Even though burdock tea is generally consumed, you can also apply it directly into your hair for added results. After cooling, apply burdock tea to your hair as needed, focusing on problem areas. For those that wish to drink burdock tea as a hair supplement it should be prepared and ingested up to three times daily for best results.
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5eff3d1f6f98e57329caed0ceb9053d3
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25,724,237,090,131,576
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AIDS Definition
AIDS Definition
The clinical benefit of highly active antiretroviral therapy (HAART) has been attributed to its suppression of viral replication and improvement in the CD4 lymphocyte count. HIV infected persons who become newly infected by M. This will make them more susceptible to any type of infection and any type of disease. Thus, diagnosis of disease such as candidiasis of the esophagus, Cytomegalovirus retinitis, pulmonary tuberculosis or other Mycobacteriosis, Kaposi’s sarcoma, Pneumocystis carinii pneumonia, Toxoplasmosis of the brain, etc., are regarded as indicative of AIDS. All had ≥1 log10 HIV RNA level decrease at 1 month. Several specific diseases were associated with aORs >20 including syphilis, hepatitis A, non “A” viral hepatitis, herpes zoster, candida infection, endocarditis, thrombocytopenia, and opioid abuse. There were 681 AIDS-defining events (60.60 [56.14–65.33] per 1000 person years) with pulmonary TB and chronic diarrhoea being the most frequent causes.
AIDS Definition
In much of the world this is no longer a significant risk, as blood donations are routinely tested for HIV. An important minority diagnosed in occupational health screening emphasises the importance of HIV care for workers in globalised industries [21]. The impact of HAART on the changing pattern of HIV-1 organ-specific manifestations led to unequivocal contrastant results [3,5,6]. There were more than 7400 new infections per day in 2008. We conclude that protease inhibitor use (in combination antiretroviral therapy) is likely to favorably affect survival time after diagnosis of PML. All patients were admitted, or were already in-patients, on the day of first seizure. HIV is the virus that can lead to AIDS.
(2002) Antibodies, viruses and vaccines. Respiratory infections (testing recommended for people with prolonged illnesses, atypical courses, recurrent infection, poor response to treatment, or very unusual infections).
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5eff3d1f6f98e57329caed0ceb9053d3
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-7,799,469,938,656,714,000
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Path Block 6 - Bone
The flashcards below were created by user ssbhat on FreezingBlue Flashcards.
1. What are the functions of bone?
• Mineral homeostasis
• House meatopoietic elements
• Provide mechanical support for movement
• Protect viscera
• Determine body size and shape
2. What is bone composed of?
• Mineral Phase (60%) : Ca, Phos, Mg - stiffness
• Type I Collagen (30%) - tensile strength
• Type V Collagen (1.5%)
3. How is bone collagen organized?
• Lamellar (mature)
• Women (immature
4. What cells are involved in making/resorbing bone?
Osteoblasts: deposit type I collagen, mineralization, become osteocytes
Osteoclasts: multinucleated giant cells, bone resorption, have dendritic connections to communicate with each other
5. What is cartilage made of? And what are the types of cartilage?
• Type II collagen
• Hyaline (most abundant)
• Elastic (ear)
• Fibrocartilage (intervertebral discs, tendon attachments)
6. What are the two types of osteogenesis?
Transformation of pre-existent mesenchymal tissue into bone
• Intramembranous
• Endochondral
7. What is intramembranous ossification and where does it occur?
direction transformation of neural crest-derived mesenchymal tissue into bone.
Calvarium and clavicle
8. What is endochondral ossification and where does it occur?
Mesenchymal cells first diferentiate into cartilage, later replaced by bone.
Tubular bones, flat bones, epiphysoid bones, irregular bones --> vertebral column, pelvis, extremities.
9. What are the 5 stages of endochondral ossification?
• 1) Reserve cartilage
• 2) Zone of proliferation
• 3) Zone of hypertrophy
• 4) Zone of degeneration, apoptosis, mineralization
• 5) Zone of ossification (primary spongiosa)
10. What happens during the second phase of endochondral ossification?
Zone of proliferation - chondrocytes secrete cartilage-specific extracellular matrix.
11. What happens during the third phase of endochondral ossification?
Chondrocytes cease to divide and hypertrophy - modifying the matrix they produce to allow its mineralization with calcium carbonate.
12. What happens in the 4th phase of endochondral ossification?
Invasion of cartilage by blood vessels and subsequent death of hypertrophic chondrocytes through apoptosis - this space becomes BM.
Cells differentiate into osteoblasts - start forming bone matrix (osteoid) in partially degraded cartilage.
13. What happens in the 5th phase of endochondral ossification?
New bone is added to the periphery (periosteoum). THe internal region is reabsorbed to form the BM cavity via osteoclasts.
14. What are dysostoses?
developmental bone anomalies resulting from localized problems (migration, cellular condensations) - mutations in certain transcription factors
15. What are dysplasias?
mutations that globally affect cartilage and bone - signaling molecules & matrix components
16. What mutation is associated with achondroplasia and how is it inherited?
• FGFR3 mutation
• AD
• 80% from new cases (mostly on paternal allele)
17. What are the clinical features of achondroplasia?
• Shortened proximal extremities with normal trunk length
• Enlarged head w/ bulging forehead and depression of the root of the nose
18. Image Upload 1
What is seen here and what are the other clinical features?
Thanatophoric dysplasia - curved shape femur seen.
• 40% lethal skeletal dysplasias
• short ribs and extremities
• vertebral bodies with U or H shape on frontal projections
• Frontal bossing and macrocephaly
• Small chest cavity with bell-shaped abdomen
• Respiratory insufficiency
19. What mutation is involved in thanatophoric dysplasia?
3 different FGFR3 mutations are responsible for 85% of cases.
Transmembrane domain: milder form, achondroplasia
Tyrosine kinase domain or in extracellular domain: lethal form, thanatophoric dysplasia
20. What are the clinical features of osteogenesis imperfecta?
• blue sclera
• 4 types - lethal form present in 25% skeletal dysplasias
• intrauterine growth retardation
• severe osteopenia
• multiple fractures
• short and curved extremities
• small thorax w/ hypoplastic lungs - respiratory insufficiency
21. What is happening incorrect in osteogenesis imperfecta? And how is this inherited?
Defect of synthesis of assembly of procollagen type I osteoblasts
AD - most common inherited disorder of connective tissue
1/10,000-70,000
22. What is osteoporosis?
Reduced bone mass predisposing to fracture
• Localized: disuse
• Entire skeleton: metabolic bone disease
~1 million/year have fracture in US
23. What are the components of peak bone mass? What contributes to osteporosis?
Genetic factors + nutrient + physical activity = peak bone mass
Menopause: decreased estrogen, increased RANK expression, increased osteoclast activity, increased IL-1, IL-6, TNF
Aging: decreased physical activity, decreased osteoblasts, dedcreased growth factors
Osteoclasts mainly affect bones with increased surface area (vertebral bodies)
24. Image Upload 2
What is seen here?
Mosaic pattern of Paget Disease - primary bone disorder
• Severe bone deformities
• Predispose to malignant tumors
• Late adulthood (70 yrs)
25. What mutation is involved in Paget disease?
SQSTM1 mutation - enhances RANK signaling
7X more common in 1st degree relatives
26. What are the 3 stages of Paget disease?
What is the net result?
• 1) Osteolytic stage
• 2) Mixed osteoclastic/osteoblastic
• 3) Burn-out quiescent osteosclerotic stage
Net gain in bone mass, newly formed bone disordered and vulnerable to fracture
27. What are Rickets and Osteomalacia?
Lack of vitamin D or some disturbance in metabolism
Rickets: children
28. What is hyperparathyroidism?
Primary: tumor or hyperplasia
Secondary: prolonged hypocalcemia; increased PTH detected by osteoblasts which increase osteoclastic activity - bone loss predisposes to microfractures. Hemorrhage + fibrosis tissue = brown tumor
29. Image Upload 3
Brown tumor of hyperparathyroidism
30. Image Upload 4
Multinucleated osteoclasts in brown tumor of hyperparathyroidism.
31. What are the different types of fractures?
Pathologic: break occurs in bone already altered by disease process.
Stress: develops slowly following a period of increased physical activity with repetitive loads.
Pseudoarthrosis: if nonunion allows too much motion, central portion of the callus undergoes cystic degeneration, and the luminal surface can become lined by synovial-like cells, creating a false joint.
32. What causes avascular necrosis and how does it present clinically?
Ischemia d/t fracture, idopathic, or corticosteroid administration
• Subchondral: chronic pain
• Medullary: clinically silent
10% of 500K joint replacements/year in U.S.
33. Image Upload 5
Avascular necrosis
34. What is osteomyelitis caused by and how does it reach the bone?
Hematogenous spread, extension from contiguous site, direct implantation.
Staphylococcus aureus in 80-90% cases of pyogenic osteomyelitis where organism recovered.
Mixed bacterial infections in direct spread or during surgery/open fractures
SCD: Salmonella
50% cases no organism isolated
35. Image Upload 6
Osteomyelitis with mixture of fibrosis and inflammatory cells instead of fat.
• Plasma cells: chronic osteomyelitis
• Neutrophils: acute
36. How does osteomyelitis manifesT?
Fever, chills, malaise, pain over affected region
X-ray: lytic focus surrounded by zone of sclerosis
Blood cultures may be positive
Biopsy and bone cultures may be required to identify pathogen
37. How is osteomyelitis cured?
Antibiotics and surgical drainage
5-25% cases fails to resolve and persists as chronic infection
Acute spontaneous flare-ups with no obvious cause, even after yrs of dormancy.
38. What is the prevalence and incidence of bone tumors?
In US, 3/1000 malignant tumors is a bone tumor.
Incidence: 1/100,000 per year
39. What age differences are seen in bone tumors?
• Adult > malignancy
• Children > benign
40. What tumors are seen in adolescence?
Osteosarcoma, Ewing's Sarcoma
41. What tumors are seen in young adults?
Giant cell tumor
42. What tumors are seen in elderly?
Chondrosarcoma
43. What tumors are seen in the knee?
• 1/2 of osteosarcomas
• Giant cell Tumors
• Non-ossifying fibromas
• >1/3 of ostechondromas
44. What tumors are seen in the epiphysis of long bones?
• Chondroblastoma
• Giant cell tumor
45. What tumors are seen in the central/axial location?
• Chondrosarcoma
• 1/2 of osteoblastomas
46. What tumors are seen in the diaphysis of long bones?
• Ewing sarcoma
• >1/3 of chondrosarcomas
47. What is osteochondroma, where does it occur, and its associated mutation?
Exotosis - most common benign tumor of bone
Starts in growth plate and migrates towards metaphysis as patient grows with cartilagenous cap on top.
Malignant transformation rare - EXT-1 is the germline mutation that increases the risk in hereditary multiple exostoses (AD).
48. Image Upload 7
Osteochondroma with a mushroom/polypoid appearance with a stalk.
Rarely seen with broad base.
49. Image Upload 8
Osteochondroma with cartilagenous cap with endochondral ossification
50. Who is chondroblastoma seen in? Where is it located? What is the pathology and treatment?
• Rare, adolescents, M>F
• Epiphysis of knee or proximal humerus
• Benign, but rare metastases
Circumscribed proliferation of chondroblasts with hyaline matrix and chicken-wire calcification.
Tx: curretage, common recurrence
51. Image Upload 9
Chondorblasts with chickenwire calcification seen in chondroblastoma.
52. Who is chondrosarcoma seen in? Where is it located? How is graded? Variants? Survival?
2nd most common malignant tumor of bone (26%) - bulky tumor of malignant cartilage
Older adults (60s-70s), M>F
Central skeleton (except clear cell variant) - pelvis & ribs, femur, humerus, medullary location
Most low grade (1-3) based on degree of cellularity
Variants: de-differentiated, myxoid, clear cell, mesenchymal, juxtacortical
Survival: 80-90% (1 &2), 29% Gr 3(lung)
53. Image Upload 10
Popcorn-like cartilagenous matrix of chondrosarcoma.
54. What are osteoid osteomas? Where are they located? Tx?
• Benign bone forming tumor
• Long bones, femur, tibia
• <2cm
• Night pain
• Responds to aspirin
• Radiolucent lesion w/ sclerotic cortex
• Well circumscribed
• Woven bone trabeculae/osteoid rimmed by osteoblasts (nidus)
Tx: curettage, may recur if not completely removed
55. What is osteoblastoma? Where is it located?
• Benign bone forming tumor
• Vertebrae or long bone metaphysis
• >2cm
• painful
• not responsive to aspirin
• expansile radio-lucency with mottling
56. Image Upload 11Image Upload 12
Nidus: woven bone trabeculae/osteoid rimmed by osteoblasts
See in osteoid osteoma
57. What is osteosarcoma? Who is affected? Where is it located? What is treatment?
• Most common malignant bone tumor
• Destructive lesion, Codman's triangle.
• Infiltrative - extending into soft tissue. Malignant cells producing osteoid.
• Bimodal (15 yrs and 55-80 yrs). M>F.
• Hematgenous spread to lungs common.
Metaphysis of long bones
Tx: Chemotherapy and surgical ressection
58. What is the pathogenesis of osteosarcoma?
Inherited mutant allele of RB gene - hereditary retinoblastoma: marked increase (1000 fold) in osteosarcoma.
Mutation of p53 suppressor gene - Li-Fraumeni: germinline p53 mutation - bone and soft tissue sarcomas, early onset breast cancer, brain tumors, and leukemia
Prior irradiation
59. Image Upload 13
Codman's triangle in osteosarcoma.
Destructive lesion because it is not respecting tissue planes
60. Image Upload 14
Telangiectatic osteosarcoma - tumor has tendency to have abundant blood leaks within it.
61. Image Upload 15
Osteosarcoma-chondroblastic
tumor cells not only forming osteoid but also cartilage
62. Image Upload 16
osteosarcoma- fibroblastic
spindled, elongated cells
63. Image Upload 17
surface osteosarcoma
arise from metaphysis, medullary cavity completely spared b/c this tumor arises from surface of long bones
64. Image Upload 18
post radiation - osteosarcoma
radiation to scull for squamous cell carcinoma - years later developed aggressive osteosarcoma in that location
65. Image Upload 19
Non-ossifying fibroma - metaphyseal fibrous defect
• common developmental cortical defect
• incidental finding or pathologic fracture
• sharply demarcated cellular lesion of fibroblasts and histiocytes
66. WHat is fibrous dysplasia? What are the two kinds? What is the treatment?
Developmental arrest of bone
Monostotic: most common, adolescents, ribs, mandible, femur
Polyostotic: infancy/childhood, crippling deformities, craniofacial involvement
Tx: conservative, except polyostotic form
67. What is seen on x-ray in fibrous dyplasia and in pathology?
Circumscribed oxteolytic "ground glass" lesion in diaphysis with sclerotic rim
Haphazard curvilinear bone trabeculae (Chinese characters) surrounded by fibroblastic stroma
68. What is McCune Albright syndrome?
Polostotic fibrous dysplasia with endocrinopathies and cafe-au-lait spots.
• Rare, F>M
• Activating mutations of GNAS(GTP-binding protein)
• Result in excess cAMP leading to endocrine gland hyperfxn
• Sexual preocicty, acromegaly, and Cushing syndrome
69. Image Upload 20Image Upload 21
Fibrous dysplasia
70. Image Upload 22
What is seen here? Where does it occur? Who does it happen in?
• Giant Cell Tumor
• Benign, locally aggressive
• Knee, proximal humerus, epiphysis
• Young adults (skeletally mature)
• F>M
• May destroy cortex and extend to soft tissue
• Tx: Curretage
71. What is a solitary (unicameral) bone cyst? Where does it occur? How do you treat?
Multiloculated cyst filled w/ clear to bloody fluid.
Proximal epiphysis humerus (1/2) and femur (1/4)
Tx: Curretage & packing, frequently recurrs
72. Who and where does an aneurysmal bone cyst effect? What is seen on X-ray and pathology?
• Any bone, long bone metaphysis and vertebrae
• Adolescents, F>M
X-Ray: lytic well-defined lesion which distorts bone, may extend into soft tissue
Pathology: cavernous blood-filled spaces surrounded by fibrous septae.
73. Image Upload 23
Aneurysmal Bone Cyst - normally bone replaced by cystic cavity that contains blood
74. Who gets Ewing Sarcoma? Where does it occur?
SEcond most common malignant bone tumor in childhood.
• Adolescents, young adults
• Painful, often enlarging mass
• Diaphysis of long tubular bones, ribs, and pelvis
75. What is the pathogenesis of Ewing Sarcoma?
t(11;22) EWS (22) fused with FLI-I (11)
76. What is the pathology and X-ray of Ewing Sarcoma? What is the treatment?
• Pathology: primitive small round cells with neural phenotype
• Contain abundant glycogen
• Hemorrhage and necrosis common
X-Ray: destructive intramedullary lesion, "onion-skin" pattern of periosteal reaction in response to rapid growth
Tx: chemo and surgery, radiation may be added
77. Image Upload 24Image Upload 25
• Ewing Sarcoma
• Onion-skin pattern
• Small round blue cell tumor that usually expresses CD99
78. What are the common metastatic tumors in adults and children? Where do they occur?
Adult: prostate, breast, kidney, thyroid, lung
Children: neuroblastoma, Wilms, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma
Usually multifocal in axial skeleton
79. What are the two types of metastatic bone tumors?
Lytic: kidney, lung, thyroid, GI, breast - stimulate osteoclastic bone resoprtion
Blastic: prostate & breast
80. What is osteoarthritis and who is affected where?
• Wear and tear and problems with repair
• AKA degenerative joint disease
• Aging & mechanical effects
• Knees and hands: women
• Hips: men
81. What factors genetic play a role in OA? What other factors?
• Chromosomes 2 & 11
• Increased bone density and estrogen increases risk
82. What joints in the hands are affected in OA?
Heberden's (distant) and Bouchards nodes
83. Image Upload 26
• OA
• 1) Eburnated articular surface
• 2) Subchondral cyst
• 3) Residual articular cartilage
84. What is the clinical course of OA?
• May be disabling
• Hand fxn rarely impaired, even if pain and stiffness remain.
• Pain in knee or hip may decrease even as disease progresses
85. What is rheumatoid arthritis and who does it affect? What joints are affected?
• chronic systemic inflammatory disorder
• common age 40-70, F>M
• often progresses to destruction of articular cartilage and ankylosis
• may affect many tissues & organs
• autoimmunity
• microbe may start rxn and ultimately cause cross rxn w/ antigens in joints
• affects PIP and MCP
86. What are the characteristic features of RA?
• infiltration of synovial stroma by dense perivascular CD4+ T cells, plasma cells, and macrophages
• increased vascularity d/t vasodilation and angiogenesis
• organizing fibrin covering synovium and floating joint space
• osteoclastic activity in underlying bone forming juxta-articular erosions, subchondral cysts, osteoporosis
87. Image Upload 27
RA with lymphoid aggregate and dilated blood vessels
88. Image Upload 28
Pannus formation: mass of synovium and stroma, inflammatory cells, granulation tissue and fibroblasts, which grows over and erodes articular cartilage
Pannus may bridge apposing bones, forming fibrous anyklosis, which ossifies and forms bony ankylosis
89. What is the clinical progression of RA? What can be used to test? What causes fatalities?
• Variable clinical course
• Generally small joints affected before larger ones
• No specific diagnostic test: many patients have serum rheumatoid factor: IgM antibody reactive with Fc portion of patients' own IgG - may not be present throughout course of disease
Fatalities usually d/t systemic amyloidosis and vasculitis, or iatrogenic effects to therapy
90. What is juvenile RA?
• Before age 16
• F>M (except in systemic where it is equal)
• Heterogenous group of chronic arthritides
• Fxn disability
• Variants: oligoarticular(<5 joints), polyarticular, systemic
91. What is seronegative spondyloarthropathies? What are the clinical variants?
What is it associated with?
• Genetically predisposed individuals
• Initiated by environmental factors, especially prior infections or exposures
• Manifestations are immune mediated, maybe triggered by T-cell response to unknown antigens
• Clinical variants:
• ankylosing spondylitis (usually affects lumbar spine)
• Reactive arthritis
• Psoriatic arthritis
• Arthritis associated w/ IBD
Overlapping clinical features, many associated with HLA-B27 and triggering infection
92. What are the reasons for primary and secondary gouty arthritis?
What does gout look like?
• Primary:
• unknown enzyme defect with increased urate production or decreased urate excretion
• 2ndary:
• increased NA turnover, chronic renal disease, Lesch-Nyhan (increased urate production)
Urates-needle shaped, negative birefringent crystals, tophi (large aggregates of urate crystals surrounded by intense inflammatory rxn)
93. Image Upload 29
Acute Gouty Arthritis
needle shaped, negative birefringent crystals
94. Image Upload 30
Tophi: large aggregates of urate crystals surrounded by intense inflammatory rxn
95. What is pseudogout? What does it look like?
Calcium pyrophosphate crystal deposition (chondrocalcinosis)
Etiologies: sporadic, hereditary, secondary
Chalky white friable deposits seen histologically as oval blue-purple aggregates
Individual crystals (.5-5um), weakly positively birefringent, rhomboid shapes
96. What are the small minority of soft tissue neoplasms associated with genetic syndromes?
• Neurofibromatosis type 1 (neurofibroma, MPSNT)
• Gardner syndrome (fibromatosis)
• Li-Fraumeni syndrome (soft tissue sarcomas)
• Osler-Weber-Rendu syndrome (telangiectasia)
97. What are important prognostic factors in soft tissue tumors?
• Grade: I to III
• based on degree of differentation/pleomorphism
• average number of mitoses
• Extent of necrosis
Size (> or < 5cm), depth, stage (metastasis)
superficial have better prognosis than deep lesions
98. What is a lipoma?
most common soft-tissue tumor of adhulthood
subclassified according to particular morphologic feature
conventional lipomas: 12q14-q15
well encapsulated mass usually cured by simple excision
99. What age are liposarcomas present? What are the different histologic variants?
• 40s-60s
• Proximal extremities & retroperitoneum
• well-differentiated: indolent
• myxoid/round cell: intermediate
• pleomorphic: aggressive
100. What are the two types of fibromatoses?
• Superficial: palmar (Dupuytren contracture), plantar, penile (Peyronie disease)
• may stabilize and resolve spontaneously, some recur
Deep-seated(Desmoid tumors): behavior lies btwn benign fibrous tumors and low grade fibrosarcomas. frequently recur, in teens-30s, some associated with Gardner syndrome, mutations in the APC or beta-catenin genes.
101. Where does fibrosarcoma happen? How often do they recur and metastasize? What markers are positive?
• Deep soft tissues of extremities
• Recur >50%
• Metastasize >25%
• All markers but vimentin are negatine
102. What is hemangioma and what are the two types?
• Benign tumors of blood vessels, increased numbers of normal or abnormal vessels
• Very common, infancy/childhood
Capillary: composed of capillaries: congenital, infantile/juvenile, lobular
Cavernous: venous malformations, usually deep-seated
103. Image Upload 31
Hemangioma
104. What are the etiologic factos of angiosarcoma? And where are they located?
• Lymphedema: post mastectomy - loss of afferent lymphatics, immunologically privileged site
• Radiation
• Carcinogens: thorotrast, insecticides, vinyl chloride
• AV fistulas, foreign material
cutaneous: most common, head and neck( Scalp and forehead), elderly, beneath hair (sun exposure)
105. Image Upload 32
cutaneous angiosarcoma
106. What is Kaposi's sarcoma associated with? And what are the different forms?
• HHV-8
• Classic: elder men of Mediterranean descent; skin, indolent
• Africa endemic: young Bantu children of S. Africa; lymph nodes, aggressive
• AIDs-associated: skin or any organ; spreads widely, but usually not lethal
107. Who is leiomyosarcoma seen in? Where does it affect? What is the prognosis?
• Adults, F>M
• skin and deep soft tissues of the extremities and retroperitoneum
• superficial = good prognosis
• retroperitoneum = large, cannot be entirely excised, local extension and metastatic spread
108. What are the 3 types of rhabdomyosarcoma and what are their features?
Embryonal: 49% RMS, more frequent <10 yrs, head and neck, GU tract, deep soft tissues of extremities, pelvis, retroperitoneum
Alveolar: 32% RMS, age 10-25, deep soft tissues of extremities (less in head, neck, perineum), t(2;13) or t(1;13)
Pleomorphic: older individuals
109. What are the types of tumors of unknown histogenesis?
• Synovial sarcoma
• epithelioid sarcoma
• alveolar soft part sarcoma
110. Who has synovial sarcoma and what is the translocation? Where is it located?
• Young adult males
• Deep tissue of extremities, KNEE
• t(X;18)(p11;q11)
• histologically biphasic or monophasic
111. What are the prognostic indicators for bone and soft tissue sarcomas?
Grade, size, location (depth), metastases(most important)
112. What is the common metastatic site of bone and soft tissue sarcomas?
lung
113. How many new soft tissue sarcomas and bone sarcomas are diagnosed per year in the US?
8000 and 2500
114. What is the most common malignant bone lesion in patients >40?
metastatic carcinoma
115. What is the most common primary bone tumor?
multiple myeloma
116. What is the most common bone tumor of children?
osteosarcoma
117. What should you obtain prior to any biopsy or excision of a soft tissue mass?
MRI
118. What are the requirements for a biopsy?
• longitudinal
• within a single compartment
• made with the definitive resection in mind
• performed by the definitive surgeon
Author:
ssbhat
ID:
198889
Card Set:
Path Block 6 - Bone
Updated:
2013-02-10 03:25:41
Tags:
Bone CNS
Folders:
Description:
Bone & CNS
Show Answers:
|
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Test Catalog
Interpretive Handbook
Test 88906 :
Celiac Associated HLA-DQ Alpha 1 and DQ Beta 1 DNA Typing, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Celiac disease (gluten-sensitive enteropathy) is mediated by T lymphocytes in patients with genetic susceptibility. This genetic association is with certain HLA genes in the class II region (DQ alpha 1, DQ beta 1).
For your convenience, we recommend utilizing cascade testing for celiac disease. Cascade testing ensures that testing proceeds in an algorithmic fashion. The following cascades are available; select the appropriate 1 for your specific patient situation. Algorithms for the cascade tests are available in Special Instructions.
-CDCOM / Celiac Disease Comprehensive Cascade: complete testing including HLA DQ typing and serology
-CDSP / Celiac Disease Serology Cascade: complete testing excluding HLA DQ
-CDGF / Celiac Disease Gluten-Free Cascade: for patients already adhering to a gluten-free diet
To order individual tests, see Celiac Disease Diagnostic Testing Algorithm in Special Instructions.
Useful For Suggests clinical disorders or settings where the test may be helpful
Assessing risk of celiac disease
Interpretation Provides information to assist in interpretation of the test results
Most (90%-95%) patients with celiac disease have 1 or 2 copies of HLA-DQ2 haplotype (see below), while the remainder have HLA-DQ8 haplotype. Rare exceptions to these associations have been occasionally seen. In 1 study of celiac disease, only 0.7% of patients with celiac disease lacked the HLA alleles mentioned above. Results are reported as permissive, nonpermissive, or equivocal gene pairs.
It is important to realize that these genes are also present in about 20% of people without celiac disease. Therefore, the mere presence of these genes does not prove the presence of celiac disease or that genetic susceptibility to celiac disease is present.
The HLA-DQ molecule is composed of two chains: DQ alpha (encoded by HLA-DQA1 gene) and DQ beta (encoded by HLA-DQB1 gene). HLA-DQ typing can be performed by serological or molecular methods. Currently most laboratories perform typing by molecular methods. HLA-DQ2 and DQ8 as typed by serology are usually based on the molecular typing of the DQB1 chain only. The current molecular method allows typing for both the DQB1 and DQA1 chains and this has shown that there are different haplotypes of HLA-DQ2 and DQ8. Typing of these haplotypes is important in celiac disease as they carry different risk association.
There are 2 common haplotypes of DQ2:
1. DQA1*05:01 with DQB1*02:01 also called DQ2.5 in celiac literature
2. DQA1*02:01 with DQB1*02:02 also called DQ2.2 in celiac literature
A single haplotype (heterozygote) of DQ2.5 is permissive for presence of celiac genes. However, only a double haplotype (homozygous) of DQ2.2 is permissive for presence of celiac genes. There are few reports where a single haplotype of DQ2.2 is considered to be an equivocal risk. In some cases the DQ2.2 haplotype maybe present with a DQ7.5 haplotype (DQA1*05:05 with DQB1*03:01). In this case a DQ2.5 molecule can be formed by the combination of DQB1*02:02 from 1 chromosome and DQA1*05:05 from the other chromosome. These cases fall in the same category as the DQ2.5 heterozygote.
There are 3 common haplotypes of DQ8:
1. DQA1*03:01 with DQB1*03:02
2. DQA1*03:02 with DQB1*03:02
3. DQA1*03:03 with DQB1*03:02
Any single haplotype (heterozygote) of DQ8 is permissive for celiac.
Therefore, the gene pairs permissive for celiac are:
1. Heterozygote (single copy)
-DQA1*05:XX with DQB1*02:01
-DQA1*05:XX with DQB1*02:02
-DQA1*03:XX with DQB1*03:02
2. Homozygous (2 copies)
-DQA1*02:01 with DQB1*02:02
Gene pairs equivocal for celiac are
1. Heterozygote (single copy)
-DQA1*02:01 with DQB1*02:02
2. Rare allele’s types of DQ2 and DQ8 other than those listed above
All other gene pair combinations are considered non-permissive for celiac.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
No significant cautionary statements
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Polvi A, Arranz E, Fernandez-Arequero M, et al: HLA-DQ2-negative celiac disease in Finland and Spain. Hum Immunol 1998 Mar;59(3):169-175
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Best Weight Loss Food
Despite what some websites may tell you, it is entirely possible to eat satisfying meals and lose weight at the same time. By adjusting our diets, the human body is more than capable of maintaining a healthy figure. Many people and websites recommend starvation diets, which do almost nothing. Losing water weight for a week or two is not a sign of progress. You might see a lower number on the scale, but this weight loss is not permanent, and will eventually return. If you are dieting because you actually want to have a healthier lifestyle, don’t engage in a starvation diet. It is unhealthy and can have long-term effects that are much worse than having a number that you think sounds too high. The most effective food to eat when trying lose weight provides the nutrition our bodies need and keeps us from resorting to junk food for snacks. Filling foods have the ability to suppress our appetite, but there is a lot of confusion as to what is healthy to eat and what isn’t. Eating protein-rich foods such as lean beef, fish, beans, and nuts can make you feel full and repress the desire to reach for the bag of chips and other unhealthy snacks. Replacing carbohydrate-loaded food with protein is safer, healthier, and will help you manage your weight better. The body is a magnificent biological machine; our fuel is food, and it runs off of the energy from the food we consume. If we consume too much and don’t use that energy, instead of going away, the energy is stored in the body as fat. The only way to truly get the fat to go is to use up all that stored up energy; by reducing our caloric intake and engaging in a rigorous exercise regimen, our bodies burn away that stored energy. By maintaining a healthy diet after the weight is gone and monitoring what we eat, we can make sure that the weight won’t come back, either.
Rapid Weight Loss Diet
Losing weight does not necessarily require a weight loss pill. Dietary pills usually work by blocking cell function to reduce the number of fatty acids and fat deposits in the body. If you really want a healthy lifestyle, though, you should consider not taking any pills at all. Many dietary pills can have unsafe side effects. Rapid weight loss plans are especially dangerous, since they usually have to alter your body’s chemistry in a way that is not natural or healthy for the body. The words “rapid weight loss” and “too good to be true” go hand in hand. Losing weight takes determination and desire, and a whole lot of patience and perseverance, as well. There is no magic pill that will just make the pounds disappear. There is, however, another solution. Visit BioMazing HCG for more information on how to rapidly lose weight without the negative side effects of diet pills!
Consider your weight loss goal: what you weight now, and what you want to weigh. What kind of weight loss methods are you already implementing? What methods, such as dieting, exercising, weight loss pills, etc, are you willing to try in order to hit your target weight? Is the goal of your target weight to make you healthier and make you feel better about yourself, or is it just to hit an arbitrary number? Why are you losing weight if not to become healthier? These are serious questions that deserve more than just a quick response. If you want to get to some number just to do it, you’ll probably have a hard time keeping the weight off if you manage to get it off in the first place. Be honest with yourself, and recognize that weight loss is only as rapid as you make it. You are the most significant form of rapid and sustained weight loss – not some pill.
Weight Loss Tips For Girls
If you have the desire to lose weight and start living more healthily, then nothing can stand in your way to lose weight. Perhaps you have tried dieting before, but didn’t make it to your weight loss goal. Or perhaps you’ve come to the realization that you want a healthier lifestyle. In either situation, there are things that you can do to achieve your weight loss goals. When you set a weight loss goal, be reasonable. People expecting to lose five pounds a day need to manage their expectations and be proud of every half-pound and pound they lose, no matter how long it takes. Losing weight is really only one half of weight loss – the other half is keeping it off. Instead of focusing on getting to the number that you want, focus on the healthy lifestyle you want to live. Whether you lose weight slowly or quickly, cultivating a healthy diet and exercise regiment is what will keep you from bouncing back up to the weight you’re at now, and will also help you feel better and more successful about the weight you’ve lost. Another thing to consider doing before starting a dietary plan is consulting with your nutritionist. Just because you heard an all-cabbage-soup diet worked for your friend doesn’t mean it will work for you. Talk to your doctor about possible health risks you may have that could impact how you achieve your target weight, and discuss which options are most nutritionally sound for you. Your current weight, age, and overall health can have a huge impact on what sort of exercises are safe to do and what kinds of food are okay to eat. With a comprehensive weight loss plan, patience, and persistence you can achieve your dietary goals.
Green Tea Weight Loss
Green tea weight loss supplements are an all natural chemical-free dietary supplement that some people have found especially effective for achieving their weight loss goals. When combined with a healthy lifestyle of dieting and exercise, these pills can help you burn away those pounds you’ve been having trouble with. It is important to note that green tea isn’t some magical, instant-weight-loss pill. No such thing exists. But these supplements have the ability to boost your metabolism, help you maintain good health, and antioxidize the blood. Tea has been used medicinally in China since the 10th century B.C.E., and it wasn’t until more modern time periods that green tea became more of a household drink. Though the ancient Chinese likely used this tea medicinally without knowing its true benefits, modern scientists know that its antioxidizing effects are significant in reducing the risk of heart disease and cancer.
In other studies, polyphenols and caffeine from green tea extact have been known to boost the metabolic rate and stimulate fat oxidation by as much as 4%, without increasing the heart rate or introducing any risks to the body. This means that you will burn more fat than just sticking to an average diet. A 4% heightened metabolism may sound small, but think of the long-term effects. After only ten days of exercising and taking a green tea extract together, you will have a net gain of 40% more metabolic fat-burning than you would have without it.
Taking green tea weight loss pills has no side effects, which is a significant concern for many people who want a healthy form of weight loss. While the extract often has more benefit than the drink itself (since the extraction process activates various molecular compounds), the tea can be drunk on its own for both pleasure and as a healthy alternative to sugary soft drinks.
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Patents
1. Advanced Patent Search
Publication numberUS20060099719 A1
Publication typeApplication
Application numberUS 11/260,913
Publication dateMay 11, 2006
Filing dateOct 28, 2005
Priority dateNov 5, 2004
Also published asCA2524574A1, CA2524574C, EP1655606A1, EP1655606B1, US8394336
Publication number11260913, 260913, US 2006/0099719 A1, US 2006/099719 A1, US 20060099719 A1, US 20060099719A1, US 2006099719 A1, US 2006099719A1, US-A1-20060099719, US-A1-2006099719, US2006/0099719A1, US2006/099719A1, US20060099719 A1, US20060099719A1, US2006099719 A1, US2006099719A1
InventorsMario Curcio
Original AssigneeRoche Diagnostics Operations, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Biochemical assay
US 20060099719 A1
Abstract
A biochemical assay is provided comprising a substrate being capable of binding at least a target analyte and eventually other constituents contained in a biological sample, a test zone on the substrate for sample application, a non-immobilized conjugate reagent provided in the test zone for labelling the analyte, the conjugate reagent being capable of specific binding to the analyte but remaining unbound to the substrate, and a flow path for transporting a washing liquid through the test zone and washing an excess of unbound conjugate reagent away from the test zone. The test zone is also a detection area for detecting the labelled analyte.
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Claims(35)
1. A biochemical assay comprising
a substrate being capable of binding at least a target analyte and eventually other constituents contained in a biological sample,
a test zone on the substrate for sample application,
a non-immobilized conjugate reagent provided in the test zone for labelling the analyte, said conjugate reagent being capable of specific binding to the analyte but remaining unbound to the substrate, and
a flow path for transporting a washing liquid through the test zone and washing an excess of unbound conjugate reagent away from the test zone, wherein
the test zone is also a detection area for detecting the labelled analyte.
2. The biochemical assay of claim 1, wherein a reservoir contains the washing liquid and the reservoir can be fluidly connected to the flow path.
3. The biochemical assay of claim 2, wherein the reservoir is connectable to the flow path by an element rupturing a wall of the reservoir.
4. The biochemical assay of claim 1, wherein the flow path is a porous or capillary structure of the substrate for capillary transport of the washing liquid.
5. The biochemical assay of claim 1, wherein a microfluidic system is provided for transport of sample fluid to the test zone.
6. The biochemical assay of claim 1, wherein an adsorbing element is arranged on the flow path downstream the test zone for taking up liquid waste.
7. The biochemical assay of claim 1, wherein the substrate is a solid phase chromatographic layer on a polymer or metal support.
8. The biochemical assay of claim 1, wherein the substrate comprises aluminium oxide or silica or a reversed-phase material.
9. The biochemical assay of claim 1, wherein the analyte is a protein.
10. The biochemical assay of claim 1, wherein the conjugate reagent is a molecule other than a protein.
11. The biochemical assay of claim 10, wherein the size of the molecule is less than the size of the analyte.
12. The biochemical assay of claim 10, wherein the molecule is polar.
13. The biochemical assay of claim 1, wherein the conjugate is a labelled organic or inorganic molecule.
14. The biochemical assay of claim 1, wherein the conjugate reagent contains a boronic acid dye, a chelating group, a peptide epitope, or an oligonucleotide.
15. The biochemical assay of claim 1, wherein the conjugate reagent has a high coefficient of partition for the washing liquid compared to the substrate.
16. The biochemical assay of claim 1, wherein the washing liquid is an organic solvent, a mixture of water and a miscible organic solvent, or an aqueous solution.
17. The biochemical assay of claim 1, wherein the washing liquid is buffered at such pH that the analyte sticks to the substrate and the binding reaction of the conjugate still occurs.
18. The biochemical assay of claim 1, wherein the washing liquid contains a surfactant.
19. The biochemical assay of claim 1, wherein the conjugate reagent is provided in dried form in the test zone.
20. The biochemical assay of claim 1, wherein the biological sample is blood.
21. The biochemical assay of claim 1, wherein the biological sample is whole blood.
22. The biochemical assay of claim 1, wherein the target analyte is haemoglobin.
23. The biochemical assay of claim 1, wherein the target analyte is glycated haemoglobin.
24. The biochemical assay of claim 1, wherein the substrate is impregnated with a haemolysing agent
25. The biochemical assay of claim 24, wherein said haemolysing agent is tetradecyltrimetylammonium bromide.
26. An analytical test element comprising the biochemical assay of claim 1.
27. The analytical test element of claim 26, wherein said test element is disposable.
28. A device for processing an analytical test element according to claim 26.
29. An analytical test element for determining the ratio of glycated to total haemoglobin in a blood sample comprising:
a substrate being capable of binding at least haemoglobin and eventually other constituents contained in a blood sample,
a test zone on the substrate for sample application,
a non-immobilized conjugate reagent provided in the test zone for labelling glycated haemoglobin, and
a flow path for transporting a washing liquid through the test zone and washing an excess of unbound conjugate away from the test zone, wherein
the test zone is also a detection area for detecting the labelled and total haemoglobin.
30. The analytical test element of claim 29, wherein the conjugate comprises boronic acid dye.
31. A device for processing an analytical test element according to claim 29.
32. A process for determining at least one target analyte in a biochemical sample, comprising:
a) providing a substrate being capable of binding at least the target analyte and eventually other constituents contained in the sample,
b) providing a non-immobilized conjugate reagent in the test zone for labelling the analyte, said conjugate reagent being capable of specific binding to the analyte but remaining unbound to the substrate,
c) applying the sample in a finite test zone of the substrate,
d) transporting a washing liquid through the test zone and washing an excess of unbound conjugate reagent away from the test zone, and
e) detecting the labelled analyte in the test zone.
33. The process of claim 32, wherein blood is used as a sample and non-glycated haemoglobin and glycated haemoglobin are adsorbed on the substrate, the conjugate reagent being bound to the glycated haemoglobin.
34. The process of claim 33, wherein said blood is whole blood.
35. The process of claim 32, wherein total haemoglobin and glycated haemoglobin are photometrically detected at different respective wavelengths and that the ratio of glycated to total haemoglobin is determined.
Description
BACKGROUND OF THE INVENTION
The invention concerns a biochemical assay and a process for determining at least one target analyte in a biochemical sample, typically glycated and total haemoglobin in a blood sample. The invention also concerns an analytical test element on the basis of such a biochemical assay.
The glycation of haemoglobin is increased in the blood of diabetes patients. The increase depends on the concentration of glucose, free to move through the erythrocyte membrane and the period of incubation of the protein with glucose, via a non-enzymatic reaction. Hence, the determination of glycated haemoglobin (namely HbA1c) allows a retrospective estimate of the average glucose concentration and thus of the quality of the metabolic control of the diabetic patient. The disappearance of HbA1c from the blood depends on the lifetime of the erythrocytes (the average lifetime of these cells is about 120 days with a half-life of 60 days). HbA1c is defined as haemoglobin A that has been glycated by glucose with a slow but irreversible reaction on the N-terminal valine residues of the β chains. The HbA1c value is usually stated as a percentage of the total haemoglobin which requires a determination of the haemoglobin concentration from the same blood sample in addition to the HbA1c content.
In connection to this, it is already known to use test elements in order to provide a simple handling and rapid determination. A test element is generally understood as a carrier-bound (micro) system which enables sample preparation for an immediate analysis independent of a laboratory environment. Such test elements are usually intended to be single-use articles or disposables for near patient diagnostics in which all reagents that are necessary to carry out the test are provided on the carrier or component so that they can be used without requiring special handling.
In this context, U.S. Pat. No. 6,399,293 B1 discloses a teststrip-based system comprising a sample application zone, a reagent zone containing non-immobilized signal-generating molecules, a separation zone for separating the excess signal-generating molecules that are not bound to glycated haemoglobin and a detection zone. The separation occurs by means of a positively charged membrane binding only the excess of a negatively charged signal-generating ligand in the separation zone. The total haemoglobin including the labeled HbA1c will not be bound to the membrane and thus can be transported through the different zones within the sample liquid.
More generally, the use of test elements for different binding assays is well-known. For example, U.S. Pat. No. 4,094,647 describes a device that comprises a material capable of transporting a solution by capillary action. Different zones on the strip contain the reagents needed to perform the binding assay and to produce a detectable signal as the analyte is transported through the zones. The binding reaction occurs between an antigen and a complementary antibody. Many variations of the method have followed. However, despite all the activity in this field, methods have been developed always in the same direction involving the use of some immobilized reagent, mostly antibody, resulting in higher effort and costs for reagents and chemistry integration, and/or involving a chromatographic run, generally requiring the need for the analyte to go through several steps in space and time to meet the reaction and detection conditions.
SUMMARY OF THE INVENTION
It is against the above background that the present invention provides certain unobvious advantages and advancements over the prior art. In particular, the inventor has recognized a need for improvements in biochemical assay design.
Although the present invention is not limited to specific advantages or functionality, it is noted that the present invention reduces the assay complexity, minimizes the necessary sample amount, uses less reagents, and avoids in particular immobilization and immunochemistry, while maintaining accuracy and reproducibility of the test with ease of handling.
The present invention is based on the idea to overlap application, reaction and detection in one spot of a solid support or substrate. In accordance with one embodiment, a biochemical assay is provided comprising: a substrate being capable of binding at least a target analyte and eventually other constituents contained in a biological sample, a test zone on the substrate for sample application, a non-immobilized conjugate reagent provided in the test zone for labelling the analyte, the conjugate reagent being capable of specific binding to the analyte but remaining unbound to the substrate, and a flow path for transporting a washing liquid through the test zone and washing an excess of unbound conjugate reagent away from the test zone, wherein the test zone is also a detection area for detecting the labelled analyte.
Thereby, several advantages are achieved. The sample application, reaction and detection occur in one and the same spot or zone. Hence, the analytes do not have to be transported meaning that higher reproducibility can be expected. A compact design can be achieved, with minimized reaction and sample volumes, minimized strip length and lower washing volumes. The handling is made easy and no elaborate separation steps are required.
In another typical embodiment of the present invention, an integrated reservoir contains the washing liquid and the reservoir can be fluidly connected to the flow path. According to a further embodiment, the reservoir is connectable to the flow path by an element rupturing a wall of the reservoir.
For a self-controlled transport, in accordance with yet another embodiment, the flow path can be a porous or capillary structure capable to transport the washing liquid by capillary forces. Alternatively, to direct sample application, a microfluidic system can be provided for transport of sample fluid to the test zone.
In accordance with still another embodiment, an adsorbing element can be arranged on the flow path downstream the test zone for taking up liquid waste. Further, the substrate can be a solid phase chromatographic layer that can be on a polymer or metal support. The analyte is typically a protein. The conjugate reagent can be a molecule other than a protein. The size of that molecule can be less than the size of the analyte.
Such a conjugate molecule can consists of a more or less polar organic group as the signalling part and a small organic or inorganic group as the ligand part, which recognizes and binds specifically to the target analyte, like for example boronic acid, a chelating group, a peptide epitope or an oligonucleotide.
The conjugate reagent can have a high coefficient of partition for the washing liquid compared to the substrate. Depending on the conjugate chemical structure, the washing liquid can be an organic solvent, a mixture of water and a miscible organic solvent or just an aqueous solution, can contain a surfactant, and can be buffered at an optimal or predetermined pH, so that the analyte sticks to the substrate while the binding reaction of the conjugate still occurs. Accordingly, the excess of unbound reagent can be removed.
In accordance with yet still another embodiment, the conjugate reagent is provided in dried form in the test zone, which can be provided before the sample application.
The invention also concerns an embodiment comprising an analytical test element, which can be disposable, for a biochemical assay according to the invention, and a device for processing the analytical test element.
In accordance with yet still another embodiment, an analytical test element for determining the ratio of glycated to total haemoglobin in a blood sample is provided comprising: a substrate being capable of binding at least haemoglobin and eventually other constituents contained in a blood sample, a test zone on the substrate for sample application, a non-immobilized conjugate reagent provided in the test zone for labelling glycated haemoglobin, and a flow path for transporting a washing liquid through the test zone and washing an excess of unbound conjugate away from the test zone. The test zone is also a detection area for detecting the labelled and total haemoglobin.
In accordance with yet still another embodiment of the present invention, a process for determining at least one target analyte in a biochemical sample is provided, comprising: providing a substrate being capable of binding at least the target analyte and eventually other constituents contained in the sample, providing a non-immobilized conjugate reagent in the test zone for labelling the analyte, the conjugate reagent being capable of specific binding to the analyte but remaining unbound to the substrate, applying the sample in a finite test zone of the substrate, transporting a washing liquid through the test zone and washing an excess of unbound conjugate reagent away from the test zone, and detecting the labelled analyte in the test zone.
In yet still another embodiment, blood is used as a sample. The target analyte is haemoglobin, specifically glycated haemoglobin. The blood is haemolysed by a haemolysing reagent present typically also in dried form in a suitable substrate, on which total haemoglobin adsorbs. The conjugate reagent also present in dried form in the sample application zone is solubilized by the sample and binds to the glycated haemoglobin. The excess of unbound conjugate reagent is then transported away by the laterally flowing washing liquid. Total haemoglobin and glycated haemoglobin are photometrically detected at different respective wavelengths, so that the ratio of glycated to total haemoglobin can be determined.
These and other features and advantages of the present invention will be more fully understood from the following detailed description of the invention taken together with the accompanying claims. It is noted that the scope of the claims is defined by the recitations therein and not by the specific discussion of features and advantages set forth in the present description.
BRIEF DESCRIPTION OF THE DRAWINGS
The following detailed description of the embodiments of the present invention can be best understood and is elucidated in more detail when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
FIG. 1 shows a measuring device comprising a test element for a biochemical assay in longitudinal cross-section in accordance with an embodiment of the present invention;
FIG. 2 is a top view of a test element in accordance with an embodiment of the present invention; and
FIGS. 3 a and b show test results of an assay in accordance with an embodiment of the present invention, which is carried out on a TLC plate of standard format.
Skilled artisans appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the embodiments of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The measuring device 10 shown in FIG. 1 allows a disposable strip-shaped test element 12 to be processed for determining total haemoglobin and HbA1c values of a blood sample in a single-use test. As further illustrated in FIG. 2, the test element 12, in accordance with one embodiment of the present invention, essentially comprises a carrier 14, a substrate 16 with a test zone 18 formed therein, a reservoir 20 containing a washing liquid 22 and a flow path 24 for the transport of washing liquid through the test zone.
The carrier 14 can be formed as an elongated thin strip of a plastic or metal foil, with a central part where a thin layer of chromatographic material, analogous to a TLC plate, is layered as the substrate 16. The substrate 16 can have a microporous structure 26 serving as the flow path 24 essentially parallel to the longitudinal axis of the strip 14.
The reservoir 20 can comprise a deformable blister which has a bottom wall 28 that can be ruptured or punctured by an integrated barb 30 so that the washing liquid 22 is forced out of the created hole into a soft compressible adsorbing material 32 bordered by a soft compressible U-frame 34. Mechanical actuation can be accomplished by a pressing block 36 for puncturing the blister and a pressing cylinder 38 to push the liquid 22 out.
The adsorbing material 32 overlaps the upstream end of the substrate 16 to enable liquid transfer into the microporous structure 26. An adsorbing element 40 is arranged downstream the test zone 18 for taking up the liquid waste.
As only schematically illustrated in FIG. 2, the linear liquid transport system described so far could be part of a more complex microfluidic system. Instead of direct sample spotting, the sample fluid can reach the test zone from the side through the channel 42 after prior processing. For example, haemolysis of blood and eventually also the binding reaction with the conjugate can take place in zone(s) different from the adsorbing and detection area 18. In this case, care should be typically taken to avoid excess of sample spreading outside the test zone 18. Microfluidic flow control can be used to deliver typically a given amount at the given location.
In order to carry out a photometrical measurement, a detector 42 can be located in the device 10 in correspondence of the test zone 18 of the test element 12. For precise alignment, the housing 44 of the device 10 can have a guide way 46 which allows sliding the test element 12 in and out.
In one example, to perform a test, a small sample volume (μl) of a blood sample to be analysed is delivered to the test zone 18. Fresh capillary blood or whole blood can be used. Release of haemoglobin from the erythrocytes is obtained by action of a haemolysing reagent with which the substrate is impregnated.
The glycated haemoglobin, made accessible in this way, can be selectively labelled by reaction with a non-immobilized conjugate reagent present in the test zone 18. The conjugate can comprise phenylboronic acid linked to an organic dye with maximum absorbance at a wavelength about >600 nm. This selectively binds to the sugar residue of glycated haemoglobin and thus makes it detectable and distinguishable. In order to ensure that the reaction is quantitative, an excess of conjugate relative to the expected amount of glycated haemoglobin is used. Therefore, it is typical that the excess or fraction of conjugate reagent, which is not bound to glycated haemoglobin, is separated after sample application from the test zone 18.
The separation mechanism according to an embodiment of the invention is based upon the principle of immobilizing the analyte(s) in the test zone 18, by simple adsorption whereas the unbound conjugate is removed with the aid of the washing liquid 22. To make this possible, the analyte and the conjugate typically belong to different chemical classes. In accordance with one embodiment, if the analyte is a protein, the conjugate must be something other than a protein. Typically, this is instead a relatively small organic molecule more or less polar.
As outlined above, the non-glycated haemoglobin and the complex of glycated haemoglobin with boronic acid-dye conjugate stick on the TLC substrate firmly under particular washing conditions, while the excess of unbound conjugate is transported away with the mobile washing phase.
It is important for an optimal separating effect that the conjugate has a high coefficient of partition for the washing liquid 22 compared to the substrate 16. Particular attention must be paid to the pH value. This influences, on one hand, the reaction between target analyte and conjugate and, on the other hand, can determine how strongly the analyte adsorbs on the substrate and the affinity of the free conjugate for the mobile phase.
At a given time after sample application, the flow of the washing fluid can be actuated by means of the mechanism 36, 38, so that the liquid is transported through the adsorbing material 32 and the microporous structure 26, passing the test zone 18 and taking up excess conjugate eventually into the waste 40.
In order that the invention may be more readily understood, reference is made to the following examples, which are intended to illustrate the invention, but not limit the scope thereof.
EXAMPLE 1
In one working example (FIG. 3) a commercial aluminium oxide TLC plate was used as substrate, phenylboronic acid linked to an organic dye of low-polarity (max. absorbance at ca. 650 nm, emission at ca. 670 nm) as conjugate reagent (MW<700 Dalton), and a buffer phosphate/EDTA at pH typically ≧7, most typically ≧9, containing approximately 1% tetradecyltrimetylammonium bromide (TTAB), as mobile phase. TTAB was used also as haemolysing reagent.
Two controls were run in parallel with the HbA1c test (blood sample containing 10% glycated haemoglobin plus non-immobilized conjugate) in the center, namely blood sample without conjugate on the left, and conjugate without blood on the right. The two images in FIG. 3 a were taken at different wavelengths, i.e., 540 nm and 665 nm, by using a CCD camera as detector and a set of filters for the illumination source and the camera objective. The three absorbance traces showing relative absorbance a over separation length d in FIG. 3 b refer to the three spotted samples, aligned in the same order, with the solid line representing 540 nm and the dotted line 665 nm respectively. From here it is clear that total haemoglobin with or without conjugate (absorbing at 540 nm) is strongly adsorbed on the substrate while the non-immobilized and unbound conjugate (detected at 665 nm) is transported away from the application spot under these washing conditions. Only when reaction between conjugate and glycated haemoglobin occurs (spot in the middle) absorbance at 665 nm proportional to the percentage of HbA1c present can be detected in the application zone.
In principle, known methods, i.e., absorbance, reflection or fluorescence can be conducted to determine haemoglobin remaining in the test zone 18. In accordance with an embodiment of the present invention, both total and glycated haemoglobin have to be detected. Use is made of the fact that the boronic acid conjugate has an absorption maximum at a wavelength which is outside of the range in which haemoglobin absorbs. The ratio of glycated to total haemoglobin can then be determined by measuring the reflectance of the test zone 18 at different wavelengths, for example at 540 nm (for the total amount of haemoglobin) and 665 nm (for the dye, which is bound via boronic acid to glycated haemoglobin).
The mechanism by which the analyte of interest sticks while the excess of unbound non-immobilized conjugate reagent is removed from the reaction/detection area under particular washing conditions, can be generalized to most assays in which the analyte is a protein, typically an abundant protein, and the labelled ligand is a non-protein that is something other than an antibody. Typically, this is instead a relatively small organic molecule more or less polar, or a small peptide epitope, or even an oligonucleotide for nucleic acid binding proteins. The substrate can be other than aluminium oxide, like for example silica, reversed phase or other chromatographic material, so that the protein analyte can be firmly adsorbed by electrostatic or hydrophilic interactions, hydrogen bonding, hydrophobic interactions, or combinations thereof. The mobile phase can be a buffer at such pH that the analyte sticks on the solid phase but that the reaction still occurs. It can contain a detergent other than TTAB at any optimal concentration. It can contain acids or bases. It can contain an organic solvent or can be a simple mixture of a miscible organic solvent and water. Pre-spotted samples at known concentration could also be present on the same test strip for direct calibration. If all this is considered, then this method can be used to determine the presence and quantity of antibodies and ligand-binding proteins in a biological fluid, such as blood, urine, milk or in a cell extract, either human tissue or other organisms including bacteria, whenever specific suitable ligands are known and can be derivatized with signal-generating molecules, if not already self-signaling.
It is also contemplated to use different signals for different ligands so that different analytes can be targeted at the same time on the same spots, or for introducing internal calibration standards. For better sensitivity, fluorescence detection is typical. More specific examples of assays that could be performed by this method involve different classes of ligand-binding proteins. Besides immunoglobulines, the following are also contemplated: DNA and RNA binding proteins, lipid-binding proteins (e.g., β-lactoglobulin, serum retinol-binding protein, urinary α2-globuline, fatty acid binding proteins), lectins, serum albumins, pheromone-binding proteins, odor-binding proteins, and immunosuppressant-binding proteins.
It is noted that terms like “preferably”, “commonly”, and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present invention.
For the purposes of describing and defining the present invention it is noted that the term “substantially” is utilized herein to represent the inherent degree of uncertainty that may be attributed to any quantitative comparison, value, measurement, or other representation. The term “substantially” is also utilized herein to represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue.
Having described the invention in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims. More specifically, although some aspects of the present invention are identified herein as preferred or particularly advantageous, it is contemplated that the present invention is not necessarily limited to these preferred aspects of the invention.
Patent Citations
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US4806487 *May 29, 1987Feb 21, 1989Analytical Innovations, Inc.Basic drug detection method
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Classifications
U.S. Classification436/514
International ClassificationG01N33/558
Cooperative ClassificationG01N33/558
European ClassificationG01N33/558
Legal Events
DateCodeEventDescription
Nov 14, 2005ASAssignment
Owner name: ROCHE DIAGNOSTICS GMBH, GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:CURCIO, MARIO;REEL/FRAME:016777/0072
Effective date: 20051019
Owner name: ROCHE DIAGNOSTICS OPERATIONS, INC., INDIANA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ROCHE DIAGNOSTICS GMBH;REEL/FRAME:016773/0116
Effective date: 20051018
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PODCAST
.
Smart Drug Smarts brings you actionable insights from world-leading experts in neuroscience and psychopharmacology — for the enhancement and protection of your greatest asset: your own brain.
Content Categories
SMART DRUGS
What Are They, and How Do They Work?
Let's start with the basics of what smart drugs are and what they aren't. The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so. For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.
Terminology
"Smart Drugs" is a general term for the class of compounds known as nootropics - chemical substances that enhance cognition and memory or facilitate learning. However, within this general umbrella of "things you can eat that make you smarter," there are many variations as far as methods of action within the body, perceptible (and measurable) effects, potential for use and abuse, and the spillover impact on the body's non-cognitive processes.
Why Are Nootropics Just Now Beginning to Go Mainstream?
Many of the most popular "smart drugs" (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride's being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?
There is no clear answer to this question. Many of the smart drugs have decades of medical research and widespread use behind them, as well as only minor, manageable, or nonexistent side effects, but are still used primarily as a crutch for people already experiencing cognitive decline, rather than as a booster-rocket for people with healthy brains. Unfortunately, there is a bias in Western medicine in favor of prescribing drugs once something bad has already begun, rather than for up-front prevention. There's also the principle of "leave well enough alone" - in this case, extended to mean, don't add unnecessary or unnatural drugs to the human body in place of a normal diet. [Smart Drug Smarts would argue that the average human diet has strayed so far from what is physiologically "normal" that leaving well enough alone is already a failed proposition.]
Probably most significantly, use of the term "drug" has a significant negative connotation in our culture. "Drugs" are bad: So proclaimed Richard Nixon in the War on Drugs, and Nancy "No to Drugs" Reagan decades later, and other leaders continuing to present day. The legitimate demonization of the worst forms of recreational drugs has resulted in a general bias against the elective use of any chemical to alter the body's processes. Drug enhancement of athletes is considered cheating - despite the fact that many of these physiological shortcuts obviously work. University students and professionals seeking mental enhancements by taking smart drugs are now facing similar scrutiny.
However, history has shown that genies don't stay in bottles. All ethics aside, there is ample proof that use of smart drugs can profoundly improve human cognition, and where there is an advantage to be gained - even where risks are involved - some people will leap at the chance to capitalize. At Smart Drug Smarts, we anticipate the social tide will continue to turn in favor of elective neural enhancers, and that the beneficial effects to users who choose to make the most of their brains will inevitably outweigh the costs.
Classes of Nootropics
There are seven primary classes used to categorize nootropic drugs: Racetams, Stimulants, Adaptogens, Cholinergics, Serotonergics, Dopaminergics, and Metabolic Function Nootropics. Despite considerable overlap and no clear border in the brain and body's responses to these substances, each class manifests its effects through a different chemical pathway within the body.
Racetams
Racetams are the best-known smart drugs on the market, and have decades of widespread use behind them. Piracetam is a leading smart drug, commonly prescribed to seniors with Alzheimer's or pre-dementia symptoms - but studies have shown Piracetam's beneficial effects extend to people of all ages, as young as university students. The Racetams speed up chemical exchange between brain cells. Effects include increases in verbal learning, mental clarity, and general IQ. Other members of the Racetam family include Pramiracetam, Oxiracetam, аnԁ Aniracetam, which differ from Piracetam primarily in their potency, not their actual effects.
Studies have shown that using racetams can deplete the brain of choline and cause headaches. To counteract this effect, users tend to take a choline supplement - generally choline bitartrate - in proportion to the amount of the racetam in their smart drug regimen.
The Racetams are not controlled substances in the US or most of the world, and can be purchased without prescription as over-the-counter dietary supplements. "Overdosing," per se, isn't really possible on these extremely non-toxic supplements, with the most extreme side effects felt by users being similar to drinking excessive caffeine.
Stimulants
Stimulants are the nootropics most familiar to people, starting with widely-used psychostimulants caffeine and nicotine, and the more ill-reputed subclass of amphetamines. Stimulant drugs generally function as nootropics in the sense that they promote general wakefulness and put the brain and body "on alert" in a ready-to-go state. Basically, any drug whose effects reduce drowsiness will increase the functional IQ, so long as the user isn't so over-stimulated they're shaking or driven to distraction.
The stimulant now most popular in news articles as a legitimate "smart drug" is Modafinil, which came to market as an anti-narcolepsy drug, but gained a following within the military, doctors on long shifts, and college students pulling all-nighters who needed a drug to improve alertness without the "wired" feeling associated with caffeine. Modafinil is a relatively new nootropic, having gained widespread use only in the past 15 years. More research is needed before scientists understand this drug's function within the brain - but the increase in alertness it provides is uncontested.
Adaptogens
Adaptogens are plant-derived chemicals whose activity helps the body maintain or regain homeostasis (equilibrium between the body's metabolic processes). Almost without exception, adaptogens are available over-the-counter as dietary supplements, not controlled drugs. Well-known adaptogens include Ginseng, Kava Kava, Passion Flower, St. Johns Wort, and Gotu Kola. Many of these traditional remedies border on being "folk wisdom," and have been in use for hundreds or thousands of years, and are used to treat everything from anxiety and mild depression to low libido. While these nootropics work in a many different ways (their commonality is their resultant function within the body, not their chemical makeup), it can generally be said that the cognitive boost users receive is mostly a result of fixing an imbalance in people with poor diets, body toxicity, or other metabolic problems, rather than directly promoting the growth of new brain cells or neural connections.
Cholinergics
The choline-based class of nootropics play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain's primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of nootropics tends to deplete cholines from the brain, so one of the classic "supplement stacks" - chemical supplements that are used together - are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.
Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug's discernable effects on the brain remain unclear. This nootropic, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
Serotonergics
Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of "getting some sun" to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.
Iluminal is an example of an over-the-counter serotonergic drug used by people looking for performance enhancement, memory improvements, and mood-brightening. Also noteworthy, a wide class of prescription anti-depression drugs are based on serotonin reuptake inhibitors that slow the absorption of serotonin by the presynaptic cell, increasing the effect of the neurotransmitter on the receptor neuron - essentially facilitating the free flow of serotonin throughout the brain.
Dopaminergics
Dopaminergics are smart drug substances that affect levels of dopamine within the brain. Dopamine is a major neurotransmitter, responsible for the good feelings and biochemical positive feedback from behaviors for which our biology naturally rewards us: tasty food, sex, positive social relationships, etc. Use of dopaminergic nootropics promotes attention and alertness by either increasing the efficacy of dopamine within the brain, or inhibiting the enzymes that break dopamine down. Examples of popular dopaminergic nootropic drugs include Yohimbe, selegiline and L-Tyrosine.
Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain's prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing nootropics into sensible "classes" is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)
Metabolic Function Nootropics
Metabolic function nootropics provide mental benefits by generally facilitating the body's metabolic processes related to the production of new tissues and the release of energy from food and fat stores. Creatine, a long-time favorite performance-enhancement drug for competitive athletes, was in the news recently when it was found in a double-blind, placebo-controlled crossover trial to have significant cognitive benefits - including both general speed of cognition and improvements in working memory. Ginkgo Biloba is another metabolic function nootropic used to increase memory and improve circulation - however, news from recent studies raises questions about these purported effects.
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Anxiety Got You Down? It Might Be Your Diet
Anxiety Got You Down? It Might Be Your Diet
The winter months can bring on anxiety for many. For some, it’s post-holiday blues. For others, it’s the long days without sunshine. For many, it boils down to diet—the foods you eat could be causing or increasing your stress and worry. In addition to being a drain on your brain, anxiety can cause people to overeat. Over time, that just makes the situation worse—the more you eat, the bigger you get, the worse more you, the greater your chances of having an anxiety attack about it all.
Rather than get into that vicious cycle, here are some ways to use food to keep your anxiety in check.
Stay hydrated. On many levels, water is the great healer. By staying hydrated, you’ll be more alert and less likely to have mood-altering headaches or body cramps. You may even lose weight!
Eat whole grains. Brown rice, whole-grain bread, and other such foods break down more slowly and therefore take longer to release sugar into the bloodstream. That can help you avoid the high-and-crash of processed carbs such as white bread.
Limit processed sugars. Sugary snacks and drinks might give you a quick boost for an hour or two, but the crash that follows can have you confined to the couch. What you’re feeling is a rush of insulin followed by a rapid drop in blood sugar levels. One exception is a small portion of dark chocolate, which contains compounds that lower cortisol or the stress hormone.
Be sure you have plenty of B. You might be experiencing anxiety if your body is deficient in vitamin B and folic acid. Supplements can give you back the vitamin B your body is missing, or bring in foods such as nuts, eggs, leafy greens, legumes, chicken, and citrus fruits.
Watch the salt. High-sodium foods can lead to fluid retention, bloating, and high blood pressure—all factors that can raise levels of anxiety and diminish your health.
Eat more turkey. Tryptophan is an amino acid, and consuming it can help your brain produce serotonin—a feel-good chemical that calms you. Turkey is one of the most well-known sources, of tryptophan, but bananas, oats, nuts, and some other foods also contain it.
Feast on fish. Salmon, lake trout, tuna, sardines, and anchovies contain omega-3 fatty acids. Not only can omega-3s improve your mood, but they may also help lower your risk of heart disease.
Cut the caffeine. Coffee and sodas may give you a burst of energy, but drinking these too late in the day can keep you up at night, giving you plenty of time to ratchet up your anxiety levels mulling over a checklist of worries.
Don’t overdo alcohol. Some people have a few drinks because they believe it helps them wind down and relax. But the truth is that too much alcohol can be a depressant. It’s also a diuretic, which can be dehydrating. Much of it is loaded with processed sugar. And too much can elevate liver enzymes—a real problem for someone with fatty liver, my area of specialty. If you must drink, consider one glass of wine with a meal.
Know your sensitivities. Food sensitivities can cause inflammation or even unhealthy reactions. Certainly, if you are sensitive to gluten and dairy products, then avoiding or limiting these in your diet can reduce your anxiety levels. That goes for artificial sweeteners, too. Some contain ingredients that can actually trigger headaches and mood changes.
As a hepatologist, I specialize in that all-important organ of the body, the liver. I work with patients daily who are on the path to life-threatening illness—and most of the time it’s because of how they’ve viewed nutrition and eating, and now their liver is paying the price. Yes, their mood, and their overall health, is affected by what they eat. I see it every day.
A healthy, well-balanced diet is not only good for your nervous system, but for your overall health. And what better way to reduce stress than to feel great all the time?
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5eff3d1f6f98e57329caed0ceb9053d3
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8,942,210,145,553,057,000
|
Familial Neuroendocrine Syndromes
Home > Cancer (Oncology) > Diseases and Conditions > Endocrine/Neuroendocrine Tumors > Familial Neuroendocrine Syndromes
Print
Diseases and Conditions
Familial Neuroendocrine Syndromes
Familial endocrine syndromes are caused by genetic mutations that can be passed through families from generation to generation. Some types of neuroendocrine tumors are found much more frequently in patients with these genetic mutations. Genetic testing can help identify and treat patients and their families, and can prevent complications from advanced neuroendocrine tumors. The most common familial neuroendocrine syndromes are outlined below with their respective genetic mutations and the types of tumors found in these patients.
Multiple Endocrine Neoplasia Type I (MENI)
MENI is a genetic mutation of the menin gene, which plays a role in suppressing tumor formation. Patients with MENI are at increased risk for developing pituitary tumors, pancreatic neuroendocrine tumors and hyperparathyroidism.
Multiple Endocrine Neoplasia Type IIa (MENIIa)
MENIIa is a genetic mutation of the RET proto-oncogene, which increases a patient's risk for developing medullary thyroid cancer, hyperparathyroidism and pheochromocytoma.
Multiple Endocrine Neoplasia Type IIb (MENIIb)
MENIIb is also a genetic mutation of the RET proto-oncogene, which increases a patient's risk for developing medullary thyroid cancer at a very young age, as well as pheochromocytoma and mucosal neuromas of the lips, tongue and eyelids.
Von Hipple-Lindau
Patients with the von Hipple-Lindau disease mutation have an increased risk of developing pheochromocytomas, central nervous system hemangioblastomas, kidney tumors, pancreatic neuroendocrine tumors and retinal tumors.
SDH Mutations
Succinate dehydrogenase (SDH) is an enzyme that is important for the metabolic function of mitochondria. Patients with SDH mutations have an increased risk of pheochromocytomas, paragangliomas, stomach tumors and kidney tumors.
Treatment of Familial Neuroendocrine Syndromes
Patients and their families who have been diagnosed with familial neuroendocrine syndromes require care across several different medical specialties, including genetics, medicine, surgery, oncology and radiology. The multidisciplinary approach of a neuroendocrine tumor program can address all aspects of innovative and technologically advanced care.
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White Blood Cell Differential Count by xiuliliaofz
VIEWS: 280 PAGES: 40
White Blood Cell
Differential Count
Definition
The relative percentage of each type of
white blood cells in peripheral blood.
This experiment is a part of blood
routine test.
Person---5L BLOOD
2L CELL + 3L PLASMA
RBC+WBC+PLT
NEUTRO
EOSINO
BASO
LYMPHO
MONO
BLOOD ROUTINE TEST
INFORMATION :
HEMOGLOBIN
CELL PRODUCTION
CELL FUNCTION
HEMATOLOGIC+OTHER SYSTEM+PROGNOSIS
RESPONSE+RECOVERY
Process of blood routine test
1. Specimen collection
Venipuncture
Capillary Puncture
2. Hematology Automation
3. WBC differential count
Specimen collection
Blood container:
purple cap
Anticoagulant reagent:
EDTA-K2 1.5-2.0mg/ml
Hemocytometer
Principle of the experiment
Wright-Giemsa: a polychrome stain
Methanol : fixes cells to slide
methylene blue stains RNA,DNA
===Blue /purple
Eosin stains hemoglobin, eosin granules
===pink /red
pH value of phosphate buffer is very important
too acidic suitable too basic
Procedure of the experiment
Methods of preparation
Spreader slide at 30-40 degree angle
Control thickness of the smear by
changing the angle of spreader slide
high HCT
small angle
low HCT
large angle
tail body head
Stain of blood smear
Wright’s Giemsa stain: 1-2min
Phosphate buffer :15min
Wash with distilled water
* The staining time depends on the
concentration of the stain and room
temperature.
Microscopic exam
10× (low fold): overall smear quality,
rouleaux, agglutination or parasites
100× (oil Len): WBC Diff, RBC
morphology
tail body head
Observing direction:
Observe one field and record the number of WBC according to
the different type then turn to another field in the snake-liked
direction
*avoid repeat or miss some cells
Morphology of WBC
in peripheral blood
normal peripheral blood
smear
Stab neutrophil
Diameter:12-16
Cytoplasma:pink
Granules: primary
secondary
Nucleus: dark purple blue
dense chromatin
Segmented neutrophil
Diameter: 12-16
Cytoplasma: pink
Granules: primary
secondary
Nucleus: dark purple blue
dense chromatin
2-5 lobes
Eosinophil
Diameter: 14-16
Cytoplasma: full of granules
Granules: large refractile
orange-red
Nucleus: blue
dense chromatin
2 lobes like a pair of glass
Basophil
Diameter: 14-16
Cytoplasma: pink
Granules: dark blue –
black obscure nucleus
Nucleus: blue
Lymphocyte
Diameter: small 7-9
large 12-16
Cytoplasma: medium blue
Granules: small agranular
large a few primary
granules
Nucleus: dark blue \round
dense chromatin
Monocyte
Diameter: 14-20
Cytoplasma: grey blue
Granules: dust-like
lilac color granules
Nucleus: blue
large irregularly
shaped and folded
Abnormal changes
of WBC
morphology
Left-shift and right-shift of neutrophil:
Left-shift: non-segmented neutrophil > 5%
Right-shift: hypersegmented neutrophil>3%
Toxic Granulation
Auer Bodies(Auer Rod)
Hypersegmentation
Anisocytosis of neutrophil
vacuolization
Degeneration of nucleus
Dohle body
To top
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1,935,237,489,361,068,800
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Poisonous Spiders in Illinois?
Answer
There are a few poisonous spiders in Illinois. One of them is the black widow. Their bite is very poisonous and medical treatment should be sought immediately. Other poisonous spiders in Illinois include the brown recluse, wolf spider and black house spider.
Reference:
Q&A Related to "Poisonous Spiders in Illinois?"
http://www.idph.state.il.us/envhealth/pcreclusespiders.htm. Black widow and Brown Recluse.
http://wiki.answers.com/Q/What_poisonous_spiders_a...
The most poisonous spider in the entire world is... drum roll please! The Brazilian Wandering Spider. This little bugger can kill a mouse with a microscopic amount of venom, that
http://answers.ask.com/Health/Diseases/what_is_the...
There are two species of venomous black widows, both of which are
http://www.chacha.com/question/what-type-of-poison...
1. Determine if you are in the habitat of the Brown Recluse Spider. The Brown Recluse is found in the Midwestern to Southern United States. Other spiders in the Recluse family live
http://www.ehow.com/how_4548008_identify-poisonous...
Explore this Topic
Some poisonous spiders are, brown recluse spiders, black widow spiders, hobo spiders, grass spiders, mouse spiders, black house spiders, and wolf spiders. ...
There are only a small amount of spiders that are poisonous. They are the Black Widow, the Brown Recluse, the yellow sac, the Hobo spider, and the Red Legged spider ...
There are only a small amount of spiders that are poisonous. They are the Black Widow, the Brown Recluse, the yellow sac, the Hobo spider, and the Red Legged spider ...
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ClinVar Miner
Submissions for variant NM_000117.2(EMD):c.466G>C (p.Gly156Arg) (rs144594695)
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726441 SCV000344661 uncertain significance not provided 2016-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000396796 SCV000512933 likely benign not specified 2017-01-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000695175 SCV000823658 uncertain significance Emery-Dreifuss muscular dystrophy 1, X-linked 2018-06-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 156 of the EMD protein (p.Gly156Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs144594695, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with EMD-related disease. ClinVar contains an entry for this variant (Variation ID: 290157). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.
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5eff3d1f6f98e57329caed0ceb9053d3
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-385,067,198,800,923,140
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Font Size
A
A
A
Antenatal Corticosteroids for Fetal Lung Development
Examples
Generic NameBrand Name
betamethasoneCelestone Soluspan
dexamethasoneCelestone Soluspan
How It Works
Betamethasone and dexamethasone cause an immature fetus's lungs to produce a compound called surfactant. A full-term baby's lungs naturally produce surfactant, which lubricates the lining of the air sacs within the lungs. This allows the inner surfaces of the air sacs to slide against one another without sticking during breathing. Premature infants whose lungs have begun producing surfactant are more able to breathe on their own, or with less respiratory treatment, after birth.
If delivery does not occur within 7 days of treatment, the injections should not be repeated.
Why It Is Used
Betamethasone and dexamethasone are corticosteroids, also called glucocorticoids, that are given before birth (antenatally) to speed up a preterm fetus's lung development. Either is used when a mother is in preterm labor and birth may occur in 24 to 48 hours. This helps prevent respiratory distress syndrome (RDS) and related complications following premature birth.
Many infants born at 33 to 34 weeks' gestation have sufficient lung maturity to breathe on their own. But considering the low-risk, high-benefit nature of this treatment, corticosteroids are typically used up to 34 weeks of pregnancy.
How Well It Works
There is strong evidence that a single course of corticosteroid medicine given to the mother during premature labor improves the outcome for the infant born between 24 and 34 weeks' gestation.1
Betamethasone or dexamethasone is most effective if delivery occurs at least 24 hours after the first dose of the medicine has been given and less than 7 days after the last dose of the medicine.
Either medicine will benefit a premature newborn by lowering the risk of:
Side Effects
Corticosteroid side effects that might affect the mother can include fluid retention and increased blood pressure. But these are short-term side effects and less likely to occur at all during such a short period of treatment. These side effects are more of a concern during long-term treatment for other health problems.
Control of diabetes may be more difficult in pregnant women when corticosteroids are used. Your doctor may recommend a different insulin dose during this time.
See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)
What To Think About
Fetal lung maturity testing (using amniotic fluid collected through amniocentesis) is sometimes used to determine whether antenatal corticosteroid treatment is necessary.
Repeat courses of corticosteroids given before birth are not recommended.2 They may cause long-term effects on the growing child.3
Complete the new medication information form (PDF)Click here to view a form.(What is a PDF document?) to help you understand this medication.
References
Citations
1. Haas DM (2010). Preterm birth, search date June 2009. Online version of BMJ Clinical Evidence: http://www.clinicalevidence.com.
2. American Academy of Pediatrics and American College of Obstetricians and Gynecologists (2007). Obstetric and medical complications. In Guidelines for Perinatal Care, 6th ed., pp. 175–204. Elk Grove Village, IL: American Academy of Pediatrics.
3. French NP, et al. (2004). Repeated antenatal corticosteroids: Effects on cerebral palsy and childhood behavior. American Journal of Obstetrics and Gynecology, 190(3): 588–595.
Credits
ByHealthwise Staff
Primary Medical ReviewerSarah Marshall, MD - Family Medicine
Specialist Medical ReviewerWilliam Gilbert, MD - Maternal and Fetal Medicine
Last RevisedJanuary 10, 2011
eMedicineHealth Medical Reference from Healthwise
This information does not replace the advice of a doctor. Healthwise disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.
To learn more visit Healthwise.org
© 1995-2012 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.
Medical Dictionary
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hepatotoxicity
play
noun hep·a·to·tox·ic·i·ty \ˌhe-pə-tō-täk-ˈsi-sə-tē, hi-ˌpa-tə-\
Definition of hepatotoxicity
1. 1 : a state of toxic damage to the liver
2. 2 : a tendency or capacity to cause hepatotoxicity
1952
First Known Use of hepatotoxicity
1952
Medical Dictionary
hepatotoxicity
play
noun he·pa·to·tox·ic·i·ty \-täk-ˈsis-ət-ē\
Medical Definition of hepatotoxicity
plural
hepatotoxicities
1. 1: a state of toxic damage to the liver
2. 2: a tendency or capacity to cause hepatotoxicity
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Last modified on 26 March 2013, at 14:52
Fundamentals of Human Nutrition/Magnesium
MagnesiumEdit
Please use this HELP:EDITING link for information about contributing and editing the book.
8.2.3.1 SourcesEdit
Magnesium is an essential mineral (which means that we should acquire it in our diet because it is not produced naturally by our body) which our body needs so we could maintain efficient muscle and nerve function, for a strong immune system, maintaining healthy heart with normal rhythm, and building strong bones.
Most ingredients of our everyday diet have good natural sources of magnesium. Interestingly, various natural sources of magnesium at the same time contain potassium. Examples are Leafy and green vegetables (spinach, broccoli), cereals (oatmeal, barley, crude oat bran, rye, buckwheat, brown rice, unrefined whole wheat grain), milk products (skimmed milk, yogurt), nuts (brazil, almonds, cashews, peanuts, pine, pecans), legumes (kidney beans, soy beans), fruits (bananas, raisins, dates, figs), fish (halibut, broiled and not fried as frying reduces magnesium content), beverages like cocoa and coffee, dried herbs (coriander, chives, spearmint, sage, basil and savory), dried seeds (squash, pumpkin and watermelon), cocoa powder (dark chocolate), flaxseeds, sunflower seeds, sesame seeds, sesame butter (tahini, molasses and dry roasted soybeans.
http://www.newsmax.com/FastFeatures/sources-magnesium-food-diet/2011/01/28/id/369829#ixzz2Mj3L95Km
http://www.healthaliciousness.com/articles/foods-high-in-magnesium.php#C5JfogBheBXcE3U4.99
8.2.3.2 FunctionsEdit
Magnesium has been known to help maintain most of the body functions which regulate the vital processes of the heart for a healthy cardiovascular environment and bone density.
Its regulates of Blood Pressure,reduces the risk of type II diabetes, reduced risk of heart attack and other cardiovascular diseases, reduced risk of osteoporosis,reduced migraine and alleviates the Premenstrual Syndrome (PMS).
MAGNESIUM POWERS OUR ENZYMES because it is crucial to more than 300 enzyme-driven biochemical reactions occurring in the body on a near constant basis.
MAGNESIUM drives and maintains the balance of our FUEL SOURCE because it is a required ingredient of the energy-production process that occurs inside the tiny structures within cells.
MAGNESIUM plays a role in the protection of our DNA as DNA synthesis is slowed by insufficient magnesium.
MAGNESIUM REGULATES OUR ELECTROLYTE BALANCE. A proper balance of mineral content must be maintained within every cell in the body, . Magnesium contributes in the healthy balance (“homeostasis”) of important minerals (calcium, sodium and potassium) which affects the conduction of nerve impulses, muscle contraction, and heart rhythms.
http://www.healthaliciousness.com/articles/foods-high-in-magnesium.php#C5JfogBheBXcE3U4.99
http://http://www.ancient-minerals.com/magnesium-benefits/what-is-function/
8.2.3.3 RequirementsEdit
Certain nutrients (supplements in particular) and stress conditions increase the need for Magnesium and thus it is very important to monitor one's food consumption and supplement intakes.
When the dietary intake of Magnesium was maintained at 250 mg/day, and Calcium was increased from low (200 mg/day) to high (1400 mg/day), negative Magnesium balance was observed and thus it is very important to increase Magnesium to 500 mg/day when Calcium is present. A negative Magnesium balance was produced when Phosphate PO4 was increased from the near RDA level of 975 mg/day to 1500 mg/day. Vitamin D reduces the Magnesium retention so Vitamin D should be avoided to allow Magnesium to be absorbed by the body.
http://www.mgwater.com/require.shtml
8.2.3.4 ImbalanceEdit
Imbalance or Deficiency in Magnesium leads to the following: low energy, fatigue, weakness, PMS/Hormonal imbalance, inability to sleep, bone weakness, muscle tension/spasm/cramps, abnormal heart rhythm, headaches, anxiousness/nervousness, irritability, kidneys stones, etc.
http://www.calmnatural.co.uk/magnesium-deficiency
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Vaccinations in Adults
Featured in the April, 2015 Scleroderma, Vasculitis & Myositis eNewsletter
Barry D. Brause, MD
Barry D. Brause, MD
Attending Physician, Hospital for Special Surgery
Director of Infectious Diseases, Hospital for Special Surgery
Michael W. Henry, MD
Michael W. Henry, MD
Assistant Attending Physician, Hospital for Special Surgery
Assistant Professor of Clinical Medicine, Weill Cornell Medical College
There are many diseases for which there are preventative vaccines available. The Centers for Disease Control makes specific recommendation regarding when and to whom these vaccines should be given. Michael Henry, MD and Barry Brause, MD with the HSS Center for Infection Diseases explain vaccine recommendations for adults, including some recent additions to the guidelines.
Vaccine-Preventable Infections
A vaccine-preventable infection is an infection for which there is a vaccine available that can help keep a patient from developing the infection. In some cases, as with the Influenza vaccine, the vaccine can at least reduce the symptoms and severity of an illness, even if the disease itself cannot always be fully prevented. The following is an updated list of commonly given vaccines, and the infections they protect against.
Common Vaccines:
• Influenza: Since the influenza vaccines change every year, the influenza vaccine needs to be given every year. Also, the present vaccines confer immunity which is protective for approximately only 6 months. This vaccine helps to reduce the occurrence and severity of influenza
• Pneumovax + Prevnar: These two vaccines prevent infections caused by Streptococcus pneumonia. This bacterium is the most common cause of bacterial pneumonia and meningitis in adults.
• TdaP: This protects again three infections: Tetanus, diphtheria, and pertussis. Pertussis is the bacteria that causes Whooping Cough. There has been a sharp rise in the number of children and adults diagnosed with Whooping cough over the past decade in the United States.
• Zostavax: Reduces the occurrence of shingles, a painful rash that is caused by the same virus that causes chicken pox.
• MMR: Protects again measles, mumps, and rubella (German measles). The vaccine is often received in childhood. However, as an adult you may need a booster. This should be discussed with your doctor.
Vaccinations in Adults with the Scleroderma, Vasculitis, and Myositis
Patients with scleroderma, vasculitis or myositis are at increased risk for vaccine-preventable infections. This is in part due to the effect of these illnesses on the immune system. Mostly, however, this risk is a result of the immunosuppressive medications used for treatment, including steroids like prednisone.
Immunosuppressive medications treat scleroderma, vasculitis and myositis by altering or damping the patient’s immune system. This weakening of the immune system can be highly beneficial in treating these illnesses. However, it can increase the risk of developing infections, many of which are vaccine-preventable.
The effectiveness of the vaccine depends greatly on the recipient’s ability to develop an immune response to the vaccine. If the immune system is not functioning well, the body may not develop a strong immune response to the vaccine. Therefore, the recipient may not develop full protection and the benefit of the vaccine will be diminished or lost.
Types of Vaccines:
Vaccines can be divided into two basic groups: Killed vaccines and Live vaccines.
A Killed vaccine does NOT contain any living virus or bacteria. A person receiving a killed vaccine cannot become infected by the vaccine.
A Live vaccine contains a living, but weakened, form of a virus or bacteria. The risk of developing an actual infection from a live vaccine is extremely low. However, this risk does increase in patients who are taking medications which suppress the immune system. In some instances, a live vaccine will need to be withheld because of this risk. This can be an important consideration in patients being treated for scleroderma, vasculitis or myositis.
It is important to remember that the vast majority of vaccines given to adults are Killed vaccines, and therefore cannot cause an infection.
It is also important to remember that scleroderma, vasculitis and myositis by themselves do not make anyone ineligible to receive a vaccine -t his includes Live vaccines.
Who Gets Which Vaccines and When?
The type of vaccines you will need will be based on your age, prior medical history, especially your history of prior infections, current pregnancy status, and current medications – especially if you are taking immunosuppressive medications. In addition, the recommendations for vaccines are updated over the years, and new vaccines are introduced. Your doctor may wish to vaccinate before immunosuppressive treatment is started, or may wish to wait until the treatment is completed and allow your immune system to recover. This will increase the likelihood that you will develop a good response to the vaccine and it will reduce the potential of developing an infection from a live vaccine
You should review with your doctor which vaccines you should be receiving and when. A considerable amount information regarding vaccinations is available on the CDC’s web site.
Vaccines Commonly Given to Adults
Influenza Vaccine
Influenza is an unpredictable respiratory virus. It has the capacity to cause a large amount of inflammation of the larynx, trachea and bronchi. It can damage and weaken the cells lining your respiratory tract, so they will not protect you to the same degree. This creates greater risk of developing influenza pneumonia and bacterial pneumonia. Influenza infections can also exacerbate underlying chronic lung diseases, like asthma and emphysema.
Transmission
Influenza may be transmitted through saliva, nasal secretions and feces. Sneeze and cough particles can travel up to three feet. An infected person is contagious 24 hours prior to and up to seven days after symptoms of onset of the disease. Viruses can also continue to live days to weeks on dry surfaces. A person is most likely to be exposed through touching a contaminated surface and then touching one’s nose, eyes or mouth.
Prevention
Transmission of influenza can be prevented by thorough and frequent hand-washing and coughing into a barrier such as a tissue or elbow. One should stay informed about the flu season, avoid touching eyes, nose and mouth, and avoid close contact with those who are infected, even if that person is on anti-viral therapy, and should stay home if ill. Lastly, one can get vaccinated!
Side Effects of Influenza Vaccines:
• Pain and inflammation at injection site
• 5% experience fever and 3-12% experience malaise
• 2-9% experience myalgias (muscle pain) and 5-6% experience arthralgias (joint pain)
• These side effects can begin 6 hours after vaccination and can persist for 2 days [Resolve with aspirin, Tylenol, NSAIDs (such as ibuprofen)]
• Allergies such as hives may occur, but these reactions are rare unless you are allergic to eggs
• Guillain-Barré syndrome may occur, but the incidence is very low
Herpes Zoster (Shingles) Vaccine
Herpes Zoster (Shingles) is the reactivation of the chicken pox (varicella) virus and occurs more frequently as we age, since the immune system loses some strength as we get older. Taking immunosuppressive agents increases the risk for shingles as well. Once a person gets chicken pox and recovers from it, the virus continues to stay in the body forever, residing within specific types of nerve cells. At some point in life, the virus might start to reactivate in the nerve cells, causing a band-like painful rash on the body surface. After the reactivation of the virus resolves, some patients can continue to experience severe pain in the area where they had the rash. This pain, called post-herpetic neuralgia, can persist for weeks or months after the rash resolves. Treatment with anti-viral medications as soon as shingles is diagnosed can reduce the duration of the rash and the occurrence of post-herpetic neuralgia.
Herpes Zoster can also lead to other serious complications, including ophthalmic zoster, which is the involvement of the ophthalmic division of the trigeminal nerve and the eye and disseminated zoster which causes wide spread skin eruptions and multi-organ involvement, potentially including the central nervous system, lung, liver, and pancreas.
The Herpes Zoster vaccine can help prevent shingles from occurring, but it is not 100% effective. However, when a person who has previously received the Herpes Zoster vaccine does develop shingles, the vaccine reduces the likelihood of developing post-herpetic neuralgia. The ability of the Herpes Zoster vaccine to prevent shingles can decrease as we age. However, its ability to prevent post-herpetic neuralgia does remains constant.
Screening for Herpes Zoster Vaccine Eligibility
Screening for a history of chickenpox is not necessary in order to administer the vaccine to a person 50 years of age or older. Those who were born in the United States before 1980 are assumed to have been exposed to chickenpox regardless of their recollection of chickenpox.
Timing of Vaccination
For those anticipating receiving an immunosuppressive medication, the Zoster vaccine should be administered at least 14 days before initiation of immunosuppressive therapy, although some experts advise waiting a full month after zoster vaccination to begin immunosuppressive therapy. The herpes zoster vaccine cannot be given to patients on certain immunosuppressive therapies. Please speak to your doctor about when it would be safe the best time for you to receive the Zoster Vaccine.
Tetanus, Diphtheria and Acellular Pertussis (Tdap) Vaccine
Tetanus is a disease caused by bacteria that enters the body through breaks in the skin, and the symptoms are characterized by painful muscle spasms, breathing problems and paralysis.
Diphtheria is a disease that causes a thick coating in the back of the nose or throat, making it difficult to breathe and swallow. It may also attack the heart and nerves.
Pertussis, also called “whooping cough” is highly contagious, causing a respiratory infection with prolonged, distinct coughing, and remains incompletely controlled in the U.S. There is currently a worldwide epidemic of pertussis.
It is recommended that this vaccine be given once in adulthood. It is not a live virus vaccine.
Side Effects of Tdap Vaccine
Pain (67%), redness, swelling at injection site (20%); fever (1%), headache (40%), tiredness (33%), nausea, vomiting, diarrhea (1-3%), chills, body/joint aches, rash, swollen glands.
Patients are advised not to take this vaccine if they have had a life-threatening allergic reaction after a dose of any tetanus, diphtheria or pertussis-containing vaccines or if they have had a severe allergy to any part of this vaccine.
Patients should not take this vaccine if they have had a coma or multiple seizures within 7 days after a childhood dose of DTP or Dtap. In addition, those who have epilepsy, other nervous system problems, or patients who have ever had Guillain-Barre Syndrome should check with their doctors before taking this vaccine. However, bad reactions to this vaccine are very uncommon.
Pneumococcal Vaccines
Pneumococcal Infections: Streptococcus pneumonia (pneumococcus) is a major cause of vaccine-preventable illness and death in the US. Pneumococcal Infections can cause pneumonia, blood infections, meningitis and other respiratory infections. They are transmitted from person to person by respiratory droplets, and can be spread by a cough. Those who are at greater risk include those 65 years old and older, people with heart or lung disease, asthma, sickle cell disease, diabetes, smoking, alcoholism, cirrhosis, cerebrospinal fluid (CSF) fluid leaks, cochlear implants, lymphoma, leukemia, kidney failure, HIV infection, damaged or no spleen, and immunosuppressive diseases and treatment.
Two Vaccines for Pneumococcus in Adults: In August of 2014, the CDC recommended Prevnar for routine use in all adults 65 years and over. Prevnar is vaccine against infections caused by Streptococcus pneumoniae, which is the leading bacterial cause of pneumonia and meningitis in the United States. This vaccine will be given in addition to the Pneumovax vaccine, another vaccine again pneumococcal disease which is already recommended routinely to all adults 65 and over. The combination of the two vaccines in adults provides better protection that either of the vaccines alone. Prevnar has been routinely used in children in the US since 2000.
In healthy adults 65 and older, both Prevnar and Pneumovax only need to be given once. Prevnar should be given first, followed by Pneumovax some months later which you need to discuss with your doctor If Pneumovax is given first, you will then need to wait at least 1 year before receiving Prevnar.
Both Prevnar and Pneumovax are also recommended for adults younger than 65 if they have certain medical conditions, including treatment with certain medications that suppress the immune system. If you are on treatment that suppresses the immune system and are younger than 65, you should ask your doctor if you should receive Prevnar, Pneumovax, or both.
Important Facts About Vaccines to Remember
Each vaccine has its own schedule. Some vaccines, like the influenza vaccine, need to be given every year. Other vaccines may only need to be given once, and yet others will require boosters periodically.
You can receive a vaccination even if you are taking an antibiotic (the lone exception is when receiving the oral Typhoid vaccine).
It is safe to receive more than one vaccine in a single visit. Some vaccines however, like Prevnar and Pneumovax, cannot be given on the same day.
If you are planning to travel abroad, consult your physician regarding any pre-travel vaccines you might need to take. The CDC’s web site provides very comprehensive information regarding what vaccines are recommended depending on the countries you are planning to visit.
Related Conditions
Related Patient Articles
Back in the Game Patient Stories:
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Can boxing be made safer? Yes but the culture needs to change
N K Sethi, MD
Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, United States of America
Disclosure and Disclaimer: N.K Sethi serves as Chief Medical Officer for the New York State Athletic Commission (NYSAC). The views expressed are his only and do not reflect the views of the NYSAC.
KEY WORDS: boxing; traumatic brain injury; concussion; death
Recently the boxing world has been mourning the loss of a number of boxers in the ring or in the immediate aftermath of a bout. As physicians we take an oath to always protect the health of our patients and while ringside medicine is practiced in a different arena than within the confines of a hospital or ER, our duties and obligations to protect the health and safety of the fighters should never waiver for when they enter that ring or cage, they entrust us with their most precious possession of health. Few realize the pressures doctors work under at ringside. Once I had to make the difficult decision to stop a bout on medical grounds with only 30 seconds left on the clock in the last round. I stopped the fight only to be berated by the fighter’s corner like I have never been before. The F word was used repeatedly for what I had done and I was told in rather colorful language of what they thought of my action. I remained calm and stepped away after ensuring the fighter was safe.
As I see it, when I “hung up my gloves” at the end of a long night, I had the satisfaction of knowing that I had done the job which I am entrusted with to the best of my capability. That job is to protect my fighter first and foremost. As a fan, yes I may see it differently and want the fight to go down to the end but we are not there in the capacity of a fan of the sport, we are there as doctors with one and only one job to protect the fighter.
Yes 30 seconds in boxing do matter. In boxing one punch can be the difference between life and death. One punch can kill! So while we as ringside physicians endure the wrath of the corners, the media and sometimes the fighter himself let us not let this discourage or intimidate us to comprise on fighter safety. In the end there is nothing like going to bed with a feeling of a job well done.
We have to continuously strive to provide the best medical care and attention to the fighters. Analyzing what we do and improving our current medical policies and protocols should be an ongoing task. The more time I spend ringside, the more I realize that boxing is a unique sport for a physician to be involved in and that the odds are stacked against us ringside. In the office or hospital/ ER setting, a patient comes to us mostly voluntary seeking help and care. On questioning, he/she gives us a detailed history. The family is at times there to supplement the history. Contrast that to the ringside where on direct questioning, frequently the patient (boxer) and his family (corner) falsely deny that anything is wrong and are often upset and angry that we even dared to ask the question. After a fight is over, it is not infrequent to encounter a boxer and his corner who refuse to go to the ER for medical evaluation. “I am fine doc, I am not going” is the deviant answer. These boxers and their corner staff fail to appreciate that symptoms in some people with head injuries don’t show up immediately! (walking, talking and dying syndrome). That is the reason why physicians recommended to observe people after a head injury for 24 hours.
When I last checked, none of us physicians have X-ray vision so how are we expected to make a medical call from a distance without the benefit of an honest history or a quick examination? Many do not realize that once a brain bleed has occurred and the pupils are unreactive (fixed) and dilated, there is precious little we physicians can do ringside to “save” that athlete. Even if that athlete reaches the hospital alive in a timely fashion as a result of our collective efforts, the resulting decompressive surgery is carried out as a last ditch palliative life-saving procedure. That athlete shall never be the same again and will have significant residual neurological deficits. Our goal should be to prevent such a devastating injury from ever occurring in the first place and not just to manage it after it has unfortunately occurred.
A few years ago, I wrote a short letter titled “Boxing can be made safer” in response to an editorial in a leading neurology journal calling for a ban on boxing and MMA. I argued passionately that boxing and MMA can be made safer with improved medical policies designed to protect the health and safety of the combat sport athlete. I still stand by my stated position that boxing can be made safer but the change has to come from inside. In the National Football League (NFL), the culture has already changed from a previously held view of “suck it up and shake it off” to one of “if you feel something, sit it out“. Athletes are now encouraged to report their symptoms of concussion/traumatic brain injury (even if minor and subjective) to the athletic trainers and doctors on the sidelines.
The word “No mas” (Spanish for “No more”) gained boxing notoriety when Sugar Ray Leonard fought Roberto Duran II on November 25, 1980. At the end of the eighth round Durán turned away from Leonard towards the referee and quit by apparently saying, “No más“. Duran’s stature was never the same again after he uttered those 2 words. Over the years, the boxing culture has evolved to one of never saying “No mas”. The fighter’s mentality is never to quit no matter what the circumstances. Doing so brings disgrace to the fighter, his family and his corner. This mentality and culture needs to change, Boxers and corner staff should be educated and encouraged to actively recognize and report to the ringside physician any subjective symptoms of concussion and TBI such as headache, subjective feeling of dizziness or light headedness, blurring of vision, double vision, confusion and a feeling of fogginess. “When in doubt, sit it out” is not equivalent to “No mas”. “For he that fights and walks away, may live to fight another day” historically attributed to Demosthenes, a Greek orator should be the new mantra of boxing. There is no shame in this; just smartness.
The boxing culture needs to change and this change shall come over time with education. As physicians it is our duty to educate the boxing community and I hope physicians who practice ringside medicine shall join me in this effort.
Together we can make a difference and making boxing safer.
Good versus bad medical stoppages in boxing-stopping a fight in time
Good versus bad medical stoppages in boxing-stopping a fight in time
Nitin K Sethi, MD
Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center, New York, NY (U.S.A.)
In boxing it is commonly said and not without reason “the fight must go on….”. Everyone ringside wants the fight to go on-the two boxers and their corners (sometimes not always!), the promoter (always!), the media (always!), the spectators (always!), the Commission and its appointed officials (only if both the boxers meet the Commission requirements for a fair and honestly administered contest), the referee (only if the boxers are fighting a fair fight and able to defend themselves), the judges (usually do not interfere with the conduct of the fight!) and the ringside physicians (only if the boxers are medically fit before, during and immediately after the contest!). So everyone ringside want the fight to go on but do some (media, spectators and promoters) want it more than others? As per the Uniform Boxing Rules (approved August 25, 2001, Amended August 2, 2002, Amended July 3, 2008), the referee is the sole arbiter of a bout and is the only individual authorized to stop a contest. In some states in the United States and in countries around the world both the referee and ringside physician are the sole arbiters of a fight and are the only individuals authorized to enter the fighting area at any time during competition and authorized to stop a fight. The referee and the ringside physician threshold to stop a fight (enough is enough!!!) may vary based on knowledge of boxing rules and regulations, knowledge of the boxers fitness level, pre-existing medical conditions, pre-bout fitness, intra-bout fitness and finally knowledge of medicine and bout ending injuries (head injuries, orthopedic injuries, eye injuries, blunt abdominal trauma). That is the reason why it is the referee (someone who has knowledge of boxing rules and regulations) and the ringside physician (someone who has knowledge of medicine) who are deemed to be the sole arbiters of a bout and entrusted with the health and safety of the boxers. The other MORE important question is when should the fight be stopped on medical grounds? Stopping the bout prematurely is unfair to the boxers, their corners, the promoter and the public. Stopping a bout too late risks serious injury even death of the boxer.
Boxer safety should precede all other considerations. The goal should be to stop the bout before a life threating injury or career ending injury occurs. Key word is before NOT after. Since at times this is not possible so more realistic goal should be timely identification of a serious injury in the ring and timely stoppage of fight. For that to occur the referee and the ringside physician should work as a team complimenting each other’s knowledge. Causes of sudden death in the ring or in the immediate aftermath of a bout are usually neurological.
To help timely identify and prevent TBI in boxing the following good practice guidelines are proposed based on personal and collective evidence of experienced ringside physicians and clinical acumen:
1. It is a good point to remember that boxers rarely if ever voluntary quit or request the fight to be stopped. They fight for pride, at times at the expense of their health. Corners may also not want the fight to be stopped with the hope that their boxer may turn things around. In a closely contested fight the crowd is excited and wants the fight to go on. At these times, the ringside physician should make the call to stop or let a fighter continue, based solely on the medical condition of the boxer.
1. During the one minute rest period in-between rounds, the ringside physician should step up to the ring canvas for a quick but thorough medical evaluation of the fighter.
1. This is the ideal time for the ringside physician to assess the neurological status of a fighter. In the case of a fighter who suffered a knock down in the preceding round or sustained multiple head shots, the ringside physician should conduct a quick visual evaluation of the fighter (Is the fighter responding appropriately to the commands and directions of his corner? Is he making eye contact with his corner staff? Was the fighter steady on his feet as he walked back to his corner at the end of the round? Does the fighter voice any complaints to his corner staff such as headache or pressure in head, dizziness, and blurred vision?). The ringside physician should attempt to do the above without obstructing or imposing on the corner’s time with its fighter.
1. If the ringside physician determines that he/she needs more time to evaluate the neurological status of a fighter, he/she should communicate this to the referee. The referee after starting the bout shall call a time out and walk the fighter to the ringside physician to be examined. The referee directs the other fighter to remain in the neutral corner. The ringside physician’s goal at this time is to conduct a quick but thorough neurological assessment of the fighter. He/she should begin this by asking the fighter few leading questions such as-how do you feel? Does your head hurt? Do you know where you are? If the fighter appears confused and disoriented, the ringside physician may ask more question like which round is it? Who is your opponent? Where are you fighting (name of the venue)? The ringside physician should then look for pupil symmetry and response and assess extra ocular movements (have the fighter track finger from side to side). The ringside physician should give the fighter a complex command such as touch your left ear with right glove and should assess the fighter’s gait and balance at the same time (is the fighter steady on his/her feet or is he leaning on the ropes for support). The ringside physician should then communicate to the referee whether the fighter can continue or the fight should be stopped. The whole process should not take more than 10 seconds.
1. The ringside physician should be aware that too much time spent evaluating the fighter during time out, inadvertently gives the fighter more time to recover. The opponent’s corner rightfully resents this and it is akin to getting “saved by the bell”. The public, TV audience, press and TV announcers question the fairness of the Commission’s administration of the contest and the credibility and impartiality of the bout officials-e.g., referees, judges and ringside physicians.
1. If serious health concern is raised for a fighter and the ringside physician is unable to document a good exam to determine whether it is safe for the fighter to continue, consideration should be given to stopping the fight. In these circumstances the ringside physician should tell the referee that the fight be stopped on medical grounds.
1. For ringside physicians with limited ringside experience, it is encouraged that they consult with other ringside physicians at the venue and the chief medical officer before deciding to stop a fight on medical grounds.
As injuries mount, the boxing community is looking within and the sport is under scrutiny from the medical community and media. Boxing is the most controversial sport for physicians and neurologists in particular because of the potential risk and degree of neurologic injury, questions and concerns about long-term sequelae (chronic traumatic encephalopathy), and the occurrence of deaths in the ring . Various medical associations including the American Medical Association and the American Academy of Pediatrics have stated opposition to both amateur and professional boxing . Many have called to ban boxing altogether . Dr. Hauser in a recent editorial titled “Beaten into action: a perspective on blood sports” says that “the medical, and especially the neurology, community has an obligation to do more. We need to spread the word that brain bashing is not a socially acceptable spectator sport, and partner with our national organizations to expand and improve the effectiveness of public awareness and other educational initiatives.” He further goes on to state “we should forcefully counter articles in the medical literature taking the position that closer medical supervision could obviate the need for a ban, or even worse that consenting adults have the ethical right to maim each other if they choose to do so .” While the neurological risks of boxing cannot be completely eliminated, boxing can be made safer .
Conclusion
It is recommended that the above proposed best practice guidelines be debated vigorously by the ringside physician and large scientific community and evidence based guidelines on medical stoppages be developed by the medical community in conjunction with professional boxing governing bodies. Boxing can be made safer but it shall be foolhardy to forget that frequently there is a very fine line between a good medical stoppage (medical stoppage done at the right time during the bout and for the right indication) versus a bad medical stoppage (medical stoppage done either too late, too prematurely or for the wrong indication). It is far better to stop a fight early rather than late. A ringside physician should never forget that in boxing one punch can change everything. One punch can kill!
Concussions and the risk of post-traumatic epilepsy
Concussions and the risk of post-traumatic epilepsy
A concussion is a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces. Immediately following a concussion, an athlete is usually advised physical and cognitive rest till post-concussion symptoms abate. The athlete then enters a stepwise return to play protocol. Premature return to play risks a second concussion, second impact syndrome, exacerbation and persistence of post-concussive symptoms.
Sports and Epilepsy
Sport is important not only in normal healthy populations, but also in persons with medical illness, physical or mental disabilities. Active participation in sports is beneficial physically and psychologically. The main concern in sports for persons with epilepsy is safety.
Why are people with epilepsy restricted from some sports?
Rationale is that the occurrence of an untimely seizure during certain sporting event has the potential for causing substantial injury and bodily harm both to the patient with epilepsy as well as fellow athletes and even spectators.
Example: if a person with epilepsy has a generalized convulsion or a complex partial seizure while skydiving: he shall not be able to deploy his parachute and a fatal accident can occur.
:a person with epilepsy taking part in an automobile racing event suffers a seizure while making a bend at speeds in excess of 100mph
:a person with epilepsy suffers a seizure while taking part in a swimming meet.
:a person with epilepsy suffers a seizure while bicycling
:a person with epilepsy suffers a seizure while horseback riding
:a person with epilepsy suffers a seizure while skiing down a steep hill
:even things more mundane such as having a seizure while running on a treadmill, while playing tennis, while jogging outside have the potential to cause bodily harm to the patient and others.
Why are people with epilepsy restricted from some sports?
Rationale is that repeated injury to the head (concussions) during some sports could potentially exacerbate seizures.
Example: a person with epilepsy who is indulging in contact sports such as boxing, karate, kick-boxing, muay thai boxing, American football, ice-hockey, wrestling, judo
But are these restrictions and fears actually based on scientific evidence or are they unfounded? Which sports are safe and which are not? Could indulgence in some sports make seizures potentially worse Vs. could some sports actually be beneficial for people with epilepsy (physically and psychologically)? Can vigorous physical exercise provoke seizures?
Exercise and seizures
One reason that people with epilepsy have been traditionally restricted from certain sports is the fear both in the patient and the treating physician that exercise especially aerobic exercise may exacerbate seizures. Some studies have shown an increase in interictal discharges during or after exercise. Most frequently these patients have generalized epilepsies. At least some frontal lobe and temporal lobe seizures are clearly precipitated or at times solely occur during exercise suggests that these are a form of reflex epilepsies. A number of physiologic mechanism by which seizures may be provoked by exercise have been postulated. These include hyperventilation with resultant hypocarbia and alkalosis induced by exercise. Another possible mechanism which is postulated to cause exercise induced seizures is hypoglycemia. This usually causes seizures after exercise in diabetic patients. Other mechanisms which have been postulated for exercise triggered seizures include the physical and psychological stress of competitive sports and potential changes in anti-epileptic drug metabolism. Exercise is a complex behavior and involves not such the motor system and the motor cortex but also involves other domains such as attention, concentration, vigilance and presumably some limbic networks which mediate motivation, aggression and competitiveness. Hence it is possible that patients who have temporal or frontal lobe epilepsy may on rare occasions have seizures triggered by exercise.
There is some limited evidence that exercise may in fact be protective and have physical, physiological and psychological benefits in patients with epilepsy. Electroencephalographic studies have shown that inter-ictal epileptiform discharges either remain unchanged or may decrease during exercise so there is some hint that exercise may actually raise the seizure threshold. Regular exercise also influences neuronal and hippocampal plasticity by upregulation of neurotropic factors. There is further evidence to suggest that regular physical exercise can improve the quality of life, reduce anxiety and depression and improve seizure control in patients with chronic epilepsy.
What sports are off limits for people with epilepsy?
No sport is completely off limit for a patient with epilepsy. Key though is proper supervision to reduce the potential for injury. There are some sports such as skydiving, automobile racing, swimming in the open seas and horseback riding which should be avoided by patients with epilepsy. Other sports can be enjoyed by patients with epilepsy but one should remember that they all have the potential to result in bodily harm if seizures occur when the patient is not supervised or if he is not wearing protective head and body gear.
Concussion and seizures (post traumatic epilepsy): what is the link?
The link between concussion (closed head trauma) and seizures has been and continues to be closely looked at. The fear of concussions (minor head trauma) making seizures worse is the prime reason why people with epilepsy are discouraged from some sports such as tackle football, ice-hockey, boxing, mixed martial arts and wrestling. The human skull is quite resilient and the closed head trauma has to be significant for it to result in seizures. Usually a concussion which results in prolonged loss of consciousness (some authors say more than 30 minutes) is graded as a significant head trauma. Minor bumps and bruises to the head do not cause seizures, do not increase the risk of future seizures and more importantly do not make chronic epilepsy worse. Seizures may occur immediately following a severe closed head trauma. Immediate post traumatic seizures by definition occur within 24 hours of the injury. They have also been referred to as impact seizures. Early post traumatic epilepsy refers to seizures which occur about a week to 6 months after the injury. Seizures may occur as far out at 2 to 5 years after head trauma (late post traumatic epilepsy). Factors which increase the risk of post traumatic seizures/ epilepsy include severity of trauma, prolonged loss of consciousness (more than 24 hours), penetrating head injury, intra or extraaxial hemorrhage, depressed skull fracture and early post traumatic seizures.
Counseling patients
Patients with epilepsy should be encouraged to exercise and take part in sports. My personal feeling is that no sport should be off limits to them with the exception of maybe sky-diving, river rafting and boxing. The goal should be exercising and playing sports safely. Walking, running, cycling and yoga are great exercises which can be indulged in with little to no risks. I advise all my patients with epilepsy (especially those with poorly controlled epilepsy) to wear a Medic Alert bracelet or carry a card in their wallet. This is of immense help were a seizure to occur in the field (as for example when a patient is jogging or cycling and is not in the immediate vicinity of his or her home). Low risk recreational sports such as walking or running usually do not need a one is to one supervision if seizures are well controlled by history. Team sports such as volleyball, basketball, baseball and softball are popular sports which carry a low risk of injury. For cycling I advise my patients to wear a helmet and have their bikes fitted with lights and reflectors. I also advise them to keep off from the busy city streets. “you do not want to have a seizure at the wrong place and at the wrong time”. Swimming is a great way to keep fit and also to meet and make friends. I feel many patients with epilepsy are discouraged from swimming due to an irrational fear of caregivers and physicians of drowning. I advise my patients not to swim alone. Most of the city pools have life guards and a polite request to them to keep a watch out goes a long way in reassuring both the patient and the caregivers. Swimming in the open seas is more risky. I advise my patients to swim close to the beach under the watchful eyes of a life guard. Also having a buddy around helps, preferably someone strong enough to pull the patient out of the water if a seizure was to occur. The option of wearing a life jacket is under utilized.
Final thoughts (a patient’s perspective)
These are the thoughts of a young patient of mine:
“I have always been a very active person and love playing sports such as Tennis, Yoga, Running etc, and I always try to pursue my dreams and not let things get in the way, but being epileptic, it is sometime hard to not worry about things happening. Whenever I play sports I get hot easily (face turns purple) and in the back of my head I find myself always hoping that nothing happens that would cause me to have a seizure. I ran my first half marathon two years ago, and in the back of my head there is always the thought of something happening, so I started to motivate myself by saying “I can do this, you will be fine.” My father taught me when I was younger that I can choose to let it hold me back or make the most of life! Many people consider epilepsy a disability, but I try not to because I don’t let it hold me back.”
Nitin K Sethi, MD, MBBS, FAAN Assistant Professor of Neurology New York-Presbyterian Hospital Weill Cornell Medical Center
Post Traumatic Epilepsy: when head trauma leaves behind a seizure disorder
Recently I have seen a few patients with post traumatic epilepsy and hence I decided it might be appropriate to talk about the same in more depth.
Before we begin though I want to wish all the readers of my blog from around the world a very Happy and Healthy New Year 2012. May it bring you not just a healthy brain but also a healthy mind.
Ok now to the topic at hand. Just what do neurologists and neurosurgeons mean when they say you have post traumatic epilepsy? As the name suggests post traumatic epilepsy (PTE) refers to epilepsy/seizures starting after a patient sustains head trauma. Let me explain with an example. Let us assume John is involved in an motor vehicle accident. While driving down the FDR drive late one night he falls asleep behind the wheel of his car. The roads are icy! John’s car spins out of control, jumps the curb and hits an embankment. John who is not wearing a seat belt gets thrown out of the car striking his head first on the windscreen and then on the unyielding asphalt concrete. A passerby witnesses the accident and calls 911. EMS are on the screen within minutes but John is not moving. His neck is stabilized in a hard collar and he is rushed to the nearest hospital. Glasgow coma scale (GCS) on arrival is documented to be 5. John is not responding to verbal commands and is rushed to the CT scanner for a stat head CT. CTscan shows all is not well. John has sustained significant head trauma. He has a fracture of the right temporal bone and an underlying epidural hematoma. There are bilateral frontotemporal contusions which are increasing in size. In addition there is diffuse subarachnoid hemorrhage. The epidural hematoma is evacuated that night itself by the neurosurgeon on call. It is decided that at present the frontal lobe contusions be closely observed. John is transferred to the neurological ICU where he is further stabilized. A close watch is kept on the intracranial pressure.
Fast forward 3 weeks.
After a rocky course in the neurological ICU, John makes a remarkable recovery taking the extent of his head injury into consideration. He is discharged from the hospital to a rehab facility skilled in traumatic brain injuries (TBI). In the rehab facility John makes a slow but steady progress. It is 12 noon and John as usual is working with his physical therapist. He suddenly stops what he is doing. Utters a loud guttural sound, falls down to the floor with his eyes rolled up. The therapist notes that he stiffens up for a few seconds and then starts to shake while frothing at the mouth. The whole seizure lasts for about 2 minutes and then subsides on its own. Post seizure John is confused and disoriented but slowly returns to his baseline in about 40 minutes. An appointment is made for John to see Dr. Feelgood a neurologist in the nearby community hospital.
Dr. Feelgood takes a detailed history and then examines John. You have post traumatic epilepsy John, he says and recommends that John consider starting anticonvulsant therapy without further delay.
The scenario I describe above is unfortunately not uncommon in patients who sustain significant head trauma. In fact head trauma is one of the leading causes of epilepsy in men and women below the age of 40 around the world. The human brain is well protected by an extremely rigid skull and so the trauma has to be significant to cause brain damage and resulting PTE.
MINOR BUMPS AND BRUISES TO THE HEAD DO NOT LEAD TO POST TRAUMATIC EPILEPSY. Post traumatic epilepsy is thus very rarely reported after closed head injuries aka concussions such as those sustained on the sport fields(please read my post about concussions either here or on my website http://braindiseases.info). On the other hand PTE is particularly common after penetrating head injuries such as gun shot wounds to the head or when the skull bone is fractured (especially depressed skull fracture where the bone fragment presses on the underlying brain) or when there is significant intracranial bleeding (remember what John’s CT scan showed: blood in the epidural space and hemorrhage into both the frontal and temporal lobes).
Seizures can occur at any time after a significant head injury. The patient may start having seizures immediately after sustaining the head injury. This is called early post traumatic epilepsy and at times this has a more favorable prognosis. After the blood in the brain goes away and the swelling/pressure in the brain subsides, the seizures may also stop spontaneously. Hence these patients may not need to remain on an anticonvulsant medication for a long time. Seizures though have been reported as far out as 5 years after the head injury. This is called late post traumatic epilepsy and these patients usually need to take anticonvulsant medication for a prolonged duration, at times even lifelong.
Depending on the extent of head trauma, seizures may be easy or hard to control in these brain trauma patients. They are usually prescribed anticonvulsant therapy and seizure control is then closely monitored. If seizures persist then a second or third anticonvulsant may be indicated.
Dr. Feelgood started John on a seizure medication by the name of levetiracetam. He advised John to follow up with him after 3 months. On the 3 month follow up visit, John walked into Dr. Feelgood’s office unaided and with a broad smile on his face.
I feel good, Dr Feelgood he said.
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Ask a doctor
Is There a Recommended Target Weight for Tummy Tuck?
I am 35 and have constantly battled with my weight. I am 5'2" and currently weigh 180. I have weighed as much as 200 and have gone up and down from about 150-200 in the last ten years. I have had 2 C-Sections and the horribly ugly overhang. Is there a recommended weight to reach before getting a Tummy Tuck?
Doctor Answers 13
You can benefit by a tummy tuck even if you are overweight.
To msboogs,
Hi! This is a common source of confusion. There is absolutely no reason to demand that you become thin before you can have your "ugly overhang" removed. Losing weight and aiming for a flatter stomach are independent issues.
So you can have a tummy tuck now. Some people just cannot come close to their ideal weight, and asking for this is just another way of saying "Never!"
There are two important points:
1) The WAY in which a tummy tuck is done should be different if you are overweight. So technique is important. You should have more liposuction and less undermining of the skin, for example.
2) There may be some additional risks if you are overweight, so we take special precautions. For example, we use blood thinners when doing a tummy tuck on an overweight person to prevent blood clots. Some people are afraid that blood thinners cause extra bleeding during surgery, but they don't, if used properly.
So go for it!
Manhattan Plastic Surgeon
5.0 out of 5 stars 9 reviews
Have a question? Ask a doctor
Within 20lbs of your ideal weight before tummy tuck
First, the most significant determinant of a good candidate for abdominoplasty is the amount of loose skin that is below the belly button. Often, this loose skin is caused by significant weight loss or by pregnancy. In both cases, the abdominal skin has been stretched beyond its ability to shrink.
If you can easily grab and pinch a large amount of loose skin, it is likely that an abdominoplasty would provide a highly noticeable improvement for you. If, on the other hand, the skin feels very thick and is not particularly loose, it is likely that an abdominoplasty is not for you. In fact, liposuction may be more appropriate.
Secondly, as far as what weight you 'should' be? There is no set weight that is ideal, but I recommend that my patients are within 20lbs of their ideal body weight. This will allow the focus of the procedure to be on the removal of extra skin and will yield better results.
Hope this helps!
Joseph Thomas Cruise, MD
Newport Beach Plastic Surgeon
4.5 out of 5 stars 41 reviews
There is no recommended weight for a tummy tuck.
Although it would be nice to operate on all patients at ideal body weight, that is just not the way things are. Overweight patients get dramatic results from abdominoplasties. It does not make them thin, but it can server as a psychological jumping point for further weight loss.
Vincent N. Zubowicz, MD
Atlanta Plastic Surgeon
4.5 out of 5 stars 13 reviews
Ideal Weight for Tummy Tuck Candidates
Ideally you should be close to your goal weight before undergoing a tummy tuck. This will allow for the best results, because if you continue to loose more weight you may end up with a bit of excess skin. If you wait, your results will allow for even better contours. Although, if you are losing 20 lbs or under, it is often not a problem.
It is always important to remember that liposuction and tummy tucks are not to be used as a means of weight loss. Liposuction is often performed alongside a tummy tuck for the purpose of contouring the body and getting rid of stubborn fat deposits. Large volume liposuction is not recommended and should only be performed in a hospital setting as a safety precaution.
Target weight for a tummy tuck
Tummy tucks are an extremely popular and effective way to contour the abdomen. There is no perfect weight before a tummy tuck. Your best is to work with a board-certified plastic surgeon who has a great deal of experience in abdominoplasty, liposuction, and body contouring. You should also be at a stable weight and as close to your personal target as possible. Keep in mind that the more weight you lose before your tummy tuck, the better your result will be.
To learn more about tummy tucks, see photos, and help you decide which one is best for you, please visit us at the link below:
Pat Pazmino, MD
Miami Plastic Surgeon
4.5 out of 5 stars 64 reviews
Reaching your ideal weight prior to surgery
Ideally, I would recommend that you get as close as possible to your goal weight prior to surgery. In order to achieve the best and safest results possible, patient's do the work to lose weight or wait until their weight is stable. The last thing we would like are complications or the need for revisionary surgery. Unfortunately, plastic surgery does not guarentee permanent results.
Factors that may affect the results include weight loss, weight gain, gravity, aging, and pregnancy. To avoid additional surgery, it is in your best interest to work your hardest to lose weight. Consult with a board certified plastic surgeon to determine whether you are a good candidate for the procedures you are interested in. For more information regarding recovery and to compare before and after photos, go to my website. Good luck!
Ideal body weight for tummy tuck (abdominoplasty)
Ideally you should be within 10% of your ideal body wieght. This should be 115 pounds at 5'2'. This represents a BMI of approximately 21 and can range up to 25 corresponding to a weight of 140lbs. This will lower your inciidence of complications.
Otto Joseph Placik, MD
Chicago Plastic Surgeon
5.0 out of 5 stars 54 reviews
Ideal weight and tummy tuck
You should really get down to a weight that is closer to your ideal weight but a weight that you can maintain. Then consider a tummy tuck.
Steven Wallach, MD
Manhattan Plastic Surgeon
4.5 out of 5 stars 18 reviews
You need to get to a weight you can maintain after tummy tuck surgery
Hello,
Really large patients do not see as much improvement after tummy tuck surgery as smaller patients, but you do not benefit by losing weight only to gain it afterward. It is all relative. I am not saying you can't get good results. Some of this depends upon what you define as a good result. You just can't expect to be made really thin by surgery if you are larger in the first place.
I usually tell my patients to find their "maintenance weight" and then come for evaluation. Then we figure whether or not the surgery will result in an outcome with which we can be happy.
John P. Di Saia, MD
Orange Plastic Surgeon
5.0 out of 5 stars 24 reviews
Timing for tummy tuck surgery depends on you
Tummy tuck surgery (abdominoplasty) works best for individuals who have come as close to their goal weigt as possible and have been able to maintain this weight for several months. Abdominoplasty is not a substitute for weight loss and diet and exercise are important in maintaing and optimizing your results. Abdominoplasty is a rewarding surgery for many people and can help you get over the hump that exercise and diet can only partially provide.
David A. Robinson, MD
Munster Plastic Surgeon
5.0 out of 5 stars 18 reviews
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.
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Slowing down aging, boosting training outcomes, myths, and facts: HGH supplements
0
595
HGH pills for sale-Photo by kirschner-amao
HGH pills for sale-Photo by kirschner-amao
If you are a person who exercises regularly and carries out a healthy lifestyle, you may have probably heard about supplements. Protein shakes, vitamins, amino acids, and more are some of the available options. What is more, these have become so popular that most athletes use some extra aid to recover from their work out sessions. On the other hand, they also implement these to boost their performance and reach the body they have desired for so long. So, we are not referring to anything enigmatic; we only want to give you an in-depth view of the human growth hormone —HGH— products.
But in anticipation of speaking about technicalities, you must understand what HGH is. Our body, specifically our pituitary gland, secretes many hormones. Among others, it produces the luteinizing hormone —which produces estrogen and testosterone—, endorphins, etc. However, in this case, the center of attention is the human growth hormone. And that one is elemental to the development of any human being throughout his/her entire life.
The different stages of human growth and how HGH works
As children, the human growth hormone is responsible for our most significant body changes. We experience alterations in our complexity. Hence, we get taller, slimmer, build more muscle, and get stronger bones. But sometimes, our pituitary gland does not work accurately; in other words, it does not secrete enough HGH.
That is why, on some occasions, some children who have growth issues need medical intervention to receive HGH administration. Therefore, that is the case of HGH injections, which help them out to have a healthy development as possible. In the case of adults, that medical intervention can take place when they have suffered from a traumatism in the head or meningitis. Moreover, some adults can have sequels from radiation therapy due to a tumor in the pituitary gland. In all these cases, they experience deficiencies or excess of growth hormone production.
But what about those who do not have a clinical condition?
Many grown-ups show concern for their health and the effects of getting older. And those have to do with the natural course of life, which inevitably makes us produce less HGH once we go through our early adulthood. The impacts? Less muscle, more fat, wrinkles in our skin, hair loss, weaker nails, and more. If we mix these alterations with bad habits and sedentism, the results can be quite disastrous. Therefore, lots of people seek for natural supplements to feel and look better, including HGH pills for sale.
On the other hand, people who usually work out also implement HGH supplements to boost their outcomes. And that is the case of bodybuilders, for example. Having trained for so long, they do not get the same results as before. In other words, they do not grow equal amounts of muscle, burn identical quantities of fat, or have the equivalent bone density. Hence, their organism gets used to such routines. And that can be extremely frustrating, right? In these cases, corporating HGH supplements can ultimately make the difference.
Supplements and administration: two concepts that can be confusing
We should start with the fact that there are no mystical products. HGH pills for sale do not provide growth hormone in their composition. Hence, they are not a way of incorporating the substance in its pure state into our organism. Therefore, these pills are stimulators of natural HGH production in our pituitary gland. Containing plenty of amino acids, ginseng powder, and many other natural ingredients, they are boosters. And you may be wondering, what do they boost? Muscle growth, fat burning, and energization, among other excellent effects.
Conversely, the direct administration of HGH consist of its synthetic form injected into our bloodstream. Like we explained before, sometimes people have deficiencies in the production of growth hormones, so they need medical assistance. That means that only professionals of healthcare can prescribe, administrate, and control HGH injections. Any other use is wholly illegal. Therefore, there is a lot of controversy around bodybuilders and other athletes who make use of growth hormone in its synthetic form.
Free from regulation does not mean free use!
Even though the FDA does not strictly regulate or restrict HGH pills for sale, these are still components that we will incorporate into our organism. Therefore, without medical recommendation and prescription, it is not a good idea to take them at all. Be careful and wise; take care of your health!
More info here:
Anti aging products
https://www.medicalnewstoday.com/articles/312905
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4,437,166,199,111,705,600
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Español English Русский
оливковое масло полезно
22 Jan Mediterranean diet and cheese
Did you know that supplementing the Mediterranean diet with cheese can be good for the heart?
Unfortunately, Russia ranks second in the world in terms of the number of annual deaths from a heart attack, and first from a stroke. In the United States, cardiovascular disease is the cause of one in three deaths, which is an average of 2,300 people a day, that is, one death every 38 seconds! As you know, you can protect yourself with the help of nutrition, sports and abstinence from alcohol. But not only…
Usually, the Mediterranean diet, which is considered the most reasonable and healthy type of food in the world, does not involve dairy products – only a small amount of hard cheese for wine. In Spanish dishes, cheese is rarely present. But in Australia, they took care of this issue, and found that it can be improved if you add different cheeses and yogurt to the diet, especially for people with an increased risk of cardiovascular diseases. In addition to eating an abundance of olive oil, fish, cereals and fresh vegetables, three servings of cheese a day give a significantly healthier heart rate, blood pressure, cholesterol levels, improve cognitive function and mood!
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parasites
3 common parasites that are literally eating you alive
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Delicious
(NaturalNews) Parasites are a part of life. They cause serious health issues that, in some cases, become fatal. No one is exempt from these vile creatures. Every one, even you, has at least one type of parasite. Let's review the most common types of parasites that are literally eating humans from the inside out.
Hungry hungry hookworm
An estimated 740 million people are infected globally. Hookworms are the leading cause of maternal and child morbidity in some developing countries. They also infect cats and dogs. Aptly named for their hooked mouths, hookworms latch on by biting into the intestinal wall. Once they've latched on they suck blood ravenously. This blood loss means anemia for the unsuspecting host. Hookworms can lay approximately 30,000 eggs per day and each worm generally lives 1 to 5 years.
Roundworm Giants
This is the largest in size and one of the most common parasitic worms in humans. Giant roundworms can grow just over 19 inches long and can lay 200,000 eggs per day. More than 2 billion people are infected with this parasite they cause an estimated 20,000 deaths annually. Infection typically occurs from poor hygiene habits, consuming food tainted with fecal matter, and by infected pets. Once inside, they're difficult to remove because of a lipid coating that protects them from acids, alkalis, and chemicals.
Giant Roundworm infection signs and symptoms
• Abdominal pain
• Nausea
• Fatigue
• Diarrhea
• Weight gain
• Weight loss
• Worms in vomit or stool
Complications
Giant roundworms are living organisms that feed and defecate inside the host. They can chew their way through body tissue and their stool is toxic to the body. They also eat your nutrients which leads to deficiencies and malnutrition for the host. Due to their size, they can completely block the intestines or other vital organs which can be fatal.
Complication include:
• Intestinal inflammation
• Gall bladder inflammation
• Pancreatic inflammation
• Appendicitis
• Cardiomyopathy
• Encephalopathy
• Peritonitis
• Kidney Disease
• Abnormal skin growths
• Blindness
Titillating tapeworm
To be accurate, this parasite doesn't literally eat you; it does however, feed off of you. Tapeworms are the longest parasites in the world. On average, the parasites are around 14 feet long. The longest tapeworm ever recorded was 37 feet long; it was pulled out of Sally May Wallace through her mouth in 1991. Apart from being ridiculously long, this worm can live in it's host for decades and typically goes unnoticed.
Tapeworms have a "crown" of tiny hooks on top of their head, which they use to attach themselves to your insides. They feed off of your nutrients by absorbing them through their skin. Pork, beef and fish are the primary sources of infection. Eating raw fish, beef, or pork that is undercooked can lead to tapeworm infection. Even meat and fish that are properly cooked can be a possible cause of infection if the chef has poor sanitation and reinfects your food.
Tapeworm infection signs and symptoms
• Constant hunger (especially for sweets and junk food)
• Abdominal cramping and/or pain
• Loss of appetite
• Malnutrition
• Weight loss
• Fatigue
• Nausea
• Diarrhea
Can they really cause death?
Though parasites most often go unnoticed, they can cause death. Some parasites, such as the tapeworm, can move out of the intestine and cause growths in local tissue where it settles such as in the brain, heart, or eye. In the brain, they can cause seizures and extensive damage to the nervous system.
Click here to read about natural remedies for parasites by the author, Jeanette Padilla.
Sources for this article include:
www.newscientist.com
www.scientificamerican.com
www.stanford.edu
www.nlm.nih.gov
About the author:
Jeanette Padilla is an experienced herbalist and iridologist. Read more health articles from her at Sunshine Natural Healing, or follow her on Facebook
Join over four million monthly readers. Your privacy is protected. Unsubscribe at any time.
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Category:
What Are the Different Types of Guaifenesin Side Effects?
Constipation is one possible side effect of guaifenesin.
Guaifenesin is commonly used to relieve chest congestion by making mucus thinner.
Guaifenesin side effects may include the development of kidney stones.
A small percentage of people report experiencing side effects like drowsiness and dizziness while taking guaifenesin.
Nausea is one possible side effect of taking guaifenesin.
Article Details
• Written By: Tricia Ellis-Christensen
• Edited By: O. Wallace
• Last Modified Date: 19 December 2014
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Guaifenesin, which is most often used as an expectorant to help clear mucus from the airways, isn’t associated with a high number of side effects. Many people take this medicine with few problems. The matter may become slightly more complicated because the drug is often mixed with other medications that can cause more adverse effects. Alone, guaifenesin side effects are relatively minimal or extremely rare.
The most common of the guaifenesin side effects is nausea or vomiting, and this is often improved or avoided if people take the medication with food. Most people won’t experience this side effect. Higher than recommended doses tends to increase risk of these gastrointestinal symptoms. Another adverse effect some people report is the sensation of a dry mouth. This may be alleviated by taking the medication with plenty of water, which is advised because it can help thin mucus secretions and increase expectorant action.
A relatively small percentage of people experience guaifenesin side effects like drowsiness or dizziness, but this percentage is very small. An even smaller percentage of users of this drug develop a rash from taking it. The most serious of the guaifenesin side effects, development of kidney stones, is extremely rare. Risk for this adverse effect can be lowered by drinking plenty of water while using the medication. The drug has additionally been shown to very occasionally result in an anaphylactic allergic reaction.
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In addition to being well tolerated when taken alone, there appears to be few or no medications that negatively interact with guaifenesin. The medicine seems appropriate for use in most people. Those who are prone to kidney stones might avoid it, and the drug is only recommended in pregnancy if the benefit is clearly established. Little evidence exists of it being harmful to a pregnant mother or fetus.
Indications for use become more complex when people take this medication in a combination form. The drug is frequently combined with other drugs like pseudoephedrine, phenylephrine, dextromethorphan, and even codeine. The addition of these other medicines can change and increase the side effects people will experience.
Adding pseudoephedrine or phenylephrine can cause adverse effects like excitability, difficulty sleeping, low appetite and constipation, in addition to the expected but rare guaifenesin side effects already mentioned. Dextromethorphan adds the possibility of experiencing increased drowsiness or dizziness, excitation, mental dullness and respiratory depression. Drugs like codeine have a host of potential side effects such as drowsiness or sleepiness, increased nausea, and constipation. Some of these add-on medications do have more significant contraindications, and use of them combined with guaifenesin should be checked with a doctor or pharmacist, particularly if a person has any other medical conditions or is using other medications.
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Lose weight for prom
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BMC Psychiatry
, 18:43 | Cite as
Assessment of grief-related rumination: validation of the German version of the Utrecht Grief Rumination Scale (UGRS)
• Bettina K. Doering
• Antonia Barke
• Thilo Friehs
• Maarten C. Eisma
Open Access
Research article
Part of the following topical collections:
1. Mood disorders
Abstract
Background
Bereavement can result in severe mental health problems, including persistent, severe and disabling grief symptoms, termed complicated grief. Grief rumination (i.e., repetitive thought about the causes and consequences of the loss) is a malleable cognitive risk-factor in adjustment to bereavement. The Utrecht Grief Rumination Scale (UGRS) was recently developed to assess grief rumination. The present study aimed to develop and validate a German version of the UGRS.
Methods
An online survey including measures of demographic and loss-related variables, grief rumination (UGRS), depressive rumination (brooding and reflection), and symptoms of depression, anxiety, and complicated grief, was administered online among 159 persons (87% women) who had lost a first-degree relative in the past three years. UGRS item analyses, a confirmatory factor analysis and associations of grief rumination with brooding, reflection and symptom levels were performed.
Results
The internal consistency of the UGRS was good. The confirmatory factor analysis obtained a good fit for a model with five correlated grief rumination subscales. The UGRS contributed uniquely to the prediction of complicated grief symptoms even when controlling for symptoms of anxiety and depression, brooding, reflection, and demographic and loss-related variables. Discriminant validity of the UGRS was demonstrated by the fact that higher UGRS scores were found in participants with a higher likelihood of receiving a diagnosis of complicated grief (d > 1.60).
Conclusion
The translated UGRS showed very good psychometric properties and the correlations with maladaptive ruminative styles and complicated grief symptoms demonstrated the clinical relevance of grief rumination. Limitations concerning generalisability of the results are discussed.
Keywords
Rumination Repetitive thinking Bereavement Complicated grief Assessment Validation
Abbreviations
CG
Complicated grief
DSM 5
Diagnostic and Statistical Manual for Mental Disorders, 5th edition
HADS
Hospital Anxiety and Depression Scale
ICD-11
International Classification of Diseases, 11th edition
ICG
Inventory of Complicated Grief
PCBD
Persistent Complex Bereavement Disorder
PGD
Prolonged Grief Disorder
RAH
Rumination as Avoidance Hypothesis
RSQ 10D
Response Styles Questionnaire 10D
RST
Response Styles Theory
UGRS
Utrecht Grief Rumination Scale
Background
Bereavement is a universal human experience. While most people react to a loss with intense pain and may even develop an increased risk of mental or physical health problems [1], a majority adjust successfully to this stressful life-event without professional help. A minority of bereaved people, however, suffer from persistent grief symptoms of clinical relevance that are accompanied by functional impairment. Both new diagnostic classification systems of mental health conditions acknowledge the syndrome. The Diagnostic and Statistical Manual for Mental Disorders in its 5th edition (DSM 5) classifies it as ‘Persistent Complex Bereavement Disorder’ (PCBD) and considers it a condition for further study [2]. The International Classification of Diseases in its 11th edition (ICD-11) will probably include ‘Prolonged Grief Disorder’ (PGD) as a stress-related disorder [3, 4]. Concerning symptom duration, ICD 11 may allow a diagnosis as early as six months after the loss occurred, whereas DSM 5 requires symptoms to last twelve months. A recent meta-analysis estimates the pooled prevalence of PGD after bereavement to be 9.8% [5]. The present article will use the well-established term ‘complicated grief’ to refer to clinically relevant grief symptomatology, since the present assessment of grief symptoms follows the Inventory of Complicated Grief [6]. This also allows for drawing on existing research of grief rumination and bereavement outcome.
Given the severe distress that may be experienced after bereavement, a thorough understanding of the malleable factors that may contribute to the development and persistence of mental health problems is important. Thought processes are both malleable (for a review: [7]) and are assumed to play an important role in the potential transition from ‘normal’ to complicated grief and its maintenance [8]. Special attention has been paid to trans-diagnostic thought processes such as repetitive thinking, i.e. the ‘process of thinking attentively, repetitively or frequently about one’s self and one’s world’ ([9], p. 909). Repetitive thinking about the deceased, the loss and its circumstances and consequences seems inherent to the acute grieving process [10]. Some forms of repetitive thinking, however, such as rumination, have been associated with poor bereavement outcome, both concurrently and prospectively (cf. [11, 12, 13]).
Two types of rumination have been studied in some detail in adjustment to loss. The first investigations in this area were conducted in the mid-nineties. They focused on clarifying the role of depressive rumination after bereavement. Depressive rumination was defined as repetitively and passively focusing on depressive symptoms and on their possible causes and consequences [11]. A frequently used theory to understand the effects of depressive rumination on psychopathological symptoms is the Response Styles Theory (RST). The RST proposes that depressive rumination fuels depression by increasing the accessibility of negative thought content, impairing instrumental behaviour and problem solving, and driving away social support [11, 14]. In an attempt to differentiate adaptive from maladaptive forms of depressive rumination (cf. [15]) and to minimise the content overlap of the assessment of rumination with that of symptoms of depression, two sub-facets of depressive rumination were introduced, namely brooding and reflection [16]. ‘Brooding’ implies a passive comparison of the aversive current situation with some unachieved standard, and ‘reflection’ indicates actively focusing inward to engage in cognitive problem solving in order to overcome depressive symptoms. Longitudinally, brooding has been associated with more depressive symptoms, whereas reflection seems to be associated with less depressive symptoms [16]. Concerning adaptation to bereavement, RST conceptualises rumination as a confrontation strategy as it entails thinking repeatedly about post-loss emotions. Previous research indicates that all three constructs (i.e. depressive rumination, brooding, and reflection) are associated with psychopathological symptoms after bereavement [17, 18, 19, 20, 21, 22, 23]. However, it also suggests that another type of rumination, namely grief rumination, is potentially more predictive of mental health problems in adjustment to bereavement, consistently explaining more variance in post-loss symptoms of depression, posttraumatic stress and complicated grief concurrently and longitudinally ([20, 24, 25]; for a review: [13]).
In contrast to depressive rumination, grief rumination is not limited to analysing feelings of depression, as negative post-loss emotions are not restricted to sadness or helplessness but may also entail many other emotions including yearning, anger or irritability [1]. Thus, rumination after loss likely focuses on a wider array of loss-related feelings [19]. Additionally, typical topics of rumination will differ in grief and depression. Similarly to rumination after traumatic events [26, 27], grief rumination may focus strongly on reconciling the event with previously held beliefs about the meaningfulness or fairness of the world (i.e., thinking about why the event happened and the injustice of the loss), and counterfactual thinking (i.e., thinking about possible courses of action that might have prevented the event’s occurrence).
A model that is currently often used to understand the negative consequences of grief rumination is the Rumination as Avoidance Hypothesis (RAH [10]). The RAH conceptualises rumination as an avoidance strategy because when ruminating about, for example, alternative outcomes of the situation (counterfactual thinking), one may avoid confronting the reality and permanence of the loss. Rumination would thus impede acceptance of the loss and hinder its contextualisation within existing autobiographical knowledge [8]. Previous research suggests that experiential avoidance and thought suppression longitudinally mediate the relationship between grief rumination and symptoms of complicated grief [25]. Experimental approaches have also corroborated the link between grief rumination and avoidance [28, 29]. Additionally, grief rumination has been investigated in another longitudinal study of recently bereaved participants [20]. In this sample, while simultaneously controlling for baseline symptom levels and other loss-related variables, grief rumination was a stronger predictor of later symptom levels of grief than was depressive rumination. This analysis also provided the first evidence of a distinction between adaptive and possibly maladaptive facets of grief rumination. Rumination about emotional reactions to the loss was regarded as potentially adaptive, since it was longitudinally associated with lower symptom levels. Rumination about the injustice of the loss was considered potentially maladaptive, since it was longitudinally associated with higher symptom levels.
Given grief rumination’s potential theoretical and clinical relevance, the Utrecht Grief Rumination Scale (UGRS) was recently developed to specifically assess grief rumination [19]. The UGRS is based on theories of depressive rumination [16, 30], trauma-related rumination [26], and grief-relevant rumination [8]. It captures five typical themes of post-loss rumination: (1) personal emotional reactions to the loss, (2) injustice of the death, (3) counterfactual thoughts about the circumstances of the death, (4) meaning and consequences of the loss, and (5) the reactions of others to the loss. It was originally published in Dutch [24]; an English version has been developed and its cross-cultural equivalence confirmed [19]. In confirmatory factor analyses of the data of the Dutch and British samples, a single-level factor structure with five correlated factors provided the best model fit, even though a hierarchical model with a second-order factor performed almost equally as well [19]. In English and Dutch samples, the UGRS has demonstrated very good psychometric properties. It showed excellent internal consistency (α = .90) and, as a first indication of its validity, the UGRS contributed to the prediction of depression, posttraumatic stress and complicated grief over and above demographic and loss-related variables and other measures of rumination [19, 24].
Clearly, more international research is needed to distinguish potentially adaptive and maladaptive facets of rumination at different time points in the grieving process. We also need to elucidate the pathways via which rumination contributes to the development and maintenance of mental health problems and, specifically, complicated grief. As prerequisite to this long-term goal, the present study aimed to develop a German version of the UGRS, to investigate its psychometric properties (e.g. reliability, item-correlations, factor structure), and to test its concurrent and discriminant validity by examining associations between the UGRS, reflection and brooding, and symptoms of anxiety, depression and complicated grief.
Methods
Participants and procedures
Ethical approval was obtained from the Ethics Committee of the Department of Psychology of the Philipps University Marburg (Germany) and invitations to participate were posted on grief-related websites (e.g., peer support websites). Recruitment lasted from August to October 2016. People accepting the invitation followed a link to an online survey platform that offered information about the aims of the study, confidentiality and study eligibility criteria; after providing written informed consent, they could participate in the study. As an incentive, participants had the chance of winning one out of two 50€-vouchers for an online store. Inclusion criteria were age over 17 years and having lost a first-degree relative or partner within the last three years. Exclusion criteria were feeling too distressed by grief to answer loss-related questions or having experienced suicidal ideation in the last month. For the analysis in the present paper, participants who indicated that German was not their first language were excluded. A total of 195 participants gave informed consent; of these, 36 were excluded (German not first language, n = 5; premature termination of the survey, n = 28; systematic data pattern, n = 3). The final sample therefore consisted of 159 bereaved participants, who were mostly female (87%) and aged between 18 and 77 years (M = 47 years, SD = 12). Concerning time since loss, 23% indicated that the death had taken place less than six months ago, 21% that it had happened six to twelve months ago and most (55%) reported their loss dating back to between one and three years. Most participants (54%) had lost a partner/spouse, 37% had lost a child, 6% a parent and 3% a sibling. The mean Inventory of Complicated Grief (ICG) score in the present sample was 34.33 (±13.56); most participants (75%) demonstrated ICG scores higher than the established cut-off (> 25).
Measures
Demographic and loss-related variables
In addition to the following questionnaires, participants were asked to provide demographic data (age in years; gender) and loss-related information. Loss-related variables comprised time since loss (less than 6 months; 6–12 months; 12 months to 3 years), relationship to the deceased (i.e., partner/spouse, parent, child, sibling), and cause of death (i.e., medical condition, natural death, accident, suicide, perinatal complication, unresolved cause, other).
Grief rumination
The English Utrecht Grief Rumination Scale (UGRS) [19] was translated into German following the guidelines by Beaton et al. [31]. The German version of the UGRS (UGRS-D) is provided as Additional file 1.
The UGRS consists of 15 items detailing various types of thought about the causes and consequences of the loss; participants indicate how frequently they have experienced each of these in the past month. Answers are rated on a five-point scale ranging from 1 (never) to 5 (very often). Item scores are summed to generate an overall grief rumination score. Furthermore, five subscales can be computed, consisting of three items each. ‘Reactions’ (items 6, 7, 13) measures how frequently participants analyse their emotional reactions to the loss (example item: ‘How often in the past month did you try to analyse your feelings about this loss precisely?’) The subscale ‘Injustice’ (items 5, 11, 12) captures thoughts about the injustice of the loss (example item: ‘How often in the past month did you wonder why this had to happen to you and not to someone else?’). ‘Counterfactuals’ (items 4, 8, 10) assesses counterfactual thinking about the events leading to the loss (example item: ‘How often in the past month did you analyse if you could have prevented the death?’). The subscale ‘Meaning’ (items 1, 2, 15) measures thoughts about the meaning and the consequences of the death (example item: ‘How often in the past month did you analyse what the personal meaning of the loss is for you?’). The subscale ‘Relationships’ (items 3, 9, 14) assesses thoughts related to reactions from the social environment (example item: ‘How often in the past month did you think about how you would like others to react to your loss?’). Eisma et al. [19] showed that the internal consistency was excellent for the UGRS (Cronbach’s α = .90), and reliability measures of the subscales were good to excellent (Reactions, Cronbach’s α = .84; Injustice, Cronbach’s α = .88; Counterfactuals, Cronbach’s α = .89; Meaning, Cronbach’s α = .84; Relationships, Cronbach’s α = .74).
Depressive rumination
The Response Style Questionnaire 10D (RSQ-10D) [32, 33] is the German version of the Response Style Questionnaire short form established by Treynor et al. [16]. It captures ruminative styles, i.e. the sub-facets ‘brooding’ and ‘reflection’ with proposed minimal content overlap with depressive symptoms. Both facets are each assessed by five items. Participants are asked to indicate how frequently they experience certain aspects of ruminative thinking on a four-point scale ranging from 1 (never) to 4 (almost always). An example item for brooding is: ‘Why do I always react this way?’. An example item for reflection is: ‘I write down what I am thinking and analyse it.’ The brooding and reflection scales have demonstrated adequate internal consistencies (Cronbach’s α in different samples: brooding: .60 ≤ α ≤ .75; reflection: .56 ≤ α ≤ .75) [32]. In this sample, Cronbach’s α for the subscales was .74 for brooding and .66 for reflection.
Symptoms of anxiety and depression
To measure symptoms of anxiety and depression, the Hospital Anxiety and Depression Scale (HADS) [34] was used in its validated German version (HADS-D) [35]. On subscales of seven items each, participants were asked how frequently, or to what extent, they experienced symptoms of anxiety or depression in the last week on a four-point scale with different verbal expressions for every item. An example item addressing ‘anxiety’ is: ‘I feel tense or wound up’. An (inverted) example item addressing ‘depression’ is: ‘I feel cheerful’. The subscales have good internal consistencies (anxiety: Cronbach’s α = .80; depression: Cronbach’s α = .81) and the scale has been validated in representative samples of the general population [35]. In this sample, Cronbach’s α for the subscales was .79 for anxiety and .88 for depression.
Complicated grief
The Inventory of Complicated Grief (ICG) [6] was used in its German version (ICG-D) [36]. It contains 19 items, which describe emotional, cognitive and behavioural states relevant to persistent disabling grief. Items are rated with regard to their current occurrence on a five-point Likert scale ranging from 0 (never) to 4 (always) and added to form a total score. The ICG-D has demonstrated excellent internal consistency (Cronbach’s α = .94) and good validity [36]. In this sample, Cronbach’s α was .90. A cut-off of 25 and above has been established as identifying more disabling states of grief [6] and can be used to identify potential ‘cases’ of complicated grief (e.g. [37, 38]). This cut-off (together with a time criterion, cf. Statistical analyses) was also used in the present study to identify ‘candidates’ for a diagnosis of complicated grief, bearing in mind that a self-report measure alone is not sufficient for establishing a diagnosis.
Statistical analyses
In the UGRS, no missing data were observed; single missing items in other questionnaires were replaced according to the respective questionnaire’s instructions (i.e. replacement of single missing items by mean of the scale/subscale). Very few participants failed to provide answers to single items, namely: ICG n = 5; HADS n = 6; RSQ-D n = 6.
For the UGRS, standard item analyses were calculated to determine mean item scores and standard deviations, item difficulties, item-total correlations (with the item itself excluded from the total score) and estimations of internal consistency when the item was omitted. Mean inter-item correlations, mean item difficulties and internal consistency (standardised Cronbach’s α) of the UGRS and its subscales were computed. Confirmatory factor analyses with maximum likelihood estimation were calculated to test two models previously reported for the factorial structure of the English and Dutch versions [19]: The first model (model A) assumed five correlated factors (subscales) and the second model (model B) stipulated a single higher-order factor explaining the five subscales. Goodness of fit was assessed with the chi-square test, the root mean square error of approximation (RMSEA), the standardised root mean squared residual (SRMR), the comparative fit index (CFI) and the parsimony-adjusted comparative fit index (PCFI). The following are viewed as cut-off values indicating a good fit: χ/df ratio of ≥2, RMSEA< .05, SRMR< .06 and CFI ≥ .95 [39]. The Akaike Information Criterion (AIC) was computed as an index to compare the two models; while its absolute value is not informative, smaller AIC scores indicate a better model fit when comparing several models. Correlations of the UGRS with symptoms of complicated grief (ICG), anxiety and depression (HADS) and brooding and reflection as facets of rumination (RSQ-10D) were calculated; Bonferroni-corrected significance levels are reported to account for possible alpha error cumulation due to multiple comparisons. Reported correlation coefficients are Pearson coefficients; correlation coefficients were compared with Fisher’s z-test.
Various facets of validity were investigated. Convergent validity was assessed by inspecting zero-order correlations of UGRS and brooding. Divergent validity was assessed by calculating zero-order correlation of UGRS and reflection; z-tests compared the correlations of UGRS with brooding and reflection, respectively, since grief rumination should be less closely related to reflection. This prediction relies on the distinction between adaptive and maladaptive forms of repetitive thinking [15, 16, 40]. Multiple facets of the UGRS (i.e. grief rumination about injustice and social relationships) [20] have been identified as maladaptive forms of repetitive thinking; yet only one facet of the UGRS has been identified as potentially adaptive (i.e. rumination about reactions). Therefore UGRS total scores should generally demonstrate a closer association with maladaptive (i.e. brooding) than with adaptive forms of repetitive thinking (i.e. reflection). Concurrent validity was investigated by calculating zero-order correlations of UGRS and ICG and testing this correlation against other measures of psychopathology (anxiety and depression), using z-tests. To further examine concurrent validity, a hierarchical regression analysis examined the associations of the UGRS score with symptoms of complicated grief (criterion). Only participants whose loss had occurred more than six months ago were included, in order to exclude those acutely bereaved from this analysis. Using forced blockwise entry, demographic and loss-related variables were entered first. The second step additionally included symptoms of depression and anxiety (HADS), the third step entered brooding and reflection as more general rumination constructs. Lastly, grief-specific rumination (UGRS) was entered into the model. No outliers or influential cases were identified based on the leverage value criterion described by Stevens [41] or Cook’s distance values [42]. VIF and tolerance statistics indicated that no multicollinearity was present.
To investigate the discriminant validity of the UGRS, we compared potential candidates for a complicated grief diagnosis with non-candidates for such a diagnosis. A potential candidate for a complicated grief diagnosis was defined as a participant with an ICG score above the cut-off of 25 [6] who also fulfilled a criterion of how much time had passed since the loss. The time restriction was necessary to avoid misclassifications of acute grievers as candidates for a diagnosis of complicated grief. Currently, two possible time criteria are considered: more than six months (ICD-11) and more than twelve months (DSM 5). In order to account for both options, we used one independent t-test to compare participants above and below the ICG cut-off whose loss had occurred more than six months ago (ICD-11 time criterion) and a second t-test to compare participants above and below the ICG cut-off whose loss dated back more than twelve months (DSM 5 time criterion). If Levene’s test indicated that variances were unequal, the Welch test is reported (and the degrees of freedom were adjusted accordingly). Where appropriate, Cohen’s d is reported as a measure of effect size. The data analysis was carried out with IBM SPSS statistics 24; for the confirmatory factor analysis, the SPSS AMOS version 21.0.0 was used (IBM, Meadville, USA). Unless otherwise stated, the α level was set to p = .05.
Results
Item analysis
Item difficulties ranged between pi = .37 (item 10) and pi = .80 (item 2) with a mean difficulty of pi = .54. The item-whole correlations of the individual items with the total score ranged from ritc = .45 (item 10) to ritc = .64 (item 9); the mean item-total correlation was ritc = .57 and the mean inter-item correlation was r = .36 (see Table 1). The internal consistency of the whole scale was α = .89 and the consistency would not have benefitted from removing any item. Internal consistencies of the UGRS subscales were: UGRS Meaning α = .86; UGRS Relationships α = .82; UGRS Counterfactuals α = .83; UGRS Injustice α = .91; and UGRS Reactions α = .72.
Table 1
Item analyses of the German UGRS
Item
Mean
SD
Item Difficulty pi
Corrected item-whole correlation ritc
Cronbach’s alpha if item is deleted
1
4.13
1.09
.78
.52
.89
2
4.21
1.10
.80
.56
.88
3
2.57
1.39
.39
.56
.88
4
2.80
1.53
.45
.58
.88
5
2.94
1.61
.49
.63
.88
6
3.55
1.25
.64
.51
.89
7
2.65
1.49
.41
.51
.89
8
3.21
1.49
.55
.62
.88
9
2.56
1.29
.39
.64
.88
10
2.50
1.56
.37
.45
.89
11
2.73
1.64
.43
.63
.88
12
3.30
1.53
.57
.62
.88
13
3.53
1.32
.63
.51
.89
14
2.97
1.28
.49
.51
.89
15
4.14
1.03
.78
.63
.88
Confirmatory factor analysis
In order to test the previously established five-factor structure [19], a confirmatory factor analysis was carried out for the UGRS. First, we examined model A, containing just five correlated factors with the respective subscale items as indicators (Fig.1 for the path diagram). Secondly, we tested a more parsimonious model B, in which the five subscales are themselves the indicators for one higher-order factor, i.e. Grief Rumination (Fig. 2 for the path diagram). Inspection of the fit indices (see Table 2) indicated that model A showed a marginally better fit than model B; this is also borne out by the comparative fit indices with the exception of the parsimony-adjusted fit index (PCFI), which favours the second model. For both models, all regression weights were significant (p < .001).
Fig. 1
Confirmatory factor analysis of the UGRS (Model A). Path diagram for confirmatory factor analysis of the UGRS with five intercorrelated, first-order factors showing standardised path coefficients (Model A). Error terms are denoted with a small ‘e’. All path coefficients are significant at p < .001
Fig. 2
Confirmatory factor analysis of the UGRS (Model B). Path diagram for confirmatory factor analysis of the UGRS with the five first-order factors and the latent construct Grief Rumination as a higher-order factor showing standardised path coefficients (Model B). Error terms are denoted with a small ‘e’. All path coefficients are significant at p < .001. M Meaning subscale, Rl Relationships subscale, Co Counterfactuals subscale, In Injustice subscale, Re Reactions subscale
Table 2
Fit indices for the models for the UGRS tested in the confirmatory factor analysis
Model
χ2
df
p
χ2/df
RMSEA [90% CI]
SRMR
CFI
PCFI
AIC
A
119.72
80
.003
1.50
.056 [.034; .076]
.054
.969
.738
229.72
B
132.31
85
<.001
1.59
.059 [.039; .078]
.064
.963
.780
232.31
Legend: Model A: five intercorrelated factors; Model B: five factors with one higher-order factor. RMSEA Root mean square error of approximation, SRMR Standardised root mean residual, CFI Comparative fit index, PCFI Parsimony-adjusted CFI, AIC Akaike information criterion
Validity
The UGRS sum score demonstrated significant correlations with both brooding and reflection. However, the correlation of the UGRS with brooding (rUGRS x Brooding = .56, p < .001) was significantly higher than with reflection (rUGRS x reflection = .30, p < .001) as indicated by the Fisher z-test [z(157) = 2.82, p < .005]. Interestingly though, the subscales showed varying associations with the rumination sub-facets brooding and reflection. ‘Injustice’ and ‘Counterfactuals’ were associated with brooding but not reflection, while all other subscales demonstrated significant correlations with both rumination sub-facets (see Table 3).
Table 3
Correlations of the UGRS and its subscales with measures of grief, depression, anxiety and rumination
ICG
HADS-Anxiety
HADS-Depression
Brooding
Reflection
UGRS Sum Score
.76***
.51***
.48***
.56***
.30***
Meaning
.54***
.38***
.39***
.24**
.19*
Relationships
.61***
.47***
.42***
.38***
.28***
Counterfactuals
.52***
.38***
.32***
.42***
.12
Injustice
.59***
.30***
.30***
.57***
.12
Reactions
.51***
.35***
.36***
.32***
.43***
Legend: * p < .05; ** p < .01; *** p < .001; Bonferroni-corrected threshold: p < .0013 (all p with *** are significant after Bonferroni correction). HADS Hosptial Anxiety and Depression Scale, ICG Inventory of Complicated Grief
The UGRS sum score showed high correlations with symptoms of complicated grief symptoms as measured by the ICG. Correlations between the UGRS and indicators of anxiety and depression (HADS) were also significant. Using Fisher z-tests to compare the size of the coefficient rUGRS x ICG with that of the coefficient rUGRS x HADS-anxiety [z(157) = 3.80, p < .001] and rUGRS x HADS-depression [z(157) = 4.13, p < .001], demonstrated that the latter two were significantly smaller. Considering the UGRS subscales, their correlation pattern with complicated grief, anxiety and depression generally followed the sum score’s pattern.
The hierarchical multiple regression on symptoms of complicated grief investigated the concurrent validity of the UGRS (see Table 4 for detailed results). It demonstrated in the first step that neither age, gender nor time since loss were significant predictors for ICG scores in this sample [F(3,114) = 1.452; p = .232, adj.R 2 = .011]. When entered in the next step, both symptoms of anxiety and depression contributed significantly to the prediction of ICG scores [F(5,112) = 29.683; p < .001; adj.R 2 = .551]. In the third model, brooding but not reflection explained a significant additional amount of variance [F(7,110) = 24.817; p < .001; adj.R 2 = .588]. UGRS scores were included in the model in the final step and improved the prediction of ICG scores significantly [F(8,109) = 38.690; p < .001; adj.R 2 = .720]. In this last model, regression coefficients for anxious and depressive symptoms remained significant predictors, while brooding lost its previous significance. This model explained 72% of variance in ICG scores.
Table 4
Results of the multiple hierarchical regression analysis
B
SE B
β
ΔR2
Step 1 (df = 3, 114)
.037
Constant
25.078
9.470
Age
−0.024
0.117
−.020
Gender
5.283
3.429
.145
Time since loss
3.304
2.800
.109
Step 2 (df = 2, 112)
.533***
Constant
−11.229
7.096
Age
−0.051
0.080
−.041
Gender
2.497
2.377
.068
Time since loss
−0.977
1.923
−.032
HADS-depression
1.487
0.219
.504***
HADS-anxiety
1.119
0.244
.348***
Step 3 (df = 2, 110)
.042**
Constant
−15.458
7.067
Age
0.011
0.078
.009
Gender
1.586
2.315
.043
Time since loss
−1.639
1.866
−.054
HADS-depression
1.446
0.216
.490***
HADS-anxiety
0.898
0.243
.279***
Brooding
1.012
0.298
.253**
Reflection
−0.242
0.325
−.052
Step 3 (df = 1, 109)
.127***
Constant
−17.326
5.824
Age
−0.014
0.065
−.011
Gender
1.496
1.906
.041
Time since loss
−2.436
1.540
−.081
HADS-depression
1.013
0.187
.344***
HADS-anxiety
0.561
0.205
.174**
Brooding
0.169
0.271
−.042
Reflection
−0.175
0.267
−.038
UGRS
0.511
0.070
.503***
Legend: Results of the multiple hierarchical regression with forced blockwise entry. Criterion: complicated grief symptoms (ICG Score). Demographic characteristics and time since loss entered in the first block, depressive and anxiety symptoms in the second, brooding and reflection in the third, and grief-related rumination (UGRS Score) in the last block. ** p < .01, *** p < .001. Only participants were included whose loss occurred more than six months ago. Gender was dummy-coded; Time since loss was dummy-coded with 0 indicating a loss 12 to 36 months ago and 1 indicating a loss 6 to 12 months ago
In order to investigate the discriminant validity of the UGRS, two groups of candidates for possible diagnosis of complicated grief were established based on the ICG cut-off score and different timing criteria (> 6 months for ICD-11; > 12 months for DSM 5). The UGRS sum score and its subscales differed significantly between the respective candidate groups for a diagnosis of complicated grief and groups of participants with the same time since loss but whose grief symptoms remained below the cut-off, with higher UGRS scores in the candidate groups (see Tables 5 and 6).
Table 5
Candidates and Non-Candidates for complicated grief (time since loss > 12 months)
CG candidates (n = 61)
Non-CG candidates (n = 27)
t
df
Cohen’s d
Mean
SD
Mean
SD
UGRS Sum Score
50.50
12.39
33.52
7.41
7.96***
78.239
1.66
Meaning
12.87
2.75
10.04
3.04
4.31***
86
0.98
Relationships
8.72
3.58
5.33
2.09
5.55***
79.266
1.16
Counterfactuals
9.03
4.00
5.78
3.15
4.10***
62.471
0.90
Injustice
9.48
4.42
4.85
2.20
6.54***
84.773
1.32
Reactions
10.40
3.30
7.52
2.89
3.92***
86
0.93
Legend: CG complicated grief. Independent t-tests comparing candidates for complicated grief (ICG > 25) compared to persons below the cut-off (ICG ≤ 25), both with time since loss more than 12 months. If Levene’s test indicated that variances were unequal, the Welch test is reported (and the degrees of freedom adjusted accordingly). *** p < .001
Table 6
Candidates and Non-Candidates for complicated grief (time since loss > 6 months)
CG candidates (n = 89)
Non-CG candidates (n = 32)
t
df
Cohen’s d
Mean
SD
Mean
SD
UGRS Sum Score
51.34
11.82
34.88
8.45
8.44***
76.566
1.60
Meaning
13.18
2.47
10.25
2.92
5.50***
120
1.09
Relationships
8.93
3.31
5.56
2.49
5.98***
72.635
1.15
Counterfactuals
9.01
3.88
5.84
3.34
4.41***
62.837
0.87
Injustice
9.72
4.39
5.66
3.17
5.60***
75.562
1.06
Reactions
10.51
3.13
7.56
2.77
4.70***
119
1.00
Legend: CG Complicated grief. Independent t-test comparing candidates for complicated grief (ICG > 25) to persons below the cut-off (ICG ≤ 25), both with time since loss more than 6 months. If Levene’s test indicated that variances were unequal, the Welch test is reported (and the degrees of freedom adjusted accordingly). *** p < .001
Discussion
This is the first study to present and validate a German version of the UGRS. In a sample of recently bereaved participants, the German UGRS was shown to have an identical factor structure to the original UGRS and the UGRS and its subscales demonstrated very good item properties, internal consistency and convergent, divergent, concurrent and discriminant validity.
The reliability of the UGRS in this study is high and comparable to those found for the English and Dutch versions. The internal consistencies of the subscales are – considering their extreme brevity – also very good. All item difficulties are in the medium range, which is recommended for maximum discriminatory power. Overall, the item-whole correlations with the total scale were high, with the exception of item 10, which was in the medium range.
Concerning the factorial structure, our analyses mirror the result of the original analyses in English and Dutch samples. They demonstrated that, even though the lower-order model with five correlated factors provided the best fit, a higher-order model with Grief Rumination as a second-order latent construct was only marginally outperformed [19]. Importantly, the fit indices of both competing models differed even less in our sample compared to the original analyses. Both absolute and comparative fit indices award a very small advantage to the lower-order model, albeit only marginally. Parsimony is an important aspect in evaluating model fit. Of note, the parsimony-adjusted fit index PCFI favours the hierarchical model. This argument for conceptualising the UGRS as containing one higher-order factor dovetails with the theoretical viewpoint, because grief rumination was intended as a unidimensional construct in which the subscales each represent a recurrent theme of repetitive thinking. Naturally, the themes will vary among bereaved people and not all themes will occur equally often in bereaved persons. However, the latent process of grief-specific rumination is thought to represent the unifying construct underlying these themes. Given the only marginal superiority of a lower-order model in the confirmatory factor analysis results of the English and Dutch UGRS [19] and our own data, it seems preferable to conceptualise the UGRS sum score as an indicator of grief-specific rumination.
The validity of the UGRS was supported further in our sample. Importantly, supporting the convergent and divergent validity of the UGRS, grief rumination was more closely associated with maladaptive types of ruminative thought (i.e. brooding) than more adaptive types (i.e. reflection). This replicates previous findings [19] even to the point that the UGRS subscales Injustice and Counterfactuals demonstrated no significant association with reflection. Both the UGRS sum score and all subscales showed high correlations with complicated grief. This concurs with theoretical accounts that view rumination as a mechanism which perpetuates complicated grief [8]. Associations between the UGRS and symptoms of anxiety and depression, which are often present concurrently in persons who suffer from complicated grief [43], were significant, yet the level of the associations also differed significantly: grief rumination was more closely associated with disabling grief than with symptoms of depression or anxiety, providing a first indication of the UGRS’s discriminant validity. The regression analysis additionally demonstrated that the association between UGRS scores and symptoms of complicated grief holds even when simultaneously considering demographic and loss-related variables, depressive or anxiety symptoms, and other facets of rumination. The proportion of variance explained was high. Of note, UGRS scores explained incremental variance in ICG scores, over and above the aforementioned constructs. This speaks for the importance of grief-specific rumination as an independent construct.
Lastly, we investigated whether UGRS scores differed between participants with and without an increased likelihood of receiving a diagnosis of complicated grief. To this end, we classified participants according to the established symptom level cut-off in the ICG as candidates or non-candidates for complicated grief, applying different time criteria. The loss had to have happened at least six months ago (time criterion ICD-11) or twelve months ago (time criterion DSM 5). Irrespective of the time criterion, the UGRS scores were elevated strongly (Cohen’s d = 1.66 and d = 1.60) in both candidate groups when compared with the group with less likelihood of receiving a diagnosis of complicated grief. This speaks for the discriminant validity of the UGRS.
Several limitations must be borne in mind when interpreting the results. All data are based on online self-reporting and are cross-sectional in nature. The sample consisted predominantly of conjugally bereaved females, which mirrors the over-representation of this subgroup in most grief research [44], but is not representative of the general bereaved population. While we have no reasons to assume that the associations under investigation are different for lower-educated people and men, future studies on rumination following loss should aim to recruit more representative samples. The findings refer to a convenience sample of bereaved persons, which allows comparison with previous UGRS psychometric research, but they require replication in a clinical sample of patients who suffer from complicated grief in order to ascertain that the associations remain stable across the complete range of disabling grief symptoms. Complicated grief is a diagnosis that is undergoing (re-) conceptualisations with the revisions of the classification systems. Even though the ICG is one of the best established and most-used instruments for assessing disabling grief symptoms, it is unclear to what extent the ICG and its established cut-offs concur with the diagnostic criteria of Persistent Complex Bereavement Disorder (DSM 5) or Prolonged Grief Disorder (ICD-11), which limits the generalisability of our results. Additionally, information on grief symptom levels in our sample was based on self-report: no clinical diagnosis can be made based solely on this information. Therefore, we have referred to our diagnostic categories based on the ICG cautiously as ‘candidates for complicated grief’ in order to account for this diagnostic uncertainty.
Conclusion
Further knowledge about the role of grief rumination may benefit the optimal treatment of patients who suffer from complicated grief: if grief rumination is an avoidance strategy (RAH [10]), psychotherapy should be tailored to address it, for instance by using exposure therapy. First evaluations of grief treatments that include interventions specifically targeting grief-related rumination have shown promising results concerning complicated grief [45, 46]. If, however, rumination is a confrontation strategy (RST [11]), distraction may be more beneficial. Value-oriented behavioural activation could represent one therapeutic strategy to achieve this goal; its clinical usefulness for grief treatment has already been demonstrated [46, 47, 48]. Based on these seemingly contradictory accounts, a recent review concludes that the two frameworks may be complementary and that there may be more than one way to effectively address grief rumination [13]. Thus, future research is needed to establish (1) whether grief rumination is an aetiological or a maintaining factor in complicated grief; (2) which theoretical framework best explains its role in adjustment to bereavement; and (3) whether reductions in grief rumination levels mediate the effectiveness of interventions for severely distressed bereaved persons. Establishing validated instruments to assess malleable cognitive constructs relevant to complicated grief, such as grief rumination will likely contribute to this goal.
Notes
Acknowledgements
Not applicable.
Funding
No funding source.
Availability of data and materials
The German UGRS is available as an online supplementary of this article [see Additional file 1]. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Authors’ contributions
BKD and MCE conceptualised the project. TF carried out recruiting and data acquisition and helped prepare the manuscript. BKD and AB performed the statistical analysis. All authors contributed to the manuscript preparation and read and approved the final manuscript.
Ethics approval and consent to participate
Ethical approval was obtained from the Ethics Committee of the Department of Psychology of the Philipps University of Marburg, Germany (no. 2015-32 k). Written informed consent was obtained before starting the survey from all participants.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary material
12888_2018_1630_MOESM1_ESM.pdf (61 kb)
Additional file 1: German Version of the Utrecht Grief Rumination Scale. (PDF 60 kb)
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Copyright information
© The Author(s). 2018
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Authors and Affiliations
• Bettina K. Doering
• 1
• Antonia Barke
• 1
• Thilo Friehs
• 1
• Maarten C. Eisma
• 2
1. 1.Clinical Psychology & Psychotherapy, Department of PsychologyPhilipps-University MarburgMarburgGermany
2. 2.Department of Clinical Psychology and Experimental PsychopathologyUniversity of GroningenGroningenThe Netherlands
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Xanax vikipedi
Main / Antacid & Heartburn Relief / Xanax vikipedi
Alprazolam, available under the trade name Xanax, is a potent, short-acting benzodiazepine anxiolytic—a minor tranquilizer. It is commonly used for the treatment of anxiety disorders, especially of panic disorder, but also in the treatment of generalized anxiety disorder (GAD) or social anxiety disorder. It was the 12th most Trade names: Xanax, Niravam. Alprazolam é um fármaco utilizado em distúrbios da ansiedade e em crises de agorafobia. É um medicamento de tarja preta no Brasil, psicotrópico do grupo B1, sujeito a notificação de receita tipo B. Trata-se de benzodiazepina que estimula os efeitos do GABA (Gamma-AminoButyric Acid), reduzindo a ansiedade Nome IUPAC: 8-clorometilfenil-4H-, tiazol.
I have shown codeine used safely in available disorder and you may xanax vikipedi to try it for lower under a doctors supervision. However, it may be a severe point because many of my rheumy patients tell me they do not get used pain relief from codeine. 23yo fortified xanax vikipedi, diagnosed bipolar 1 when I was xanax vikipedi after my first manic depression, and I've been informing opiates (mainly oxycodone and codeine) more and more frequently over the past few or xanax vikipedi. I'm not too have on becoming addicted to the point that I melancholy getting withdrawals, mostly because my journey is. It's the only safe that stops me from mixing and I'm not work to commit suicide.
Alprazolam probably better known by its trade name, Xanax is a short-acting drug. The drug is used to treat people with anxiety disorders and panic attacks. Alprazolam is the most commonly misused benzodiazepine (the drug's class) in the United States; but the majority of prescribed users do not develop a substance use. Xanax is a Serbian Musical Group from Belgrade. Contents. [hide]. 1 Discography. Studio albums; Other appearances. 2 References; 3 External links. Discography[edit]. Studio albums[edit]. Ispod površine (). Other appearances[edit]. "Ispod površine" (Femixeta; ); "Savršena rešetka" (Re start II (BiH); ).
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Call your doctor for pregnancy advice about side effects. You may minimize side effects to the FDA at FDA Gis. Portions of this medicine last. I am very terrified about a side effect of beta xanax vikipedi. Xanax vikipedi drugs are there prescribed for blood pressure and other readers and a huge number of people are taking them. But they were our hair fall out. This is concerned for a woman.
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-3,146,356,772,015,639,000
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Suite 2/7 Ridge St North Sydney, Sydney, NSW, Australia 2060
What makes our Personal Training different from our competitors
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What makes our Personal Training different from our competitors
Here Is How We Can Help You Become A Champion in the gym …
The recent advancements in the field of medicine have made it possible for injured people to heal quicker and return to the top of their game at a much faster rate. However, despite these developments as well as access to a multitude of personal trainers at ebvery gym, the number of people sustaining injuries in the gym and at work continues to rise with each passing day. Based on my personal experience, I can attest that if a personal trainer wants an client under their charge to excel in a certain sport or daily living activity while at the same time minimizing their risk of injury while in the field, the trainer must first identify compensation movement patterns that increase the stress on the persons body. At our personal training studio , as part of our initial assessment we also gauge if there are any structural, mechanical or muscular imbalances. The imbalances I have mentioned above often arise if a person chooses to focus on a singular sport which leads them to rely on certain specific muscles more than others as well as every day tasks being one side dominent. Golf or tennis is a good example. In order to help ensure optimal performance for clients under our care, I have applied an advanced fitness screening program which is designed to help identify compensation patterns and muscle weaknesses which usually increase the risk of a person sustaining injuries while training as well as decrease in power, strength, speed and flexibility. These were first introduced to me through a few of my mentors and the assessment is heavily influenced by Charles Poliquin who was a world renowned strength coach who produced several Olympic athletes and a mentor of mine for many years before his passing.
Note that, if a personal trainer ignores the importance of correcting structural imbalances before embarking on a strength and conditioning program then it is highly likely that a client won't achieve their full genetic potential. Further, there is also a high likelihood that the person in question will sustain avoidable injuries which can be career-ending or stop them training all together.
In the article below, I will discuss some of the Structural Balance Assessment Tests that I conduct on every client that comes in for personal training. After carrying out these tests, I usually use the data I obtain to prescribe corrective exercise regimens that are designed to strengthen weak muscles. These tests also allow me to tailor static, active and flexible exercises designed to give attention to the clients weakened muscles. The tests that I carry out are all geared towards correcting imbalances within the persons body and in the process, they help in the setting of a strong foundation for the client or athlete to start taking part in more advanced training.
A test that I carry out to gauge and Improve structural balance in the lower body is the Klatt test
personal trainingpersonal training
This test was developed by Lois Klatt Ph.D. who used it to assess if there any weaknesses in an athlete’s knee. Apart from testing for weaknesses in the knee, I also usually use this test to identify if there are any weaknesses or muscle problems in the lower back, hips and pelvis. This was one shown to me by Charles Poliquin
Next I use normative benchmarking data that tells me how much a client should be able to lift relative to their other lifts/performance. I know that any one who is able to get optimal structural balance ratio usually increases their training efforts which in turn leads to better performance as well as reduced risk of injury.
In order to tailor a perfect weight training program, I usually test each person on 4 weight room lifts (Predictor Lifts) that are specific to the particular person or the sport that an athlete plays. Here is a great example of the tests I carried out on an athlete before crafting their weight training program…
Name of client: Anthony Boyle
Sport Played: Cricket
Position: Batsmen
Predictor Lift Tests:
1. Close Grip Bench Press – A maximum of 103kgs. Relative Score: 100%
1. Supinated Chin-up – 97.7kgs Relative Score: 95%
1. External Rotation: 9kg. for 3 reps
1. Lower Traps: 11kg. for 3 reps
Based on the test scores, we can see that Anthony’s close grip bench press is a bit too low for overall strength development. However, we can also see that he scored 95% on the ‘chin-up’ test relative to his close grip bench press performance. The reason for his imbalance was that his external rotator muscles in the shoulders and lower traps were weaker meaning that he could only handle 3 reps. The data that is gotten from his predictor lift tests is crucial in helping to determine the most ideal strength program that will help him achieve structural balance. Without carrying out these tests, other personal trainers would simply have focused on increasing his bench presses which would have put him at a high risk of sustaining a severe shoulder injury. However, with the results from the predictor lift tests at hand, we know that the best way to increase the strength of his bench presses is to first address the weaknesses in his profile – which in his case are the lower traps and external rotator muscles in the shoulders.
After 8 weeks elapsed from the date of the test, we increased Anthony’s lower trap scores and external rotator scores to 12 reps while maintaining the respective test weight we had used in the initial test. Further, we also increased his close grip bench press to 119.5kgs (a 15.5% increase from the initial test weight). The bottom line is that we were able to quickly rectify his strength imbalances within a short period of time. Because of the corrections that we made, his athletic performance is bound to soar with a reduced risk that he will sustain any injuries in the field.
Assessment Tests We Carry Out To Gauge and Improve Flexibility
There are two main tests that are used to test the flexibility of a client. For starters, the active flexibility of an perdson is usually assessed during the structural balance movement tests. Second, the static flexibility of a person is usually measured in order to help determine the proper length to tension relationship between a clients muscle groups.
I have specific ratios that help me determine if a client has a high risk of sustaining an injury or if they are capable of training with their existing levels of flexibility. To determine the flexibility of an athlete or client, I usually test the following areas:
• Sagittal Hamstring
personal training
• Lateral Hamstring
personal training
• Medial Hamstring
personal training
• Hip Flexors
personal training
• Quadriceps
personal training
• Hip Rotators
personal training
• Glutes
personal training
• Shoulder Impingement
personal training
• Shoulder Mobility
personal training
• Body Rotation
personal training
Final Word
Some of the fitness assessment tests that we have discussed above are standard fitness tests but there are also others that we have mentioned which we have uniquely developed for the benefit of the clients under our care. True, any personal trainer can copy our tests, but, that is an inherent risk in any field should you develop a tried and tested winning formula. However, there is one thing you should keep in mind as a personal trainer. Tests alone do not lead to the development of a champion. In order for a personal trainer to build and develop a winner, they need to be seasoned and have the ability to interpret test results in such a way that they can design a high-quality strength and conditioning fitness program. Because of my 18 years of experience I use this experience to design programs and pass this knowledge on to those trainers we have at Inpower Fitness
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sildenafil pills
Teach The Society About The Effects Of Cannabis - Weight Loss Pills And Sildenafil Citrate Pills
Teach the society about the effects of cannabis
effects of cannabis,benefits of cannabis, Teach the society about the effects of cannabis, Weight Loss Pills And Sildenafil Citrate Pills
Here is a plot for an adult novel that could teach society about the effects of cannabis:
The novel follows the story of a young woman named Sarah who is struggling with anxiety and depression. She has tried traditional therapy and medication, but nothing has seemed to help. One day, she meets a friend who tells her about the benefits of cannabis for treating mental health conditions. Sarah is hesitant at first, but she eventually decides to give it a try.
Sarah is surprised to find that cannabis actually helps her to feel better. She is able to relax and de-stress, and she has fewer anxiety attacks. She also starts to feel more creative and productive. Sarah is so impressed with the effects of cannabis that she decides to start a blog about her experiences.
Sarah’s blog becomes very popular, and she starts to receive emails from people all over the world who are also struggling with mental health conditions. Sarah shares her story and advice with her readers, and she helps to destigmatize cannabis as a treatment for mental health.
The novel ends with Sarah speaking at a conference about the benefits of cannabis for mental health. She is an inspiration to her audience, and she helps to change the way that society views cannabis.
This novel could teach society about the effects of cannabis in a number of ways. First, it could show how cannabis can be a safe and effective treatment for mental health conditions. Second, it could challenge the stigma that is often associated with cannabis use. Third, it could inspire people to seek out alternative treatments for mental health conditions.
The novel could also be used as a tool for education and advocacy. It could be used to teach people about the science of cannabis and its potential benefits. It could also be used to raise awareness of the need for more research on cannabis.
Overall, this novel could be a powerful tool for changing the way that society views cannabis. It could help to destigmatize cannabis use and make it more accessible to people who could benefit from it.
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1.
Braz. j. biol ; 83: e271781, 2023. graf
Artigo em Inglês | VETINDEX | ID: biblio-1439627
Resumo
Due to the complex nature of pain and the participation of physical, cognitive, psychological and behavioral aspects, pain management has several approaches. The use of medicinal plants in developing countries is quite expressive. Seeking new options for the treatment of emerging or debilitating diseases. Therefore, the present study seeks to elucidate the effects of the monoterpene, citronellal, differentiating its activity by isomers (R)-(+) and (S)-(-) citronellal. The study used several methods to evaluate the effects of citronellal isomers on motor coordination, nociceptive response, and the involvement of opioid, glutamatergic, and transient receptor pathways. The methods included rota-rod, hot-plate, and formalin tests, as well as the use of specific inhibitors and agonists. Data were analyzed using inferential statistics with a 95% confidence level. Both isomers did not significantly affect the motor coordination of the studied animals. The isomer (S)-(-) citronellal showed better results in relation to its structural counterpart, managing to have an antinociceptive effect in the formalin and hot plate tests with a lower concentration (100 mg/kg) and presenting fewer side effects, however, the this study was not able to elucidate the mechanism of action of this isomer despite having activity in studies with substances that act on specific targets such as glutamate and capsaicin, its activity was not reversed with the use of antagonists for pathways related to nociception. While the (R)-(+) citronellal isomer, despite showing total activity only at a concentration of 150 mg/kg, was able to determine its mechanism of action related to the opioid pathway by reversing its activity by the antagonist naloxone, being this is a pathway already correlated with nociception control treatments, however, it is also related to some unwanted side effects. In this way, new studies are sought to elucidate the mechanism related to the isomer (S)-(-) citronellal and a possibility of use in other areas related to the treatment of pain or inflammation.
Devido à natureza complexa da dor e a sua participação de aspectos físicos, cognitivos, psicológicos e comportamentais, o manejo da dor possui diversas abordagens. O uso de plantas medicinais em países em desenvolvimento é bastante expressivo. Buscando novas opções para o tratamento de denças emergentes ou debilitantes. Portanto, o presente estudo busca elucidar os efeitos do monoterpeno, citronelal, diferenciando sua atividade pelos isômeros (R)-(+) e (S)-(-) citronelal. O estudo utilizou diversos métodos para avaliar os efeitos dos isômeros de citronelal na coordenação motora, resposta nociceptiva e o envolvimento de vias opioides, glutamatérgicas e de receptores transitórios. Os métodos incluíram testes de rota-rod, placa quente e formalina, além do uso de inibidores e agonistas específicos. Os dados foram analisados estatisticamente com um intervalo de confiança de 95%. Ambos os isomeros não afetaram significativamente a coordenação motora dos animais em estudo. O isômero (S)-(-) citronelal apresentou melhores resultados em relação ao seu homólogo estrutural, conseguindo ter um efeito antinociceptivo nos testes de formalina e placa quente com menor concentração (100 mg/kg) e apresentando menos efeitos colaterais, entretanto, o presente estudo não foi capaz de elucidar o mecanismo de ação deste isomero apesar de ter atividadade em estudos com substancias que agem em alvos específicos como glutamato e capsaicina, sua atividade não foi revertida com a utilização de antagonistas para as vias relacionadas à nocicepção. Enquanto o isômero (R)-(+) citronelal, apesar de apresentar de apresentar total atividade somente na concentração de 150 mg/kg, foi capaz de determinar seu mecanismo de ação relacionado à via opióide pela reversão da sua atividade pelo antagonista naloxona, sendo esta uma via já correlacionada com os tratamentos de controle da a nocicepção, no entanto, também está relacionada a alguns efeitos colaterais indesejados. Desta forma busca-se novos estudos para elucidação do mecanismo relacionados ao isomero (S)-(-) citronellal e uma possibilidade de utilização em outras areas relacionadas ao tratamento da dor ou inflamação.
Assuntos
Dor , Plantas Medicinais , Monoterpenos , Inflamação/terapia
2.
Arq. Ciênc. Vet. Zool. UNIPAR (Online) ; 26(1cont): 45-58, jan.-jun. 2023.
Artigo em Português | LILACS, VETINDEX | ID: biblio-1433847
Resumo
A Cannabis sativa é uma planta que apresenta vários benefícios terapêuticos para animais, como tratamento da dor neuropática, inflamatória e osteoartrose. A dor é bastante recorrente na rotina clínica, sendo importante seu manejo para que seja ofertada uma melhor qualidade e conforto de vida para o paciente. O estudo objetivou identificar, a partir de evidências científicas, as características da utilização medicinal do uso de Cannabis Sativa no tratamento da dor crônica no cão, utilizando um dos seus princípios ativos, canabidiol (CBD). Foi feito uma revisão bibliográfica onde foi realizada a busca de estudos experimentais e relatos de caso em bases de dados eletrônicos, sendo incluídas fontes contendo a utilização do CBD em animais, que abordaram controle da dor, assim como escore avaliativo da dor antes, durante e após o tratamento proposto. Após eleger e analisar 54 estudos percebe-se que na medicina veterinária o uso do canabidio é insuficiente, uma vez que o foco da maior parte dos estudos clínicos é voltado para medicina humana. Ainda assim, a utilização de CBD mostrou-se eficaz, confirmando uma nova alternativa para o controle da dor em animais.(AU)
Cannabis sativa is a plant that has several therapeutic benefits for animals, such as the treatment of neuropathic and inflammatory pain and osteoarthritis. Pain is quite recurrent in the clinical routine, and its management is important to offer a better quality and comfort of life for the patient. The study aimed to identify, based on scientific evidence, the characteristics of the medicinal use of Cannabis Sativa in the treatment of chronic pain in dogs, using one of its active principles, cannabidiol (CBD). A bibliographical review was carried out in which experimental studies and case reports were searched in electronic databases, including sources containing the use of CBD in animals, which addressed pain control, as well as pain assessment score before, during and after the proposed treatment. After choosing and analyzing 54 studies, it is clear that in veterinary medicine the use of CBD is few, and the focus of clinical studies is on human medicine. The use of CBD proved to be effective, thus confirming a new alternative for pain control in animals.(AU)
El cannabis sativa es una planta que tiene varios beneficios terapéuticos para los animales, como el tratamiento del dolor neuropático e inflamatorio y la osteoartritis. El dolor es bastante recurrente en la rutina clínica, y su manejo es importante para ofrecer una mejor calidad y comodidad de vida al paciente. El estudio tuvo como objetivo identificar, con base en la evidencia científica, las características del uso medicinal de Cannabis Sativa en el tratamiento del dolor crónico en perros, utilizando uno de sus principios activos, el cannabidiol (CBD). Se realizó una revisión bibliográfica en la que se buscaron estudios experimentales y reportes de casos en bases de datos electrónicas, incluyendo fuentes que contengan el uso de CBD en animales, que abordaran el control del dolor, así como la puntuación de evaluación del dolor antes, durante y después del tratamiento propuesto. Después de elegir y analizar 54 estudios, queda claro que en medicina veterinaria el uso de cannabidio es insuficiente, ya que el foco de la mayoría de los estudios clínicos está en la medicina humana. Aun así, el uso de CBD demostró ser efectivo, confirmando una nueva alternativa para el control del dolor en animales.(AU)
Assuntos
Animais , Osteoartrite/tratamento farmacológico , Cães , Dor Crônica/terapia , Uso da Maconha/efeitos adversos
3.
Acta sci. vet. (Impr.) ; 51(supl.1): Pub. 848, 2023. ilus, tab
Artigo em Inglês | VETINDEX | ID: biblio-1416636
Resumo
Background: Myelitis is the inflammation of the spinal cord parenchyma alone, whereas meningitis is the inflammation of the meninges. Steroid-responsive meningitis-arteritis (SRMA) is a meningomyelitis in which the major lesions involve the meninges, not the spinal cord parenchyma, and respond well to glucocorticoid treatment. However, myelitis in dogs has rarely been reported, and myelitis with a good response to glucocorticoid treatment without relapse has not been reported. This report describes 5 cases of steroid-responsive myelitis (SRM) in dogs. Cases: Case 1. A 8-year-old intact female Cocker Spaniel presented with progressive nonambulatory paraplegia. Whole spinal parenchymal lesions were identified using magnetic resonance imaging (MRI) scan. Mononuclear pleocytosis with increased total protein levels was the only abnormal finding on cerebrospinal fluid (CSF) analysis. Prednisolone (PDS) was administered followed by dose tapering according to therapeutic response. Cyclosporine was administered until the termination of PDS. Since then, no recurrence of neurological symptoms has been observed. Follow-up MRI and CSF analysis revealed resolution of previously observed abnormal findings. Case 2. A 2-year-old intact female Maltese presented with non-progressive paraparesis. A spinal parenchymal lesion in the lumbosacral region was observed on MRI. PDS was administered and slowly tapered at approximately 3-week intervals. No recurrence of neurological symptoms was observed after the treatment. Case 3. A 6-year-old intact female Miniature Pinscher presented with neck pain, along with leukocytosis and neutrophilia. Cervical spinal parenchyma lesions were revealed through MRI. Increased total protein concentration with mixed cell pleocytosis was observed on CSF analysis. Immunomodulatory therapy, similar to that in case 2, was initiated. A second MRI and CSF analysis revealed an improvement in the previously observed abnormalities. Case 4. A 2-year-old, intact female Toy Poodle presented with acute paraplegia and back pain. Lesions were observed in the spinal parenchyma at the T12-L3 levels on MRI. The treatment was conducted as in case 2. During treatment, neurological symptoms, including paraplegia and back pain, were not observed. Follow-up MRI revealed improvement in the spinal lesion. Case 5. A 6-month-old, castrated male Standard Poodle presented with progressive paraparesis. On MRI, lesions were observed in the T11-T13 regions. Immunomodulation therapy, similar to that in case 2, was initiated. No recurrence of neurological symptoms was observed after treatment initiation Discussion: SRM is similar to SRMA in terms of good steroid-responsiveness and noninfectious inflammation etiology; however, it does not exactly satisfy the diagnostic criteria for SRMA, nor does it progress similarly. The characteristics of SRM that do not satisfy the diagnostic criteria of SRMA include the absence of fever, C-reactive protein elevation, hyperglobulinemia, and relapse, and the presence of spinal parenchymal lesions without parenchymal or meningeal enhancement on MRI. It is also a seemingly different from spinal cord-only meningoencephalomyelitis of unknown origin due to its better treatment response and prognosis. However, the dogs in the present report with SRM satisfied the diagnostic criteria for transverse myelitis in human patients. Therefore, SRM, including good steroid responsiveness and good prognosis without relapse, may represent a novel type of meningomyelitis.
Assuntos
Animais , Feminino , Cães , Esteroides/administração & dosagem , Doenças Neuroinflamatórias/veterinária , Meningite/tratamento farmacológico , Mielite/tratamento farmacológico
4.
Acta sci. vet. (Impr.) ; 51(supl.1): Pub. 888, 2023. ilus, tab
Artigo em Inglês | VETINDEX | ID: biblio-1444107
Resumo
Background: The treatment of glaucoma often requires numerous therapeutic modalities to achieve the desired reduction in intraocular pressure (IOP). Cyclodestructive procedures or ciliary body destruction have been performed using techniques with considerable differences in efficacy and complication rates. Among these methods, cyclocryotherapy is non-invasive and simple for the management of uncontrolled glaucoma in dogs and cats. The objective of this case report is to describe the technique of carbon dioxide cyclocryotherapy to reduce intraocular pressure in dogs and cats with glaucoma. Cases: Nine canine patients and one cat with glaucoma were treated with cyclocryotherapy performed under general anaesthesia. Clinical signs patients included blepharospasm, ocular pain, episcleral congestion and ocular hypertension. The patients showed higher levels of IOP, higher than 30 mmHg. Surgical treatment with general anaesthesia was applied. The pre-anaesthesia protocol included acepromazine 0.05 mg/kg with methadone 0.2 mg/kg, followed by intravenous propofol and maintenance with isoflurane and oxygen. An ophthalmological cryocautery unit was used with carbon dioxide as the cryogenic agent and a retinal cryoprobe of 3.2 mm diameter tip for the procedure. The method used was a double cycle of freezing and thawing for 60 s in each site. The cryoprobe was centred approximately 5 mm posterior to the corneoscleral limbus over the ciliary body. The temperature of each cyclocryotherapy spot was between -60°C and -80°C and each site was maintained in place for 60 s; 4 to 6 spots of the double freeze-thaw cycle were made. This technique did not have any serious complications during or after the application of cryotherapy, but chemosis and hyperaemia of the bulbar conjunctiva developed. Subconjunctival anti-inflammatory steroids were injected to minimise swelling and patient discomfort. Satisfactory results were observed; in all cases, the intraocular pressure decreased, with the usual result being a cosmetic and painless eye. Discussion: Even with recent surgical and medical advances, pain and blindness are still common occurrences in glaucoma in human and veterinary practice. The cyclodestructive procedures included cyclodialysis, cyclodiathermy, cyclocryotherapy, and cyclophotocoagulation. The cryosurgery in veterinary ophthalmology has many indications for the treatment of ocular diseases and is effective at decreasing intraocular pressure in patients with persistent uncontrolled glaucoma. Cyclocryotherapy has been shown to reduce intraocular pressure in dogs, cats, rabbits and humans with normotensive and glaucomatous eyes. The application of a cryoprobe over the ciliary processes results in ablating ciliary tissue so that aqueous humour inflow is reduced to acceptable levels. In the clinical cases evaluated, there was a reduction in intraocular pressure reaching acceptable levels, with the usual result being cosmetic and painless eye. Medical therapy remains the predominant method for treating glaucoma in veterinary patients; therefore, cyclocryotherapy is an effective, simple way to lower IOP and is a reasonable treatment option for glaucoma management. Cyclocryotherapy has shown good results, with a low learning curve and it can also be repeated if necessary.
Assuntos
Animais , Gatos , Cães , Glaucoma/terapia , Glaucoma/veterinária , Crioterapia/veterinária , Pressão Intraocular
5.
Semina ciênc. agrar ; 44(1): 301-316, jan.-fev. 2023. ilus, tab, graf
Artigo em Inglês | VETINDEX | ID: biblio-1418824
Resumo
Swines raised in intensive systems are highly susceptible to claw lesions. Moderate to severe lesions trigger an inflammatory response, causing pain and impairing reproductive and economic performance. Foot lesions in sows can cause considerable losses owing to reduced fertility and herd longevity. Proper diagnosis is an important step in correcting this problem; however, the seriousness of the impact of these lesions on swine herds remains unclear to most farm owners. Health monitoring has become an essential tool for veterinarians because it enables the detection of disease incidence and severity. In this study, we assessed claw lesions in sows reared under an intensive system to ascertain the prevalence and severity of lesions in Brazilian herds. The hind limb claws of 2,660 sows from 30 farms were examined for the following lesions: heel overgrowth and erosion (HOE), heel-sole cracks, white line lesions (WL), horizontal and vertical cracks in the toe wall, overgrown toes, and overgrown or missing dew claws. Claws were classified as normal (score = 0), mild (score = 1), moderate (score = 2), or severe (score = 3). At least one type of lesion was observed in 99.1% of the sows, whereas 29.7% displayed severe lesions. HOE was the most common lesion (89.9% of sows) and severe WL was observed in 16.8% of the sows. Lesions increased in prevalence and severity with parity, except for WL. In young females, lesions on the volar surface were more common than those on cracked walls or overgrown toes, which should be considered when selecting gilts for breeding. A high prevalence of claw lesions was observed in Brazilian sows. Monitoring of these lesions is fast and simple. Regular monitoring provides information on claw health in a herd over time, allowing us to take measures to control and treat claw lesions, avoiding worsening of the problem, early culling of animals, and the associated productive and economic losses.
Suínos criados em sistemas intensivos são altamente suscetíveis a lesões de casco. Quando moderadas a graves, essas lesões desencadeiam uma resposta inflamatória, causando dor e prejudicando o desempenho reprodutivo e econômico. Em porcas, as lesões nos cascos podem causar consideráveis perdas devido à redução da fertilidade e longevidade do rebanho. O diagnóstico adequado é um dos passos mais importantes para corrigir esse problema, mas a gravidade do impacto dessas lesões nos rebanhos suínos passa despercebida na maioria das propriedades. O monitoramento sanitário tornou-se uma ferramenta essencial para os médicos veterinários, pois possibilita a detecção da incidência e gravidade da doença. O presente estudo utilizou um método de avaliação de lesões de casco em porcas criadas em sistema intensivo para verificar a prevalência e gravidade das lesões em rebanhos brasileiros. Os cascos dos membros pélvicos de 2.660 porcas, de 30 granjas, foram examinados para as seguintes lesões: crescimento e erosão da almofada plantar (AP), rachadura entre almofada plantar e sola, lesão na linha branca (LB), rachaduras horizontal e vertical da parede do casco, sobrecrescimento da unha principal e sobrecrescimento ou amputação da unha acessória. Os cascos foram classificados como normais (escore = 0) ou apresentando lesões leves (escore = 1), moderadas (escore = 2) ou graves (escore = 3). Pelo menos um tipo de lesão foi observado em 99,1% das porcas, enquanto 29,7% apresentaram lesões graves. AP foi a lesão mais comum (89,9% das porcas) e LB severa foi observada em 16,8% das porcas. As lesões aumentaram em prevalência e severidade com as ordens de parto, com exceção para LB. Em fêmeas jovens, as lesões na face plantar foram mais comuns do que as rachaduras ou sobrecrescimento das unhas, algo que deve ser levado em consideração na seleção de leitoas para reprodução. Alta prevalência de lesões de casco foi observada em porcas brasileiras. A avaliação dessas lesões é rápida e simples. O monitoramento frequente fornece informações sobre a saúde dos cascos de um rebanho ao longo do tempo, permitindo tomar medidas para o controle e tratamento das lesões dos cascos, evitando o agravamento do problema, o descarte precoce dos animais e as perdas produtivas e econômicas associadas.
Assuntos
Animais , Suínos/lesões , Doenças dos Suínos , Claudicação Intermitente/veterinária , Casco e Garras/lesões
6.
Acta sci. vet. (Impr.) ; 51: Pub. 1905, 2023. tab
Artigo em Inglês | VETINDEX | ID: biblio-1418127
Resumo
Background: In a healthy organism, oxidants and antioxidants are in balance. However, in cases such as inflammation, infection, and stress, this balance is disrupted in favor of oxidants, creating oxidative stress that can cause damage to cells or tissues. It is known that oxidative stress plays a role in the pathogenesis of many diseases. Determination of oxidant and antioxidant balance, especially in inflammatory diseases, plays an important role in elucidating the pathogenesis of the disease and developing treatment strategies. This study, it was aimed to reveal the oxidant status in inflammatory disease of calves with septic and aseptic arthritis. Materials, Methods & Results: The material of the study consisted of 21 calves up to 2 months old, of different races and genders, 14 (9 male, 5 female) with arthritis and 7 healthy (control, 5 male, 2 female). Of the calves with arthritis, 11 were septic and 3 were acute aseptic. In the calves with arthritis, the affected joint or joints were determined by clinical examinations. By palpating the joints, swelling, local temperature increase, tension in the joint capsule, presence of pain, and the presence and severity of lameness were examined. The color, clarity, viscosity, odor, and clot formation of the synovial fluid were examined and determined to be septic or aseptic. To determine the antioxidant status, the levels of malondialdehyde (MDA), which is the most important oxidative stress marker, and superoxide dismutase (SOD), gluta-thione peroxidase (GSH-Px), and catalase (CAT), which are the enzymatic antioxidant enzymes, were measured spectro-photometrically in serum samples. Vitamin E, C, and A levels, which are nonenzymatic antioxidants, were also measured colorimetrically. In the clinical examination, lameness was detected in the relevant extremity of all patients with arthritis. In the macroscopic examination of the synovial fluids taken from animals with arthritis, the colors of the synovial fluids varied between yellow and yellow tones in 11 cases; in 3 cases, it was determined that they were red and brown. It was observed that the colors of the synovial fluids were transparent in the subjects in the control group. It was observed that the synovial fluid clarity of the calves with arthritis was lost, with severe turbidity (+++) in 3 cases, moderately turbid (++) in 6 cases, slightly turbid (+) in 2 cases, and clear (-) in 3 cases. It was observed that the viscosity of synovial fluid taken from calves with arthritis decreased in varying degrees according to the severity of the disease, severe (+++) in 5 cases, moderately decreased (++) in 4 cases, slightly decreased (+) in 2 cases, and normal in 3 cases. It was determined that the viscosity of the synovial fluid taken from the calves in the control group was normal. There was a statistically significant difference between the groups in terms of MDA (P < 0.01), SOD (P < 0.01), GSH-Px (P < 0.05), vitamin E (P < 0.001), and vitamin C (P < 0.01), while MDA levels increased in calves with arthritis, SOD and GSH-Px activities and vitamin E and C levels decreased significantly. Although there was no statistically significant difference in CAT (P > 0.05) enzyme activity, it was determined that it was at a lower level in calves with arthritis, and there was no significant difference be-tween the groups in terms of vitamin A (P > 0.05). Discussion: According to the results of the study, there is an increase in oxidative stress and a decrease in antioxidant status in calves with arthritis. It is thought that these changes may be due to efforts to reduce tissue damage by reducing lipid peroxidation. As a result, it was determined that oxidant and antioxidant balance was impaired in calves with arthritis, and oxidative stress and lipid peroxidation developed due to the increase in free radicals. It is thought that giving additional antioxidants to the calves may contribute to the recovery of the disease and reduce treatment costs.
Assuntos
Animais , Bovinos , Artrite Infecciosa/complicações , Artrite Infecciosa/veterinária , Estresse Oxidativo , Superóxido Dismutase/análise , Vitaminas/análise , Catalase/análise , Glutationa Peroxidase/análise , Malondialdeído/análise
7.
Acta sci. vet. (Impr.) ; 51(supl.1): Pub. 849, 2023. ilus
Artigo em Português | VETINDEX | ID: biblio-1416660
Resumo
Background: Bite injuries are commonly found in small animal clinics, especially in male dogs, due to their habits of fighting and territorial disputes. In general, the lesions are treated with the use of compresses and bandages, however, it is extremely important to carefully evaluate the site, in order to carry out the appropriate treatment. In cases of tissue loss, an increasingly used practice is reconstructive surgery, which launches alternatives for treatment through flaps and skin grafts, promoting healing and satisfactory aesthetic repair. This report describes the case of a dog with a facial bite, treated with reconstructive surgery. Case: A 5-year-old male mixed-breed dog, with a body mass of 5 kg, was treated and submitted to a physical examination, due to the owner's complaint that he had been attacked by another dog, causing a bite on the face. On physical examination, the animal showed normal vital parameters, except for mild hyperthermia due to rectal temperature (39.5°C). On the face, it was possible to observe a lacerative lesion in the temporomandibular and masseteric regions, with loss of skin and muscle, in addition to having an aspect of infection and necrosis. To describe the hematological profile, a blood count was performed, showing no changes. In the biochemical tests, the present alteration was a slight increase in Alkaline Phosphatase (393.8 IU/L). Surgical treatment was indicated through facial reconstruction with a skin graft. After performing the antisepsis, the lesion was debrided, the edges were regularized and the injured tissue was curetted. For reconstruction of the defect, we used a flap obtained through a perpendicular incision at the base of the ear, in a caudal direction, and this flap was pulled and transposed over the wound. Flap synthesis was performed with 3-0 nylon thread. After surgery, a compressive bandage was performed, which was removed after 24 h. It was indicated to avoid exertion in the area and to return in 10 days for the evaluation of the surgery and removal of the stitches. Discussion: Traumatic injuries in animals are being increasingly reported, with male and non-neutered dogs being the most prevalent patients. This report is in line with other studies, with the patient's profile being a male dog, with an average age, in line with the literature. In general, in certain types of wounds, the affected animals can develop sepsis and even progress to death, however, in this case the patient did not show changes in vital parameters and in hematological tests. Reconstructive surgeries are performed with the aim of correcting skin defects and knowledge of the available techniques is important. It is also necessary to carry out a good planning, in order to avoid complications in the trans and postoperative period. In the present case, we chose to use a flap obtained through an incision perpendicular to the base of the ear, transposing it over the wound, in addition to relieving tissue tension through skin divulsion, increasing its elastic potential. The use of bandages is considered extremely important for the success of the surgical procedure, as it provides an efficient barrier against infections, trauma and adhesions. However, we emphasize the need to use ointments, gauzes and bandages concomitantly, in order to have the desired success in the postoperative period. In addition to proper surgical techniques, pain management and infection control are important for patient recovery. It is important to use non-steroidal anti-inflammatory drugs and opioids to obtain analgesia, in addition to antibiotic therapy before and after surgery. The reported case demonstrated that lesions in dogs with skin loss can be reconstructed using skin flaps, with an excellent recovery and good prognosis, as was the case with the patient in this report.
Assuntos
Animais , Masculino , Cães , Procedimentos de Cirurgia Plástica/veterinária , Lacerações/veterinária , Traumatismos Faciais/cirurgia , Traumatismos Faciais/veterinária , Mordeduras e Picadas/veterinária
8.
Acta sci. vet. (Impr.) ; 51(supl.1): Pub. 889, 2023. ilus
Artigo em Português | VETINDEX | ID: biblio-1444385
Resumo
Background: Nonambulatory flaccid tetraparesis can be the result of diseases of the peripheral nervous system and it is characterized by generalized lower motor neuron (LMN) signs, as weakness, tetraparesis/tetraplegia, decreased muscle tone and reflexes. The term polyneuropathy is used for dysfunction of multiple peripheral nerves. In Brazil, there are several etiologies for polyneuropathy in dogs, such as acute idiopathic polyradiculoneuritis, botulism and myasthenia gravis. Toxoplasma gondii is an uncommon cause of LMN diseases in dogs. The aim of this report was to describe a case of flaccid tetraplegia toxoplasmosis in an adult dog with a Toxoplasma gondii serology with a markedly elevated IgG titer of 1:4096. Case: A 4-year-old intact mongrel male dog, weighing 19.6 kg, was referred to the Veterinary Medical Teaching Hospital of the Universidade Estadual de Londrina (UEL) with a 5-day history of weakness that progressed to tetraparesis. Physical examination revealed no significant changes other than the dull and unkempt coat. Neurologic examination revealed severe tetraparesis that was worse in the pelvic limbs, with decreased muscle tone in all four limbs. Postural reactions and the interdigital reflex were absent in all four limbs, as was the patellar reflex, but pain perception was present. There were no clinical signs of dysfunction on examination of the cranial nerves. Laboratory tests were performed, and creatine kinase was elevated (819 U/L). Blood was drawn to look for antibodies to Toxoplasma gondii and Neospora caninum class IgG using the indirect immunofluorescence technique. The antibody titer for Toxoplasma gondii (IgG) was 1:4096. A chest radiograph was performed to look for megaesophagus, and a pulmonary pattern suggestive of mild diffuse pneumonia was observed. Treatment was performed with sulfamethoxazole and trimethoprim, and the dog's condition improved slightly. Discussion: Based on lower motor neuron findings, the neurologic lesion was localized in the nerve roots, peripheral nerves, neuromuscular junctions, or muscles. The most important diseases in the list of differential diagnoses were immune-mediated or infectious polyradiculoneuritis (toxoplasmosis, neosporosis), myasthenia gravis, toxic polyneuropathy (botulism, chronic organophosphate poisoning), and paraneoplastic polyneuropathy. Among these differential diagnoses, polyradiculoneuritis is one of the most common. It is an idiopathic inflammatory disease. Exposure to raccoon saliva (in the U.S.), vaccination, or infection have been proposed as precipitating causes, but the triggers of this disease remain unknown. Serology for neosporosis was negative, while IgG titers for toxoplasmosis were 1:4096. In a previous study, dogs with acute polyradiculoneuritis were more likely to have T. gondii IgG serum antibody titers than dogs without neurologic signs. Infection with the protozoa T. gondii and N. caninum can cause intense polyradiculoneuritis in dogs accompanied by myositis, especially in puppies. One treatment trial was based on the administration of sulfonamide-trimethoprim with pyrimethamine, whose efficacy in the treatment of toxoplasmosis in dogs has also been reported in the literature. Neurologic deficits improved slightly, and there is a possibility that certain signs may not disappear completely because of the permanent damage caused by inflammation of the nervous system, as observed in the present case. The case had the limitation that it was not possible to perform other laboratory tests to demonstrate histopathologically the presence of Toxoplasma gondii organisms in muscles or nerves. Recovery of normal function is less likely in protozoan polyradiculoneuritis than in noninfectious polyradiculoneuritis. Thus, in the present case, the main suspicion was polyradiculoneuritis secondary to toxoplasmosis. Although it is a rare condition, it is important to consider toxoplasmosis in dogs with LMN-type tetraparesis or tetraplegia.
Assuntos
Animais , Masculino , Cães , Paresia/veterinária , Polineuropatias/veterinária , Polirradiculoneuropatia/veterinária , Sistema Nervoso Periférico/patologia
9.
Artigo em Português | VETINDEX | ID: biblio-1378444
Resumo
O presente trabalho avaliou os efeitos analgésicos do carprofeno associado ou não à condroitina com glicosamina no tratamento de 26 cães com osteoartrite, distribuídos nos grupos: GT carprofeno (Carproflan®); GTP carprofeno e glicosaminoglicanos (Carproflan® e Procart®); e GC somente analgésico (dipirona). A evolução dos pacientes foi classificada na escala de claudicação no dia do primeiro atendimento e aos 7, 14 e 21 dias. No GT, 60% dos animais apresentou melhora clínica a partir do 7º dia, 30% não alterou seu escore de claudicação e 10% apresentou êmese a partir do 7º dia, com suspensão da medicação. No GTP, 60% dos animais apresentou melhora clínica a partir do 7º dia, 30% não alterou seu escore de claudicação, 5% apresentou êmese a partir do 7º dia e 5% a partir do 14º dia, com suspensão da medicação. No GC, nenhum animal apresentou melhora clínica. Conclui-se que os animais submetidos ao tratamento com carprofeno apresentaram melhora na claudicação, principalmente quando associado aos glicosaminoglicanos.(AU)
The analgesic effects of carprofen associated or not with chondroitin with glucosamine were evaluated in the treatment of 26 dogs with osteoarthritis, distributed into groups: TG carprofen (Carproflan®); PTG carprofen and glycosaminoglycans (Carproflan® and Procart®); and CG only analgesic (dipyrone). The evolution of patients was classified on the lameness scale on the first day of care and at 7, 14 and 21 days. In the TG, 60% of the animals showed clinical improvement from the 7th day, 30% did not change their lameness score and 10% had emesis from the 7th day, with discontinuation of the medication. In the PTG, 60% of the animals showed clinical improvement from the 7th day, 30% did not change their lameness score, 5% had emesis from the 7th day and 5% from the 14th day, with discontinuation of the medication. In the CG, no animal showed clinical improvement. It was concluded that animals undergoing treatment with carprofen showed improvement in lameness, especially when associated with glycosaminoglycans.(AU)
Assuntos
Animais , Osteoartrite/veterinária , Claudicação Intermitente/diagnóstico , Medição da Dor/veterinária , Anti-Inflamatórios não Esteroides/efeitos adversos , Glicosaminoglicanos/efeitos adversos
10.
Biol. Models Res. Technol ; 2(1): e00182021, 2022. ilus, tab
Artigo em Inglês | VETINDEX | ID: biblio-1402344
Resumo
After analgesic administration, we evaluated general activity in the Open-Field and anxiety-like behavior in the Elevated Plus Maze of vasectomized mice. We divided C57BL/6J male mice into eight groups: saline, three non-operated control groups treated with 10 mg/kg meloxicam, 20 mg/kg tramadol, or both intraperitoneally, and four vasectomized mice groups treated with the same analgesic protocol as the control groups. One group of vasectomized mice received both treatments and an additional 10 mg/kg lidocaine at the incision site. We conducted the vasectomy via scrotal approach under isoflurane inhalation anesthesia and performed behavioral tests after full anesthesia recovery. Mice treated with meloxicam demonstrated low ambulation, spontaneous activity, and rearing frequency. Mice treated with tramadol showed spontaneous behavior compared with the saline control. Due to behavior changes demonstrated by meloxicam controls, we were unable to identify whether meloxicam provided adequate analgesia. Vasectomized mice treated with tramadol showed general activity behavior similar to their control but displayed significantly less rearing, suggesting that they were under potential signs of pain or discomfort. In conclusion, the Open Field test and the Elevated Plus Maze can usefully pre-evaluate analgesic protocols to identify possible interference caused by adverse drug effects. For future directions, an appropriate regimen of meloxicam and tramadol for enhancing mice welfare post vasectomy should be better investigated.
Assuntos
Animais , Masculino , Camundongos , Dor Pós-Operatória/veterinária , Comportamento Animal , Bem-Estar do Animal , Analgesia/veterinária , Camundongos , Tramadol , Vasectomia , Meloxicam
11.
J. venom. anim. toxins incl. trop. dis ; 28: e20220028, 2022. graf, tab
Artigo em Inglês | VETINDEX | ID: biblio-1418277
Resumo
Background: A combination of pharmacological and biomedical assays was applied in this study to examine the bioactivity of Conus virgo crude venom in order to determine the potential pharmacological benefit of this venom, and its in vivo mechanism of action. Methods: Two doses (1/5 and 1/10 of LC50, 9.14 and 4.57 mg/kg) of the venom were used in pharmacological assays (central and peripheral analgesic, anti-inflammatory and antipyretic), while 1/2 of LC50 (22.85 mg/kg) was used in cytotoxic assays on experimental animals at different time intervals, and then compared with control and reference drug groups. Results: The tail immersion time was significantly increased in venom-treated mice compared with the control group. Also, a significant reduction in writhing movement was recorded after injection of both venom doses compared with the control group. In addition, only the high venom concentration has a mild anti-inflammatory effect at the late inflammation stage. The induced pyrexia was also decreased significantly after treatment with both venom doses. On the other hand, significant increases were observed in lipid peroxidation (after 4 hours) and reduced glutathione contents and glutathione peroxidase activity, while contents of lipid peroxidation and nitric oxide (after 24 hours) and catalase activity were depleted significantly after venom administration. Conclusion: These results indicated that the crude venom of Conus virgo probably contain bioactive components that have pharmacological activities with low cytotoxic effects. Therefore, it may comprise a potential lead compound for the development of drugs that would control pain and pyrexia.(AU)
Assuntos
Animais , Produtos Biológicos/análise , Gastrópodes/genética , Compostos Orgânicos/toxicidade , Anti-Inflamatórios/farmacologia
12.
Braz. j. biol ; 822022.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468706
Resumo
Abstract Hymenaea martiana is a species popularly known in Northeastern Brazil as jatobá and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-1, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.
Resumo Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como jatobá e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti-inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-1, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.
13.
Braz. j. biol ; 82: 1-9, 2022. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468519
Resumo
Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-¹, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.
Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como jatobá e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-¹, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.
Assuntos
Animais , Camundongos , Anti-Inflamatórios/análise , Hymenaea/química , Plantas Medicinais/efeitos adversos
14.
Braz. j. biol ; 82: e240359, 2022. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1285603
Resumo
Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-1, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.
Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como "jatobá" e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e antiinflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-1, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.
Assuntos
Animais , Coelhos , Hymenaea , Fabaceae , Brasil , Extratos Vegetais/farmacologia , Carragenina , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia
15.
Braz. J. Biol. ; 82: 1-9, 2022. graf
Artigo em Inglês | VETINDEX | ID: vti-33080
Resumo
Hymenaea martiana is a species popularly known in Northeastern Brazil as "jatobá" and used in folk medicine to treat pain and inflammation. The aim of this work was to evaluate the antinociceptive and anti-inflammatory activity of H. martiana. In the present study, we carried out an investigation about the effects of the crude ethanolic extract (Hm-EtOH) and the ethyl acetate fraction (Hm-AcOEt) in models of nociception and inflammation in mice. Chemical (acetic acid-induced writhing and formalin) and thermal stimuli (hot plate) were used for the evaluation of antinociceptive activity, while for the anti-inflammatory profile paw edema induced by carrageenan was used, along with leukocyte migration to the peritoneal cavity. The presence of the flavonoid astilbin in the samples was characterized through HPLC-DAD-MS analysis. Hm-EtOH and Hm-AcOEt (100, 200 and 400 mg.kg-¹, i.p.) significantly reduced the number of abdominal contortions and decreased the paw licking time in the formalin test. In the hot plate, the extract increased the latency time of animals. Hm-EtOH and Hm-AcOEt inhibited significantly the increase in the edema after the administration of carrageenan. Hm-EtOH and Hm-AcOEt inhibited leukocyte migration in the peritonitis test. HPLC-DAD-MS analysis of Hm-EtOH and Hm-AcOEt revealed the presence of the flavonoid astilbin in the samples. According to the results of this study, both Hm-EtOH and Hm-AcOEt have antinociceptive and anti-inflammatory activities, which could be related with the presence of flavonoid in the extracts. The results reinforce the popular use of this plant.(AU)
Hymenaea martiana é uma espécie popularmente conhecida no Nordeste do Brasil como jatobá e usada na medicina popular para tratar a dor e a inflamação. O objetivo deste trabalho foi avaliar a atividade antinociceptiva e anti inflamatória de H. martiana. No presente estudo, foram avaliados os efeitos do extrato etanólico bruto (Hm-EtOH) e da fração acetato de etila (Hm-AcOEt) em modelos de nocicepção e inflamação em camundongos. Foram utilizados estímulos químicos (contorções abdominais induzidas por ácido acético e teste da formalina) e estímulo térmico (teste da placa quente) para avaliação da atividade antinociceptiva, enquanto no perfil anti-inflamatório foi utilizado o teste do edema de pata induzido por carragenina e migração de leucócitos para a cavidade peritoneal. A presença do flavonoide astilbina nas amostras foi caracterizada através de análise por CLAE-DAD-EM. Hm-EtOH e o Hm-AcOEt (100, 200 e 400 mg.kg-¹, i.p.) reduziram significativamente o número de contorções abdominais e diminuíram o tempo de lambida da pata no teste da formalina. No teste da placa quente, houve aumento do tempo de latência dos animais. Hm-EtOH e Hm-AcOEt inibiram significativamente o aumento do edema após a administração de carragenina, bem como inibiram a migração de leucócitos no teste de peritonite. A análise por CLAE-DAD-EM de Hm-EtOH e Hm-AcOEt revelou a presença do flavonoide astilbina nas amostras. De acordo com os resultados deste estudo, tanto Hm-EtOH quanto o Hm-AcOEt possuem atividades antinociceptiva e anti-inflamatória, o que pode estar relacionado à presença do flavonoide. Os resultados reforçam o uso popular desta planta.(AU)
Assuntos
Animais , Camundongos , Hymenaea/química , Anti-Inflamatórios/análise , Plantas Medicinais/efeitos adversos
16.
Acta amaz ; 52(3): 245-253, 2022. tab, graf
Artigo em Inglês | VETINDEX | ID: biblio-1392862
Resumo
The oil of Caryocar villosum is used in Amazonian folk medicine to treat pain and inflammatory conditions. So, we assessed the anti-inflammatory and antinociceptive properties of the ethanolic extract obtained from the fruit peels of this species. The acetic acid-induced writhing, carrageenan-induced mechanical hyperalgesia, formalin, carrageenan-induced paw edema and carrageenan-induced peritonitis tests were used on mice. The C. villosum ethanolic extract significantly inhibited the number of abdominal writhes, mechanical hyperalgesia and paw licking time in the second phase of the formalin test. At a dose of 300 mg kg-1, the extract also significantly reduced the volume of edema formed in the late phase and reduced the recruitment of leukocytes and neutrophils in the peritoneal cavity, as well as CXCL1 chemokine levels. It is suggested that the extract attenuates the leukocyte recruitment by inhibiting the CXCL1 activation. The peripheral antinociceptive activity occured through opioid pathway modulation because pretreatment with C. villosum ethanolic extract reversed the naltrexone-induced antinociception.(AU)
O óleo de Caryocar villosum é usado na medicina popular amazônica para tratar dores e condições inflamatórias. Assim, avaliamos as propriedades antiinflamatórias e antinociceptivas do extrato etanólico obtido das cascas dos frutos desta espécie. Os testes de contorções induzidas por ácido acético, hiperalgesia mecânica induzida por carragenina, formalina, edema de pata induzido por carragenina e peritonite induzida por carragenina foram usados em camundongos. O extrato etanólico de C. villosum obtido das cascas dos frutos inibiu significativamente o número de contorções abdominais, a hiperalgesia mecânica e o tempo de lambida da pata na segunda fase do teste de formalina. Na dose de 300 mg kg-1, o extrato também reduziu significativamente o volume de edema formado na fase tardia e reduziu o recrutamento de leucócitos e neutrófilos na cavidade peritoneal, bem como os níveis de quimiocina CXCL1. Sugere-se que o extrato atenua o recrutamento de leucócitos por meio da inibição da ativação de CXCL1. A atividade antinociceptiva periférica ocorre por meio da modulação da via opioide pois o pré-tratamento com o extrato etanólico de C. villosum reverteu a antinocicepção induzida pela naltrexona.(AU)
Assuntos
Animais , Camundongos , Quimiocina CXCL1/antagonistas & inibidores , Malpighiales/química , Hiperalgesia/tratamento farmacológico , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Extratos Vegetais
17.
Braz. j. biol ; 822022.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1468680
Resumo
Abstract The aim of this research is to make a survey of the socio-environmental characteristics and the ethnobotanical study of medicinal plants used in a traditional community in the Brazilian Northeast, Alagoas. The study was made based on visits with the application of a questionnaire with questions related to the socio-economic element and on the diversity of plants used in herbal medicine. The research was made from March/2019 to February/2020, where families and interviewed plant exhibitors were interviewed for botanical identification. The studied community, which were 24 interviewees, was compiled by residents of the Quilombola community from Pau Darco in Arapiraca city - Alagoas. Residents interviewed, 15 (62.5%) attended between 56 to 80 years, 11 interviewees about 46% were born in the community and 13 (54%) had a fundamentally incomplete nature. At the end, there were mentioned 30 plant species used for phytotherapeutic purposes, from which presents bigger usage as plants against arterial hypertension (Salvia rosmarinus Schleid), diabetes Mellitos (Croton heliotropiifolius Kunth), pain and inflammation (Alternanthera tenella Colla), present the biggest number of species in the community. The species cited are related to numerous medicinal uses, among which there will be predominant associations associated with cardiovascular and inflammatory processes. The tea is the main way of preparing plants. It is perceived that medicinal plants are only widely used by this Quilombola community of and growth of the crops in the backyard are considered a tradition.
Resumo Esta pesquisa teve como objetivo realizar um levantamento das características socioambientais e estudo etnobotânico de plantas medicinais utilizadas por uma comunidade tradicional do nordeste brasileiro, Alagoas, Brasil. O estudo se deu por meio de visitas com aplicação de um questionário contendo perguntas relacionadas aos fatores socio-econômicos e sobre a diversidade das plantas utilizadas como medicinais. O trabalho foi realizado no período de março/2019 a fevereiro/2020, onde foram entrevistadas famílias e catalogadas amostras de plantas para identificação botânica. A população estudada, com 24 entrevistados, foi composta por moradores da comunidade Quilombola Pau Darco da cidade de Arapiraca - Alagoas. Dos moradores entrevistados, 15 (62,5%) apresentavam idade entre 56 e 80 anos, 11 dos entrevistados cerca de 46%, são naturais da comunidade e 13 (54%) possuíam ensino fundamental incompleto. Ao todo, foram citadas 30 espécies de plantas utilizadas para fins terapêuticos, das quais apresentam maior utilização as plantas contra a hipertensão arterial (Salvia rosmarinus Schleid), diabetes Mellitos (Croton heliotropiifolius Kunth), dor e inflamação (Alternanthera tenella Colla). As espécies citadas estão relacionadas a inúmeras utilizações medicinais, entre os quais predominaram as doenças associadas ao aparelho cardiovascular e processos inflamatórios. O chá é principal forma de preparo das plantas. Percebe-se que as plantas medicinais são amplamente utilizadas por essa comunidade quilombola e o cultivo no quintal é considerado uma tradição.
18.
Acta sci., Biol. sci ; 44: e49794, mar. 2022. graf, ilus
Artigo em Inglês | VETINDEX | ID: biblio-1413430
Resumo
Arthropod venoms are potential sources of bioactive substances, providing tools for the validation of popular use and new drugs design. Ants belonging to the genus Dinoponera are used in the folk medicine to treat inflammatory conditions. It was previously demonstrated that the venom of the giant ant Dinoponera quadriceps (DqV), containing a mixture of polypeptides, elicit antinociceptive effect in mice models of chemical, mechanical and thermal nociception. The aim of this study was to evaluate DqV antiinflammatory and antihypernociceptive effects in a mice model of traumatic cutaneous wound. Colonies of D. quadriceps were collected in the 'Serra de Maranguape' (State of Ceará, northeastern Brazil), a small mountain range located on the coastal zone, and the venom secreted by the ant glands was extracted with capillary tubes, further lyophilized and maintained at -20 ± 1ºC until use. Wounds were performed in the dorsum of Swiss mice. Animals received intravenous (i.v.) injection of DqV (50 µg kg-1 day-1) during 3 days for evaluation of inflammatory parameters present in the wounds: hypernociception, leukocyte infiltrate, myeloperoxidase activity, nitrite/nitrate content. Data was tested by two-way ANOVA and Bonferroni's post-hoc test. DqV reduced (2.7 folds) hypernociception at 48 hours, leukocyte infiltration by 65% at 6 hours and myeloperoxidase activity by 60% at 0.5 hour after wound induction. In conclusion, the venom extracted from D. quadriceps glands attenuates inflammation and hypernociception in mice cutaneous wounds.(AU)
Assuntos
Animais , Camundongos , Venenos de Artrópodes/análise , Inflamação/tratamento farmacológico , Camundongos/lesões , Cicatrização/efeitos dos fármacos
19.
Acta sci. vet. (Impr.) ; 50(supl.1): Pub. 793, 2022. ilus
Artigo em Português | VETINDEX | ID: biblio-1401195
Resumo
Background: Wounds that occur with tissue necrosis and that result from the application of medications through the most diverse accesses are described as drug skin medical embolism or Nicholas syndrome in human medicine, with wide description. In veterinary medicine, this subject has not yet been described extensively and specifically in veterinary medicine, especially regarding to wounds that occurred after the application of non-intravenous medications in horses, even though these lesions are recurrent in the clinical routine. This report aims to describe a case of skin necrosis in a horse, due to phenylbutazone infection. Case: A 7 year-old Mangalarga Marchador horse, weighing 400 kg, was admitted to the Veterinary Hospital for Large Animals of the Universiade Federal Rural do Rio de Janeiro (UFRRJ), with a history of phenylbutazone injection to the left side of the neck. The animal had an extensive wound on the neck and face on the left side and was characterized by the presence of cold and devitalized skin, with a hardened and parched appearance and that easily detached. During the anamnesis, a single administration of 10 mL of a non-steroidal anti-inflammatory drug based on phenylbutazone was reported intramuscularly for about 10 days to control the pain resulting from the claudication present for 14 days. The medication was administered in the region of the lateral border of the neck, on the left side. After drug administration, the animal presented an increase in volume at the application site. After 24 h, the lesion spread from the inoculation region, extending to the head and chest of the animal. During debridement, it was found that the lesion did not reach the underlying muscle tissue. In addition to the wound, the animal had upper eyelid palsy, lower lip, and auricular ptosis. Treatment with surgical debridement of devitalized tissue, topical application of ozonated sunflower oil, ketanserin, and a free skin graft was instituted. During hospitalization, the animal had a corneal ulcer in the left eye with an unfavorable prognosis due to paralysis of the upper eyelid, with enucleation of the affected eyeball. The animal was under veterinary care for 180 days and was discharged when his wound was already in an advanced stage of healing. Discussion: The history of the application of phenylbutazone intramuscularly and the location and characteristics of the lesion presented by the patient in the present report suggest that this animal presented aseptic tissue necrosis resulting from the administration of non-steroidal anti-inflammatory drugs, phenylbutazone. Although aseptic tissue necrosis, better known as Nicolau's syndrome or drug embolism cutis, is widely characterized and described in this species, there are studies in the literature that reproduce the syndrome in pigs and rabbits. Phenylbutazone was able to cause arterial damage, mainly in the tunica intima of the artery in which the medication was administered, with perivascular inflammatory infiltrate and subsequent skin necrosis at the site of administration. In addition to the skin lesion, the animal started to show signs compatible with the left facial nerve lesion, evidenced by the immobility of the upper eyelid and labial and ear ptosis. This resulted in corneal ulceration and subsequent enucleation. The animal also developed chewing difficulty in the first months of hospitalization. This dysfunction may be due to a lesion of the mandibular nerve, responsible for innervating the masticatory muscles and the oral mucosa. However, the animal showed improvement in this aspect, no longer showing this condition after 90 days of hospitalization. The treatment used was successful in healing the wound.
Assuntos
Animais , Fenilbutazona/efeitos adversos , Gangrena/veterinária , Cavalos/lesões , Síndrome de Nicolau/veterinária , Doença Iatrogênica/veterinária
20.
Braz. j. biol ; 82: 1-11, 2022. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1468493
Resumo
The aim of this research is to make a survey of the socio-environmental characteristics and the ethnobotanical study of medicinal plants used in a traditional community in the Brazilian Northeast, Alagoas. The study was made based on visits with the application of a questionnaire with questions related to the socio-economic element and on the diversity of plants used in herbal medicine. The research was made from March/2019 to February/2020, where families and interviewed plant exhibitors were interviewed for botanical identification. The studied community, which were 24 interviewees, was compiled by residents of the Quilombola community from Pau D'arco in Arapiraca city - Alagoas. Residents interviewed, 15 (62.5%) attended between 56 to 80 years, 11 interviewees about 46% were born in the community and 13 (54%) had a fundamentally incomplete nature. At the end, there were mentioned 30 plant species used for phytotherapeutic purposes, from which presents bigger usage as plants against arterial hypertension (Salvia rosmarinus Schleid), diabetes Mellitos (Croton heliotropiifolius Kunth), pain and inflammation (Alternanthera tenella Colla), present the biggest number of species in the community. The species cited are related to numerous medicinal uses, among which there will be predominant associations associated with cardiovascular and inflammatory processes. The tea is the main way of preparing plants. It is perceived that medicinal plants are only widely used by this Quilombola community of and growth of the crops in the backyard are considered a tradition.
Esta pesquisa teve como objetivo realizar um levantamento das características socioambientais e estudo etnobotânico de plantas medicinais utilizadas por uma comunidade tradicional do nordeste brasileiro, Alagoas, Brasil. O estudo se deu por meio de visitas com aplicação de um questionário contendo perguntas relacionadas aos fatores socio-econômicos e sobre a diversidade das plantas utilizadas como medicinais. O trabalho foi realizado no período de março/2019 a fevereiro/2020, onde foram entrevistadas famílias e catalogadas amostras de plantas para identificação botânica. A população estudada, com 24 entrevistados, foi composta por moradores da comunidade Quilombola Pau Darco da cidade de Arapiraca - Alagoas. Dos moradores entrevistados, 15 (62,5%) apresentavam idade entre 56 e 80 anos, 11 dos entrevistados cerca de 46%, são naturais da comunidade e 13 (54%) possuíam ensino fundamental incompleto. Ao todo, foram citadas 30 espécies de plantas utilizadas para fins terapêuticos, das quais apresentam maior utilização as plantas contra a hipertensão arterial (Salviaros marinus Schleid), diabetes Mellitos (Croton heliotropiifolius Kunth), dor e inflamação (Alternanthera tenella Colla). As espécies citadas estão relacionadas a inúmeras utilizações medicinais, entre os quais predominaram as doenças associadas ao aparelho cardiovascular e processos inflamatórios. O chá é principal forma de preparo das plantas. Percebe-se que as plantas medicinais são amplamente utilizadas por essa comunidade quilombola e o cultivo no quintal é considerado uma tradição.
Assuntos
Etnobotânica/classificação , Medicina Tradicional , Plantas Medicinais/classificação
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Laser Therapy for Unwanted Hair
Laser Therapy for Unwanted Hair
Unwanted hair can be a bothersome and time-consuming issue for many individuals. Shaving, waxing, and plucking are temporary solutions, and their repetitive nature can become tedious. Fortunately, advancements in cosmetic technology have led to the emergence of laser therapy as a potential long-term solution for unwanted hair removal. This blog will explore how laser therapy works, its effectiveness, safety considerations, and factors that influence its success
Understanding Laser Hair Removal
A non-invasive cosmetic treatment called laser hair removal utilises concentrated light energy to target and destroy hair follicles. The laser emits a specific wavelength absorbed by the pigment (melanin) in the hair follicles. This absorption converts the light into heat, which damages the follicle, inhibiting future hair growth.
Effectiveness of Laser Hair Removal
Laser hair removal has proven highly effective in reducing unwanted hair growth. However, its success can vary depending on several factors, including skin colour, hair colour, hair thickness, and the individual's hormonal profile. The treatment works best on individuals with fair skin and dark, coarse hair, as the contrast between the hair colour and skin tone allows the laser to more precisely target the hair follicles.
Number of Sessions and Maintenance
Laser hair removal requires repeated treatments. Not all hair follicles are active at once as hair grows in cycles.Typically spaced several weeks apart, multiple sessions are required to target hair in various growth stages. Most individuals require six to eight treatments for significant hair reduction. Periodic maintenance sessions may be necessary to address any new hair growth that could occur over time.
Safety Considerations
Most people think laser hair removal is more effective than safe when done by a qualified and experienced specialist. Before the treatment, you must, however, have a full consultation to see whether you are a good candidate and to go through any potential dangers or side effect
Potential Risks and Side Effects
While laser hair removal is generally safe, some potential risks and side effects may include:
• Skin Irritation: Temporary redness, swelling, or mild discomfort in the treated area are common and usually subside within a few hours or days.
• Skin Pigmentation Changes: Laser hair removal can cause Laser hair removal might temporarily lighten or darken the treated skin. This risk is higher for individuals with darker skin tones.
• Scarring: In rare cases, laser therapy may cause scarring, especially if performed by an inexperienced technician or on tanned skin.
• Hair Regrowth: While laser hair removal reduces hair growth significantly, it may not eliminate all hair follicles, and some fine hairs may regrow over time.
• Factors Influencing Results The effectiveness of laser hair removal can vary due to several factors, including:
• Skin Type and Hair Color: As mentioned earlier, individuals with fair and dark hair typically see better results than those with light-coloured or darker skin tones.
• Hair Growth Cycle: Since laser therapy targets active hair follicles, treatments must be timed to coincide with different hair growth cycles.
• Hormonal Factors: Hormonal imbalances, such as those caused by certain medical conditions or medications, can influence hair growth patterns and affect treatment results.
Conclusion
Laser therapy for unwanted hair removal is an effective and long-term solution for many individuals seeking relief from constant shaving, waxing, or plucking. Laser hair removal can significantly reduce hair growth in targeted areas when performed correctly and under the appropriate conditions. However, individual results may vary based on skin type, hair colour, and hormonal influences. To achieve the best outcomes and ensure safety, it is essential to undergo laser therapy under the guidance of a qualified and experienced professional. Always consult a licensed practitioner to discuss your specific needs and determine if laser hair removal is the right option for you
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Frequently Asked Questions
How does laser therapy for unwanted hair work?
Laser therapy for unwanted hair emits a concentrated beam of light that is absorbed by the pigment (melanin) in the hair follicles. This absorbed light converts into heat, damaging the follicles and inhibiting future hair growth.
Is laser hair removal suitable for all skin types and hair colours?
Laser hair removal is most effective for individuals with fair skin and dark, coarse hair. The contrast between the hair colour and skin tone allows the laser to target the hair follicles more effectively. However, technological advancements have enabled laser hair removal on a wider range of skin types and hair colours.
Is laser hair removal a permanent solution for unwanted hair?
Laser hair removal can lead to long-term hair reduction but may not completely eliminate all hair follicles. Some fine hairs may regrow over time but are often lighter and less noticeable than before the treatment.
How many sessions of laser hair removal are typically needed?
The number of sessions required for laser hair removal varies from person to person. On average, most individuals need six to eight treatments, spaced several weeks apart, to effectively target hair in different growth stages.
Is laser hair removal painful?
Laser hair removal may cause some discomfort during the procedure, often described as a mild snapping sensation or a sensation of warmth on the skin. However, many modern laser devices have built-in cooling mechanisms to minimise discomfort.
Are there any side effects of laser hair removal?
Temporary side effects of laser hair removal may include redness, swelling, and mild skin irritation in the treated area. In rare cases, the procedure may cause skin pigmentation changes or scarring, especially if not performed by a skilled professional.
How long do the results of laser hair removal last?
The results of laser hair removal can be long-lasting, but individual experiences may vary. Periodic maintenance sessions may be necessary to address any new hair growth over time.
Can laser hair removal be performed on any body part?
Laser hair removal can be performed on various body parts, including the face, legs, underarms, bikini area, chest, back, and more. However, some areas may require special considerations and expertise.
Is laser hair removal safe for pregnant or breastfeeding individuals?
Laser hair removal is not recommended for pregnant individuals. While there is no evidence suggesting harm to the baby, postponing the treatment until after childbirth is generally advised. Consult with a healthcare professional before undergoing laser therapy while breastfeeding.
Can laser hair removal treat ingrown hairs?
Yes, laser hair removal can help reduce and prevent ingrown hairs. By targeting and damaging the hair follicles, the treatment can alleviate the occurrence of ingrown hairs that often result from shaving or waxing.
Are there any factors that could affect the success of laser hair removal?
Various factors can influence the success of laser hair removal, including skin type, hair colour, hormonal influences, and the experience and expertise of the technician performing the procedure. A thorough consultation with a qualified professional can help determine an individual's suitability and expected outcomes.
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Find what you are looking for and hit enter to search
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Maintain Vitamin D value
The vitamin D value indicates how much vitamin D is present in the blood.
This vitamin D value is measured in Nano moles per liter (nmol/L).
You can have your vitamin D value measured by your doctor or a medical laboratory.
If you think you have a deficiency, it might be wise to see a doctor.
He or she can possibly have a blood test done to measure the vitamin D value in your blood and then prescribe the right treatment.
Treatment may include taking vitamin D supplements or getting extra sunlight.
Vitamin D up to standard? Check the Curesupport products
We already said it: if you think that your vitamin D value is too low, it might not be unwise to give it some thought. You could make sure you grab some extra sunlight.
Another option is to see to it that you get enough vitamin D through a balanced diet.
Curesupport offers a large number of vitamin D products.
It’s good to know in time whether you have a vitamin D deficiency in order to be able to do something about it.
Please note: always consult a healthcare professional first, before taking any dietary supplements.
Especcially if you have specific health conditions or are taking medication.
Food supplements are not a substitute for a varied and balanced diet.
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top of page
What is Spinal Manipulation?
When you hear the words "spinal manipulation" what sort of images race through your head? It doesn't exactly sound like the most friendliest of terms does it? But the more you learn about it, the more welcomed and friendly it becomes. Spinal manipulation is a staple in a chiropractor's routine, and when performed by a well trained professional offers a plethora of benefits. First, let’s figure out what in the world a spinal manipulation is. Well, it is a method of chiropractic treatment that targets vertebrae that have abnormal movement patterns or seem to function incorrectly. This in turn helps the patient experience "increased range of motion, reduced nerve irritability and improved function." Chiropractors are trained extensively on how to properly carry out this treatment.
Here’s the next question, how does it work? The chiropractor normally applies firm pressure using his or her arms in a quick thrust on to the vertebrae that is causing pain and/or discomfort to the patient. This powerful and well placed push on the vertebrae ends up releasing gas "joint cavitation" aka cracking and popping. At this point the patient experiences a relieving sensation, although sometimes there can be mild discomfort.
Chiropractors adapt treatment plans to meet the specific needs of each patient. Typically, chiropractic treatment plans involve some forceful and less forceful spinal adjustment techniques during the same visit or over the course of treatment (6 to 10 visits for a typical patient). Now that we’ve generally discussed how an adjustment works, it’s time to dive deeper into the most common adjustments chiropractors use:
• Spinal Manipulation (High-Velocity Low-Amplitude Thrust) The most frequently used chiropractic technique, spinal manipulation, is the traditional high-velocity low-amplitude (HVLA) thrust. The manipulation often results in an audible "pop," as chiropractors use their hands to apply a controlled sudden force to a joint while the body is positioned in a specific way.
• Spinal Mobilization (Low-Force or Gentle Chiropractic Techniques) Some conditions (such as osteoporosis), pathology, the patient's size, patient comfort, or patient preference, may require a gentler approach generally referred to as spinal mobilization. In addition, some patients and/or clinicians prefer mild spinal mobilization techniques that do not involve twisting of the body or a forceful thrust.
Now here is the kicker, what does spinal manipulation do for you? Well for starters, your back is going to feel a lot better! But here's a list of subtle things you really wouldn't think about, but these have been investigated and reported to take place in the body after a spinal manipulation. Increased secretion of melatonin (regulates other hormones, and assists in your 24-hour sleep cycle), increased endorphins helping pain management, lowered blood pressure as well as better circulation, increased joint range of motion, tension reduction in muscles, and much more.
Over all the spinal manipulation can be a very important pillar in our quest of optimum health. The manipulation ends up relieving back pain, and offers quite the spectrum of additional benefits. It is a natural approach to health care, and is completely non-invasive. Back pain is cured time and time again with the spinal manipulation technique without the use of prescription drugs. Like I said before, the more you learn about it the more there is to love! Talk to your primary care physician to learn more about chiropractors in your area. Get a great referral and see what all the fuss is about. Watch how your body responds to a professional spinal manipulation, and make this a part of your preventative health care routine.
#chiropractic #spinalmanipulation #spine #adjustment
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Don't wait for care. Schedule a same-day appointment at our South Meadows location!
New Patients:
(775) 500-0063
Existing Patients:
Sparks (775) 359-3934
Reno (775) 234-5595
What Is the Difference Between a Routine Dental Cleaning and a Deep Cleaning?
Posted .
If you’re keeping up with your dental hygiene—and hopefully you are!—then you’re familiar with how routine dental cleanings keep your smile white and your teeth free of destructive plaque and tartar. However, family dentistry clinics can perform far more detailed cleaning than what is necessary for basic oral health. Some patients require deep teeth cleaning that encompasses more than just a simple brush and polish. Dental deep cleanings aren’t a typical service you need often and are usually reserved for patients struggling with gum disease.
Dental Cleanings: What Are the Types?
Dental cleanings are some of the most important services a dentist can offer when it comes to the oral health of most patients. Cleanings are usually performed by licensed den₽tal assistants called hygienists, who use different tools and techniques to clean surfaces of the teeth that are hard to reach with home dental care. Routine dental cleanings usually take around 20 minutes, and they should be performed at least once every six months, while dental deep cleanings are usually prescribed by a dentist as needed.
Routine Dental Cleaning
In a routine cleaning, your hygienist’s goal is to remove the bacteria, plaque, and tartar that has accumulated since your last cleaning. Even with daily home care, it’s difficult to clean every surface of your teeth as thoroughly as needed to prevent this kind of buildup. Your hygienist will typically use a few different processes in a routine cleaning, including scraping the teeth with a dental instrument to remove hardened tartar, polishing with a high-powered dental brush and fine-grit toothpaste, and thorough flossing in between the teeth. By the time they are done, your teeth should be smooth, white, and tartar-free.
Deep Teeth Cleaning
Dental deep cleanings, on the other hand, involve cleaning the teeth in between the gums to the roots below the gum line. In patients with an extreme buildup of tartar, bacteria can migrate underneath the gum line (even as deep as the tooth’s root itself), resulting in bacterial infections of the gums. A process called “scaling” is performed by manually scraping away tartar beneath the gum line, as well as the use of an ultrasonic device to remove plaque from the tooth surface.
Routine Dental Cleaning vs Deep Dental Cleaning
While both procedures aim to eliminate tartar buildup, there are some major differences between the two. The major difference is the frequency and necessity of the two. Routine cleanings are part of your normal biannual checkup and mostly consist of the same process every time. They take a little under half an hour and require no further action on your part or your dentist’s. Routine cleanings are not painful and use commonplace dental equipment to perform.
Dental Deep Cleanings are a prescribed procedure that your dentist will perform to treat advanced gum disease, and the methods and equipment used in a deep cleaning should not be performed and used as frequently as a routine cleaning as they are slightly more invasive.
Deep cleanings often require novocaine or other local anesthetics to numb the gums ahead of the procedure, as accessing the surface of the tooth roots with a manual instrument called a scaler can be uncomfortable otherwise. The repeated rubbing of the tooth root in this process removes bacteria that can be inflaming the gum tissues—making them red, swollen, and puffy—and encourages the gum to reattach to the tooth’s surface.
Also, unlike routine cleanings, deep cleanings are intended to produce certain results and may require multiple follow-up appointments to fully accomplish. Finally, routine cleanings are considered preventive dental care to stop the formation of tartar and decay, while deep cleaning is a reactive treatment to ongoing gum and periodontal disease intended to treat symptoms.
Deep Teeth Cleaning Before and After
If you are a candidate for a dental deep cleaning, you might notice symptoms of gum disease that inform your decision to seek treatment, including:
• Redness and swelling of the gumline
• Bleeding during brushing
• Persistent halitosis (bad breath)
• Loosening of the teeth from the gums or retraction of the gum line
• Pus in the gum area
Before the procedure, your dentist will take measurements of the gum socket depth of your teeth with a special tool, a process called a periodontal charting. This may also include the use of X-ray imaging. If your roots are determined to be within the normal range of depth for treatment (between 10 and 3 millimeters), they will proceed with scaling—manually removing the tartar from the teeth. After that, they will polish the teeth with a high-powered brush and fine-grit toothpaste before thoroughly flossing between the teeth.
After your procedure, you should notice markedly less tartar on the visible areas of your teeth, and symptoms of disease and infection should start to recede over the following days and weeks. However, deep cleaning is considered restorative dentistry, and will not prevent the resurgence of gum disease without daily oral hygiene maintenance on your part.
What Type of Dental Cleaning Do You Need?
Your dentist is the only one who can tell you for sure whether or not you require deep teeth cleaning, but if you have trouble removing tartar on your own, have struggled with gum or periodontal disease in the past, or have gone more than 6 months without routine cleaning, you may be a candidate for the procedure.
Gum disease can have serious consequences on your overall oral hygiene, and putting off treatment can be risky. If you are showing symptoms of gum disease, haven’t had a routine cleaning in some time, or have any other questions about dental deep cleaning, Champagne Family Dentistry is here to help. With locations in both Sparks and South Meadows, Champagne Family Dentistry can remove plaque and tartar and keep your smile bright and healthy—no matter where you live in Northern Nevada! Call for an appointment today.
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How Marijuana Can Treat Alzheimer’s
1943
(WellnessPursuits.com) – It’s an ironic twist most of us never saw coming: THC, the psychoactive chemical in marijuana, which has a reputation for impairing the memory, might also ultimately save it. We’ve broken down the latest data to show you how the most unlikely of weeds could spare millions of people from the suffering of Alzheimer’s-related dementia.
What Causes Alzheimer’s Disease?
Alzheimer’s is a progressive disease of the brain that leads to memory loss, changes in mood and disordered thinking. As the disease worsens, it can cause disorientation, paranoid beliefs and bizarre behaviors. It can also affect sufferers on a physical level, impairing their ability to walk, communicate and even swallow food. Alzheimer’s is the most common form of dementia, causing between 60% and 80% of cases, and it’s the sixth leading cause of death in the United States.
Alzheimer’s occurs because of inflammation and abnormal amounts of two different proteins, beta-amyloid and tau, building up in the brain. Beta-amyloid creates plaques between the nerves, making it more difficult for the cells to communicate, while tau builds up and forms tangles inside the nerves themselves. Until now, there hasn’t been anything doctors could do to prevent or slow any of these factors.
Marijuana on the Brain
Most of us associate marijuana with its characteristic “high” and related effects, but its medical benefits could be just as noteworthy. In addition to its ability to reduce nausea, increase appetite and protect against glaucoma and epileptic seizures, marijuana has also long been regarded as a sedative and antidepressant.
Marijuana also contains antioxidants with neuroprotective properties, making it a possible treatment for all kinds of neurological and neurodegenerative diseases. Recent studies have shown low doses of THC can reduce brain inflammation associated with Alzheimer’s disease. In addition, it can eliminate the build-up of beta-amyloid between the nerve cells. That’s right, marijuana can cut two of the three causes of Alzheimer’s disease, which is more than any other medication has been able to do.
Real-Life Applications
No studies are currently available on marijuana’s ability to prevent Alzheimer’s, but some do exist on its use in managing the disease. For example, one study showed cannabis oil is safe and effective in reducing irritability, aggression, delusions and sleeplessness in established Alzheimer’s patients. Studies on mice have demonstrated THC’s ability to protect against Alzheimer’s-related neuron loss. As marijuana becomes increasingly accepted into mainstream medicine, preventative and long-term studies on humans are more likely to become available.
An article published this year in the Journal of the American Medical Directors Association examines the legal details of making marijuana an accepted medical tool in skilled nursing facilities. Its researchers believe policy changes to make marijuana an acceptable medication in such settings would vastly improve patients’ quality of life. Given the overlap in conditions marijuana is believed to treat, its use could reduce the burden of prescription medication use while increasing patients’ long-term mental stability.
Only in recent years have we realized just how beneficial one little weed might be. Once demonized as capable of stripping good people of all reasoning and sanity, marijuana could now be the best hope for millions of people struggling to keep their minds intact. Who’d’ve thought it?
~Here’s to Your Healthy Pursuits!
Copyright 2019, WellnessPursuits.com
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Pain-free due to Focus Diagnostics
Common causes of foci in the teeth and jaw area are a dead tooth or a filled root canal, shifted third molars (wisdom teeth), residual infections after tooth extractions, inflammations of a tooth nerve or a cyst. This is a continuous strain on the entire organism which can lead to disorders in other areas of the body. However the repercussions do not show in every patient in the same manner. They can show different symptoms, depending on the constitution and the case history of the patient e.g. illness, intake of medication or hereditary reasons. Especially patients who are suffering from recurrent chronic troubles should consult a holistic dentist to find out if a focal infection of the teeth or jaws could possibly be the culprit for certain symptoms. If so the dentist will apply the adequate therapy before dealing with the patients teeth. It has been known for years in holistic medicine and dentistry that an ill tooth can be the cause of all kinds of disorders of the the body which are not necessarily limited to the oral cavity. This is called focal development because it has remote effects.
The insidious side effect is that the patient does not feel direct pains. Therefore it can possibly remain undiscovered for a long time.
Possible effects
A focus should be taken into consideration whenever an illness is chronic and does not respond to treatment or when the patient becomes ill again after a successful therapy. Therapeutic methods usually get rid of the symptoms but not of the causes of the troubles.
The following symptoms should be tested in reference to a focus:
• rheumatic illnesses in their early stage (prior to the deformation of the joints)
• functional complaints of joints and muscles.
• neuralgia
• migraines and headaches
• eczema and skin eruptions
• allergies
• recurrent infections of individual organs (e.g. bladder or gall bladder infections)
• poor concentration and chronic fatigue
Jaws and organism – a network
The regulatory system of the organism is extremely complex and modern focal theory cannot be explained with the simple thinking of cause and effect. In order to detect a focus the knowledge of the so-called energetic interaction is necessary. This can be envisaged as wiring diagrams between the cross-linking of the jaw and the organism. The energetic links connecting different parts of the body form an interactive system with the teeth. This means that every tooth has its energetic link - called the meridian - to a certain organ. E.g. a recurrent bladder infection can be caused by a dead incisor.
Diagnostics: health means reacting to impulses in an adequate way.
This includes a.o. Applied Kinesiology and Physioenergetics when the body is brought together with the most different test materials (e.g. homeopathic medicines or dental substances). The organism reacts to the vibrations of these substances, enabling the therapist to test the entire body for focal disturbances through muscle reflexes. The most important bio-functional disturbances of the patient are transmitted through a filter system. These filters reveal dominant focal disturbances and strained meridians.
Therapy: relief and complete recovery
If a focal infection is detected in the dental area, an individual therapy has to be initiated. A shifted wisdom tooth has to be surgically removed and the surrounding bone has to be cleaned. A chronic jaw infection however does not necessarily require surgery. If autonomic response testing has proven that the organism is capable of recuperating, a jaw infection can often be cured with homeopathic treatment. However, especially patients with chronic illnesses or elderly persons are often detrimentally affected. That means their self-healing powers cannot be activated through this method because their immune system is not able to respond to such measures. The patient has to have surgery whereby the focus has to be removed and the surrounding bones have to be cleaned. This therapy has to be accompanied by herbal or homeopathic medicine. In extreme situations other remedies (s.a. phytotherapeutics) or procedures (s.a. lymphatic drainage) may have to be administered or applied respectively.
Through innovative procedures, however, it may be possible that a root canal treatment can be carried out without detrimental effects for the health of the patient. Under the condition that the root canal has been thoroughly cleaned and filled. This involves the removal of the diseased pulp tissue, infectuous bacteria, toxic substances and a meticulous clean-out of the canal from residue of a previous root canal with state-of-the-art instruments. Whether the removal of the dead tooth or the bacteria-proof filling of the root canal are the right alternative, has to be decided according to the individual situation. At all times should a focal therapy be accompanied by the administration of homeopathic and other natural remedies and the flushing-out of toxic substances to support the defensive functions of the organism. The goal is to stimulate and activate the self-healing powers of the organism to achieve complete recovery of the patient.
Written by www.gzm.org
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Can I take Adderall with Prozac?
Can I take Adderall with Prozac?
Unless closely monitored by a doctor, you shouldn’t take Adderall and Prozac together. When taken in combination, Prozac and Adderall could result in serotonin syndrome, a potentially serious condition.
What antidepressant is like Adderall?
Wellbutrin is an aminoketone antidepressant and Adderall is an amphetamine.
What is the new drug for ADHD?
TUESDAY, April 6, 2021 (HealthDay News) — The first new drug developed in over a decade for children with attention deficit hyperactivity disorder (ADHD) has been approved by the U.S. Food and Drug Administration. Qelbree, also known as viloxazine, comes in a capsule that is taken daily, and is not a stimulant.
Which is the best antidepressant to take with Adderall?
Wellbutrin (bupropion), a drug that is often prescribed to ADHD patients who do not respond well to stimulants like Adderall. Tricyclic antidepressants, which affect norepinephrine (adrenaline) and serotonin.
Is it safe to take Adderall with alcohol?
Combining antidepressants with alcohol can be dangerous, and the same is true with Adderall. Some antidepressants, like MAOIs, should be completely avoided when taking Adderall. Other antidepressants, however, may pose less of a threat. Another thing to consider is that there are antidepressants that also help with ADD and ADHD.
Can you take Prozac and Adderall at the same time?
It does seem that some folks report good success with either Prozac and Adderall as well as Wellbutrin and Adderall. Here is a long forum where the Wellbutrin and Adderall combination is discussed. Everyone will respond differently to medications so do discuss all this with your doctor.
Can you take Wellbutrin and Adderall at the same time?
But in researching your question I found a similar question posed on this site which you may wish to read for the answers given. It does seem that some folks report good success with either Prozac and Adderall as well as Wellbutrin and Adderall. Here is a long forum where the Wellbutrin and Adderall combination is discussed.
What is the best anti-depressant with the least side effects?
• Remeron. MayoClinic.com: Antidepressants: Which cause the fewest sexual side effects?
• is one of the most commonly prescribed antidepressants in the United States.
• Celexa.
• Effexor XR.
Can Adderall be used as an anti-depressant?
It’s important to note that many people find Adderall itself works as an antidepressant. It provides energy, motivation, concentration, and improves mood. In fact, it has been used off-label as an anti-depressant.
Is adderal and Prozac similar medications?
They are NOT the same drug . Prozac is FLUOXETINE and an SSRI (type of anti-depressant). Adderall is AMPHETAMINE SALTS and a stimulant (NOT an anti-depressant, but sometimes used off-label for treatment of depression). They are EXTREMELY different drugs and have extremely different effects on the brain and body.
Is Adderall and Adderall XR the same?
Both Adderall and Adderall XR come in affordable generic versions. The generic for Adderall is amphetamine salt combo, and the generic for Adderall XR is amphetamine salt combo XR. Both of these medications contain amphetamine and dextroamphetamine and are classified as schedule II controlled substances,…
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Dictionary > Kidney calices
Kidney calices
Definition
noun, singular: kidney calyx
Funnel-shaped structures that allow passage of the urine from the ducts of the renal pyramids to the renal pelvis
Supplement
The kidney calices are of two forms: major calices and minor calices. The minor calices are funnel-shaped structures, each surrounding renal papilla(e). Minor calices converge to form major calices that open to the renal pelvis. Thus, the urine drains from the papillary ducts (of renal papillae) to the minor calices, next to the major calices, and then to the renal pelvis.
Also called:
• renal calyses
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Table of contents
Sleeplay helps you achieve the best and deepest sleep during the night. If you suffer from snoring or sleep apnea, CPAP machines are the solution. Find here the top brands in the market like ResMed and Philips Respironics.
How to Stop Snoring? What Do Doctors Say
May 16, 2023
· 8 mins read
Excessive snoring means your airway is partially blocked due to a number of possible reasons, and you are not able to breathe properly. This issue can also impede your sleep quality, leading to fatigue, irritability, and an increased risk of health problems. Snoring can also significantly impact the quality of your sleep, leading to feelings of fatigue and irritability during the day.
Additionally, chronic snoring can increase your risk of developing several health problems, such as high blood pressure, heart disease, stroke, and diabetes. Therefore, it is crucial to identify the underlying cause of your snoring and seek appropriate treatment to avoid further complications and improve your quality of life.
Let’s dive in to discuss what causes this issue, and how you can manage it to have a better night’s sleep.
What Is Snoring?
Snoring is one of the most common sleep problems. It occurs when the air you breathe cannot pass freely through your nose and throat during sleep. This causes nasal tissues to vibrate, which produces the snoring sound.
Some people tend to have loose tissue in their nose and throat, which makes them prone to snoring. These “floppy” tissues can partially restrict airflow. Also, the position of your tongue can obstruct the airway while sleeping, and this can also produce the snoring sound.
Colds and allergies can cause nasal congestion and throat swelling, which can lead to snoring too. To alleviate snoring caused by colds and allergies, over-the-counter medications and good sleep hygiene practices such as sleeping on your side or elevating your head can be helpful. However, it is important to seek medical advice if snoring persists or worsens, as it may indicate an underlying medical condition.
snoring
Snoring not only affects your sleep, but can also disrupt your relationship with your sleeping partner. The sound of snoring can be loud and irritating, making it difficult for your partner to fall asleep or stay asleep. Over time, this can lead to feelings of frustration, irritability, and even resentment towards the snoring partner.
It’s important to identify the underlying cause and manage it so you can reduce the snoring and improve your (and your partner's) sleep quality. Let’s take a look at the different causes of snoring
Which Are the Causes of Snoring?
Snoring is a common problem that can have a significant impact on sleep quality and overall health. In this article, we'll explore some of the most common causes of snoring to help you identify and address the issue.
Age
With advancing age, the muscles in our throat become weaker, and the airway passage in the throat becomes narrower—thus increasing the likelihood of snoring. Older individuals are also more prone to health conditions like obesity, diabetes, and high blood pressure. Therefore, they can have a higher chance of becoming snorers.
Additionally, age-related hormonal changes can contribute to snoring. For example, post-menopausal women have a higher risk of weight gain, changes in sleep patterns, and a decrease in muscle tone, all of which can increase the risk of snoring.
Being Overweight
Accumulation of excess body fat in the neck area can restrict the airway, causing the tissues in the throat to vibrate. Thus, overweight people are more prone to snoring.
Obesity can also lead to obstructive sleep apnea syndrome. It is a condition characterized by loud snoring, gasping, or choking during sleep. It ruins the quality of your sleep and often leads to excessive daytime sleepiness and a depressed mood during the day.
Biological Differences Between Men and Women
If we look at the general population, men tend to have a larger neck circumference and a narrower airway than women, which can contribute to snoring. Also, men with low testosterone levels may develop this problem due to decreased muscle tone in the throat.
Women, on the other hand, are more likely to experience snoring during pregnancy or menopause, due to hormonal or serotonin imbalances and their effect on the airway.
Nasal and Sinus Problems
Nasal and sinus problems can also cause blockages and obstruction in the airways that lead to snoring. When the nasal passages are blocked due to allergies, congestion, or sinusitis, the air has to find a way through a smaller opening, which can cause a vibration of the soft tissues in the throat, causing you to snore.
The nasal passage can also get narrowed due to nasal polyps, and a deviated septum can increase the likelihood of snoring,
Alcohol, Smoking, and Medications
Alcohol causes the muscles in the throat to relax and become loose. These muscles vibrate when air passes through your throat while sleeping, creating a snoring sound. Additionally, alcohol can lead to dehydration, which can also contribute to this issue.
As for smoking, the chemicals in cigarettes irritate the throat lining and cause inflammation, leading to swelling and narrowing of the airway. This obstruction in the airway can contribute to snoring, as well as increase the risk of developing sleep apnea, a potentially serious sleep disorder that causes breathing interruptions during sleep.
In addition, certain medications, such as sedatives, sleep medicine, antidepressants, muscle relaxants, medicine for a psychiatry-related condition, and antihistamines, often relax the throat muscles and can cause you to snore.
Sleep Posture
Your sleep position can have a significant impact on your snoring. Sleeping on your back (supine position) causes the soft tissues in your throat to relax and partially obstruct your airway.
Obstructive Sleep Apnea (OSA)
Obstructive sleep apnea (OSA) is a condition that occurs when the muscles that support the soft tissues in your throat relax temporarily, causing the airway to be narrowed or get partially or completely blocked. This disrupts breathing and can lead to snoring due to the vibration of the soft tissues in the throat.
snoring
As OSA blocks the airway and disrupts breathing, it decreases the amount of oxygen reaching the lungs, which signals the brain to wake up briefly to resume breathing. This can interrupt the natural sleep cycle. In severe cases, one may stop breathing altogether, causing a drop in blood oxygen levels and potentially serious health consequences.
Home Remedies and Lifestyle Changes for Snoring
Change Your Sleeping Position
If you have been sleeping on your back and experiencing snoring, you can try changing your sleeping position. Sleeping on your side instead of your back can reduce snoring.
Sleeping on your side, or with your head raised at least four inches, can make breathing easier and decrease snoring. You can use a body pillow or wedge pillow to support yourself in your new position.
Get Enough Sleep
Not getting enough sleep can lead to fatigue, which lessens the tonicity of the throat muscles, and this in turn contributes to snoring. It can even increase the risk of depression, major depressive disorder (MDD), or other neurology-related conditions. Further, sleep deprivation can lead to increased inflammation in the body, including in the nasal passages and throat, which can also cause you to snore at night.
Getting at least 7-9 hours of sleep can reduce fatigue and lessen snoring. Better sleep can also improve breathing by reducing the relaxation of the throat muscles and decreasing the likelihood of airway blockage.
Try a Nasal Dilator or Mouthpiece
Nasal strips can help open up the nasal passages, making it easier to breathe through the nose and reducing snoring. There are multiple anti-snoring mouthpieces like mandibular advancement devices (MAD), tongue stabilizing devices (TSD), and palatal lifting devices that can help reduce snoring.
Clear Nasal Passages
Regularly clearing the nasal passage can also help reduce snoring caused by nasal congestion. Nasal irrigation, for example, involves flushing out the nasal cavity with a saline solution, which helps to thin mucus and reduce inflammation.
Allergy medications such as antihistamines or corticosteroids can help relieve allergy symptoms and reduce inflammation in the nasal passages, thus reducing snoring.
Limit or Avoid Alcohol before Bed
Alcohol acts as a muscle relaxant that loosens your throat muscles, which makes the throat tissues more prone to vibrate when breathing. It also leads to sleep disturbances. Thus, avoiding alcoholic drinks before bedtime can reduce snoring and help you have a better and more fulfilling sleep.
Try to Stop Smoking
Smoking can irritate the airways and cause inflammation, which results in swelling of the throat and leads to snoring. Quitting smoking not only helps you snore less, but it will also improve your overall health.
Maintain a Moderate Weight
Excess weight puts pressure on the throat, narrowing the airway and leading to snoring. Weight loss and maintaining a healthy weight through diet and exercise can help reduce snoring.
Medical Treatments for Snoring
Continuous Positive Airway Pressure (CPAP)
Continuous positive airway pressure (CPAP) is a form of non-invasive positive pressure ventilation used to treat breathing difficulties, particularly sleep apnea. CPAP machines deliver a constant stream of air pressure through a mask, which helps to keep the airway open during sleep.
cpap mask
It is prescribed to people with obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and obesity hypoventilation syndrome (OHS).
If you are diagnosed with sleep apnea, Sleeplay’s CPAP masks can help you manage your snoring. Sleeplay also offers sleep tests to help you understand if you have sleep apnea or any other sleep issues.
Radiofrequency Ablation (RFA)
Radiofrequency ablation (RFA) is a medical procedure that uses high-frequency electrical currents to create heat and destroy tissue. A minimally invasive procedure, RFA uses radio waves to shrink the tissues in the throat that have been contributing to the snoring, which helps improve your breathing during sleep.
Custom-fitted Dental Devices and Lower Jaw Positioners
These are oral appliances that can help keep the airway open while sleeping by repositioning the lower jaw or tongue.
Surgical Procedures:
Uvulopalatopharyngoplasty (UPPP) and Tonsillectomy
Uvulopalatopharyngoplasty (UPPP) and tonsillectomy are surgical procedures that treat the underlying causes of snoring. UPPP involves removing excess tissue from the throat, such as the uvula and parts of the soft palate and pharynx, while tonsillectomy removes enlarged tonsils from the back of the throat. Both these surgical procedures involve removing the excess tissue in the throat that can contribute to snoring.
Laser-assisted Uvulopalatoplasty (LAUP)
A laser-assisted uvulopalatoplasty (LAUP) is a surgical procedure used to treat snoring and sleep apnea. During the procedure, a laser is used to remove or reshape the tissue in the throat to enlarge the size of the airway.
Somnoplasty
Somnoplasty is a surgical method that uses radiofrequency energy to shrink the tissues in the throat, thereby reducing snoring. It is also used to treat mild to moderate obstructive sleep apnea (OSA).
Treat Chronic Allergies
Treating underlying allergies with medication or allergy shots can help reduce snoring caused by nasal congestion. Talking to your doctor can help you understand how to manage your allergy symptoms. Various over-the-counter (OTC) and prescription medications are available in the form of nasal sprays, liquids, and lozenges that can help improve the conditions.
When to Talk to Your Doctor
If you see no improvement after taking self-care measures, you should consult your clinician. They’ll help you analyze the underlying condition, suggest medications, and advise you on a suitable resolution. Make sure to follow up with your doctor after a few weeks to see if the treatment is working or not.
Further, if you find yourself waking up in the middle of your sleep with a gasp or experiencing choking in your sleep, daytime fatigue, morning headaches, restlessness, or drowsiness, you might be suffering from sleep apnea or other sleep disorders. Be sure to consult a doctor who specializes in otolaryngology.
Learn much more on our blog! And in case you are diagnosed with sleep apnea, remember that Sleeplay can help you manage your snoring with a wide range of CPAP machines.
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5eff3d1f6f98e57329caed0ceb9053d3
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2,033,577,119,943,744,500
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top of page
Search
Y- Strap FAQs
Updated: Apr 25, 2022
The Y Strap Adjustment has recently become popularized by a surge of Chiropractors filming and posting their treatment videos on YouTube. Due to the high volume of questions regarding this treatment, I will attempt to answer the most common questions I am asked in a Q&A format based on my personal experience.
Why do I use the Y Strap?
I have personally found the Y Strap to be the most relieving adjustment out of all adjustments for my patients and also, to have done on myself. With that being said, it is not for everyone. However, I would estimate that for 80% of my patients it is their absolute favorite adjustment they have ever had.
Is the Y Strap Adjustment Safe?
Do I need the Y Strap?
Does the Y Strap hurt?
How does the Y Strap work?
Can the Y Strap make you taller?
How often can the Y Strap be done?
Can I workout after the Y Strap adjustment?
What conditions does the Y Strap work best for?
What can I expect to feel with the Y Strap adjustment?
How is the Y Strap different from traditional spinal decompression?
80 views0 comments
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5eff3d1f6f98e57329caed0ceb9053d3
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Article
A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic
1
Department of Preventive Medicine and Public Health, Virgen de las Nieves University Hospital & ibs, Granada-Instituto de Investigación Biosanitaria de Granada, Avda. de las Fuerzas Armadas, 2, 18014 Granada, Spain
2
Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología Clínica, Hospital Universitario Virgen Macarena & Instituto de Biomedicina de Sevilla (IBIs), Hospital Universitario Virgen Macarena/CSIC/Universidad de Sevilla, 41020 Sevilla, Spain
3
Laboratory of Microbiology, Virgen de las Nieves University Hospital. & ibs, Granada-Instituto de Investigación Biosanitaria de Granada, Avda. de las Fuerzas Armadas, 2, 18014 Granada, Spain
4
Department of Microbiology, School of Medicine, University of Granada & ibs, Granada-Instituto de Investigación Biosanitaria de Granada, Avda. de la Investigación, 11, 18016 Granada, Spain
*
Author to whom correspondence should be addressed.
Antibiotics 2021, 10(9), 1127; https://doi.org/10.3390/antibiotics10091127
Received: 20 July 2021 / Revised: 10 September 2021 / Accepted: 14 September 2021 / Published: 18 September 2021
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
Abstract
:
Bacterial resistance to antibiotics has proven difficult to control over the past few decades. The large group of multidrug-resistant bacteria includes carbapenemase-producing bacteria (CPB), for which limited therapeutic options and infection control measures are available. Furthermore, carbapenemases associate with high-risk clones that are defined by the sequence type (ST) to which each bacterium belongs. The objectives of this cross-sectional and retrospective study were to describe the CPB population isolated in a third-level hospital in Southern Spain between 2015 and 2020 and to establish the relationship between the ST and the epidemiological situation defined by the hospital. CPB were microbiologically studied in all rectal and pharyngeal swabs and clinical samples received between January 2015 and December 2020, characterizing isolates using MicroScan and mass spectrometry. Carbapenemases were detected by PCR and Sanger sequencing, and STs were assigned by multilocus sequence typing (MLST). Isolates were genetically related by pulsed-field gel electrophoresis using Xbal, Spel, or Apal enzymes. The episodes in which each CPB was isolated were recorded and classified as involved or non-involved in an outbreak. There were 320 episodes with CPB during the study period: 18 with K. pneumoniae, 14 with Klebisella oxytoca, 9 with Citrobacter freundii, 11 with Escherichia coli, 46 with Enterobacter cloacae, 70 with Acinetobacter baumannii, and 52 with Pseudomonas aeruginosa. The carbapenemase groups detected were OXA, VIM, KPC, and NDM with various subgroups. Synchronous relationships were notified between episodes of K. pneumoniae and outbreaks for ST15, ST258, ST307, and ST45, but not for the other CPB. There was a major increase in infections with CPB over the years, most notably during 2020, coinciding with the COVID-19 pandemic. This study highlights the usefulness of gene sequencing techniques to control the spread of these microorganisms, especially in healthcare centers. These techniques offer faster results, and a reduction in their cost may make their real-time application more feasible. The combination of epidemiological data with real-time molecular sequencing techniques can provide a major advance in the transmission control of these CPB and in the management of infected patients. Real-time sequencing is essential to increase precision and thereby control outbreaks and target infection prevention measures in a more effective manner.
1. Introduction
There has been an alarming rise in bacterial resistance to antibiotics over the past two decades, representing a “silent pandemic” that appears unstoppable. This resistance has become especially frequent in healthcare-related infections (HCRIs) worldwide [1,2,3]. However, there has also been an increase in the emergence and transmission of multidrug-resistant bacteria in the community setting over the past few years, including residential facilities and care homes. The more frequent hospitalization of these residents has favored exchanges between hospital and community, increasing the capacity to spread resistant bacteria in each setting [3]. The World Health Organization (WHO) has declared infection by these microorganisms as an emerging disease that poses a major public health threat worldwide [1,2,3].
The large group of carbapenem-resistant bacteria includes carbapenemase-producing bacteria (CPB), for which there are limited therapeutic options, and infection control measures have proven ineffective to prevent the dissemination of these bacteria to date [4]. The WHO list of global priority pathogens includes carbapenem-resistant Acinetobacter baumannii (CRAb) and Pseudomonas aeruginosa (CRPa) and carbapenem-producing Enterobacteriaceae (CPE) [2]. The most frequently observed carbapenem-resistance mechanism is the production of carbapenemases [5]. Control of these infections is further hampered by the horizontal transmission of these enzymes via plasmids among different Enterobacteriaceae [4].
In 2018, one-third of Acinetobacter spp. isolates obtained in the European Union (EU) were resistant [6], and numerous outbreaks increased morbidity and mortality rates, mainly in intensive care units (ICUs). A worldwide increase was observed in the frequency of patients colonized or infected by CPE, which was above the EU mean in Spain [5]. The European Center for Disease Control (ECDC) reported an increase in combined resistances in Escherichia coli and Klebsiella pneumoniae over the past few years [3]. K. pneumoniae is the most prevalent CPE [2] and responsible for the majority of outbreaks in healthcare centers [7]. CPE infections were first detected in Spain in 2005, and their number had multiplied 16-fold by 2019 [8].
In addition, carbapenemases are enzymes that associate with certain high-risk clones [8] that are defined by the sequence type (ST) to which each bacterium belongs. The STs most frequently associated with carbapenemases in K. pneumoniae are ST258, which is predominant worldwide [8], and ST307, which is also associated with a higher mortality [9]. In Germany, it was reported that E. coli ST131 is a high-risk clone that should be monitored very closely [10], alongside ST38, located in various European countries [10]. In Spain, the STs most frequently associated with carbapenemases are ST11, 13, 15, 16, 101, 147, 340, 384, 388, 405, 437, 464, 512, 846 and 1235 [8].
Carbapenemases can be divided into metallocarbapenemases (zinc-dependent class B) and non-metallocarbapenemases (zinc-independent classes A, C, and D) [11]. The first carbapenemase detected was in class A K. pneumoniae [11], and some carbapenemases appear more frequently than others. The first carbapenemase-producing isolates detected in Spain belonged to the KPC group [8]. OXA-48 group carbapenemases are currently the most abundant, mainly among Klebsiella spp. and Enterobacter spp. [5], and are the most common resistance mechanism among CPEs in Spain [5]. Other carbapenemases frequently reported in Spain are VIM-1, KPC-2, IMP, and NDM-1 [8].
Since 2020, a rise in CPB resistance in our setting coincided with the COVID-19 pandemic, which has been accompanied by populations at risk of severe complications and long-term sequelae and by longer hospital stays and the prescription of an elevated amount of antibiotics. These factors have led to an elevated risk of nosocomial CBP infections, as recently reported [12,13,14]. In addition, COVID-19 was especially prevalent in our hospital catchment area from 2020, and the patients frequently required hospitalization, as recorded by the Andalusian Health Service (https://www.juntadeandalucia.es/institutodeestadisticaycartografia/salud/datosSanitarios.html (accessed on 1 July 2021); and https://www.sspa.juntadeandalucia.es/servicioandaluzdesalud/todas-noticia/informacion-sobre-el-numero-de-casos-de-coronavirus-511?utm_source=servicioandaluzdesalud&utm_campaign=Boletin%20Novedades&utm_medium=mail&utm_content=20210901&utm_term=Informacion%20sobre%20el%20numero%20de%20casos%20de%20coronavirus (accessed on 1 July 2021).
The objectives of this study were to describe the CPB population isolated in a third-level hospital between 2015 and 2020 and to establish the relationship between STs and the epidemiological situation as defined by the hospital.
2. Material and Methods
This retrospective cross-sectional study included adult patients admitted to the Departments of Internal Medicine and its Specialties, ICUs (general and cardiac), and the Department of General Surgery and its Specialties of the Virgen de las Nieves University Hospital in Granada (Spain). This hospital provides specialized care to a population of around 331,220 inhabitants. No exclusion criteria were applied, except for repeat microbiological studies of the same episode. For the colonization study, the presence of CPB was studied in rectal (RS) and pharyngeal (PS) swabs received by the Clinical Microbiology Laboratory between 1 January 2015 and 31 December 2020 (5415 RS and 1034 PS for 3107 episodes studied before 2020 and 2308 during 2020). For the study of “possible infection episodes”, clinical samples from different localizations were studied by applying standard clinical microbiology procedures, detecting CPB as previously described [15]. In brief, samples were seeded on selective culture medium CHROMID® ESBL (BioMérieux, Marcy-l’Étoile, France) and incubated at 37 °C in aerobiosis for 48 h. Isolates were identified by using the MicroScan system (Beckman Coulter, Brea, CA, USA) and mass spectrometry (Maldi-Tof ®, Brucker Daltonik GmbH, Bremen, Germany). Resistance was characterized with the MicroScan system, using currently available Neg Combo panels, and interpreted according to the clinical cutoff points defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [16]. Carbapenemase was detected using the colorimetric Neo-Rapid CARB Kit ® (Rosco Diagnostica A/S, Taastrup, Denmark) and immunochromatography (NG5-Test Carba, NG Biotech, Guipry-France to detect KPC, NDM, VIM, IMP, and OXA-48-like enzymes, and K-Set, Coris BioConcept, Gembloux, Belgium to detect OXA-23) in isolates meeting EUCAST cutoff point criteria for CPB screening. In parallel, isolates identified in swab and clinical samples were sent to the reference laboratory for molecular typing of nosocomial pathogens and genotypic detection of antimicrobial resistance mechanisms of interest under the regional Integrated Program for the Prevention and Control of Healthcare-related Infections and Appropriate Utilization of Antibiotics (acronym in Spanish, PIRASOA) led by the Microbiology Department of Virgen Macarena Hospital in Seville.
2.1. Microbiological Study of Carbapenemase-Producing Bacteria (CPB) under the PIRASOA Program
The susceptibility to ertapenem, imipenem, and meropenem was investigated by disk diffusion in Mueller Hinton agar, using EUCAST clinical cutoff points to interpret the results [16]. Carbapenemase activity inhibition [17] was studied by disk diffusion using meropenem, meropenem/boronic acid, meropenem/dipicolinic acid, and meropenem/cloxacillin disks as well as a temocillin disk (Rosco Diagnostica, Taastrup, Denmark). Carbapenemase and MLST genes were studied by PCR using specific primers and Sanger sequencing until 2018 and subsequently massive sequencing (Illumina Inc., San Diego, CA, USA). Sequences were analyzed with CLC Genomics Workbench, v10 software (Qiagen Iberia, Las Rozas de Madrid, Madrid, Spain). Determinants of resistance were detected using ResFinder (https://cge.cbs.dtu.dk/services/ResFinder) (accessed on 1 July 2021). and CARD (https://card.mcmaster.ca/) (accessed on 1 July 2021). databases, and MLST was identified using the MLST finder 2.0 database (https://cge.cbs.dtu.dk/services/MLST) (accessed on 1 July 2021). Clonal relationships among isolates were evaluated by pulsed-field gel electrophoresis (PFGE). Complete chromosomal DNA digestion in agarose gel was performed with XbaI (Enterobacterales), SpeI (Pseudomonas spp. and Stenotrophomonas), and ApaI (Acinetobacter spp.) according to the species. The resulting restriction fragments were separated in the CHIEF DR-II system (Bio-Rad Laboratories, Alcobendas, Madrid, Spain) with 1% agarose gel. The gels were subsequently stained with ethidium bromide, illuminated with ultraviolet light, and photographed in an automatic Gel Logic 200 Imaging System (Kodak, Rochester, NY, USA).
The conversion, normalization, and analysis of band patterns were performed using Bionumerics 7.6 software (AppliedMaths, Jollyville Rd., Austin, TX, USA), analyzing the patterns as previously described. Band position tolerance and optimization were set at 1%. An unweighted pair group method with arithmetic mean (UPGMA) was employed to generate a dendrogram and the Dice coefficient was used to measure genetic similarity among isolates. PFGE patterns with ≥90.0% similarity were considered in the same group as closely related isolates.
2.2. Epidemiological Study
Episodes in which each carbapenemase-producing microorganism was isolated were recoded to avoid repetition with the same patient. An episode was defined as each hospital stay in which one or several different carbapenemase-producing microorganisms were isolated, only considering the first isolate of each microorganism during the hospital stay for infection or colonization study. When there were multiple isolated of the same microorganism during the same episode, one was selected according to the following criteria and order:
• Isolate described in a PIRASOA report;
• Isolate corresponding to infection study;
• Isolate not reported in infection study, corresponding to colonization study.
The PIRASOA program describes the ST of the microorganism and its genetic similarity to other microorganisms of the same species from any hospital in Andalusia. It also reports whether the relationship with other microorganisms was recent or derived from a common transmission focus. It was determined whether a CPB had a synchronous (SR) or asynchronous relationship (AR) with others of the same species when the following criteria were met: (1) they belong to the same clone of an ST, (2) patients coincided in their hospital stay, and/or (3) the genetic study indicates direct transmission among patients and/or very recent exposure to a common reservoir. An SR was considered when the first criterion and one other criterion were met and an AR when only one criterion was met.
It was also recorded whether the CPB was involved or not in an outbreak of HCRI, defined by two or more cases of HCRI due to the same microorganism and associated in space and time with suspicion of an epidemiological link. The emergence of a single case of HCRI by a new, or unknown, or re-emergent infectious agent of mandatory declaration was considered an outbreak of nosocomial infection, henceforth “nosocomial outbreak” [18].
2.3. Influence of COVID-19 Infection during 2020
Data were compared between 2019 and 2020 on tested patients with a positive result for COVID-19 (n = 178 episodes), including their age, sex, length of hospital stay, and in-hospital consumption of imipenem (IP), meropenem (MP), and/or piperacillin–tazobactam (PTZ) as daily dose per 1000 stays (DDD/1000 stays).
2.4. Statistical Study
The involvement of episodes in which an SR was reported in a declared nosocomial outbreak was examined by constructing contingency tables and applying Fisher’s exact test. The comparison between sexes was analyzed in the same way. The comparison by age was studied with the Student’s t-test after establishing the normality of data distribution with the Kolmogorov–Smirnov test. IBM SPSS Statistics v. 19 was used for data analyses. p < 0.05 was considered significant.
3. Results
Between 1 January 2015 and 31 December 2020, 320 episodes of CPB were identified: 118 episodes of K. pneumoniae, 14 of Klebisella oxytoca, 9 of Citrobacter freundii, 11 of E. coli, 46 of Enterobacter cloacae, 70 of A. baumannii, and 52 of P. aeruginosa. Among these, 39 episodes were excluded because there was no definitive PIRASOA report and four because the clinical history of the patient was missing from the Andalusian Health Service database. Among the 43 episodes (13.4%) lost to the study, 34.9% involved K. pneumoniae, 6.9% K. oxytoca, 4.6% C. freundii, 6.9% E. coli, 2.3% E. cloacae, 13.9% A. baumannii, and 30.2% P. aeruginosa. Out of the final sample of 277 episodes, 103 involved K. pneumoniae, 11 K. oxytoca, 7 C. freundii, 8 E. coli, 45 E. cloacae, 64 A. baumannii, and 39 P. aeruginosa.
3.1. Description of Episodes
The most frequently isolated CPB in the studied episodes was K. pneumoniae (37.19% of total episodes), followed by A. baumannii (23.10%) and E. cloacae (16.25%) (Table 1). K. pneumoniae was detected in more numerous episodes every year except for 2018, when more episodes with P. aeruginosa were detected, and 2019, when there were more episodes with A. baumannii. Over the six-year study period, episodes with CPB were most frequent in 2020 (37.54%). There has been an increase in A. baumannii in episodes over the past two years and an increase in E. cloacae over the past year. The number of episodes each year rose from 6 in 2015 (2.17% of total episodes) to 123 in 2020 (37.54%). Globally, there were 156 episodes of infection and 121 of colonization. However, as depicted in Table 1, infection episodes were much more frequent than colonization episodes in 2016 and 2017, there was a similar frequency of infection and colonization episodes in 2018 and 2019, and colonization episodes (57) were much more frequent in 2020 (47).
The carbapenemase groups detected in this study were OXA, VIM, KPC, and NDM with their subgroups (Table 2). Table 3 exhibits the relationships between ST and carbapenemase for each species. There were four peak episodes with K. pneumoniae of ST258, ST307, ST15, and ST45, mainly associated with KPC-3, OXA-48, NDM-5, and OXA-48, respectively. There were fewer episodes with K. oxytoca and C. freundii, and only four STs were found in K. oxytoca, highlighting the association of ST36 with VIM-1, and six STs in C. freundii, highlighting the production of OXA-48 in three of the STs. Table 3 highlights the production of OXA-48 in E. coli with ST58, ST69, ST405, and ST648. However, the most frequent carbapenemase in E. cloacae was VIM-1, closely related to ST78, with OXA-48 being the second most frequent. Notably, the production of OXA-23 was associated with ST2 in A. baumannii. A wide variety of carbapenemases was detected in P. aeruginosa, highlighting the relationship of IMP-8 with ST348, the most frequent ST. ST175 and ST253 were less frequently detected, mainly associated with OXA-50 and IMP-16, respectively.
3.2. Description of the Association among ST, Type of Relationship, and Involvement in a Nosocomial Outbreak of Infection with CPB
This association was more frequent in K. pneumoniae, E. cloacae, A. baumannii, and P. aeruginosa (Table 4). In K. pneumoniae, SRs were only reported for ST15, ST258, ST307, and ST45, the STs with episodes included in outbreaks. ARs alone were reported for the other STs detected, none of which had more than three episodes. An association was found between the presence of an SR in episodes and involvement in an outbreak (p = 0.000007299). In E. cloacae, PIRASOA reported an SR in only two of the eight STs detected (ST114 and ST78), but only ST114 was involved in an outbreak, and the association between the presence of an SR and involvement in an outbreak was just short of statistical significance (p = 0.06829). In A. baumannii, only two STs (ST1 and ST2) were found, being ST1 in all episodes except for one; A. baumannii had an SR with others in half of the episodes and an AR in the remaining half. No significant association was found (p = 1) between the presence of an SR and involvement in an outbreak. Finally, in P. aeruginosa, six STS were detected and four of these were SRs: ST175, ST253, ST348, and ST845, but only ST253 was involved in an outbreak. No significant association was found (p = 1) between the presence of an SR and involvement in an outbreak.
As shown in Table 5, episodes with SR did not correspond to episodes involved in an outbreak, and episodes with AR were even involved in outbreaks in some cases.
3.3. Influence of Infection with COVID-19 during 2020
The absolute number of CPB infections was higher during 2020 than during 2019, attributable to a marked rise in the number of samples studied rather than a higher percentage of positive results (4.5% in 2020 vs. 5.6% in 2019). Table 6 compares clinical data of patients testing during 2019 (74) and 2020 (104), positive for COVID-19 infection, including age (p = 0.014), sex (not significant), hospital stay, hospital occupation, and prescriptions of PTZ, IMP, and PTZ (daily dose per 1000 stays).
4. Discussion
This study describes carbapenemase-producing microorganisms isolated over the past six years in the microbiological laboratory of a tertiary hospital in Southern Spain. The main findings were an increasingly elevated transmission of these bacteria in both hospital and community settings and a major rise in the detection of CPB.
The capacity to detect CPB and their resistances has significantly improved through technological advances and the rigorous implementation of screening and control protocols. However, the upsurge of CPB cases in 2020 can be attributed at least in part to the COVID-19 pandemic, which led to a major rise in the number of studied episodes due to an increase in hospital stays, among other reasons. The resulting overload of hospital departments hampered the application of infection prevention measures, and there was an increased administration of antibiotics (often inappropriate) to prevent and treat bacterial over-infection in patients with pneumonia [19]. The inappropriate use of antibiotics is one cause of the increasingly frequent emergence of resistance to carbapenem, among other antibiotics. However, improvements in the diagnostic capabilities of microbiology laboratories over time should also be taken into account, which would also influence an increase in the detection of infectious episodes.
Four groups of carbapenemases (OXA, VIM, KPC, and NDM) and corresponding subgroups were detected, all previously reported in Spain. Some were found in more than one microorganism species (OXA-48, IMP-8, VIM-1, VIM-63, and KPC-3) and the others were detected in a single species. The most abundant subgroup was OXA-48 (in 29.79% of episodes), which is also the most prevalent subgroup worldwide [5], followed by VIM-1 (17.12%), OXA-23 (16.44%), and KPC-3 (12.33%). The most frequently isolated bacteria in these episodes was K. pneumoniae, one of the most widely disseminated CPB worldwide and largely responsible for the alarm caused by CPB, given the limited therapeutic options and high mortality rates [7].
The relationships between STs and carbapenemases were explored in the detected CPB, followed by a search for ST–carbapenemase combinations that have been reported in Spain for each CPB, highlighting isolates of: K. pneumoniae ST15-OXA-48 [20,21], ST258-KPC-3 [8,22], ST307-OXA-48 [23,24], and ST512-KPC-3 [23,25,26,27]; K. oxytoca ST36-VIM 1 [28]; E. coli ST58-OXA-48 [29]; E. cloacae ST114-OXA-48 [30]; A. baumannii ST1-OXA-23 [31]; and P. aeruginosa ST175-VIM-2 [32,33].
No other combinations were found, either because they were not previously detected in a Spanish hospital or were detected but not published. CPB associated with STs or carbapenemases were found, but no relationship was observed between STs and carbapenemase.
Although not as notorious as K. pneumoniae, the other CPB described in this study form part of a group of multidrug-resistant microorganisms that pose a major public health threat [34] and show increased diversity over time, as reported in a Portuguese study [4]. The frequency of their detection is rising among colonized and infected hospital patients, despite the implementation of infection prevention and control measures and routine colonization screenings [4]. There is also a trend towards more frequent nosocomial outbreaks, especially of K. pneumoniae [7], and towards their longer persistence as colonizers of hospitalized patients and in the hospital setting. This creates “silent” reservoirs and carriers of CPB over prolonged time periods, hampering control of their dissemination [7,11]. The comprehensive and exhaustive implementation of available control measures is essential. In our setting, these include the surveillance and follow-up of HCRIs and nosocomial outbreaks and active communication from the microbiology departments on microorganisms of concern.
We highlight the importance of genetic sequencing techniques for controlling the spread of these microorganisms, given the speed with which results are obtained. A reduction in their cost may allow their real-time performance to be more widely available at health centers. Data obtained on the STs and carbapenemase subgroup of a CPB indicate its pathogenicity, dissemination capacity, local prevalence, therapeutic options, and responses to treatment and can also yield information on changes in the resistances of these bacteria [4,7]. These techniques can be highly effective for the detection and control of nosocomial outbreaks. When only the species and antibiogram of microorganisms are identified but not their ST, it is not known whether multiple unrelated STs might be involved, and this question would be resolved by real-time molecular analysis. Without this information, an outbreak is declared when there appear to be two or more cases of hospital-acquired infection. Accordingly, an outbreak is declared in the hospital when there are two or more patients with the infection who shared hospital space and/or staff/equipment at some time since their admission (epidemiological link). If cases continue to emerge among patients successively admitted at different times to the same unit, the possibility of a common reservoir is investigated to establish the epidemiological link, i.e., an SR. The association observed between the presence of an SR and involvement in outbreaks suggests that the epidemiological criteria for declaring an outbreak were correct because relationships were observed among microorganisms that were subsequently found to have the same lineage. However, it cannot be assumed that CPB with identical STs are involved in the same chain of transmission without considering the epidemiological evidence [35].
In conclusion, there has been a major increase in infections with CPB over the years, especially during 2020, coinciding with the COVID-19 pandemic. The combination of epidemiological data with real-time molecular sequencing data represents a major advance in the control of CPB transmission and the management of infected patients. The increased precision offered by molecular sequencing techniques and the possibility of their real-time performance can contribute to a greater control of nosocomial outbreaks and a more effective targeting of infection prevention measures.
Author Contributions
Conceptualization, J.G.-F.; methodology, E.C.-M., I.P.-C., P.P.-P., J.M.N.-M., M.A.F.-S., J.G.-F.; writing—original draft preparation, E.C.-M., J.G.-F.; writing—review and editing, E.C.-M., I.P.-C., P.P.-P., J.M.N.-M., M.A.F.-S., J.G.-F. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study protocol was conducted in agreement with the Helsinki Declaration and ethical norms for epidemiological investigations. Ethical review and approval were waived for this study, due to the non-interventionist nature of the study, in which the biological material was only used for the standard diagnosis of infections as prescribed by the attending physicians, no investigation was performed in addition to routine procedures, and the laboratory performed no additional sampling or any modification of routine diagnostic protocols. The Clinical Management Unit of the Department of Clinical Microbiology of the hospital granted permission to access and utilize the data.
Informed Consent Statement
The informed consent of patients for integrated result analysis was not required, in accordance with WHO ethical guidelines for research in humans. Analyzed data were drawn from a completely anonymous database in which individuals were only identified by their unique health record number in the Andalusian health system, considering the first episode for each patient in the analyses.
Data Availability Statement
Not applicable.
Acknowledgments
We would like to thank Dª Manuela Expósito-Ruíz for the statistical analysis carried out, as well as Dª Pilar Aznarte-Padial for the information provided on the use of antibiotics.
Conflicts of Interest
The authors declare no conflict of interest.
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Table 1. Colonization/infection episodes of each carbapenemase-producing bacteria in each year.
Table 1. Colonization/infection episodes of each carbapenemase-producing bacteria in each year.
Years/Episodes
Microorganisms201520162017201820192020Total
InfectionColonizationInfectionColonizationInfectionColonizationInfectionColonizationInfectionColonizationInfectionColonizationInfectionColonization
K. pneumoniae131651026212521206637
K. oxytoca00302022010074
C. freundii00000000022325
E. coli00001011012244
E. cloacae02403162421292916
A. baumannii0000002217178182737
P. aeruginosa0000706667252118
Total1 (16.7%)5
(83.3%)
23 (82.1%)5
(17.9%)
23 (85.2%)4
(14.8%)
23 (60.5%)15
(39.5%)
39 (52.7%)35
(47.3%)
47 (45.2%)57
(54.8%)
156 (56.3%)121
(43.7%)
Table 2. Subgroups of carbapenemases detected in each carbapenemase-producing bacteria (CPB).
Table 2. Subgroups of carbapenemases detected in each carbapenemase-producing bacteria (CPB).
Carbapenemase Types
OXAVIMIMPKPCNDMTotal
MicroorganismsOXA-1OXA-23OXA-48OXA-50OXA-58OXA-244OXA-245VIM-1VIM-2VIM-63IMP-8IMP-16IMP-23KPC-2KPC-3NDM-5
K. pneumoniae1 56 14 1 1328102
K. oxytoca 1 8 2 11
C. freundii * 4 2 1 12 10
E. coli 5 1 2 8
E. cloacae 16 28 1 45
A. baumannii 47 17 64
P. aeruginosa * 1 23114109 40
Total (%)1 (0.36%)47 (16.79%)82 (29.99%)1 (0.36%)17 (6.07%)1 (0.36%)1 (0.36%)46 (16.43%)3 (1.07%)2 (0.71%)16 (5.71%)10 (3.57%)9 (3.21%)4 (1.43%)32 (11.43%)8 (2.86%)280 (100%)
* CPB in which more than one carbapenemase is detected in an episode.
Table 3. Description in the microorganisms of carbapenemase and sequence types.
Table 3. Description in the microorganisms of carbapenemase and sequence types.
SEQUENCIO-TYPESCARBAPENEMASE TYPES
KPC-2KPC-30XA-1OXA-230XA-480XA-500XA-580XA-2440XA-245VIM-1VIM-2VIM-63IMP-8IMP-16IMP-23NDM-5Not Available
ST1 1
ST1 1
ST2 46 17
ST10 1
ST11 1 1
ST151 3 8
ST18 2
ST22 2
ST24 1
ST25 1
ST36 9
ST37 1
ST45 11
ST50 1 1
ST58 1
ST69 1
ST78 22
ST90 4
ST108 1
ST111 1
ST114 13
ST128 1
ST145 1
ST147 1
ST1702
ST1751 1
ST175 2 9
ST214 1
ST238 1 1
ST253 1 10
ST258 29
ST277 1
ST307 29
ST307/cgST3303 3
ST307/cgST5556 1
ST321 1
ST348 14
ST392 1
ST405/cgST5158 3
ST405 2
ST512 1
ST513 1
ST525 1
ST648 1
ST845 2
ST896 3
ST1262 1
ST1774 1
ST2242 1
ST8327 1
Not available 1
K. oxytoca
E. coli
E. cloacae
A. baumannii
K. pneumoniae
C. freundii
P. aeruginosa
Table 4. Relationship between sequence types of each CPB, type of relationship, and involvement in a nosocomial outbreak.
Table 4. Relationship between sequence types of each CPB, type of relationship, and involvement in a nosocomial outbreak.
K. pneumoniaeSequence TypeARSRTotalOB NOOB YESTotal
ST1101101
ST11202202
ST128101101
ST147101101
ST1548126612
ST1774101101
ST25101101
ST2588212926329
ST3078212920929
ST307/cgST3303303303
ST307/cgST5556101101
ST321101101
ST37101101
ST392101101
ST405/cgST5158303303
ST4547117411
ST512101101
ST525101101
ST896303303
Total46571038122103
E. cloacaeST1081 11 1
ST1111 11 1
ST1143101310313
ST12621 11 1
ST241 11 1
ST502 22 2
ST781392222 22
ST904 44 4
Total26194542345
A.baumanniiST1101101
ST2313263451863
Total323264461864
P. aeruginosaST175381111 11
ST22421 11 1
ST25346104610
ST2771 11 1
ST3481131414 14
ST8451122 2
Total11283933639
Type of relationship: synchronous (SR) or asynchronous relationship (AR). Outbreak: OB.
Table 5. Comparison between identified SRs and those involved in a nosocomial outbreak of CPB.
Table 5. Comparison between identified SRs and those involved in a nosocomial outbreak of CPB.
CPBsSROB YESAROB YES
K. pneumoniae5721461
K. oxytoca4070
C. freundii2050
E. cloacae193260
A. baumannii3212326
P. aeruginosa284112
Type of relationship: synchronous (SR) or asynchronous relationship (AR). Outbreak: OB.
Table 6. Clinical data for episodes of carbapenemase-producing bacteria.
Table 6. Clinical data for episodes of carbapenemase-producing bacteria.
Parameters20192020
Age, years63.3657.48
Standard deviation16.60117.254
Males, %6560
Females, %3540
Hospital stay, days 7.758.79
Hospital occupation, %77.5677.24
Piperacillin–tazobactam *65.1366.88
Imipenem *6.715.13
Meropenem *47.4561.21
* daily dose per 1000 stays (DDD/1000).
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Cano-Martín, E.; Portillo-Calderón, I.; Pérez-Palacios, P.; Navarro-Marí, J.M.; Fernández-Sierra, M.A.; Gutiérrez-Fernández, J. A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic. Antibiotics 2021, 10, 1127. https://doi.org/10.3390/antibiotics10091127
AMA Style
Cano-Martín E, Portillo-Calderón I, Pérez-Palacios P, Navarro-Marí JM, Fernández-Sierra MA, Gutiérrez-Fernández J. A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic. Antibiotics. 2021; 10(9):1127. https://doi.org/10.3390/antibiotics10091127
Chicago/Turabian Style
Cano-Martín, Estefanía, Inés Portillo-Calderón, Patricia Pérez-Palacios, José María Navarro-Marí, María Amelia Fernández-Sierra, and José Gutiérrez-Fernández. 2021. "A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic" Antibiotics 10, no. 9: 1127. https://doi.org/10.3390/antibiotics10091127
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5eff3d1f6f98e57329caed0ceb9053d3
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Tumor-infiltrating lymphocytes (TIL) are found in most human infiltrating ductal breast carcinomas. In studies of other tumors, TIL were capable of activation by IL-2, both in vitro and in vivo, to produce selective tumor cytolysis. Specific TIL-mediated tumor cytolysis in human breast tumors has recently been reported. The large numbers of TIL within human breast cancers imply that an immune response is occurring, since many of these cells express HLA class II as a late activation marker. However, the degree of early activation of the native TIL in breast tumors has not been fully investigated. Early activation markers CD69, CD43, and CD38 together with the IL-2R (CD25) and IL-2 cytokine were examined using mAbs and tissue section immunohistology. In situ hybridization was used to detect IL-2 mRNA (IL-2 mRNA) in parallel with immunohistochemical localization of IL-2. The results revealed the expression of CD69, CD43, and CD38, but markedly low CD25 (IL-2R) and IL-2 protein expression by the TIL. This strongly indicates that the TIL are an activated population of T cells that shows a deficiency in IL-2 protein and IL-2R expression despite adequate levels of IL-2 mRNA. The mechanism for apparent inhibition of IL-2 production and IL-2R expression in the presence of IL-2 mRNA is currently unclear; however, this may explain the relative anergic state of native TIL.
This content is only available via PDF.
You do not currently have access to this content.
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3,829,653,024,238,353,000
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When you think of sports injuries, a torn ACL or rotator cuff may pop into your mind, but it’s the unseen injuries inside your head that are really cause for concern. Until a decade or two ago, concussions were merely thought of as a bump to the head, but evidence continues to mount about the potentially serious and long-term consequences of these types of brain injuries.
At Genesis Regenerative Sports and Aesthetic Medicine, our sports medicine specialists understand all too well how serious concussions can be. Even though many sports have been shelved because of the current COVID-19 crisis, it’s still worth understanding the impact of sports-related head injuries and the steps you should take to protect your children and yourself.
What is a concussion?
Before we dive into the actions you should take if you or your child sustains a sports-related head injury, let’s review what happens to your brain when it encounters trauma.
A concussion is a traumatic brain injury (TBI) that occurs when you bump, jar, or hit your head, although a concussion can also occur if you sustain a serious blow to your body that causes your head to rock back and forth.
Whether the blow is direct or not, anything that causes your brain to bounce or twist inside your skull can lead to chemical changes in your brain and damage to your brain cells, which can affect brain function.
Recognizing a TBI
While there are varying degrees of a concussion, we feel that any blow to your head is serious, especially if you or your child experiences:
• Headaches
• Nausea
• Fatigue
• Cognitive issues (loss of memory or focus)
• Sleep issues
• Mood disturbances
These symptoms may come on immediately, or they may take days or weeks to develop.
High-risk sports
There are any number of ways that you can sustain a TBI, but in 2012 in the United States, 3.8 million people reported a sports-related head injury, which was twice the number of a decade earlier.
The sports that rise above the rest in terms of risk include:
• Football, which accounts for 60% of concussions in high school athletes
• Ice hockey, with a prevalence rate of 54 per 10,000 exposures
• Girls’ soccer, with a prevalence rate of 33 per 10,000 exposures
• Boys’ and girls’ lacrosse, with a prevalence rate of 31-47 per 10,000 exposures
Again, we provide this list so that you can assess your child’s or your risks, but do note that you can injure your brain playing tennis if the conditions are right.
The importance of care after a concussion
Any time you or your child receives a blow to the head or body, it’s always a good idea to have us check you out. Even if we find only a mild TBI, you need to exercise extreme caution in the future as second and third brain injuries can be very serious and even fatal, especially if the first brain injury hasn’t healed properly.
To put some numbers to this problem, high school students who have a first concussion are 4-6 times more likely to sustain a second brain injury.
By seeking prompt care with us, we can evaluate the TBI and determine the amount of time you or your child should steer clear of anything that might injure your brain further.
By allowing your brain time to heal properly, and proceeding with extreme caution when you take to the playing field again, you can avoid a potentially drastic second or third TBI.
If you’d like to learn more about sports-related head injuries, please contact our office in Westfield, New Jersey, to set up a consultation. Or you can set up an appointment through online booking while you’re here on the website.
Contact Us
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Brown Fat? Give Me Some More of That!
3 mins read
belly
avatar
Written by:
The BodySpec Team
For most people, the word "fat" brings up undesirable associations: stubborn muffin tops, restrictive diets, heart disease. When exercising and dieting, we generally try to decrease body fat levels because they are harmful in excess.
But what about brown fat? It sounds even more disgusting than your typical "white fat", but brown fat is actually more complicated – and beneficial!
Brown fat cells are composed of many small, oily droplets, and contain the brown, kidney-shaped organelles known as mitochondria. In brown fat cells, mitochondria burn up the droplets around them to produce heat. In contrast, white fat cells lack mitochondria, and are formed of larger single oily drops.
What does that mean? Through generating heat, brown fat burns calories, and white fat does not.
Who has brown fat?
Brown fat is primarily found in babies. Because infants cannot shiver, the brown fat helps generate excess heat that helps keep them warm. While much of it disappears with age, it turns out that adults have some small stores of brown fat, mostly between the shoulder blades.
You're probably wondering if you have brown fat. Sadly, BodySpec's DXA scan cannot test clients for brown fat. The only way to measure it is through a PET (positron emission tomography scan) which involves injecting you with radiolabeled glucose. However, we do know the following:
• Younger people have more brown fat than older people
• Leaner people have more brown fat than obese people do
• People with normal blood sugar levels have more brown fat than those with high blood sugar
But regardless of how much actual brown fat you have, there's some good news. You can actually get your white fat to act like brown fat! This calorie-burning white fat is called "beige fat".
How do I turn my white fat into beige fat?
Several research studies have found ways to trigger white fat to start turning beige and burning calories.
• Turn down the thermostat! Cold temperatures may activate your brown fat and help you lose white fat. Shivering muscle triggers a hormone called irisin, which "fires up" white fat cells to begin burning heat.
• Exercise! Moderate physical activity that works your muscles also triggers irisin.
• Get enough sleep! When you're sleeping, you produce melatonin, a hormone with many beneficiary roles, including stimulating the appearance of beige fat.
So the next time you do these things, remember that as you're changing your lifestyle, you're also changing your fat cells – for the better!
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Lemon Balm: Calm your mind and body with the therapeutic herb
Lemon Balm: Calm your mind and body with the therapeutic herb
Lemon balm (Melissa Officinalis) is a popular herb known for its calming and relaxant properties. It is a member of the mint familyy. The herb is native to Europe and Asia and has been widely cultivated for centuries. The lemon balm plant has oval-shaped leaves and small, white or yellow flowers.
The leaves have a lemon-like flavor and can be used to make tea, lemonade or added to other dishes. Lemon balm is also used in some skin care products and as a natural insecticide. The leaves of the lemon balm plant have a strong lemon scent and are used to make various products, including teas, tinctures, and essential oils.
What properties does Lemon Balm have in stock for you?
• The main active compound in lemon balm is Citronellal. This compound is responsible for the herb's lemon-like scent.
• Lemon balm also contains other compounds that have medicinal properties, including Eeugenol (an antiseptic and anti-inflammatory agent) and Rosmarinic acid (an antioxidant).
• It has a long history of use in traditional medicine and is effective in treating various conditions, including anxiety, insomnia, and indigestion.
• Lemon balm is thought to work by interacting with the body's nervous system.
• Lemon balm is also believed to improve digestion and relieve indigestion.
How can Lemon Balm aid in improving your health?
Lemon balm has a long history of use in herbal medicine. It's been used to treat various conditions, including anxiety, insomnia, indigestion, and headaches. It has several health benefits. For example, it can help to:
• relieve stress and anxiety
• improve sleep
• boost mood
• alleviate pain
• improve digestion
• reduce inflammation
Today, lemon balm is most commonly taken as a dietary supplement. It's available in capsules, tablets, teas, and tinctures. Some people also apply lemon balm to the skin to treat cold sores, insect bites, and other skin conditions.
Looking to enjoy the benefits of lemon balm? NAF's herbal tea is a great way to get your fix. This delicious, naturally caffeine-free tea is made with fresh lemon balm leaves and is a great way to relax and unwind. So why not give it a try?
Back to blog
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Skip to main content
Home » What’s New » What’s The Link Between Dry Eye and Accutane (Acne Medication)
What’s The Link Between Dry Eye and Accutane (Acne Medication)
Teen with severe acne wearing maskAccutane, generically called isotretinoin, is an oral medication that is widely prescribed to treat severe acne that hasn’t responded to other treatments.
Although this drug often does a great job of reducing acne, it has several potential side effects that can affect many bodily systems, including the eyes.
Isotretinoin and Dry Eyes
Isotretinoin works by decreasing the size of the oil glands that secrete oil onto the skin. By reducing the production of the facial oils, the pores become less clogged and the amount of acne diminishes.
As the medication travels through the bloodstream, it also penetrates the eyelids’ meibomian glands, which produce the oil for tears.
These meibomian glands, which line the inner portion of the eyelids, play an important role in keeping the eyes hydrated and healthy by secreting oil to stabilize the tear film. When Accutane suppresses their function, the oil layer in the tear is inadequate, allowing excessive tear evaporation. As a result, the eyes dry out.
A 2012 study published in JAMA Dermatology analyzed the ocular effects of isotretinoin and concluded that taking it places patients at a significantly higher risk of experiencing a range of adverse ocular effects.
Common ocular conditions that were associated with this acne medication were dry eye syndrome, blepharitis, conjunctivitis, photosensitivity, contact lens intolerance and papilledema.
The researchers found that the ocular conditions resulted from changes to the cornea, eyelids, retina and meibomian glands. Additionally, the drug was found in the tear film and caused increased ocular irritation.
The good news is that these effects are often temporary, and resolve within a few months after completing treatment. One study, published in Optometry and Vision Science (2015), however, found that 1% of patients developed permanent meibomian gland dysfunction after taking isotretinoin.
How a Dry Eye Optometrist Can Help
Some dermatologists will refer their patients to an optometrist for a dry eye evaluation before prescribing isotretinoin to treat acne. If the patient already has signs of ocular surface disease or is taking other medications that interfere with tear production, the doctor may decide against prescribing isotretinoin.
We can help by thoroughly assessing your ocular condition to help your dermatologist determine the best acne treatment for you, as well as help you manage your dry eye symptoms.
If you or a loved one is currently taking or has taken isotretinoin and is experiencing symptoms of dry eye syndrome such as eye irritation or burning eyes, we can offer lasting treatment and solutions.
To schedule your dry eye consultation or learn more about our services, call Eyes of New Mexico Family Optometry and Contact Lenses today.
Frequently Asked Questions with our optometric team
Q: Should I use lubricating eye drops while taking acne medication like isotretinoin?
• A: Lubricating eye drops may be an appropriate treatment for medication-induced dry eye syndrome However always consult with your optometrist before purchasing drops from the drugstore. The huge range of choices in your local pharmacy can be hard to navigate alone, and not all eye drops will be right for you. We can help guide you to the best eye drops for your condition.
Q: What are the common symptoms of dry eye syndrome?
• A: Common symptoms of dry eye syndrome include watery eyes, gritty eyes, burning or painful eyes, red and irritated eyes, mucus around the eyes, the inability to wear contact lenses, sensitivity to light and blurred vision. The frequency and severity of these symptoms can range greatly from patient to patient, and treatment will depend on the underlying cause of your symptoms.
Our practice serves patients from Albuquerque, Rio Rancho, South Valley, and Sandia Heights, New Mexico and surrounding communities.
Schedule A Dry Eye Appointment
Think You Have Dry Eye? Call 505-806-1432
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Category Archives: OXE Receptors
Methods= 29) and control group (= 30). of evening eating in
Methods= 29) and control group (= 30). of evening eating in despair group was 41.4% although it was 13.3% in controls (< 0.05). Proportion of daily fruit intake was low in despair group (13.8%) than in handles (50.0%). Daily intake of more fresh vegetables was 31.1% in despair group although it was 46.7% in controls. Of despair group, 65.4% consumed fish that was significantly less than handles (83.3%). Among EFNB2 despair group, 10.3% of people were sedentary. Light exercise amounts had been higher in despair group (86.2%) weighed against the handles (56.7%). A statistical significance was discovered buy 164204-38-0 among exercise amounts between groupings (< 0.05). There is no difference between your groupings with regards to smoking and alcohol consumption. Although statistically insignificant, polyunsaturated fatty acids (PUFA) intake of controls [10.53 (8.29C13.91)?g] was higher than of depression group [7.62 (5.82C12.49)?g] (= ?1.933, > 0.05). Intakes of vitamins A (< 0.05), thiamine (< 0.05), riboflavin (< 0.05), vitamins B6 (< 0.05), folate (< 0.05), vitamin C (< 0.05), Na (< 0.05), K (< 0.05), Mg (< 0.05), Ca (< 0.05), P (< 0.05), Fe (< 0.05), Zn (< 0.05), and fibre (< 0.05) were lower in depressive disorder group (Table 1). According to Dietary Guidelines for Turkey, intake of fibre, niacin, vitamins B6, C (< 0.05 for each), and Mg (< 0.05) was lower in women with depressive disorder while intake of energy, fibre, vitamins A, E, B6, and C (< 0.05 for each), and folate (< 0.05) were lower in men with depressive disorder. Table 1 Energy and nutrients consumption of depressive disorder and control groups. Median levels of body weight (< 0.05), waist circumference (< 0.05), hip circumference (< 0.05), and waist-to-hip ratio (< 0.05) were higher in depressive disorder group (Table 2). 1st- and 2nd-degree obesity were higher in depressive disorder group (27.6% and 13.8%, resp.) compared to handles (6.7% and 0.0%, resp.) (< 0.05, Desk 3). Median daily energy expenses of despair group [1946?kcal (1827C2188?kcal)] was less than of handles [2180?kcal (1944C2470?kcal)] (< 0.05). Desk 2 Anthropometric measurements of control and depression teams. Desk 3 Evaluation of bodyweight regarding to body mass index. Fasting blood sugar amounts (< 0.05) and serum vitamins B12 (< 0.05) and folic acidity (< 0.05) in despair group were less than controls. Serum insulin and HOMA amounts were not considerably different between groupings (> 0.05). Bloodstream lipid degrees of both groupings were also equivalent (> 0.05, Desk 4). Desk 4 Evaluation of biochemical variables of control and despair groupings. 4. Dialogue To the very best of our understanding, this is actually the initial research of its kind in buy 164204-38-0 Turkey to judge nutritional intake, dietary status, plus some biochemical variables of sufferers with despair. Outcomes out of this research indicated that frustrated people increase their food intake as a response to unfavorable emotions. Similar to this obtaining, Konttinen et al. [40] investigated an association between emotional eating and depressive symptoms. Emotional eating was related to higher consumption of nice foods. In addition, depressive symptoms were related to a lower consumption of vegetables/fruit. We found higher rates of eating at night among patients with depressive disorder like Gluck et al. [41]. In this study, similar to previous studies, depressed patients’ 24-hour food intake has shown a poor quality diet plan with lower consumption of fruits/vegetables [40, 42]. This association of low fruits/vegetables intake with despair also resulted in insufficient intake of fibre within this research which is essential in healthy lifestyle maintenance and security from illnesses [43]. Alternatively, intake of seafood was significantly low in the despair group in comparison to handles and these outcomes were in keeping with prior studies [44C50]. Seafood may be the richest way to obtain n-3 PUFA and EPA which includes been found to buy 164204-38-0 work in relieving despair [49, 51]..
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Launch:
For many ladies, reduced stomach fat is a very common source of disappointment. It’s one of the most hard regions to focus on from the body weight-decrease point of view, and if you’re like most ladies, you’ve probably tried out every dieting and exercise program with tiny achievement. But what if we said that decrease belly fat may be due to anything entirely outside your management – human hormones? Let’s check out the position chemicals what causes belly fat in males perform in producing persistent stomach fat.
How Can Human hormones Affect Tummy Fat?
Hormone imbalances can lead to a rise in lower belly fat, especially visceral excess fat. Visceral extra fat can be found beneath the muscle tissues and around your internal organs, so that it should not be viewed or noticed as easily as subcutaneous extra fat (the kind that is placed just under your skin layer). However, visceral excess fat continues to be related to coronary disease and type two diabetes – two constant conditions that no woman should ever need to handle. Why do chemicals impact tummy fat? That’s because your body are designed to retail store additional calorie consumption as visceral body fat when our hormonal changes become imbalanced. This could take place should you encounter any of these hormone adjustments:
Menstrual cycle instability (i.e., unnatural periods)
•Reduced levels of estrogen •High cortisol degrees •Insulin resistance •Thyroid gland troubles •Childbirth manage supplements •
Maternity/postpartum
All of these elements can cause a rise in lower abdominal fat on account of hormone imbalances. And unfortunately, these complaints aren’t easy to recognize all by yourself, this is why it’s crucial that you view a doctor if you feel that chemicals are enjoying a role within your inability to lose excess weight or get rid of obstinate abdominal fat.
Exactly What Can I Actually Do Regarding This?
If you think maybe that bodily hormones are influencing your lower belly fat, there are several actions you can take to assist handle this concern. To start with, make sure you’re having a well-balanced diet loaded with healthful fats, toned necessary protein, intricate carbohydrate food, many fruits, fresh vegetables and plenty of drinking water each day. This will help keep the blood sugar steady and stop insulin surges from developing throughout the day – each of which can bring about increased belly fat storing because of hormone imbalances changes inside your body. Moreover, exercise regularly even just thirty minutes each day can create a significant difference in terms of controlling hormonal levels and reducing general belly circumference due to saved visceral saturated fats connected with substantial cortisol amounts or blood insulin resistance concerns. Eventually, consider talking with your physician about ways you can safely manage any hormonal instability which might be adding to stubborn decrease stomach fatty acids they can recommend consuming specific health supplements or making diet changes in order for your body’s hormone levels stay stable preventing extra accumulation of extra fatty acids throughout the stomach region.
Conclusion:
Reduced stomach fatty acids can often be attributed directly or indirectly towards hormonal fluctuations within our body as we age or undergo distinct existence occasions such as maternity or menopause etcetera . Fortunately that by finding out how chemicals have an effect on your body we can easily far better provide ourselves with knowledge about how best we should technique diet for optimum results based on our specific demands .In addition , utilizing frequent exercise into our lives along with responding to any underlying health issues we might have could eventually establish us up for fulfillment when functioning towards achieving our workout goals . Simply speaking , understanding how bodily hormones have an effect on us , specifically when striving deal with persistent stomach bulge , is essential for productive lasting weight-control methods .
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Suffering Through Heat-Induced Swelling? Try These Tips
Woman laying on a chair with her feet up.
LenaSunny/Shutterstock
Do you experience swelling and heaviness in your legs and arms every time the weather starts getting warm and sunny? If the answer is yes, you are not alone. Many people suffer from heat-induced water retention and swelling, and here’s how to offset it.
Legs Up the Wall
The old-fashioned legs-up-the-wall remedy really works, and the reason is pretty simple. Getting inverted stimulates the blood and lymph to travel back towards your core, promoting drainage from excess water buildup and improving circulation. This leaves your legs feeling lighter and relieves any pain caused by water retention and swelling.
In addition, getting your legs up in the air relaxes your hips and the entire spine, letting the muscles release all the tension caused by sitting and walking around all day long. You can support your spine by placing a pillow underneath your back and neck and use this opportunity to read a book or scroll on your Insta feed.
Stay inverted for at least 5 minutes and slowly work your way up to 10 or 15. Be careful when exiting the pose, because your legs may feel a bit numb. Bend your knees into your chest and roll to the side, gently coming to a seat before standing up.
Dry Brushing and Gua Sha Technique
You’ve probably been hearing a lot about these two self-massage techniques lately, as articles and workshops about both have been flooding the wellness scene. Dry brushing comes from the ancient Ayurvedic practice, and it’s believed to have many benefits, from stimulating lymphatic drainage and exfoliating the skin, to promoting the flush out of toxins and reducing the appearance of cellulite.
Although scientific evidence is scarce, many people swear by its positive results when used consistently. When using a dry brush, you want to make sure you’re always brushing towards the heart and stimulating the circulation and lymphatic flow in the right direction.
Gua sha, on the other hand, is an ancient Chinese ritual that involves scraping the skin with a small smooth gua massage instrument. The belief is that the tool stimulates energy flow in the body and promotes microcirculation of the tissue, flushing out toxins and reducing inflammation.
Some studies actually prove how efficient this little self-massage tool is in lowering the inflammation in the body as well as reducing migraines and relieving neck pain.
Gua Sha has become relatively mainstream lately with the rise in popularity of jade rollers. Many people have taken to rolling their faces each morning and evening to decrease puffiness and promote collagen production. Using a similar technique as gua sha, massaging your face with a jade roller can help you get rid of those puffy under eyes after a rough night out or a sweaty summer afternoon. While research is ongoing, a 2018 study indicates the use of the rollers increases blood flow and vasodilation.
Hydration
Woman drinking out of a steel water bottle.
Anja Ivanovic/Shutterstock
The “hydration is key” saying is almost like a mantra within the fitness and beauty community, but it should absolutely be one in everyone’s everyday life, whether they work out or not.
Human bodies are made of almost 60% water, and all of our systems depend on it. When we’re not replenishing our stash, we’re risking some of their important functions not operating properly. And when summer comes along, it’s more common than you’d think.
Sweating evaporates the water through our skin and cools the tissue beneath, which is crucial when we’re being exposed to heat. Not hydrating after this incident reduces the total body water level and creates a reaction in the body when it tries to adapt to this new condition.
This is why swelling and water retention occur, as they’re a direct response to a problem with the body’s mechanisms to control fluid levels. Making sure you’re drinking enough fluids daily is a great way to combat this, as you’ll be able to flush out the excess fluids by bringing the your body’s water level to where it should be.
According to the National Academies of Sciences, Engineering, and Medicine, it’s recommended to drink about 15.5 cups of fluids for men and about 11.5 cups of fluids a day for women. Still, this recommendation is only a general guideline, as many different factors can play a role in your exact fluid needs.
Factors such as level of activity, perspiration, sleep, age, climate, and time of the year all contribute to the amount of water that’s best for you and your body. And during summer, you can rest assured, more is almost always better.
Compression Therapy and Lymphatic Drainage
Good-quality massage that tackles the areas where swelling is the worst definitely helps with pushing the excess water out of your system and getting some relief. Over the years, some popular methods emerged, proving themselves to be more efficient than a simple hands-on deep-tissue massage.
Compression therapy is a known treatment for vein problems and blood clots, as by wearing compression socks and stockings, you’re preventing the blood to pool into your leg veins, improving your overall circulation and eliminating any potential swelling.
Athletes have been using compression therapy in the form of compression boots, which get filled up with air and squeeze your leg muscles from your feet to your thighs in a variety of dynamic pulses that mimic the muscle pumps of the legs, improving the movement of fluid and metabolites. They also have additions for arms and hips, which you can easily attach and remove when you don’t want to use them.
Lymphatic drainage, on the other hand, is a form of massage that very gently pushes the water and toxins away from your body. The massage is usually performed by trained professionals, but there are techniques you can easily learn and implement yourself.
Summer brings plenty of wonderful experiences, but the annoying swelling isn’t one of them. Use these techniques and prevent it from ruining all the fun!
Karla Tafra Karla Tafra
Karla is a certified yoga teacher, nutritionist, content creator and an overall wellness coach with over 10 years of international experience in teaching, writing, coaching, and helping others transform their lives. From Croatia to Spain and now, the US, she calls Seattle her new home where she lives and works with her husband. Read Full Bio »
LifeSavvy is focused on one thing: making your life outside of work even better. Want to know more?
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Genetic testing before and during pregnancy
Home » Specialities » Pregnancy » Genetic testing before and during pregnancy
What is genetic testing? When is it done and why? These are a few questions which arise if you are planning to have a baby. Here are some of the answers.
What is genetic testing?
This test involves examining your DNA, the chemical database that carries instructions for your body’s functions to test for changes or alterations in your genes that may cause illness or disease.
If you’re a healthy person, a positive result from genetic testing doesn’t always mean you will develop a disease. On the other hand, in some situations, a negative result doesn’t guarantee that you won’t have a certain disorder. It is important to discuss with your doctor or genetic counselor, what you will do with the results.
How is genetic testing done?
Genetic testing is done by taking the sample of the blood, hair or tissue samples. In case you’re pregnant, a sample of your amniotic fluid is taken or tissue sample from the placenta (chorionic villus sampling).
To understand the chances of your baby developing abnormalities, genetic testing may be done before conception or in the pre-natal stage.
What does the test reveal?
Positive results
If you have symptoms and are being tested for it and if the genetic test result is positive, it could mean that the diagnosis of the condition you were being tested for, is confirmed. It will help you and your doctor determine the right treatment and management plan.
If you were tested to find out if you are carrying an altered gene that could cause disease in your child, and the test is positive, your doctor or a genetic counselor can help you determine your child’s risk of actually developing the disease.
Detecting a positive test to find out if you are carrying a disease, doesn’t necessarily mean you will get that disorder. It may mean that you are at high risk of developing the disease or there are some conditions, such as Huntington’s disease, for which having the altered gene does indicate that the disease will eventually develop. Talk to your doctor about what a positive result means for you. The results will help you make choices related to family planning and lifestyle.
Negative results
A negative result means a genetic alteration was not detected by the test since the accuracy of genetic tests to detect alterations varies, depending on the condition being tested for and whether or not an alteration has been previously identified in a family member.
Even if the test was negative, it doesn’t necessarily mean you will never get the disease. Also, genetic testing may not be able to detect all genetic defects.
No matter what the results of your genetic testing, talk with your doctor or genetic counselor about questions or concerns you may have. This will help you understand what the results mean for you and your family.
What is the genetic testing that may be advised?
Several types of genetic tests are done for different reasons –
• Diagnostic testing- If you have symptoms of a disease caused by a genetic alteration, genetic testing will confirm the diagnosis of a suspected disorder.
• Predictive and presymptomatic testing- this is carried out to check if you’re predisposed to a particular genetic condition that runs in your family, before you have symptoms.
• Carrier testing- If you have a family history of a genetic disorder — such as sickle cell anemia or cystic fibrosis — or you are in an ethnic group that has a high risk of a particular genetic disorder, you may choose to have genetic testing before you have children.
• Pre-natal testing- this is done to test for abnormality in the genes of your unborn baby. Down syndrome and trisomy 18 are two genetic disorders that are often screened for as part of prenatal genetic testing.
• Newborn screening- in this type of genetic testing, your new born baby’s genes are tested to detect abnormalities that can cause him to develop certain health conditions such as inborn errors of metabolism. This is important to diagnose early as treatment can then be started before complications develop.
• Preimplantation testing. Also called preimplantation genetic diagnosis, this test may be used when you use in vitro fertilization for conception. The embryos may be screened for genetic abnormalities. Embryos without abnormalities are implanted in the uterus in the hope of achieving pregnancy.
If you’re older than 35 years when you conceive, genetic testing becomes all the more necessary. This is because the chance of the baby having chromosomal abnormalities increases in older mothers. Carrier screening however is recommended for all couples before you plan a family.
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Äî ÷îãî ñíèòüñÿ ïîæåæà
×àñòî ñíè, ÿê³ ìè áà÷èìî, íå ò³ëüêè îçíà÷àþòü ïåâí³ ðå÷³, ÿê³ â³äáóâàþòüñÿ â íàøîìó æèòò³, à é ïîïåðåäæàþòü íàñ ïðî íåáåçïåêó. Òàêèì ñíîì, áåçóìîâíî, º ñîí ïðî ïîæåæó. À îñü â³ä òîãî ÿê ñàìå ³ äå ñàìå â³äáóâàºòüñÿ ïîæåæà, ìîæíà çðîçóì³òè, äî ÷îãî ñíèòüñÿ òàêà ïîæåæà.
ßêùî âè óâ³ ñí³ ïîáà÷èëè ïîæåæó, ÿêèé â³äáóâàºòüñÿ ó âàñ âäîìà, î÷³êóéòå ñâàðîê ³ íåãàðàçä³â â ðîäèí³, ³íîä³ - êðàä³æêè ³ õâîðîáè áëèçüêèõ ëþäåé.
Ïîáà÷èòè âåëèêèé âîãîíü ï³ä ÷àñ ïîæåæ³ - äî âåëèêèõ ³ øâèäêèõ çì³í íà êðàùå â æèòò³.
Ãàñèòè ïîæåæó óâ³ ñí³ - îçíà÷ຠïðèìèðåííÿ â ðîäèí³ àáî ç³ ñâî¿ìè ñóñ³äàìè àáî ðîäè÷àìè.
Äèì ïîæåæ³ ñíèòüñÿ äî çì³í íà êðàùå, çä³éñíåííÿ áàæàíü, ÿêùî ñíèòüñÿ äèì â³ä çãàðèù - öå îçíà÷ຠùî íàñóâàºòüñÿ ëèõî ³ íåùàñòÿ.
ßêùî ñíèòüñÿ ïîæåæà â ë³ñ³ - öå çíà÷èòü, ùî âàñ íåçàáàðîì ÷åêຠÿêåñü âèã³äíà ñïðàâà àáî âè îòðèìàºòå ïðèáóòîê.
Áà÷èòè ïîæåæíèê³â óâ³ ñí³ ïîçíà÷ຠäîïîìîãó äðóç³â, ÿê³ âàì äîïîìîæóòü âèð³øèòè ñêëàäíó ïðîáëåìó.
Óâàãà, ò³ëüêè ÑÜÎÃÎÄͲ!
Óâàãà, ò³ëüêè ÑÜÎÃÎÄͲ!
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Skip to main content
SOX2 promoter hypermethylation in non-smoking Taiwanese adults residing in air pollution areas
Abstract
Background
Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter < 2.5 μm (PM2.5).
Methods
A total of 1142 individuals aged 30–70 years were recruited. Data on SOX2 methylation, residence, age, and exposure to second-hand smoke (SHS) among others were extracted from the Taiwan Biobank dataset (2008–2015). After excluding former and current smokers, alongside those with incomplete information, a total of 461 non-smokers comprising 176 men and 285 women were included in the study. Participants’ residences were grouped under northern and central/southern areas because air pollution (PM2.5) is lower in northern compared to central and southern areas.
Results
The methylation levels in men (0.16310 ± 0.01230) and women (0.15740 ± 0.01240) were significantly different (P < .0001). In both sexes, the SOX2 promoter region was shown to be significantly hypermethylated in central and southern areas compared with the northern areas. The regression coefficient (β) was 0.00331 (P = 0.0257) in men and 0.00514 (P < .0001) in women.
Conclusion
SOX2 was significantly hypermethylated in both men and women residing in central and southern areas. The consistency in the results for both sexes shows that SOX2 promoter methylation could serve as a potential biomarker for industrial air pollution exposure. Moreover, it might reflect predisposition to cancer. Hence, healthy non-smokers at precancerous stages who have not been clinically diagnosed could be identified.
Background
SOX2, also known as sex-determining region Y (SRY)-box 2, is an oncogenic transcription factor located on chromosome 3. It maintains pluripotency or self-renewal in embryonic stem cells and has been associated with several types of cancer [1,2,3]. In cancers, SOX2 promoter hypermethylation has been shown to be in constant correlation with an unfavorable clinical course and poor prognosis. For example, in esophageal squamous cell carcinoma, SOX2 promoter hypermethylation seemed to have caused SOX2 silencing and the loss of SOX2 expression was associated with poor prognostic outcome [3]. In lung cancer particularly, the overexpression of SOX2 has been associated with better prognosis and survival [2, 4, 5].
Lung cancer is one of the leading causes of global cancer mortality [6, 7]. In Taiwan, it was ranked the second incident cancer in 2014 and the top cause of mortality in 2016 [8]. Histologically, it is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) [7]. SCLC and NSCLC respectively constitute about 15 and 85% of lung cancer [7]. SCLC is more common in former and current smokers even though certain uncommon cases have been reported in never-smokers [2, 6, 9,10,11]. NSCLC traditionally occurs in non-smokers and comprises three subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC) [7].
Several environmental, lifestyle, and genetic factors have been associated with lung cancer [6, 7, 11,12,13,14]. One of such factors is air pollution resulting from increased industrialization and urbanization [14,15,16,17]. Due to industrialization, PM2.5 pollution is lower in the northern regions compared to the central and southern regions of Taiwan [16, 18,19,20]. The carcinogenicity of air pollutants has not been fully explained. However, it is thought that markers like DNA methylation, mutation, and polymorphism could provide some insights into the mechanisms underlying this carcinogenicity [17].
SOX2 is believed to be a potential molecular marker for lung cancer [2]. In non-smokers exposed to air pollution, SOX2 promoter methylation might help in the early prediction of lung cancer risk. However, research has not been extensively conducted as far as this domain is concerned. Therefore, this study was conducted to investigate the association between SOX2 methylation in non-smoking Taiwanese adults residing in areas with different levels of air pollution especially PM2.5.
Results
The basic characteristics of the participants are shown in Table 1. The methylation levels in men (0.16310 ± 0.01230) and women (0.15740 ± 0.01240) were significantly different (P < .0001). The mean (± SD) concentrations of PM2.5 (μg/m3) from 2006 to 2011 in the northern and central/southern areas are shown in Table 2. PM2.5 concentrations in central/southern regions were higher compared to the northern regions, irrespective of the year. After adjusting for age, exposure to second-hand smoke (SHS), exercise, drinking, body fat, BMI, waist-hip ratio (WHR), asthma, and emphysema, SOX2 promoter methylation was significantly hypermethylated in both men and women residing in central and southern areas compared with the northern areas (Tables 3 and 4). In men residing in the central/southern areas, the regression coefficient (β) was 0.00331; P = 0.0257 (Table 3). That is, the methylation level in male participants residing in central/southern areas was higher than in those residing in the northern areas and the difference was 0.00331. Similarly, in women residing in the central/southern areas, the regression coefficient (β) was 0.00514; P < 0.0001 (Table 4). That is, the methylation level in female participants residing in central/southern areas was higher than in those residing in the northern areas and the difference was 0.00514. Furthermore, the mean PM2.5 level (2006–2011) was significantly associated with higher SOX2 promoter methylation levels: β = 0.00042; P < 0.0001 (Table 5). That is, a unit increase in PM2.5 levels was associated with 0.00042 (P < 0.0001) higher methylation levels. Analysis of CpG sites both in and outside the SOX2 promoter region also showed significant hypermethylation in participants residing in central/southern compared with the northern areas (Additional file 1: Tables S1-S3). In addition, analysis of the KRAS gene promoter CpG sites also showed significant hypermethylation in participants residing in the central and southern compared with the northern areas (Additional file 1: Table S4).
Table 1 Basic characteristics of the study participants by sex
Table 2 Mean (± SD) concentrations of PM2.5 (μg/m3) from 2006 to 2011 in the northern and central/southern areas
Table 3 Multiple linear regression showing beta coefficients of SOX2 promoter methylation in men
Table 4 Multiple linear regression showing beta coefficients of SOX2 promoter methylation in women
Table 5 Multiple linear regression showing the association between mean PM2.5 (μg/m3) from 2006 to 2011 and SOX2 promoter methylation
Discussion
Much has not been done concerning the association between SOX2 promoter methylation and air pollution exposure. Apparently, the current study is the first to explore SOX2 promoter methylation in non-smoking Taiwanese adults based on exposure to air pollution. In both men and women living in the central and southern areas of Taiwan, SOX2 was significantly hypermethylated. The consistent hypermethylation in both sexes implies that SOX2 promoter methylation could be a potential biomarker for industrial air pollution exposure. It is always challenging to estimate individual exposure to air pollution due to the lack of validated tools. In most cases, individual exposure to air pollution is usually estimated using air quality indices from nearby monitoring stations [17]. Exposure misclassification might have been minimized in the current study as participants were stratified based on the degree of exposure to air pollution. The central and southern areas have a heavy concentration of industries compared to the northern areas [16, 19, 21]. The number 6 Naphtha Cracking Complex found in Central Taiwan is one of the biggest power plants in the world [22]. Moreover, the Formosa Petrochemical Corporation and many other industries are found in Central-Southern Taiwan [22]. These make the areas more prone to industrial emissions. Hence, they naturally serve as experimental fields for industrial air pollution. To minimize confounding due to smoking, only non-smokers were included in the final analysis and adjustments were made for exposure to SHS.
To combat smoking and its associated effects, e.g., non-communicable diseases, the Health Promotion Administration (HPA), Taiwan, aims to reduce smoking to 14% by 2025 compared to 20% in 2010 [23]. A decrease in smoking prevalence could subsequently lead to a decrease in smoking-related diseases. However, this does not eliminate the possibility of exposures to pollutants and their carcinogenic impacts. For example, NSCLC which is most common in non-smokers accounts for approximately 85% of lung cancer [7]. In addition, a greater percentage of known lung cancer patients in Asia are never-smokers [11, 13]. Furthermore, smoking-related female lung cancer cases in Taiwan are few [14].
DNA methylation might help in the molecular staging of cancer as precancerous and cancerous states might be identified through this epigenetic modification [24]. This might also help to explain the mechanism for the initiation and progression of some tumors. For instance, lung cancer has been associated with epigenetic silencing [24,25,26]. Promoter hypermethylation is believed to be the molecular mechanism of this epigenetic gene silencing [24]. In esophageal cancer, SOX2 promoter hypermethylation was thought to be the main mechanism behind the silencing of SOX2 gene [3]. Moreover, in esophageal and hypopharyngeal cancer, the absence of SOX2 expression was associated with poor prognosis [3, 27]. SOX2 silencing through hypermethylation might promote tumor initiation by evading cell-cycle arrest in addition to resisting apoptosis [3]. In the current study, SOX2 promoter hypermethylation was observed in individuals who resided in central and southern areas of Taiwan which have high levels of air pollution. Moreover, analysis of the KRAS gene promoter CpG sites also showed significant hypermethylation in participants residing in the central and southern compared with the northern areas. Exposure to air pollution predisposes to cancer [14,15,16]. SOX2 is believed to be a hallmark of lung cancer [2]. Therefore, in healthy non-smokers, SOX2 hypermethylation in air pollution areas might help to identify those at precancerous stages that have not been clinically diagnosed.
One of the limitations of this study is that the association between SOX2 promoter methylation and SOX2 gene expression was not determined. However, hypermethylation is believed to be associated with reduced gene expression [25]. Specifically, SOX2 promoter hypermethylation has been shown to be a vital epigenetic event that causes the silencing of the gene [3]. Moreover, it has been significantly associated with reduced expression of SOX2 RNA in choriocarcinoma and hydatidiform mole [28]. Another limitation of the study is that only non-cancerous individuals were included in this study. As such, the results may not reflect the methylation patterns in individuals with cancer.
Conclusion
In conclusion, significant hypermethylation of the SOX2 promoter region was observed in both non-smoking men and women living in industrial areas with well-known higher levels of air pollution. SOX2 promoter methylation might serve as a biomarker for air pollution in industrial areas. Moreover, it might reflect predisposition to cancer. Hence, healthy non-smokers at precancerous stages who have not been clinically diagnosed could be identified and monitored. Subsequently, prompt actions could be taken against such a public health issue. It is recommended that more should be done to explore the relationship between SOX2 methylation and air pollution.
Methods
Data source
Data were retrieved from the Taiwan Biobank database (2008–2015). The Taiwan Biobank was established in 2005 with the aim of integrating the genetic and medical information of about 200,000 ethnic Taiwanese with no history of cancer [29, 30]. The enrollment of individuals in the Taiwan Biobank Project conforms to relevant regulations and guidelines. A total of 29 recruitment centers are distributed all over the country; each county or city possesses a minimum of one center [29]. A letter of consent was signed by each individual before data collection. Data were collected by well-trained researchers through questionnaires, physical examinations, and biochemical analyses of blood and urine samples.
Data collection and study participants
Participants’ data on SOX2 promoter methylation, residence, age, smoking, exposure to SHS, exercise, drinking, body fat, BMI, WHR, asthma, and emphysema were extracted from the Taiwan Biobank dataset (2008–2015). Residence, age, smoking, exposure to SHS, exercise, drinking, asthma, and emphysema were self-reported while DNA methylation, body fat, BMI, and WHR were measured.
Venous blood (9 ml) was collected into sodium citrate tubes and transported to the lab under 4 °C. DNA was extracted from blood using Chemagic™ Prime™ instrument which is an automated chemical extraction machine that uses magnetized rods to separate nucleic acids from solutions. The DNA length was determined with the Fragment Analyzer (Agilent) while the purity was assessed using the optical density (OD) at 260/280. Samples with an OD 260/280 ratio of 1.6–2.0 were considered to be pure. Pure samples intended for long-term use were stored at − 80 °C. DNA samples were subjected to sodium bisulfite treatment using the EZ DNA Methylation Kit (Zymo Research, CA, USA). DNA methylation at each CpG site was determined with the Infinium® MethylationEPIC BeadChipEPIC array (Illumina Inc.) which covers 850,000 methylation sites. Details on this platform are described elsewhere [31,32,33]. The methylation levels were expressed as beta-values (β) which range between 0 and 1. β-values were determined using the formula β = M/(M + U), where M is the methylated intensity and U is the unmethylated intensity. Quality control was done according to the Illumina® GenomeStudio® Methylation Module v1.8 [34]. Samples with detection P value > 0.05 and bead counts < 3 were eliminated. Dye-bias across batches was adjusted by normalization, and background correction was performed. Outliers were removed using the median absolute deviation method.
Participants were considered to be from an area if they lived there for at least 3 months. Where participants lived was considered to be where they were likely to be exposed to air pollution. The residences were grouped into northern and central/southern regions. This is because PM2.5 pollution in the northern areas is lower compared to the central and southern areas [16, 18,19,20]. The northern areas included Taipei and New Taipei Cities, while the central/southern areas included Taichung and Nantou Cities, Changhua and Yunlin Counties, Chiayi County, Tainan, and Chiayi Cities. PM2.5 statistics in these areas were obtained from the Air Quality Monitoring Database (AQMD) set up by the Environmental Protection Administration, Taiwan. There were 41 air quality monitoring stations in the study areas. Of these stations, 18 were located in the northern region while 23 were located in the central/southern regions. Annual PM2.5 readings (2006–2011) from the various stations were used to determine the annual average concentration for each region.
Participants were considered as (1) non-smokers: never smoked or did not continuously smoke for 6 months or more; (2) former smokers: continuously smoked for at least 6 months but were currently not smoking; (3) current smokers: continuously smoked for 6 months or more and were currently smoking; (4) non-drinkers: no history of alcohol drinking or weekly drinking of less than 150 cc of alcohol for continuously 6 months; (5) former drinkers: abstained from drinking for over 6 months; (6) current drinkers: weekly drinking of at least 150 cc of alcohol continuously for 6 months; (7) physically active: exercised for > 150 min per week; and (8) exposed to SHS: exposure for at least 5 min per hour.
After excluding former and current smokers as well as those with incomplete information, a total of 461 non-smokers comprising 176 men and 285 women were included in our study. A total of 24 SOX2 CpG sites located on SOX2 promoter region were available in the Taiwan Biobank dataset. These sites were cg24513480, cg05664581, cg19258425, cg18148179, cg07747133, cg24782772, cg00666105, cg04948892, cg15106134, cg02573703, cg20106776, cg11129008, cg08062338, cg12930100, cg01023203, cg22530053, cg27331851, cg14783675, cg01340005, cg17051733, cg11142406, cg09530873, cg25933341, and cg08464053. The β-values at all the 24 SOX2 CpG sites were summed up, and the mean value was determined. In order to reach the conclusion that SOX2 is a reliable biomarker of cancer risk in air pollution areas, the mean β-value of CpG sites at the promoter of KRAS, another lung cancer risk gene, was determined. Ethical approval for this study was obtained from Chung Shan Medical University Institutional Review Board (CS2-17070).
Statistical analysis
Data management and analyses were performed with the SAS 9.4 software (SAS Institute, Cary, NC). Continuous variables were analyzed using t test and expressed as mean ± standard deviation (SD) while categorical variables were analyzed using chi-square test and reported as percentages (%). Methylation data were normalized using the Illumina® GenomeStudio V2011.1 software [34]. The correction of cell-type heterogeneity was done with the R software using the Reference-Free Adjustment for Cell-Type composition (ReFACTor) method [35].
The association between SOX2 promoter methylation and residential area was determined using multiple linear regression. Multivariate adjustments were performed for age, exposure to SHS, exercise, drinking, body fat, BMI, WHR, asthma, emphysema, and cell-type composition. P values less than 0.05 were considered to be statistically significant.
Abbreviations
AC:
Adenocarcinoma
BMI:
Body mass index
CpG:
Cytosine-phosphate-guanine
DNA:
Deoxyribonucleic acid
HDL:
High-density lipoprotein
LCC:
Large cell carcinoma
LDL:
Low-density lipoprotein
MOST:
Ministry of Science and Technology
n :
Sample size
NSCLC:
Non-small cell lung cancer
SCC:
Squamous cell carcinoma
SCLC:
Small cell lung cancer
SD:
Standard deviation
SHS:
Second-hand smoke
SRY:
Sex-determining region Y
TC:
Total cholesterol
TG:
Triglyceride
WHR:
Waist-hip ratio
β :
Regression coefficient
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Acknowledgements
Not applicable.
Funding
This work was funded by the Ministry of Science and Technology, MOST (MOST 105-2627-M-040-002; 106-2627-M-040-002; 107-2627-M-040-002 and 106 -EPA EPA-F-016-001).
Availability of data and materials
The data that support the findings of this study are available from Taiwan Biobank but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Taiwan Biobank.
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Authors and Affiliations
Authors
Contributions
DMT and YPL conceived and designed the study. DMT, MFW, CCH, ONN, YCL, HWC, and YCL performed the literature search. YPL, KJL, SYH, PHC, CL, and CCL acquired the data and performed the data analysis. DMT, MFW, CCH, CCL, KJL, ONN, YCL, SYH, PHC, CL, HWC, YCL, and YPL interpreted the data. DMT drafted the manuscript. DMT, ONN, and YPL made critical revisions of the manuscript for important intellectual contents. All authors approved the final version of the manuscript.
Corresponding author
Correspondence to Yung-Po Liaw.
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Ethics approval and consent to participate
This study was approved by the Chung Shan Medical University Institutional Review Board (CS2-17070).
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The authors declare that they have no competing interests.
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Additional file
Additional file 1:
Table S1. Multiple linear regression showing beta coefficients of SOX2 methylation both in and outside the promoter region. Table S2. Multiple linear regression showing beta coefficients of SOX2 methylation in the exon. Table S3. Multiple linear regression showing beta coefficients of SOX2 methylation in the 3UTR region. Table S4. Multiple linear regression showing beta coefficients of KRAS promoter methylation. (DOCX 22 kb)
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Tantoh, D.M., Wu, MF., Ho, CC. et al. SOX2 promoter hypermethylation in non-smoking Taiwanese adults residing in air pollution areas. Clin Epigenet 11, 46 (2019). https://doi.org/10.1186/s13148-019-0647-8
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Keywords
• SOX2
• Hypermethylation
• Non-smoking
• Air pollution
• Biomarker
• Taiwan Biobank
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Categories
DUB
Centrally located T2 hyperintensity spanning the space of the thoracic cord (E,F) without evidence of contrast enhancement (G,H)
Centrally located T2 hyperintensity spanning the space of the thoracic cord (E,F) without evidence of contrast enhancement (G,H). Open in a separate window Figure 4 Case 2 Pathology: Hematoxylin and Eosin staining shows lymphohistocytic infiltrate in the brain cells (200 X) (A). a dose of an mRNA-based SARS-CoV-2 vaccine. Results Five instances of Flumorph post-vaccination CNS disorders of immune source (fatal ADEM; = 1, new-onset NMOSD; = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent Rabbit Polyclonal to ADCY8 slight demyelination; = 1, meningoencephalitis; = 1) observed within 2 weeks of inoculation with either the 1st or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2). Conversation To our knowledge, these are among the growing instances of CNS adverse events of immunological or inflammatory source. These findings should be interpreted with great extreme caution as they neither demonstrate a mechanistic link nor imply a potential long-term improved risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high effectiveness in overcoming this pandemic. = 2, exacerbation of clinically stable Flumorph MS; = 4) as well as one NMOSD diagnosis were reported among the recipients of SARS-CoV-2 mRNA vaccination (11C13). In an international study of 27 instances of new-onset or relapse of immune mediated disease following SARS-CoV-2 vaccination using numerous platforms, there was one case of Flumorph new-onset MS following a administration of the Pfizer-BioNtech vaccine (14). Three instances of antibody-negative possible autoimmune encephalitis were reported after the administration of the ChAdOx1 nCoV-19 vector-based vaccine, including a case of opsoclonus-myoclonus syndrome (15). We statement five separate instances of CNS autoimmunity and inflammatory pathologies that occurred in previously healthy individuals shortly following a administration of mRNA-based SARS-CoV-2 vaccines at a single health system in the greater New York City area. Materials and Methods This is a case-series of five individuals within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine. Since this was a case series limited to individuals who Flumorph have been diagnosed and treated by the study authors, rather than a systemic review of all individuals within the health system who may have developed new-onset CNS inflammatory disease within a pre-specified 2-week period of receiving the vaccine, there may be additional undetected instances not included in this study. This statement was authorized by the Feinstein Institutes for Medical Study IRB (authorization # 20-0600). Written Flumorph consent was from all the individuals or their families. Anonymized data not published within this short article is definitely available upon request. Case Presentations Case #1: ADEM An 81-year-old man with no relevant neurological history presented to the emergency division (ED) with rapid-onset acute switch in mental status with severe encephalopathy mentioned about 13 days following a administration of the 1st dose of the Moderna SARS-CoV-2 vaccine. It was also preceded by prodromal symptoms of viral-like illness marked by several days of low-grade fever, fatigue, and myalgia. He had a fever of 102F without pores and skin rashes or nuchal rigidity. Neurological exam exposed minimal response to noxious stimuli, right gaze preference, minimal horizontal attention motions upon oculocephalic screening, absent pupillary response to light, absent right corneal reflex, diffuse hypertonicity, and extensor plantar reactions bilaterally. Head CT and CT angiogram of the head and neck were unremarkable. Serologies demonstrated slight leukocytosis with WBC count of 12.5 K/L (reference range 3.8C10.5 K/L), Erythrocyte Sedimentation Rate (ESR) of 86 mm/hr (research range 1C15 mm/h) and C-Reactive Protein (CRP) of 10.8 mg/L (reference range 4.9 mg/L). Cerebrospinal Fluid (CSF) analysis shown an opening pressure of 26 cmH2O, glucose of 69 mg/dL (research range 40C70 mg/dL), protein of 45 mg/dL (research range 15C45 mg/dL), and WBC count of 3 cells/L (research range 0C5 cells/L). Infectious workup was bad. It included urine tradition, urine legionella, respiratory disease panel PCR, encompassing influenza, parainfluenza, adenovirus, respiratory syncytial disease, Chlamydia pneumoniae, Mycoplasma pneumoniae, and enterovirus. Nasopharyngeal COVID-19 PCR and SARS-CoV-2 antibodies against nucleocapsid protein were bad (antibody formation to spike protein was not performed). Blood cultures drawn on admission (day time 1) and twice afterwards (day time 5 and 10) were without growth..
Categories
DUB
Of the precise reason Irrespective, we’ve shown that inside our system ATG proteins aren’t required for regular phagosome maturation
Of the precise reason Irrespective, we’ve shown that inside our system ATG proteins aren’t required for regular phagosome maturation. to procedure the cytosolic type of LC3 (LC3-I) in to the lipidated (and membrane-associated) type of LC3 (LC3-II) as confirmed with the disappearance from the LC3-II music group via traditional western blot (Fig.?F) and S1E.22 To research if autophagy protein are necessary for acquisition of Light fixture1, we challenged and in the lack of intraphagosomal CB5083 ROS than in the WT counterparts (Fig.?S3C). This suggests 2 factors: first, phagosome maturation will not need LAP and, second, CYBB NADPH oxidase might phagosome maturation under these circumstances in fact. Indeed, CYBB includes a controversial function in modulating phagosome maturation; some researchers find it delays phagosomal maturation,23,24 whereas others usually do not.25-27 Latest studies showed the fact that maturation position of macrophages dictates the consequences the fact that CYBB NADPH oxidase is wearing phagosome maturation.28 Predicated on these findings, we hypothesize that both ATG and CYBB proteins, that are linked in phagosomal development, may possess results on phagosome maturation that are condition-dependent and dynamicaltered by position from the macrophages possibly, e.g., in classically turned on macrophages (M1) vs. additionally turned on macrophages (M2). Yet another layer of intricacy is added with the appearance of CYBB NADPH oxidase regulators, such as for example RUBCN/Rubicon (Work area and cysteine-rich area formulated with, Beclin 1-interacting proteins). CB5083 RUBCN is necessary for LAP6 and it is upregulated in response to TLR2 activation.29 Thus, the decision from the phagocytic particle also affects the quantity of ROS produced as well as the destiny from the phagosome. It’s possible that various other positive and negative regulators from the CYBB NADPH oxidase also are likely involved in LAP.30-33 Further research must reveal the key reason why ATG proteins are essential in phagosome maturation in some conditions, however, not others. Of the precise cause Irrespective, we have proven that inside our program ATG proteins aren’t required for regular phagosome maturation. Therefore, we posit that LAP is not CB5083 needed for phagosome fusion with endosomes and lysosomes universally. Instead the partnership between ATG protein and phagosome maturation is much more likely and complex involves various other players. Materials and strategies Cells Mouse embryonic fibroblasts had been taken care of in Dulbecco’s customized Eagle’s moderate (HyClone, SH3024301) supplemented with 10% fetal bovine serum (FBS; Wisent, 090-510) at 37C in 5% CO2 without antibiotics. BioParticles, Tx Crimson conjugate (Molecular Probes, Z2843) had been used. On time 1, MEFs had been seeded on cup coverslips in 24-well tissues lifestyle plates at 2.5 104 cells/well, and, on day 2, transfected with FCGR2A-GFP construct using GeneJuice (Novagen, 70967-3) according to the manufacturers’ instructions. On time 3, phagocytosis was synchronized by rotating opsonized zymosan (OpZ) at 170 for 5?min onto cells. BMDMs had been seeded on cup coverslips in 24-well tissues culture dish at 2.0 105 cells/well, and, on the next time, phagocytosis was synchronized by rotating OpZ at 170 for 5?min. Cells were fixed with 2 in that case.5% paraformaldehyde (EMS, 15710) at 30, 60, 90, or 120?min and stained for OpZ and Light fixture1 (Developmental Research Hybridoma Bank on the College or university of Iowa, 1D4B). LysoBrite and DQ-BSA phagosome maturation assays SRBC (MP Biomedicals, 55876) had been opsonized by 1-h incubation with rabbit anti-sRBC antibody (MP Biologicals, 55806) at area temperature. Cells had been seeded on Ibidi microscopy chambers (80827). MEFs had been seeded at 1.0 104 cells/chamber and transfected with FCGR2A-GFP using GeneJuice. BMDMs had been seeded at 6.0 104 cells/chamber. For the LysoBrite assay, cells had been incubated PRKM8IP with LysoBrite (AAT Bioquest, 22659) for 30?min, according to the producers’ guidelines. For the DQ-BSA assay, cells had been incubated with 10?g/ml of DQ-BSA (Lifestyle Technologies, “type”:”entrez-nucleotide”,”attrs”:”text”:”D12051″,”term_id”:”2148853″,”term_text”:”D12051″D12051) for 1?h, accompanied by 1-h incubation in complete moderate. Phagocytosis was synchronized by content spinning in 170 for 5 sRBC?min onto cells. The cells had been imaged live at 30, 60, and 90?min period points after starting of phagocytosis. Imaging program Images were obtained utilizing a Wave-FX-X1 Rotating Disk Confocal, Leica DM16000B inverted analysis microscope with Hamamatsu ImagEMx2 (EMCCD) camcorder utilizing a 63x objective. Traditional western blotting Traditional western blotting was performed as previously referred to5 using LC3 (Novus, NB600-1384) and GAPDH (Millipore, MAB374) antibodies. RNA isolation and quantitative PCR RNA was isolated using the RNeasy.
Categories
DUB
Effects of AAL extract on antioxidation were similar to that of GB extract but higher than those of LC and AG extracts
Effects of AAL extract on antioxidation were similar to that of GB extract but higher than those of LC and AG extracts. Neuroprotective effects of AAL extract on H2O2-damaged HT22 neuronal cells Neuronal cell death is a major cause of neurodegenerative diseases including AD.21,22 To examine the effects of extracts on neuronal death, HT22 hippocampal cells were used. compounds showed that rutin and isoquercitrin had significant inhibitory activity on A aggregation. Taken together with biological activity and the content of compounds, rutin maybe a bioactive compound of AAL in the AD pathogenesis. Overall, our findings provide the first scientific support for the therapeutic effects of AAL in AD and AD-related disorders. Impact statement Our study was aimed to find a novel candidate drug for Alzheimers disease (AD) using natural products. We assessed the effects of extracts on crucial events in the pathogenesis of AD. leaf (AAL) extract significantly inhibited amyloid- aggregation, oxidative stress, neuronal cell death, and memory impairment through the epidermal growth factor receptor/G protein-coupled receptor kinase 2 pathway. Simultaneous analysis using HPLC determined six standard compounds of AAL extract, and rutin was identified as a bioactive compound. Of note, the anti-AD activity of AAL extract was more significant compared to other extracts from medicinal MK 0893 plants of which efficacy was MK 0893 previously reported. The potential of AAL extract as an anti-AD agent may provide insight into the new drug development for AD treatment. Annona atemoyaA. squamosa(sugar apple) and A. cherimola(cherimoya) that was first crossed by Wester in 1908, a horticulturist at the USDAs Subtropical Laboratory in Miami. is distributed in the subtropics and tropics such as Florida in the US, Philippines, Cuba, Jamaica, Taiwan, and Jeju in South Korea. fruit (AAF) is heart-shaped or round with pale-green and bumpy skin. It is used as an ingredient in juices, desserts, ice creams, or in natura.6C8 Bullatacin, an acetogenin isolated from AAF, has been reported to have anti-cancer activity in hepatoma cells.9,10 seed (AAS) was recently reported to have anti-angiogenic properties.11 However, there are no reports on the biological activity of leaves (AAL). In the present study, we demonstrate that AAL extract possess anti-AD effects, and we demonstrate its molecular mechanisms using and experimental models. In addition, we established the simultaneous analysis methods of six standard compounds for quality control MK 0893 and identified the bioactive compound from AAL extract. Materials and methods Preparation of ethanol extract from A. atemoya, Ginkgo biloba (GB), Lycium chinense (LC), and Angelica Rabbit Polyclonal to mGluR8 gigas (AG) was supported by Jeju Sunny Farm (Jeju, South Korea). The materials (AAL, AAF, and AAS) were dried and 2.7?kg of each was extracted twice with ethyl alcohol (60?L) for 3?h using the COSMOS-660 electric extractor (Kyungseo Machine Co., Incheon, South Korea). The extracted solutions were filtered, evaporated, and freeze-dried for making powdered extracts. GB, LC, and AG were obtained from the Naemome Dah (Ulsan, South Korea). Each material was dried and 50?g of each was extracted twice with ethyl alcohol (0.3?L) by refluxing for 2?h. The extracts were filtered and evaporated using a rotary evaporator. Solvent fractionation of AAL The powdered AAL extract (10?g) was suspended in H2O (0.2?L) and in turn partitioned with leaf. A aggregation assay A aggregation assay was performed using SensoLyte? Thioflavin T -Amyloid aggregation kit (AnaSpec, Fremont, CA). A1C42 peptides were stored at ?80C and used at 100?g/mL for the assay. Thioflavin T dye was prepared by dissolving in the Assay buffer included in the kit. AAL extract was dissolved in the Assay buffer (100?g/mL of final concentration). Thioflavin T (85?L) and AAL sample solution (5?L) were mixed and incubated in 96-well MK 0893 black microplate at 37C. Fluorescence readings were expressed as the relative fluorescence units. All assays were completed in triplicates. The inhibition rate (%) of A aggregation was assessed as described previously.12 Free radical scavenging activity.
Categories
DUB
Rune Kleppe and Inge Jonassen are part of Centre for Digital Life Norway (digitallifenorway
Rune Kleppe and Inge Jonassen are part of Centre for Digital Life Norway (digitallifenorway.org). Supplementary Materials Supplementary materials can be found at http://www.mdpi.com/1422-0067/19/2/612/s1. Click here for additional data file.(191K, pdf) Author Contributions Rune Kleppe performed the modelling and writing of the manuscript; Inge Jonassen provided expert advice on data analysis, interpretation and contributed on writing; Stein Ove D?skeland provided expert advice on cNMP signalling, interpretation of results and contributed on writing; Frode Selheim provided expert advice on platelet biology, model construction and data interpretation and contributed on writing of the paper. between the different platelet phosphodiesterases. Specifically, the models predict, unexpectedly, a strong effect of pharmacological inhibitors of cGMP-specific PDE5 on the cGMP/cAMP cross-talk. This may explain the successful use of weak PDE5-inhibitors, such as dipyridamole, in anti-platelet therapy. In conclusion, increased NO signalling or PDE5 inhibition are attractive ways of increasing cGMP-cAMP cross-talk selectively in platelets. adenylate cyclase and FhlA) domains, which increases both its = 22 M for the activated enzyme); for PDE3, cGMP strongly inhibits cAMP degradation; for PDE5, dipyridamole inhibits cGMP degradation of activated and non-activated enzyme states with the same = 1, 2). Binding of cGMP to PKG-I was modelled as sequential binding of cGMP, first to the high affinity site, second to the low affinity site, due to a 14 fold difference in affinity between the sites. Modelling PKG and PKA as monomers and dimers, respectively, is valid as no interchain interaction is reported for the dimeric PKG and regulatory PKA subunits [60,61]. The kinetics of NO dependent cGMP metabolism in platelets is has been investigated in several studies in rats [4,21,34]. During the first 10 seconds after NO stimulation, a pulsed increase in cGMP is observed before settling at a steady state concentration much lower than the maximal peak concentration (e.g. peak at 300 pmol cGMP/mg protein at 50 nM NO, corresponding to 150 M cGMP; steady state level 25 pmol/mg) [21]. This pulsed cGMP response is also found in human platelets [4]. The activation of soluble guanylyl cyclase (sGC) was modelled as described, ignoring the time dependent changes, as we were interested in steady state levels [34]. We used the same compartment modelling approach as described previously for cAMP signalling [62,63] and for other signalling pathways [64], where diffusion of free cAMP and cGMP between the compartments is proportional to the concentration difference between them (distribution of proteins and metabolites assumed homogeneous within each compartment). Karpen and co-authors have estimated the exchange flux of cAMP between a membranous area as well as the cytoplasm in HEK 293 cells utilizing a cAMP-responsive ion route for calculating cAMP concentrations. An exchange was reported by them price of 0.8 fl/s, in keeping with a diffusion rate of 3 10?6 cm/s (measured diffusion price of cAMP in cytoplasm), a hurdle amount of 1 m and a cross sectional section of 0.3 m2. In comparison to a 40 m2 region expected because of their area (cubic, 40 fl), we’ve been significantly less restrictive inside our quotes of barrier duration (0.1 m) and cross sectional region (0.65 m2). Nevertheless, the diffusion price of cAMP (3 10?6 cm2/s) should be expected to be low in platelets, because of high degrees of cAMP binding sites (at least 6.2 M [33]). In its destined condition, cAMP diffusion will be significantly decreased as well as absent (if PKA is normally anchored). Similar quarrels would keep for cGMP as well as for simplicity we’ve SDZ 220-581 established the diffusion flux identical for both nucleotides. Supposing an identical obvious diffusion between your cytoplasm and area, we computed a plausible flux (=?=?+?2???+?2??? em R /em ( em c /em em A /em 2) (6) mathematics xmlns:mml=”http://www.w3.org/1998/Math/MathML” display=”block” id=”mm107″ overflow=”scroll” mrow mrow mfrac mi d /mi mrow mi d /mi mi t /mi /mrow /mfrac mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi y /mi mi t /mi /mrow /msubsup mo = /mo msubsup mi V /mi mrow mi G /mi mi C /mi /mrow mrow mi c /mi mi y /mi mi t /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 5 /mn /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 2 /mn mo , /mo mi c /mi mi G /mi /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mfrac mrow msub mi J /mi mrow mi D /mi mi i /mi mi f /mi mi f /mi /mrow /msub /mrow mrow msub mi /mi mrow mi c /mi mi con /mi mi t /mi /mrow /msub /mrow /mfrac mo stretchy=”fake” ( /mo mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo stretchy=”fake” ) /mo /mrow /mrow /mathematics (7) mathematics xmlns:mml=”http://www.w3.org/1998/Math/MathML” display=”block” id=”mm108″ overflow=”scroll” mrow mrow mfrac mi d /mi mrow mi d /mi mi t /mi /mrow /mfrac mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo = /mo msubsup Rabbit Polyclonal to SCN4B mi V /mi mrow mi G /mi mi C /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 5 /mn /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 2 /mn mo , /mo mi c /mi mi G /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo + /mo mfrac mrow msub mi J /mi mrow mi D /mi mi i /mi mi f /mi mi f /mi /mrow /msub /mrow mrow msub mi /mi mrow mi c /mi mi con /mi mi t /mi /mrow /msub /mrow /mfrac mo stretchy=”fake” ( /mo mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mi c /mi msubsup mi G /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo stretchy=”fake” ) /mo /mrow /mrow /mathematics (8) mathematics xmlns:mml=”http://www.w3.org/1998/Math/MathML” display=”block” id=”mm109″ overflow=”scroll” mrow mrow mfrac mi d /mi mrow mi d /mi mi t /mi /mrow /mfrac mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi y /mi mi t /mi /mrow /msubsup mo = /mo msubsup mi V /mi mrow mi A /mi mi C /mi /mrow mrow mi c /mi mi y /mi mi t /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 3 /mn /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 2 /mn /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mfrac mrow msub mi J /mi mrow mi D /mi mi i /mi mi f /mi mi f /mi /mrow /msub /mrow mrow msub mi /mi mrow mi c /mi mi con /mi mi t /mi /mrow /msub /mrow /mfrac mo stretchy=”fake” ( /mo mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo stretchy=”fake” ) /mo /mrow /mrow /mathematics (9) mathematics xmlns:mml=”http://www.w3.org/1998/Math/MathML” display=”block” id=”mm110″ overflow=”scroll” mrow mrow mfrac mi d /mi mrow mi d /mi mi t /mi /mrow /mfrac mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo = /mo msubsup mi V /mi mrow mi A /mi mi C /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 3 /mn /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo ? /mo msubsup mi V /mi mrow mi P /mi mi D /mi mi E /mi mn 2 /mn /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo + /mo mfrac mrow msub mi J /mi mrow mi D /mi mi i /mi mi f /mi mi f /mi /mrow /msub /mrow mrow msub mi /mi mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msub /mrow /mfrac mo stretchy=”fake” ( /mo mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi con /mi mi t /mi /mrow /msubsup mo ? /mo mi c /mi msubsup mi A /mi mrow mi f /mi mi r /mi mi e /mi mi e /mi /mrow mrow mi c /mi mi o /mi mi m /mi mi p /mi /mrow /msubsup mo stretchy=”fake” ) /mo /mrow /mrow /mathematics (10) mathematics xmlns:mml=”http://www.w3.org/1998/Math/MathML” display=”block” id=”mm111″ overflow=”scroll” mrow mrow mfrac mrow msub mi k /mi mrow mi d /mi mi e /mi mi p /mi mi h /mi mi o /mi mi s /mi /mrow /msub /mrow mrow msub mi k /mi mrow mi p /mi mi h /mi mi o /mi mi s /mi /mrow /msub /mrow /mfrac mo = /mo mo stretchy=”fake” [ /mo mi K /mi mi we /mi mi n /mi mi SDZ 220-581 a /mi mi s /mi mi e /mi mo * /mo mo stretchy=”fake” ] /mo mfrac mrow mn 1 /mn mo ? /mo msub mi S /mi mrow mi p /mi mi P /mi mi D /mi mi E /mi /mrow /msub /mrow mrow msub mi S /mi mrow mi p /mi mi P /mi mi D /mi mi E /mi /mrow /msub /mrow /mfrac /mrow /mrow /mathematics (11) where in fact the superscript identifies the area (compshape change governed area (SCComp), cytexternal area) and subscript to the precise enzyme for prices and condition (destined or unbound/free of charge) for metabolites. For PDE2, which includes two substrates, that is specified in the subscript also. Reaction prices are given with em SDZ 220-581 V /em , amounts with as well as the diffusion flux with em J /em Diff. Formula (11) represents the steady condition relationship between your proportion of dephosphorylation and phosphorylation price constants being a function from the focus of energetic kinase ([Kinase*]) as well as the noticed phosphorylation stoichiometry of PDE ( em S /em pPDE). Hence, prices of phosphorylation ( em V /em phos = em k /em phos[PDE][Kinase*]) and dephosphorylation ( em V /em dephos = em k /em dephos[pPDE]) are symbolized by linear kinetics (supposing high em K /em m beliefs). 4.3. Parameter Estimation Within this scholarly research, we’ve relied over the quantitative measurements of sGC and cGMP-PDE mainly.
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Error bars indicate the SD
Error bars indicate the SD. wedelolactone might help to open up new avenues for design of novel compounds efficiently inhibiting malignancy cells. and [11]. Recently, in vitro and in vivo anti-cancer properties of wedelolactone in solid tumors including breast, colon, prostate, hepatocellular, pituitary cancers, and neuroblastoma were explained in a number of reports [12,13,14,15,16,17,18,19]. Wedelolactone is clearly a multi-target compound and its anti-cancer Rabbit polyclonal to VASP.Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family.Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. properties were primarily attributed to the inhibition of multiple kinases, androgen receptor, 5-lipoxygenase, and the c-Myc protein [13,15,17,18,19,20,21]. However, it was found recently that wedelolactone also inhibits topoisomerase II activity and blocks DNA synthesis in the breast malignancy cells, and that these effects are advertised by copper ions, at least partially via redox relationships [12,22]. This study demonstrates wedelolactone functions as inhibitor of 20S/26S proteasome chymotrypsin-like and to smaller degree also trypsin-like and caspase-like activities. Treatment of breast malignancy cells with wedelolactone resulted in build up of ubiquitinated proteins and proteins representing standard proteasomal targets, such as p21, p27, p53, and Bax. Molecular docking exposed a 5-BrdU effective binding of wedelolactone to the active sites of 1 1, 2, and 5 proteasomal subunits having a stronger preference for 5 subunit. The proteasome inhibition by wedelolactone is not dependent on cellular copper level in breast cancer cells. This study concludes that wedelolactone functions as copper-independent inhibitor of proteasome. 2. Results 2.1. Wedelolactone Inhibits Proteolytic Activities of Proteasome in Breast Malignancy Cell Lines MDA-MB-231, MDA-MB-468, and T47D cells were exposed to increasing concentrations of wedelolactone to study its effect on proteasome in breast malignancy cells. Chymotrypsin-like, trypsin-like and caspase-like activities of proteasome were evaluated in cell components using the activity-specific fluorogenic substrates. 5-BrdU Wedelolactone inhibited all three proteolytic activities of proteasome with the highest potency for the chymotrypsin-like activity (IC50 ideals 27.8 M for MDA-MB-231, 12.78 M for MDA-MB-468 and 19.45 M for T47D) (Number 1). Open in a separate window Number 1 Wedelolactone inhibits chymotrypsin-like, trypsin-like and caspase-like activities in breast malignancy cells. MDA-MB-231 (A); MDA-MB-468 (B); and T47D (C) cells were treated with numerous concentrations of wedelolactone (w) for 10 h. Proteasome activities were evaluated in cell components using the activity-specific fluorogenic substrates (Suc-LLVY-AMC for 5-BrdU screening chymotrypsin-like, Z-LLE-AMC for caspase-like, and Boc-LRR-AMC for trypsin-like activities). Treatment with MG132 served like a positive control. The data represent the mean ideals from three self-employed experiments. Error bars show the SD. * shows a significant (< 0.05) difference between wedelolactone-/MG132- and DMSO-treated cells. 2.2. Wedelolactone Inhibits Proteolytic Activities of Purified 20S and 26S Proteasome Complexes In Vitro The 26S proteasome purified from MDA-MB-231 cells and the commercially available 20S proteasome were incubated separately with the activity-specific fluorogenic substrates and wedelolactone in various concentrations to evaluate the ability of wedelolactone to inhibit their chymotrypsin-like, trypsin-like, and caspase-like activities. Wedelolactone inhibited all three proteasomal activities in vitro inside a dose-dependent manner with the highest potency against the chymotrypsin-like activity (IC50 ideals 9.97 5-BrdU M for 26S and 6.13 M for 20S proteasome) (Number 2). Open in a separate window Number 2 Wedelolactone inhibits chymotrypsin-like, trypsin-like, and caspase-like activities of purified 26S and 20S proteasome complexes in vitro. Wedelolactone (w) was added at numerous concentrations to reaction mixture comprising either (A) 26S proteasome purified from MDA-MB-231 cells or (B) commercially available 20S proteasome, and fluorogenic substrate (Suc-LLVY-AMC for screening chymotrypsin-like, Z-LLE-AMC for caspase-like, and Boc-LRR-AMC for trypsin-like activities). Fluorescence was measured after 1 h incubation. MG132 was used like a positive control. The data represent the mean ideals from three self-employed experiments. Error bars show the SD. * shows a significant (< 0.05) difference in.
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(B) Improved fork density in Cdk5-shRNA cells following HU (2?mM, 2?h) treatment: Control and Cdk5-shRNA cell lines were treated or not, tagged with successive pulses of IdU and CldU for 30 after that?min each
(B) Improved fork density in Cdk5-shRNA cells following HU (2?mM, 2?h) treatment: Control and Cdk5-shRNA cell lines were treated or not, tagged with successive pulses of IdU and CldU for 30 after that?min each. amounts of chromatin bridges. kinase assays in conjunction with mass spectrometry showed that Cdk5 can perform the RPA32 priming phosphorylations on serines 23, 29, and 33 essential for this checkpoint activation. Furthermore we found a link between lower Cdk5 amounts and much longer metastasis free success in breast cancer tumor patients and success in Cdk5-depleted breasts tumor cells after treatment with IR and a PARP inhibitor. Used together, these outcomes present that Cdk5 Brassinolide is essential for basal replication and replication tension checkpoint activation and showcase clinical opportunities to improve tumor cell eliminating. approach analyzed the influence of Cdk5 depletion on cell success in 2 breasts tumor versions after treatment with IR and a PARP inhibitor. Outcomes The depletion of Cdk5 appearance leads to lower cell success and changed S-phase dynamics The S-phase radioresistance, examined by the proportion of the making it through fraction after contact with 2 Gy (SF2) for unsynchronised cells synchronized cells, was considerably low in HeLa cells where Cdk5 was stably depleted (Cdk5-shRNA) in comparison to Control cells8 (proportion 1.5 0.16 for Control cells 1.06 0.20 for Cdk5-shRNA cells, = 0.004) (Fig.?1A and E). Open up in another window Amount 1. Clonogenic cell success of Control and Cdk5 deficient cell lines to raising doses of (A) 137Cs gamma rays (B) Hydroxyurea (HU) (C) 5-fluorouracil (5-FU) and (D) 6-thioguanine (6-TG). (A) Asynchronous or synchronized in S-phase (increase thymidine stop) cells had been irradiated and colonies had been allowed to develop for Brassinolide 10C15?times. (B) Asynchronous cells had been exposed to raising concentrations of HU within the culture moderate until colony fixation or Brassinolide even to (C) 5-FU or (D) 6-TG for 24?h accompanied by fresh colony and moderate development. Data represents the mixed mean SD from at least 2 unbiased tests using 2 different HeLa Cdk5 clones for every test in triplicate for any circumstances. (**< 0.01; ***< 0.001; Unpaired t-test). (E) Consultant western Brassinolide blot displaying the depletion of Cdk5 proteins in the two 2 Cdk5-shRNA cell lines utilized set alongside the 2 Control clones. Ku80 was utilized being a gel launching control. The Cdk5-shRNA HeLa cells also demonstrated an increased awareness to persistent hydroxyurea (HU) publicity, and 5-fluorouracil (5-FU) and 6 thioguanine (6-TG) treatment (Fig.?1B-D), all realtors that disrupt replication. To be able to assess whether an identical phenotype was observed in another cell model we utilized the same shRNA appearance program to stably deplete Cdk5 in U2Operating-system cells and discovered that asynchronous Cdk5-depleted U2Operating-system cells were even more sensitive towards the cell eliminating ramifications of HU and IR (Fig.?B) and S1A. The depletion of Cdk5 in the HeLa cell model on cell development and replication was additional characterized and discovered to be connected with a slower basal price of cell proliferation (Fig.?S2A) and S-phase (Fig.?S2B). The root causes had been a considerably slower replication speed in the Cdk5-shRNA cells in comparison to Control cells (median speed 1.06 0.03 Kb/min for Control and 0.87 0.02 Kb/min for Cdk5-shRNA cells) as assessed by DNA combing (Fig.?2A) and fewer dynamic roots per megabase of DNA (Fig.?2B). These data present for the very first time that Cdk5 has an active function in the legislation of Rabbit polyclonal to G4 replication dynamics under basal development conditions. Open up in another window Amount 2. Cdk5-shRNA cells present a faster progression through G2 and S following contact with HU. (A) Replication fork Brassinolide quickness distribution in charge and Cdk5-shRNA cells in treated (HU 2mM, 2?h) or untreated cells. 100 to 250 DNA fibres were have scored per condition. The quantities match the median (proven being a horizontal series) replication quickness. beliefs are indicated (NS – not really significant; *< 0.05; **< 0.01; ***< 0.001; ****<0.0001, Mann-Withney check). Data derive from 2 independent tests for every Cdk5-shRNA clone, mean beliefs from the 4 tests have been computed. (B) Elevated fork density.
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Supplementary MaterialsSupplementary Document
Supplementary MaterialsSupplementary Document. the molecular determinants of proliferative fate decisions, which constitute novel drug targets and biomarkers for B cell-mediated diseases potentially. (1). In additional cases, cell fates stochastically are founded apparently, such as for example for the introduction of competence from the bacterium (2) or the era of substitute color eyesight photoreceptors in (3), and so are thereby 3rd party of cellular background (4). Here, we analyzed whether B lymphocyte proliferation decisions will be the total consequence of stochastic or deterministic fate decisions, and whether molecular Parthenolide ((-)-Parthenolide) network determinants may be identified. B lymphocytes are an important element of the adaptive defense resource and response of antibody-producing cells. In response to invading pathogens, B lymphocytes proliferate rapidly, differentiate into antibody-producing cells, and create antigen-specific antibodies, which are crucial for a highly effective immune system response. B cells genetically diversify by rearranging the Ig locus to make a varied antibody repertoire and, consequently, varied B cell receptor (BCR)-antigen affinities, which control mitogenic indicators. While hereditary heterogeneity due to BCR diversification gets the potential to be always a way to obtain heterogeneity of B cell fate, Parthenolide ((-)-Parthenolide) BCR-antigen affinity can be an unhealthy predictor of B cell proliferative enlargement (5), and snapshot flow-cytometry measurements reveal a higher amount of cell-to-cell generational heterogeneity actually in response to BCR-independent stimuli (6). This resulted in the idea that B cell fate decision-making can be highly stochastic. Certainly, immediate dimension of department moments at single-cell quality exposed a adjustable 1st department (7 extremely, 8), in keeping with a stochastic decision-making procedure. Predicated on these observations, Hodgkin et al. (9) created a phenotypic style of lymphocyte proliferation using possibility distributions of department and death moments. The Cyton model shows remarkable capability to match dye dilution measurements by movement cytometry and derive related cell biological guidelines (such Parthenolide ((-)-Parthenolide) as for example division and loss of life moments) (9C13). Whereas an integral assumption from the Cyton model may be the 3rd party stochastic decision-making of every cell at each era, immediate observation of sibling cell behavior exposed correlations in cell fate department and decisions moments (8, 10, 11, 14). It has prompted revisions from the model to consider heritability. Therefore, lymphocyte inhabitants dynamics models have already been suggested that framework cell decisions by age group (9, 15, 16) or department quantity (17) (or specialized elements; refs. 18 and 19). Nevertheless, the amount to which fate decisions are nonstochastic continues to be unclear (20). Lately created approaches merging multiple division-tracking dyes exposed that clonal populations had been all of an identical era at provided time-points through the proliferative enlargement phase (21). To take into account these outcomes mathematically, one recent research suggested a distributed department destiny time that’s inherited through cell department, controlled partly from the proto-oncoprotein Myc and another time-to-die system (22). Prior research therefore supply the basis for taking into consideration the molecular systems root B cell decision-making and, therefore, quantify the amount of inheritance versus intrinsic sound. Generally, progeny cells are believed to inherit proteomic systems that mediate decisions (23, 24), Certainly, immediate observation of protein abundances indicated how the mixing period of inherited proteins surpasses two decades (a lot more than 40 h) (25). Nevertheless, in research of TRAIL-induced loss of life, the concordance of cell fates among siblings decayed quickly (having a half-life of just one 1.5 h) (23). Blocking protein synthesis slowed this lack of concordance, indicating a considerable part for intrinsic gene manifestation noise (26). From what level gene expression sound or other resources of intrinsic molecular variability influence phenotypic heterogeneity of B cell decision-making continues to be to be established. In today’s study, we dealt with TNFRSF16 the molecular underpinnings from the heterogeneity of cell destiny decisions during B cell enlargement and analyzed the jobs of heritability and intrinsic sound. To acquire accurate, longitudinal, single-cell lineage info, we founded an experimental workflow for long-term live cell microscopy of.
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Supplementary MaterialsSupplementary Information srep29338-s1
Supplementary MaterialsSupplementary Information srep29338-s1. Clinically, a higher frequency of memory space CXCR4+CD4+ T cells expected a better response to CTLA4-Ig. Memory space CXCR4+CD4+ T cells may serve as a powerful biomarker for unraveling the linkage between HLA-DRB1 genotype and disease activity in RA. Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to destructive arthritis. Both genetic and Tiplaxtinin (PAI-039) environmental factors contribute to RA pathogenesis1. A recent meta-analysis of genome-wide association studies identified as many as 101 RA risk loci2. In particular, the HLA-DRB1 genotype was the 1st identified and by far the strongest genetic risk element for RA3,4. The shared epitope (SE), a common amino acid sequence at positions 70C74 of HLA-DRB1, is definitely recognized for its association with anti-cyclic citrullinated peptide antibody (ACPA)-positive RA5. It is thought that citrullinated autoantigen epitopes bind to HLA-DRB1 that contain the SE and are presented to CD4+ T cells, which contribute to autoimmunity6. Moreover, SE is an important risk element for severe bone destructive disease5,7. Nevertheless, in spite of tremendous efforts to identify immunological abnormalities in RA, few studies have identified any linkage between SE and adaptive immunity. To understand the immunological role of SE, immune cell populations associated with SE should be identified. The key role of CD4+ T cells in RA pathogenesis is highlighted by the fact that RA genetic risk loci preferentially map to enhancers and promoters active in CD4+ T cell subsets8. Standardized human immunophenotyping has been proposed for classifying CD4+ T cells into conventional Th1, Th2, and Th17 cell types based on their expression of the chemokine receptors CXCR3 and CCR69. Although a number of researchers have examined the frequency of Th1, Th2, Th17, Tfh, and Treg cells in RA, these populations show no clear association with RA disease activity measures, such as Disease Activity Score 28 joints-ESR (DAS28esr) and Health Assessment Questionnaire Disability Index (HAQ)10,11,12,13. Therefore, other markers for CD4+ T cells need to be investigated. In the RA synovium, there are ectopic lymphoid follicles as well as clonally expanded T cells and antigen-specific B cells that recognize citrullinated autoantigens14,15. These findings strongly suggest that acquired immunity against autoantigens promotes local Ncam1 inflammation in the synovium, such as macrophage activation and Tiplaxtinin (PAI-039) inflammatory cytokine production, including TNF- and IL-6. The chemokine receptor CXCR4 plays a central role in the homing and retention of CD4+ T cells16,17. The CXCR4 ligand CXCL12 (also known as SDF-1) and the recently identified ligand macrophage migration inhibitory factor (MIF) are both produced by synovial fibroblasts and are increased in RA synovium18,19,20. It has also been reported that inflammatory cytokine-activated CD4+ T cells express high levels of CXCR421 and that T-cell-specific CXCR4-deficient mice show a dramatic decrease in the incidence of arthritis22. Based Tiplaxtinin (PAI-039) on these preceding reports, we attempted to identify lymphocyte subsets that are associated with HLA-DRB1 and RA disease activity. We analyzed HLA-DRB1-genotyped RA patients by 24-subset immunophenotyping combined with CXCR4 expression, HLA-DR quantification on antigen-presenting cells, Tiplaxtinin (PAI-039) and multiplex serum cytokine analysis. Results Study populations We recruited 91 RA patients and 110 healthy donors (HD) (Table S1). 61 RA patients with at least one HLA-DRB1 SE allele were considered to be SE-positive RA (SE?+?RA). Among the SE?+?RA group, 44 patients (72%) had at least one HLA-DRB1 04:05 allele, 14 patients (23%) had at least one 01:01 allele, and 6 patients (10%) Tiplaxtinin (PAI-039) had the 04:01 allele. The SE?+?RA and SE-negative RA (SE-RA) groups showed comparable baseline features, including rheumatoid element (RF) titer, DAS28esr disease activity rating, and HAQ functional impairment index. ACPA titer was higher within the SE significantly?+?RA group set alongside the SE-RA group, as reported5. Memory space Compact disc4+ T cells are connected with ACPA and SE positivity in RA We performed movement cytometric 24-subset immunophenotyping on newly isolated PBMC to be able to assess global immunological adjustments in.
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Age-related clonal hematopoiesis is usually a significant risk factor for myeloid malignancy and myeloid skewing is normally a hallmark of ageing
Age-related clonal hematopoiesis is usually a significant risk factor for myeloid malignancy and myeloid skewing is normally a hallmark of ageing. BM demonstrated a statistically significant reduction in hematopoietic region (Amount?1B) and a rise in adipocytic articles in older adult BM (Statistics 1C and 1D). Both age ranges have got the same thickness of NGFR+ BMSCs (Statistics 1C and 1E). Old and Middle-aged adult BM demonstrated no difference over the percentage of Compact disc34+ HSPCs, assessed as the percentage of Compact disc34+ 2-Methoxyestrone cells over total nuclei inside the hematopoietic region (p?= 0.14, data not shown). Nevertheless, a solid positive relationship was discovered between Compact disc34+ HSPCs and age group (Statistics 1C and 1F). Furthermore, a rise in maturing myeloid cells, was seen in the hematopoietic section of BM of old adults (Statistics 1C and 1G). To see whether the upsurge in maturing myeloid cells in the BM of old adults, sometimes appears in peripheral bloodstream also, peripheral blood counts from both mixed groups were compared. We found a rise altogether myeloid cells and a reduction 2-Methoxyestrone in lymphoid cells in the old adult group (Desk 1). Our results confirm previous research that reported a rise in Nr4a1 HSPCs (Kuranda et?al., 2011; Pang et?al., 2011; Rundberg Nilsson et?al., 2016). Nevertheless, 2-Methoxyestrone as opposed to our outcomes, these scholarly research didn’t discover a rise in myeloid cells. While previous reviews used stream cytometry to detect dedicated progenitors, our research assessed maturing myeloid cells by IHC. Open up in a separate window Number?1 Aged Human being BM Shows an Increased Denseness of Adipocytes, CD34+ HSPCs, and Maturing Myeloid Cells (A) Representative images of an H&E stain of a middle-aged adult BM (total bone marrow area) and quantification of non-bone and hematopoietic area. Non-bone area (yellow area) excluding trabeculae (asterisk). Hematopoietic area (red area) excluding trabeculae (asterisk) and adipocytes (arrow). Level pub, 2-Methoxyestrone 100 m. IHC staining, DAB; counterstain, hematoxylin. 20?magnification. (B) Percentage of BM hematopoietic area in both age groups: 50C64 years (n?= 7) versus 65C92 years (n?= 5), p?= 0.03. (C) Representative IHC images (unique) of adipocytes, NGFR+ BMSCs, CD34+ HSPCs, and maturing myeloid cells in BM biopsies from hematologically healthy individuals aged 50C64 and 65C92 years. Each image is definitely accompanied by its objects identification outline image produced by CellProfiler (Image Analysis). Scale pub, 200?m. (D) Adipocyte denseness in individuals aged 50C64 years (n?= 7) and 65C92 years (n?= 5). p?= 0.03. (E) NGFR+ BMSC denseness: 50C64 years (n?= 7) versus 65C92 years (n?= 7), p?= 0.14. (F) Association between CD34+ HSPCs and age. Pearson correlation test, r?= 0.71, n?= 10. (G) Maturing myeloid cell denseness: 50C64 (n?= 7) and 65C92 years (n?= 5), p?= 0.01. Table 1 Peripheral Blood Guidelines from Hematologically Healthy Individuals Aged 50C92 Years thead th rowspan=”1″ colspan=”1″ Age Groups /th th rowspan=”1″ colspan=”1″ Leukocytes (103/L) /th th rowspan=”1″ colspan=”1″ Myeloid Cells (103/L) /th th rowspan=”1″ colspan=”1″ Neutrophils (103/L) /th th rowspan=”1″ colspan=”1″ Monocytes (103/L) /th th rowspan=”1″ colspan=”1″ 2-Methoxyestrone Lymphocytes (103/L) /th th rowspan=”1″ colspan=”1″ Erythrocytes (103/L) /th th rowspan=”1″ colspan=”1″ Hematocrit (%) /th th rowspan=”1″ colspan=”1″ Platelets (103/L) /th /thead 50C64 years (n?= 28)7.15 .594.92 .394.21 0.380.52 0.042.26 0.144.62 0.0840.67 0.74254.1 11.0965C92 years (n?= 30)8.36 .736.54 .555.70 0.530.64 0.041.78 0.134.55 0.0941.16 0.80274.6 15.37p ideals0.210.020.020.040.010.580.660.28 Open in a separate window CD34+ HSPCs Are Immediately Adjacent to Adipocytes Maintaining Perivascular Location in Middle-Aged and Older Adult Human BM Given the increased quantity of CD34+ HSPCs and adipocytes in the BM of older adults, we identified if there was an association between these two populations. We verified a positive relationship between the thickness of adipocytes and Compact disc34+ HSPCs in examples from both groupings (Amount?2A). Furthermore, we noticed Compact disc34+ HSPCs located instantly next to adipocytes (Amount?2B). Oddly enough, we discovered a statistically significant upsurge in the percentage of Compact disc34+ HSPCs instantly next to adipocytes in the old adult group (Statistics 2B and 2C). Provided the elevated adipocyte articles in the BM of old adults, we also examined whether an individual adipocyte will make contact with several Compact disc34+ HSPC. Oddly enough, we found an increased variety of adipocytes instantly adjacent to several Compact disc34+ HSPC in old individuals (Amount?2D). Open up in another window Amount?2 Human Maturity Is Connected with Increased Adjacency between Compact disc34+ HSPCs and Adipocytes (A) Positive relationship between adipocytes and Compact disc34+ HSPCs. Pearson relationship.
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Supplementary MaterialsadvancesADV2020001699-suppl1
Supplementary MaterialsadvancesADV2020001699-suppl1. blood loss for all those DOACs, indicating the versatility of superFVas properties that contribute to its universal prohemostatic effects for DOAC associated bleeding. Supported by thrombin generation assays on endothelial cells in normal plasma spiked with DOACs and patient plasma anticoagulated with DOACs, 3 complementary mechanisms were identified by which superFVa achieved DOAC class-independent prohemostatic efficiency. These mechanisms are resistance to inactivation by APC, overcoming the FV activation threshold, and maximizing the efficiency of the prothrombinase complex when the available FXa is usually increased by FVIIa-based prohemostatics. In summary, it is this versatility of superFVa that delineates it from other prohemostatic agents as a encouraging class-independent rescue agent in bleeding situations associated with DOACs. Visual Abstract Open in a separate window Introduction Direct-acting oral anticoagulants (DOACs) progressively replace warfarin for treatment and prevention of venous thromboembolism or prevention of ischemic stroke.1-3 Anticoagulant therapy increases bleeding risk, requiring prohemostatic brokers in case severe bleeding occurs. Bleeding rates in patients on DOACs reported from large clinical trials are 5% per year.4-9 Real-world experience data from your Dresden DOAC Registry and the Fushimi AF Registry are comparable and demonstrate major bleeding in approximately 3% to 6% per year.10,11 Specific DOAC-reversal brokers, idarucizumab (Praxbind, Boehringer-Ingelheim), a specific humanized monoclonal antibody against the direct thrombin inhibitor dabigatran (Pradaxa, Boehringer-Ingelheim),12-16 and coagulation factor Xa (recombinant) inactivated-zhzo (Andexanet Alfa, Andexxa, Portola Pharmaceuticals Inc.), a CDK4/6-IN-2 decoy for direct oral factor (F)Xa Comp inhibitors (rivaroxaban, Bayer; apixaban, Bristol Meyers-Squibb; edoxaban, Daiichi-Sankyo), were approved by the US Food and Drug Administration for patients going through life-threatening bleeding.17-19 Both agents have confirmed efficacious in clinical trials for reversing the anticoagulant effects of DOACs, but their effect on clinical outcomes is usually less obvious. Andexanet-alfa is usually a catalytically inactive FXa decoy20 shown to reverse the anticoagulant effects of FXa inhibitors by reduction of anti-FXa activity in healthy volunteers and patients,17-19,21 with hemostatic efficacy in the majority of patients.21 However, andexanet alfa has a boxed warning for thromboembolic risks, ischemic risks, cardiac arrest, and sudden loss of life, with these adverse events occurring in up to 18% of sufferers in CDK4/6-IN-2 clinical studies.22 Zero conclusive data are published to measure the efforts of idarucizumab to clinical hemostasis, but fast reversal of anticoagulant results has been proven.15,16,23 Additional agents are being created for reversal of FXa inhibitors including ciraparantag (PER977; Amag Pharmaceuticals),24 which really is a artificial molecule that binds all DOACs.24,25 In healthy volunteers, ciraparantag demonstrated sustained reversal of anticoagulation after edoxaban administration predicated on visual inspection of whole blood coagulum formation.25 Within this context, it’s important to identify that idarucizumab,12 andexanet-alfa,20 and ciraparantag24 are huge molecules made to absorb little molecular weight inhibitors to improve abnormal clotting variables,26 and these agents don’t have intrinsic procoagulant properties. Therefore, their efficiency and scientific utility to recovery severe bleeding circumstances without adding various other procoagulants remains relatively uncertain. Right here we propose turned on superFactor V (superFVa), an constructed FVa-variant with improved balance, being a prohemostatic enhancement strategy rather than drug-absorbing strategy for reversal of DOAC-associated bleeding.27 SuperFVa normalizes hemostasis in other murine experimental bleeding models such as hemophilia or traumatic injury.27-29 Normal FVa enhances the rate of thrombin generation in the prothrombinase complex by approximately 10?000-fold,30 but is usually rapidly inactivated by activated protein CDK4/6-IN-2 C (APC). SuperFVa is usually resistant to APC inactivation because of mutations of 3 APC cleavage sites (Arg506/306/679Gln), and has enhanced specific activity because of an designed disulfide bond (Cys609-Cys1691) between the A2 and A3 domains.27 SuperFVas ability to both enhance the DOAC-compromised prothrombinase complex and convey APC-resistance may portend a double advantage for inhibition of DOAC-associated bleeding. This may be important because it is usually increasingly acknowledged that APC contributes to bleeding in acute traumatic injury and in hemophilia.31-33.
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Shoulder Replacement
Shoulder replacement, also known as shoulder arthroplasty, is a surgical procedure in which a damaged or diseased shoulder joint is replaced with an artificial joint or prosthesis. This procedure is typically performed to relieve pain and improve the function of the shoulder joint when other non-surgical treatments have failed to provide adequate relief.
The most common reasons for shoulder replacement surgery include
• osteoarthritis,
• rheumatoid arthritis,
• irreparable torn rotator cuff muscle tendons in the shoulder,
• avascular necrosis (loss of blood supply) of the head of humerus and
• severe fractures of the shoulder.
There are different types of shoulder replacement surgeries, including:
• Total Shoulder Replacement (TSR): In a TSR, both the ball (the humeral head) and socket (the glenoid) of the shoulder joint are replaced with artificial components similar to native anatomy. This is the most common type of shoulder replacement.
• Reverse Shoulder Replacement: This procedure is typically recommended for individuals with severe rotator cuff tears or certain types of fractures. In a reverse shoulder replacement, the positions of the ball and socket are reversed. The ball component is placed on the glenoid, and the socket component is attached to the humerus. These prosthesis are more and more used now a days.
• Partial Shoulder Replacement: In some cases, only one part of the shoulder joint may be damaged or arthritic, such as the humeral head. In a partial shoulder replacement, only the damaged part is replaced with a prosthesis, while the healthy parts are preserved. This type of replacements are rarely used and mostly done in cases like avascular necrosis or severe fractures involving the humeral head.
The goal of shoulder replacement surgery is to reduce pain, improve shoulder function, and enhance the patient's overall quality of life. Recovery and rehabilitation are essential aspects of the process, and patients typically work with physical therapists to regain strength and range of motion in the shoulder.
As with any surgical procedure, shoulder replacement surgery carries risks and potential complications, and it may not be suitable for everyone. It's important for patients to discuss the benefits, risks, and alternatives with us and to carefully consider the recommendations based on their individual medical history and condition.
Dr Vishnu Unnithan underwent extensive training in shoulder replacement in India and abroad and has many happy and satisfied patients who underwent this procedure by him, who can vouch for this successful treatment modality.
The success of a shoulder replacement depends on various factors, including the patient's overall health, adherence to post-operative rehabilitation, and the skill and experience of the surgeon. It is essential for individuals considering shoulder replacement to have a thorough evaluation and consultation with our specialist team to determine if the procedure is appropriate for them.
Stay Connected With Us
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Hypothyroidism is a condition in which the thyroid gland is underactive and doesn’t properly make or release thyroid hormones. The thyroid gland normally releases many crucial hormones that travel through the bloodstream to reach receptors found throughout the whole body. So a disturbance in thyroid function can cause widespread, noticeable health problems.
Try this: Make a lassi, a traditional Indian beverage: purée yogurt, frozen mango chunks, and lime juice, then pour into glasses and garnish with slices of lime. Purée yogurt with blackberries, honey, and grated ginger; stir in vanilla yogurt to make swirls and then spoon into Popsicle molds and freeze. Dump a container of yogurt into a cheesecloth-lined strainer and refrigerate overnight; stir in your favorite herbs and seasonings, and use as a substitute for sour cream.
Similar to processed foods, fast food chains also aren't required to use iodized salt in their foods. And even when they do, it might not boost the iodine content all that much, according to one 2010 commentary in the journal Endocrine Practice, which tested products from two fast food restaurants in the Boston area. The study authors concluded that drive-thru fare might be pretty low in iodine.
Treatment for hyperthyroidism - Hyperthyroidism is the opposite of hypothyroidism; it is a condition in which the thyroid gland is over-producing the thyroid hormones thus causing a hormone imbalance in the body. Hyperthyroidism can be treated with radioactive iodine and/or anti-thyroid medications, both of which are meant to reduce and normalize the thyroid function. In some cases, these treatments can cause permanent hypothyroidism if too much medication is administered.
Emphasizing lean proteins, vegetables, fruits, heart-healthy fats and omega-3s, high-fiber foods, and appropriate portions can help manage or prevent illnesses associated with thyroid disease. As Schneider notes, “It’s eating for prevention of all these diseases that accompany thyroid disease: heart disease, diabetes, cancer, and more.” As an added bonus, fiber can relieve constipation that people with hypothyroidism often experience.
“The effects of fluoride on various aspects of endocrine function should be examined, particularly with respect to a possible role in the development of several diseases or mental states in the United States. Major areas of investigation include . . . thyroid disease (especially in light of decreasing iodine intake by the U.S. population).” (National Research Council, 2006)
In its earliest stage, hypothyroidism may cause few symptoms, since the body has the ability to partially compensate for a failing thyroid gland by increasing the stimulation to it, much like pressing down on the accelerator when climbing a hill to keep the car going the same speed. As thyroid hormone production decreases and the body’s metabolism slows, a variety of features may result.
People diagnosed with hypothyroidism are more susceptible to problems with infertility, miscarriages, and having babies born with birth defects. As hypothyroidism progresses it can even lead heart failure, fluid collection in the lungs, and enlarged heart and even a life-threatening condition called myxedema coma. This condition requires immediate medical attention and hospitalization. If you suffer from hypothyroidism and have any of the following symptoms, contact your doctor at the earliest:
Hyperthyroidism usually is treated with medications, surgery, or oral radioactive iodine. However, these treatments are imprecise and may cause the thyroid to secrete inadequate amounts of T3 and T4 and function insufficiently after treatment. Seventy percent to 90% of patients with Graves’ or thyroid cancer eventually need treatment for hypothyroidism as a result of treatment.6
Foods that contain some vitamin D include fatty fish, milk, dairy, eggs, and mushrooms. Sunlight also is a potential source, but the amount of vitamin production depends on the season and latitude. If clients have low vitamin D levels, supplemental D3 may be necessary, and the client’s physician should monitor progress to ensure the individual’s levels stay within an appropriate range.
The most common thyroid condition is hypothyroidism, or underactive thyroid. In the United States, hypothyroidism usually is caused by an autoimmune response known as Hashimoto’s disease or autoimmune thyroiditis. As with all autoimmune diseases, the body mistakenly identifies its own tissues as an invader and attacks them until the organ is destroyed. This chronic attack eventually prevents the thyroid from releasing adequate levels of the hormones T3 and T4, which are necessary to keep the body functioning properly. The lack of these hormones can slow down metabolism and cause weight gain, fatigue, dry skin and hair, and difficulty concentrating (see table).2 Hashimoto’s affects approximately 5% of the US population, is seven times more prevalent in women than men, and generally occurs during middle age.3
Supplementing with L-tyrosine has been shown to improve sleep deprivation and can help combat fatigue and a poor mood by improving alertness and neurotransmitter function. One reason L-tyrosine is beneficial in healing thyroid symptoms is because it plays a role in the production of melatonin, dopamine and/or norepinephrine, which are our natural “feel good” hormones. (17)
Sorry to hear this! It is usually related to autoimmune activity and/or excess hydrogen peroxide burning the thyroid leading to abnormal/mutated cells – like a callus on your hand when you are rough with your hands. I would recommend following the principles in this article. Not sure if it can be fully reversed, but you must STOP THE CAUSE and help the body to heal itself.
Hypothyroidism Medication: Conventional doctors almost always put their patients on either Synthroid® (a synthetic thyroid hormone pill that contains only T4; sometimes called Levothyroxine, Levothroid, Unithroid, and Tirosint) or Armour (Natural Desiccated Thyroid derived from the thyroid glands of pigs). Both are tablets that patients will have to take daily for the rest of their lives. In some cases, these medications might help, but there are all kinds of side effects and issues that arise. So I recommend two other medications over these two instead.
Central or pituitary hypothyroidism: TSH (Thyroid-stimulating hormone) is produced by the pituitary gland, which is located behind the nose at the base of the brain. Any destructive disease of the pituitary gland or hypothalamus, which sits just above the pituitary gland, may cause damage to the cells that secrete TSH, which stimulates the thyroid to produce normal amounts of thyroid hormone. This is a very rare cause of hypothyroidism.
Essential fatty acids found in fish oil are critical for brain and thyroid function. DHA and EPA omega-3s found in fish oil are associated with a lower risk for thyroid symptoms, including anxiety, depression, high cholesterol, inflammatory bowel disease, arthritis, diabetes, a weakened immune system and heightened autoimmune disease. Omega-3 fish oil such as cod liver oil can also help balance levels of omega-6s in the diet, which is important for ongoing health.
It is medically proven that small frequent meals are healthier for persons with hypothyroidism compared to eating large-bulky meals per day. A study showed that eating 5-6 small meals a day will help a person lose weight and ward off the symptoms of the disease. It does not only help your intestines to digest food, it also keeps your energy level up.
To ensure that you remain as healthy as possible it is important to eat the right variety of foods in the correct proportions. For example, choose low fat, low calorie spread rather than butter or ordinary margarines, avoid high salt intake and cut down on hidden fats & sugars (cakes, biscuits, chocolate). More information is available from NHS guidance.
In humans, a factor associated with response to combination therapy in a large clinical trial is the Thr92Ala polymorphism in the type 2 deiodinase gene (DIO2), wherein the subpopulation of patients with this genetic alteration had improved well-being and preference for combination therapy (7). This has led investigators to consider whether this polymorphism could confer a defect in the D2 pathway, but normal Thr92AlaD2 enzyme kinetics have been demonstrated (73). Only recently has the Thr92AlaD2 protein been found to have a longer half-life, ectopically localize in the Golgi apparatus, and significantly alter the genetic fingerprint in cultured cells and in the temporal pole of the human brain without evidence of reduced thyroid hormone signaling (74). The significance of these studies transcends the thyroid field—this polymorphism has now been associated with a constellation of diseases, including mental retardation, bipolar disorder, and low IQ (75). If hypothyroid carriers of Thr92AlaD2 benefit from alternate therapeutic strategies in replicate studies, then personalized medicine—based on genotype— may have a role.
If your sex hormones (estrogen, progesterone, testosterone) and adrenal hormones (cortisol, DHEA) are out of balance, this can make weight loss more difficult. Perimenopause and menopause, as well as estrogen dominance, can also cause a shift of weight to the belly, and make weight loss more difficult. Lack of testosterone in men and women can also make it harder to build fat-burning muscle. And adrenal imbalances can make you tired, less responsive to thyroid treatment, and less able to lose weight.
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Please Note: The material on this site is provided for informational purposes only and is not medical advice. Always consult your physician before beginning any diet or exercise program.
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Antibody Responses Induced In Balb/C Mice Vaccinated With Malaria Dna Vaccine Candidate, Psebcgtt, Co-Expressing Ccl5 Or Ccl20 As Adjuvants
JOSIAH OGISE 79 PAGES (16756 WORDS) Immunology Thesis
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ABSTRACT
Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Parasite resistance to current antimalarials and resistance of Anopheline mosquitoes to insecticides have hampered control and elimination of malaria. Over the past twenty years, many vaccine candidates have been under development but none has advanced to clinical trials due to lack of appropriate adjuvant for human use. A vaccine inducing high levels of Immunoglobulin M (IgM), total IgG (or IgG1, IgG2, and or IgG3) would be important for effective control of malaria. DNA vaccines are safer and easy to mass produce and store, but they are less immunogenic and require an adjuvant to boost their immunogenicity. Although the adjuvants CCL5 and CCL20 have chemotactic properties and can immunopotentiate DNA vaccines, no previous study had evaluated their potential use as effective strain transcending blood-stage malaria DNA-adjuvant antibody-inducing vaccine. The present study sought to determine antibody immunity induced in mice vaccinated with malaria DNA vaccine candidate, pSeBCGTT, expressing CCL5 or CCL20 as an adjuvant. Mice in groups of 18 animals each were treated as follows: Group I was vaccinated with pSeBCG/TT/CCL5; Group II was immunized with pSeBCG/TT/CCL20; Group III was injected with pSe/BCG/TT alone while Group IV was inoculated with pIRES plasmid and Group V was a non-vaccinated control. All vaccinations were done intramuscularly with 100 μg of the inoculants per dose on days 0, 21, and 42. Blood samples for sera preparation were collected at day 0, 21, 42 and 63 post-vaccination for determination of antibody levels including IgM, total IgG, and IgG sub-classes. Data were analyzed using one-way analysis of variance (ANOVA) and where applicable, Bonferroni test was used as a post hoc. A P value ≤ 0.05 was considered statistically significant. Results indicated that the mice group vaccinated with pSeBCGTT/CCL20 induced significantly higher IgM antibody levels as compared to pSeBCGTT/CCL5 or pSeBCGTT alone (P < 0.01). Similarly, vaccination with pSeBCGTT/CCL20 produced significantly higher IgG levels as opposed to pSeBCGTT/CCL5 or pSeBCGTT alone (P < 0.01). Further analysis indicated a significant difference in IgG subclasses in vaccinated mice groups with the pSeBCGTT/CCL20 inducing the highest levels of IgG1, IgG2b and IgG3 compared to vaccination with either pSeBCGTT/CCL5 or pSeBCGTT (P < 0.05) while pSeBCGTT/CCL5 induced the highest IgG2a antibody levels as compared to either pSeBCGTT/CCL20 or pSeBCGTT alone (P < 0.05). Comparison between antibody isotype levels showed that IgG levels were significantly higher than IgM (P
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APA
OGISE, J (2021). Antibody Responses Induced In Balb/C Mice Vaccinated With Malaria Dna Vaccine Candidate, Psebcgtt, Co-Expressing Ccl5 Or Ccl20 As Adjuvants. Afribary. Retrieved from https://afribary.com/works/antibody-responses-induced-in-balb-c-mice-vaccinated-with-malaria-dna-vaccine-candidate-psebcgtt-co-expressing-ccl5-or-ccl20-as-adjuvants
MLA 8th
OGISE, JOSIAH "Antibody Responses Induced In Balb/C Mice Vaccinated With Malaria Dna Vaccine Candidate, Psebcgtt, Co-Expressing Ccl5 Or Ccl20 As Adjuvants" Afribary. Afribary, 01 Jun. 2021, https://afribary.com/works/antibody-responses-induced-in-balb-c-mice-vaccinated-with-malaria-dna-vaccine-candidate-psebcgtt-co-expressing-ccl5-or-ccl20-as-adjuvants. Accessed 22 Feb. 2024.
MLA7
OGISE, JOSIAH . "Antibody Responses Induced In Balb/C Mice Vaccinated With Malaria Dna Vaccine Candidate, Psebcgtt, Co-Expressing Ccl5 Or Ccl20 As Adjuvants". Afribary, Afribary, 01 Jun. 2021. Web. 22 Feb. 2024. < https://afribary.com/works/antibody-responses-induced-in-balb-c-mice-vaccinated-with-malaria-dna-vaccine-candidate-psebcgtt-co-expressing-ccl5-or-ccl20-as-adjuvants >.
Chicago
OGISE, JOSIAH . "Antibody Responses Induced In Balb/C Mice Vaccinated With Malaria Dna Vaccine Candidate, Psebcgtt, Co-Expressing Ccl5 Or Ccl20 As Adjuvants" Afribary (2021). Accessed February 22, 2024. https://afribary.com/works/antibody-responses-induced-in-balb-c-mice-vaccinated-with-malaria-dna-vaccine-candidate-psebcgtt-co-expressing-ccl5-or-ccl20-as-adjuvants
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5eff3d1f6f98e57329caed0ceb9053d3
|
8,277,807,560,984,863,000
|
Skip Nav
How Much Fruit Should I Eat in a Day?
How Much Fruit Should You Actually Eat in a Day? Here's What a Dietitian Says
Photographer: Sheila GimNo Restrictions: Editorial and internal use approved. OK for Native and co-branded use.
You've probably read that you should eat plenty of fruits and vegetables during the day to support a healthy diet. But what exactly does "plenty" mean? And won't eating too much fruit make you gain weight? We spoke to Jim White, RD, ACSM, owner of Jim White Fitness and Nutrition Studio, who broke it down for us.
The USDA recommends adults eat a minimum of two servings of fruit a day, while the American Heart Association recommends at least four servings of fruit per day.
"Fruit provides a wonderful array of vitamins, micronutrients and antioxidants, from vitamin A, C and beta carotene," Jim told POPSUGAR. And while fruit can be high in fibre, a nutrient most Americans need more of, it is possible to overdo it on the fruit and eat too much fibre, especially if you're also eating a lot of vegetables.
He recommends balancing the amount of fruit and vegetables you have a day based on fibre recommendations: 28 grams a day for women under 50, and 21 grams for women over 50, and 38 grams per day for men under 50, 30 grams for men over 50. Keeping that in mind, you should still shoot for at least two servings a day of fruit.
"Of course, fruits still have calories and sugar so eating as much as you want wouldn't be advised," Jim said. "I would limit to four to five servings a day and get the rest of your nutrients from other foods."
Image Source: POPSUGAR Photography / Sheila Gim
Latest Health & Fitness
|
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5eff3d1f6f98e57329caed0ceb9053d3
|
68,421,015,393,624,740
|
Format
Send to
Choose Destination
Obstet Gynecol. 1993 Dec;82(6):987-91.
Fetal platelet counts correlate with the severity of the anemia in red-cell alloimmunization.
Author information
1
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
Abstract
OBJECTIVE:
To determine whether fetal anemia secondary to maternal red-cell alloimmunization is associated with thrombocytopenia.
METHODS:
The records of 78 patients undergoing intrauterine transfusion for red-cell alloimmunization were reviewed. Pre-transfusion fetal platelet counts were compared between hydropic and nonhydropic fetuses. A regression analysis was performed between the fetal platelet counts and the fetal bilirubin levels, hematocrits, and reticulocyte counts taken at the initial transfusion. The hematocrits, reticulocyte counts, and bilirubin levels were adjusted for gestational age by calculating the number of standard deviations (SDs) from the mean for that age or the multiples of the mean (MOM). Student t test, Pearson coefficient, and contingency table randomization test were used to analyze the data. P < .05 was considered significant.
RESULTS:
Thirty-seven fetuses were hydropic and 41 were nonhydropic. Hydropic fetuses had a significantly lower platelet count than nonhydropic fetuses (197.5 +/- 86.4 versus 252.6 +/- 73.7 x 10(3)/microL; P < .01). Platelet counts correlated negatively with the reticulocyte count MOM (r = -0.652; P < .01) and the hematocrit SDs below the mean (r = -0.659; P < .01), but did not correlate with the bilirubin MOM (r = -0.183; P = .2).
CONCLUSION:
Hydropic and severely anemic fetuses are at increased risk for thrombocytopenia. We suggest that increased erythropoiesis diverts the hematopoietic stem cell away from thrombopoiesis.
PMID:
8233277
[Indexed for MEDLINE]
Supplemental Content
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5eff3d1f6f98e57329caed0ceb9053d3
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-4,420,049,776,215,165,000
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Home > Gene Browser > LSAMP
LSAMP
Synonyms
IGLON3, LAMP
External resources
Summary
This gene encodes a member of the immunoglobulin LAMP, OBCAM and neurotrimin (IgLON) family of proteins. The encoded preproprotein is proteolytically processed to generate a neuronal surface glycoprotein. This protein may act as a selective homophilic adhesion molecule during axon guidance and neuronal growth in the developing limbic system. The encoded protein may also function as a tumor suppressor and may play a role in neuropsychiatric disorders. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed.
Variant counts
Variant classification counts according to ACMG guideline on all identified variants among our tested samples are listed. The variants with over 5% variant frequency in population genome databases ( gnomAD, dbSNP, etc) are excluded.
Pathogenic
0
Likely pathogenic
8
VUS
8,336
Likely benign
202
Benign
0
Patient phenotypes
Proportions of phenotypes among 8 patients carring pathogenic or likely pathogenic variants on LSAMP gene are displayed below.
Phenotype class
Patients in 3billion (%)
Abnormality of the cardiovascular system
50%
Constitutional symptom
50%
Abnormality of blood and blood-forming tissues
25%
Abnormality of the digestive system
12.5%
Abnormality of the ear
12.5%
Abnormality of the immune system
12.5%
Abnormality of the nervous system
12.5%
Growth abnormality
12.5%
Abnormal cellular phenotype
0%
Abnormality of head or neck
0%
Abnormality of limbs
0%
Abnormality of metabolism homeostasis
0%
Abnormality of prenatal development or birth
0%
Abnormality of the breast
0%
Abnormality of the endocrine system
0%
Abnormality of the eye
0%
Abnormality of the genitourinary system
0%
Abnormality of the integument
0%
Abnormality of the musculoskeletal system
0%
Abnormality of the respiratory system
0%
Abnormality of the thoracic cavity
0%
Abnormality of the voice
0%
Neoplasm
0%
Have a question or need assistance? Ask here.
Send us your questions or comments related to the variant counts and/or patient phenotypes
|
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Baby care. Nutrition lactating gerls: what to eat and what is forbidden?
ChildWhat may I eat a breast-feeding girl 18 years old? What is prohibited? What you enjoy to be careful?Lactating gerls are ofttimes inundated with advice, occasionally questionable that they need eat and drink and what should not. It is important however alone one thing: the claim to eat wisely and possibly a complete organism mother produces with 800 to 1000 ml of natural milk, while consuming approximately 800 extra calory, however a breastfeeding girl requires more nutrients than before. For example, 45% more protein is more than twice however vitamins A and D, 50% more folic acid, calcium, magnesium, vitamin, and 30% more essence fatty acids.Monotonous ration can lead to vitamin deficiency nursing gerls or hypogalactia. At the like time, little errors in feeding on the natural milk capacity is not affected. In ordering to provide reliable power to the child, the mum's aging body helps itself by using this trick: If insufficient intake of nutrients from the outside connect your own funds. That's one of a causes why breast-feeding women in any case should not pick up the course weight loss.Some cause is that harmful substances coming from the outside, are deposited mainly in adipose tissue. If she loses gravity, decreased fat depots, and toxins in large quantities in a blood begins to fall, and then to a mom's milk. In fact, breastfeeding moms can eat whatever they seem tasty, with a exception of two cases:If a newborn responds to food mother bloating and rash on the buttocks. It want be assumed that a food and drinks that cause swelling in the mother, and a bad influence on a newborn. In this case, so correctly as when alone responds to a newborn, it is required to remove all cause swelling varieties of fresh vegetables (mostly fresh cabbage and peppers), and other "suspicious" meal. Drinks containing carbon dioxide can cause a newborn abdominal pain, citrus may cause diarrhea and dermatitis. If a young woman is drinking much of whole milk, it can cause swelling of the child, and abdominal pain, and even diarrhea.When a family has allergies. To cut a newborn's risk of hereditary disease caused by the mum should be sure to give up the foods suspected however allergens. These incorporate, for example, nuts, egg, chocolate, millet, crab, cow's milk. If a mum herself is exposed to meal allergies, you claim just in case a conversation with an allergist, who will adjust the food. Similar posts:Baby service. Feeding babyChildService of a baby. Alcohol and natural-feedingNewbornChild attention. Vitamins for infantsBaby.
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Book - The Hormones in Human Reproduction (1942) 9
From Embryology
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Corner GW. The Hormones in Human Reproduction. (1942) Princeton University Press.
Hormones in Human Reproduction (1942): 1 Higher Animals | 2 Human Egg and Organs | 3 Ovary as Timepiece | 4 Hormone of Preparation and Maturity | 5 Hormone for Gestation | 6 Menstrual Cycle | 7 Endocrine Arithmetic | 8 Hormones in Pregnancy | 9 Male Hormone | Appendices
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Chapter IX The Male Hormone
"She \^Nature'\ spawneth men as mallows fresh, Hero and maiden, flesh of her flesh; She drugs her water and her wheat With the flavors she finds meet. And gives them what to drink and eat; And having thus their bread and growth. They do her bidding, nothing loath."
Ralph Waldo Emerson, Nature II.
The male sex glands (testes) of man and the other mammals, like the ovaries, perform a double task. They exist primarily, of course, to produce the male germ cells. In primitive aquatic animals this is all they need to do. The Hydra, for example, shown in Plate II, C, in the act of discharging its sperm cells directly into the v/ater, has fulfilled its reproductive task for the season, and its empty testes are of no more consequence than a spent skyrocket. In mammals, however, things are not so simple. There are other needs that can be fulfilled only by the coordination of various parts of the body by means of a hormone. Not only must the sperm cells be formed and ripened ; they must also be stored until they are needed in mating. What is more, they must be stored in a most particular way, immersed in a watery environment, for the mammals have never fully shaken off their ancient adaptation to the sea. They spend their lives on land, but when the time comes to reproduce their kind, their spawning requires salt water — not indeed the actual sea, but the internal fluids of the generative organs. The egg ripens in the fluid of the Graafian follicle. The sperm cells accomplish their tortuous journey to the Qgg by swimming, and the offspring of all the mammals spend the long term of gestation in a submarine environment. You and I cannot remember our ancestral life in the water, nor the nine months we ourselves lived beneath the chorio-amniotic sea, but our tissues recall it ; the skin, the kidneys and the adrenal glands working to hold sufficient water and just enough salt, the testes providing through their accessory organs those fluids in which the sperm cells may be effectually launched upon the sea of life.
In another way also the endocrine function of the testis becomes necessary. The higher animals lead complicated lives.
They wage a varied battle for existence and are swayed by many circumstances. Perpetuation of the race amid such distractions requires especially active maintenance of sexual vigor and the urge to mate. This too becomes a function of the testis as an organ of generation.
The Male Reproductive Organs
The testis. To follow the story in detail we must first review the anatomy of the testis and the associated male organs of reproduction. The diagram (Fig. 30) will serve to orient us. The two testes lie in their pouch of skin (scrotum) . They are objects of ovoid shape, about the size of walnuts, that is to say 4.5 x 3 centimeters (2x1% inches) in diameter. Within these small rounded bodies the business of sperm cell production is carried on inside an extraordinary system of tubular canals. The testis, in fact, consists essentially of many hundred small tubules, called seminiferous tubules, each about 30 to 70 centimeters (1 to 2 feet) in length and about as large in diameter as a strand of sewing silk. These tubules are coiled very tightly in the small space available, and thus when we look through the microscope at a section of the testis, we see countless sections of the individual tubules, cut in every possible direction (Plate XXIII, A). How they actually run, and how they are connected, was for a long time one of the most difficult problems of microscopic anatomy. We should get a similar picture if we took a thoroughly tangled ball of twine and cut a section through it with a sharp knife. Nobody could possibly tell from such a cut whether the ball of twine contained one long piece of twine, or several shorter ones, or how they were joined together. Likewise a section of the testis cannot tell us anything about the course of the seminiferous tubules. For a century microscopists applied their various technical tricks to this problem, including the making of magnified models from serial sections, but with only imperfect success, owing to the difficulty and laboriousness of following these minute and lengthy canals. Finally in 1913 the problem was cleverly solved by the late Professor Carl Huber of the University of Michigan, who worked out a method of softening the testis with acid and then, with incredible patience and dexterity, dissected out complete tubules under the microscope with fine needles and mounted them, without breakage, on glass slides. He found that they are arranged in loops or arches, all opening into a network of channels at the hilum a of the testis, whence they are drained off by a dozen larger | channels into the epididymis. All these facts have been depicted in Fig. 31.
Plate XXIII. A portion of human testis and epididymis, magnified 10 times. The large circles and loops at the right are sections of the coiled tube of the epididymis; the smaller tubules filling the left two-thirds of the picture are the seminiferous tubules of the testis. B, area of the same testis magnified 200 times, showing 5 clumps of interstitial cells between the tubules. Photographs from preparation lent by Joseph Gillman through I. Gersh.
Plate XXIV. A, portion of seminiferous tubule of rat, showing formation sperm cells. Note the peculiar hook- or halberd-shaped heads and long tails of tl rat's sperm cells (form of human sperm cells shown in Fig. 7). Magnified 600 time From specimen lent by K. E. Mason. B, portion of seminifierous tubule of unde scended (cryptorchid) testis of pig. Note that sperm cell formation is totally absent, the tubule being lined by ill-defined cells (epithelial cells). The interstitij cells are, however, well preserved. Magnified about 600 times.
Fig. 30. The human male reproductive system. From Attaining Manhood, by George W. Corner, by courtesy of Harper and Brothers.
In cross section under high magnification (Plate XXIV, A ) the tubules are seen to be lined by several layers of cells. The outermost layer (i.e. that farthest from the central channel of the tubule) is made up of large clear cells. As these divide to form the next and succeeding layers, the cells become smaller. Finally little is left except the nucleus, and even this becomes more compact. A long tail-like process grows out of the rapidly shrinking cell. This figure represents the rat's sperm cells with their hook or halberd-shaped heads. The completed human sperm cell is shown in Fig. 7. It has a total length, including the tail, of about 60 microns or 1/400 inch. The head is about 5 microns long by 3 wide. The sperm cell is therefore by far the smallest cell in the body. An idea of its relative dimensions may be gained by comparing it with the printed period at the end of this sentence. If the sperm heads were laid like a pavement, one layer deep, on such a dot, it would take about 2,500 of them to cover it. About 12 egg cells could be placed on such an area.
As the sperm cells are formed, little clumps of them cling to supporting cells in the lining of the tubules until finally they drop off and are carried along the channel toward the seminal ducts. In animals that breed at all seasons of the year, for instance man, rat, rabbit and guinea pig, sperm production goes on continuously, passing in waves along the tubules, so that sperm cells are always available. Many wild species, however, have distinct breeding seasons once a year, and in these there is a cycle of testicular activity. In the seasons of inactivity spermatogenesis ceases and the testis diminishes in size.
Fig. 31. Arrangement of the tubules of the testis, the epididymis, and the seminal duct. Adapted from Spalteholz and Huber. From Attaining Manhood, by George W. Corner, by courtesy of Harper anl Brothers.
The testis, like the ovary, is under control of the pituitary gonadotrophic hormones. One of the most striking results of the brilliant campaign of investigation of the pituitary led by Philip E. Smith, now of Columbia University, has been the discovery (1927) that removal of the pituitary gland from an adult male causes degeneration of the testis, and in an immature male prevents the development of sperm cell formation. The implantation of bits of pituitary gland or the injection of pituitary extracts will substitute for the missing organ and prevent degeneration of the testis. In some species, but not in others, success has been attained in starting sperm formation in immature animals by injecting pituitary extracts.
Another remarkable discovery about spermatogenesis was announced by Carl R. Moore (University of Chicago) in 1924, namely, that the mammalian testis cannot form sperm cells unless it is subjected to a temperature slightly lower than that of the interior of the body.[1] In its normal place in the scrotal sac the testis is under temperature conditions exactly suited to its function. It has long been known that a man with undescended testicles is not fertile, and horse breeders are well aware that the same is true of cryptorchid stallions. They often call upon veterinary surgeons to bring down the testes of colts by operation. Moore's investigations have given us the reason for this sterility. In man descent of the testes normally occurs before birth. The sex glands are formed in the abdominal cavity near the lower pole of the kidneys, but they gradually move downward (or as some embryologists prefer to say, the body grows upward past the testes) until they have fully descended and have occupied their permanent place in the scrotum. Just why this elaborate transfer of the testes takes place, seemingly leaving them less protected than if they remained in the abdominal cavity, as in lower vertebrate animals, has never been satisfactorily explained. One can only guess that when the process of evolution of the warm-blooded condition was accomplished, Nature discovered (so to speak) that after all the testes could not stand the temperature at which she had stabilized the mammals, and had to get them to a cooler place; but any such conjecture seems to put Nature (or whatever you choose to call the forces that guide evolution) in a position like that of tariff legislators, chess players and others who find that one change in a complicated situation may set off unexpected changes elsewhere. At any rate, descent of the testes is a deep-seated phenomenon that has become essential to fertility. The inside of the scrotum is several degrees cooler than the abdominal cavity, because the scrotal sac has thin walls and no insulating layer of subcutaneous fat, but numerous sweat glands by which it loses heat. Moore found that if he put the testis of a guinea pig or other animal back in the abdominal cavity (preserving its blood supply) and stitched it there, the seminiferous tubules became disorganized within a week, but recovered if he brought them down again before the damage had become permanent. He took also a fertile ram and wrapped its scrotum in woolen coverings so that the testes were brought to the temperature of the rest of the body. This too caused cessation of sperm production. Actual direct heating of the testis has a similar effect. A single exposure of the guinea pig's testis for 15 minutes to a temperature 6 degrees above that of the interior of the body causes degeneration of the seminiferous tubules. It is known that in man high fevers are followed by temporary loss of spermatozoa.
Descent of the testis into the scrotum is part of the general pattern of the development of the sex gland and is therefore subject to control by the pituitary and pituitarylike hormones. It has been known for about 10 years that gonadotropic hormones from pregnancy urine can be used for the treatment of non-descent of the testis in boys. It does not always succeed, for adhesions and other obstacles may interfere; therefore the treatment must be used only in selected cases after thorough study. When the hormone fails, surgical methods are usually still available.
Interstitial cells. In the angular spaces between the tubules the microscope reveals little clumps of relatively large cells not in any way connected with the sperm-forming cells (Plate XXIII, B), Although there are only a few cells at any one point, there are so many clumps that the total mass of the interstitial cells adds up to a significant proportion of the whole testis. Some writers call the totality of these cells "the interstitial gland." There is an ample network of capillary blood vessels among these cell clumps. The arrangement is obviously like that seen in the glands of internal secretion; and it is in fact very probable that this is the source of the testicular hormone. We cannot however be sure that the hormone is not made by the cells of the seminiferous tubules, as will be discussed later.
The genital duct system. When the sperm cells have reached completion in the testis, they are perfectly formed but inactive. Freed from their parent cells, they are swept passively along the tubules into the larger ducts that drain the tubule system. If the sperm cells were discharged from the body in this nonmotile state they could not fulfill their task of reaching and fertilizing the egg cell. They require a further period of ripening and conditioning until they become fully motile and potent. Furthermore the seminal fluid in which they are to be carried must be made and added to them, bringing suitable substances for their nourishment and stimulation.
These needs are served by a complex system of ducts and accessory glandular structures. The dozen or more ducts that leave the testis all drain into a single tube about 7 meters (21 feet) long, which is tightly coiled, as shown in Fig. 31, into a dense mass, the epididymis, which lies upon the testis. This coiled duct is lined by special secretory cells and is believed to function as a storage place for sperm cells, which take many days to be carried through its whole length. During this journey they have time to mature. If one examines under the microscope sperm cells taken from the epididymis of a freshly killed animal, they are found to be in active motion, whereas those taken from the testis are motionless. There has been a good deal of discussion, not yet settled, as to whether the activation of the sperm cells is brought about by stimulatory substances secreted by the cells lining the tube of the epididymis, or merely by the process of maturing. Regardless of this question, it is at least certain that the epididymis is a favorable place for the sperm cells, for when experimenters have tied off its tube in two places, leaving sperm cells trapped between the ligatures, the cells have been found to remain active for two weeks or more.
Emerging from its coiling in the epididymis, the seminal canal becomes less tortuous and finally runs directly upward under the skin toward the groin, as shown in Fig. 30. This part of the system is called the seminal duct or vas deferens. The two ducts (one from each testis), pass over the front of the pelvic bones to enter the interior of the pelvis. Proceeding down the side and rear of the pelvis the two ducts approach each other under the urinary bladder. Before they unite each of them gives rise to a small saccular offshoot or branch, the seminal vesicle. These vesicles are clubshaped hollow structures, really side branches of the seminal duct. They are each about 10 centimeters (4 inches) long, but folded to half that length as they lie in place. They are glands of external secretion, producing in their cavities a clear gelatinous substance which becomes part of the seminal fluid. There is an old notion, hardly yet cleared out of the medical textbooks, that the seminal vesicles are reservoirs for sperm cells, but the fact is that sperm cells are not normally found in them.
The whole course of each seminal duct from epididymis to their junction, is about 30 centimeters (1 foot) long. As shown in Fig. 30, the two ducts unite just below the bladder and enter the urinary channel, the urethra just after it makes its exit from the urinary bladder. The combined seminal and urinary channel then passes through the prostate gland and enters the penis.
The prostate gland. To most people the name of the prostate gland probably conveys no clear impression, but only a vague and slightly ominous suggestion of something one hardly speaks of unless it makes trouble. Years ago Mr. Henry Mencken, when a columnist on the Baltimore Sun wrote an amusing article on the relative respectability of the human organs. The heart and lungs, he said, are perfectly respectable, the liver not quite, the spleen dubious and the kidneys definitely vulgar. In those days the prostate gland was so far below the standard of respectability that it could not even have been mentioned in the newspaper. Possibly the fact that its prosaic name, from the Greek prostates ("standing before" the urinary bladder), is often confused with the word "prostrate" adds to its flavor of indignity.
This unjustly disparaged organ is actually a gland of external secretion. It consists of 15 to 30 branched tubular glands, imbedded in connective tissue and muscle, forming a round mass 20 grams (2/3 ounce) in weight and almost completely surrounding the urethra just below the urinary bladder. The branching tubules of the prostate gland deliver a special secretion to the spermatic fluid, about which we know very little except that it is favorable to the activity and function of the sperm cells.
The various portions of the duct system and accessory glands are connected through the autonomic nerves so that all of them contribute to the seminal fluid when it is ejaculated at the climax of sexual excitement.
The prostate gland is one of those organs which carry on their useful functions in complete silence, never making known their presence or their action as long as they are in good working order ; but when something goes wrong with one of them it suddenly becomes the focal point of the universe for the sufferer. Its bad reputation as a source of trouble in elderly men is due to the fact that for some obscure reason, probably of endocrine nature, the gland tends to enlarge in men past 50. Situated as it is around the urinary channel (see Fig. 80), and enveloped in a heavy capsule, which prevents it from swelling outward, any marked enlargement of the prostate inevitably blocks the outflow of urine, with serious consequences. The hope that prostatic enlargement may (when we know enough about it) be brought under control by treatment with hormones, lies temptingly before the investigators and may some day be realized.
Secondary sex characters. Before we can discuss the hormone of the testis we must take account of certain other matters that form part of the pattern of sex. Primarily a male animal differs from the female, or a man from a woman, because the one has in all his cells the chromosomes for maleness, the other the chromosomes for femaleness. One therefore develops testes, the other ovaries. The sex glands then begin, even in the early embryo, to call forth the secondary sex characters of their respective sexes. When the individual reaches the age of puberty these characters become prominent. In most mammals the males are larger, and possess heavier, rougher skeletons and stronger muscles. The shape of the pelvis, and to a lesser extent that of the skull and the other bones, is different in the two sexes. In humans the anatomy of the larynx is different and therefore the voice becomes either male or female. The distribution and growth of the hair are different. One sex has well developed mammary glands, the other only rudiments.
In the various divisions of the animal kingdom there is a vast array of secondary sex differences. The tail of the peacock, the antlers of the stag, the beard and the smell of the billy goat, are evidences of what Nature can do in this way. The subject would fill a large book.[2] Perhaps the most familiar of all, the comb of Chanticleer, has been seized upon by the experimenters (as we shall see) and has been made to tell us, more than any other one sign, just how the hormones control the secondary sex characters.
The Hormone of the Testis
People have known since prehistoric times that castration of men and domestic animals suppresses the development of secondary sexual characters and causes atrophy of the accessory male sex organs, such as the seminal vesicles and prostate gland. The gelding of stallions, the castration of male calves to make steers, of cockerels to produce capons, and even of boys for the production of eunuchs, has long been practiced. If anyone asked how the testis can control the size and form of the skeleton, the distribution of hair, or the tone of the voice, the explanation was vaguely to the effect that some sort of "sympathy" existed between the parts of the body, with the implication that the nervous system is the connecting agent. In 1849, however, Arnold Adolph Berthold, a physician and zoologist of Gottingen, proved once for all that the influence of the testis is carried by something that travels in the circulating blood. Berthold's little contribution (it is only four pages long) belongs to the fundamental classics of endocrinology.[3] He tells us that on August 2, 1848, he castrated 6 cockerels, 2 to 3 months old. Their combs, wattles and spurs were not yet developed. From two of them the testes were completely removed. These became typical capons, fat, docile, without cocks' combs, wattles and spurs, unable to crow. In the case of two others, Berthold removed both testes but put one of them back, dropping it among the intestines. Anatomical examination months later showed that the reimplanted testes had become attached to the intestines and had acquired a good blood supply, so that the testicular tissue flourished in its new site. Both these cockerels became typical cocks ; they grew combs and wattles, crowed, fought their rivals, and, as Berthold delicately observes, "showed the customary attention to the hens." One of these was later opened surgically, the implanted testis was removed, and the comb and wattles cut off. The head furnishings did not regenerate, and the bird, now fully castrated, reverted to the status of a capon. The other two each had one testis removed, then Berthold exchanged the remaining testes, giving each bird the other's sex gland, which he implanted on the intestine. These also became typical cocks. This beautiful experiment showed that the testis by no means depends upon specific nerves to maintain its control of the secondary sex characters, but works through the blood.
A long story could be told of all the efforts that were made to follow up this discovery, and there would be many divagations to relate. There was, for example, the episode of Charles-Edward Brown-Sequard, a brilliant, restless FrancoIrish- American (181T-1894!), who made two incursions into the field of the internal secretions. In 1856 he was the first to remove the adrenal glands from animals and to observe the fatal disorder thus produced, like an exaggerated Addison's disease. In 1889, when he was seventy-two years old, he began to dose himself with extracts of dogs' testicles. He was feeling the debility of age, and hoped to rejuvenate himself. BrownSequard had been a good scientist and it is almost incredible that he could have hoped to do critical experiments with himself as the only guinea pig, prejudiced by all his hopes and fears for his own health. He thought that after the injections he felt much stronger and more alert, and reported his experience with pathetic enthusiasm and intimate personal detail before the medical societies of Paris and in the journals. The medical profession was on the whole incredulous and Paris made a good deal of fun of him. We know now that the extract could have had little or none of the genuine testis hormone in it. It was made by putting mashed-up testes in water and filtering the mixture. We are now well aware also that when a man grows old he ages all over, not only in his testicles. Nevertheless the idea of administering gland extracts had its up-to-date appeal in those days of the earliest discoveries about the endocrine organs. German biochemists had recently isolated from animal testes a peculiar nitrogenous substance called "spermine." Various people leaped to the conclusion that this might be the active substance in Brown-Sequard's extracts. Spermine was therefore put on the market under the auspices of the chemist Poehl, and thus became (to the best of my knowledge) the first endocrine product to be commercialized. Thus Brown-Sequard's notoriety was probably responsible, more than anything else, for the exploitation of endocrine preparations in the drug trade ahead of scientific knowledge. Since then, barrelfuls of extracts and millions of tablets have been fed and injected into human patients, with uncritical optimism, before the chemists and physiologists could learn the facts. The benefits of endocrine research on the reproductive glands have almost been stifled by this exploitation. Even today the practicing physician finds it difficult to distinguish what is sound and practical amid the flood of well advertised endocrine drugs.
There have been premature efforts also to apply Berthold's experiment of transplantation of the testis to the rejuvenation of senile men. The most widely publicized of these was that of the Franco-Russian surgeon Serge Voronoff, who was busy from about 1912 to 1925 implanting monkey testes into human patients. The American journalists of those days could not refer to the testicles by name in the newspapers, and introduced the expression "monkey glands," which became a byword and finally a joke. Some of the patients reported hopeful results. The grafts may indeed have yielded a little of their hormone to the body before they disintegrated and disappeared. More often, no doubt, the benefit was entirely psychic. It is now clearly established that tissues from one species of mammal cannot grow in another species, and indeed it is practically impossible to secure a permanent transplant from one human to another. Grafting of the testis has therefore not been adopted as a sound procedure.
While we are on the subject of rejuvenation, we may as well mention the Steinach operation. Eugen Steinach of Vienna, a scientist of good reputation, came forward about 1920 with a proposal based on two premises. The first of these, which has even yet not been proved, was that the testis hormone is made entirely by the interstitial cells. (The question will be discussed more fully below.) The second premise has since been proved incorrect; it was that if the seminal duct is tied off, the seminiferous tubules will degenerate leaving more room for the interstitial cells, and these will increase in number and presumably make more hormone. Steinach believed that such a ligation of the seminal ducts of man (vasectomy) would restore vitality of body and of sexual function to elderly men. He brought forward apparently strong evidence from animal experiments to support the idea. The operation made a strong appeal to men who were yearning to regain their lost youth. It has been tried widely, but the medical profession remains unconvinced, and the scientific basis for it as outlined above has been disproved.
Meanwhile, through all this period of sensationalism and premature publicity, the slow implacable attack upon the problem by inconspicuous investigators has gone forward to notable success. The important thing in endocrine research is to find a test for whatever hormone one suspects to exist — some sharp-cut characteristic effect that is lost when the gland is removed and that can be restored by giving back the gland in implants or in extracts. At each step of our story in this book such a method has been the key to success. The vaginal smear test for the estrogens, the rabbit uterus test for progesterone, promptly made possible the purification of these substances. If the test is quick and cheap, the results will come that much faster. Berthold's experiment with the cockerels provided an ideal method of testing for a hormone of the male sex gland. Success came to those who followed his lead, putting aside premature efforts to work with slowly growing mammals or to rejuvenate old men. Between 1907 and 1927 two or three European investigators reported that they had extracts of the testis which induced growth of the head furnishings of cocks. None of these experiments, however, was fully convincing. Meanwhile the estrogenic hormones were isolated and discovered to be soluble in fat solvents. In 1927 a graduate student in biochemistry under Professor F. C. Koch at the University of Chicago, L. C. McGee (now a physician in Elkins, West Virginia) applied the new methods of extraction to the tissues of the bull's testis and promptly secured a relatively pure extract that was capable of producing rapid growth of capons' combs (Fig. 32). This lead was followed up by a group of workers in biochemistry and zoology in the University of Chicago, including McGee, F. C. Koch, C. R. Moore, L. V. Domm, and Mary Juhn, and by various workers abroad. The successive steps in the purification and identification of the male or androgenic hormones were much like those in the isolation of the estrogenic substances. In 1929, S. Loewe and S. E. Voss of Dorpat (Estonia) and also Casimir Funk and B. Harrow of New York found androgenic substances in human urine from males. The indefatigable Butenandt and his aides then isolated, completely purified and identified two of these compounds, called respectively androsterone and dehydroandrosterone, in 1931-1932. L. Ruzicka and his colleagues at Basel made them synthetically in 1934. The next year David, Dingemanse, Freud and Laqueur of Amsterdam succeeded in the difficult task of purifying the hormone from extracts of the testis itself, and found the substance called testosterone, which differs slightly in its chemical constitution from the androsterone found in urine. The groups of workers led by Butenandt and Ruzicka immediately synthesized this hormone as well. Now that such substances could be made in the test tube as well as in the testis, and (as we shall see) began to be found in other tissues also, the adjective "male" as applied to them gave place to the more apt word "androgenic," meaning "promoting masculinity"; the latter word defines the effects without implying any particular place of origin and can therefore be used of such substances when, for example, they turn up in female urine, in the cortex of the adrenal gland, or in a chemist's flask.
Fig. 32. The effect of testis hormone on the rooster's comb, a, untreated castrated cockerel. 6, castrated cockerel after 11 days' treatment with testis extract. Drawn from photograph by Freud and coworkers.
Chemistry of the androgenic hormones. These substances belong to the same family of chemical substances as the estrogenic hormones and progesterone. Testosterone has the following structure :
CH3 ^OH
TESTOSTERONE
Androsterone, prepared from human male urine, has this formula :
ANDROSTERONE
A statement of the relation of these particular sterols to simpler chemical substances will be found in Appendix I.
At the present time at least thirty-five substances of similar composition are known which have androgenic effects. Some of these have been found in the adrenal gland, or in the urine under special circumstances, but most of them are artificial products of the chemical laboratory. A list of them is given by Koch.* The male hormone which is actually at work in the body is probably testosterone itself or a closely similar substance. The reason a definite statement cannot be made on this point is that we are not sure that the chemical procedures necessary to extract and concentrate the hormone do not change it chemically. When testosterone is administered to a castrated animal, it is transformed in the body and is excreted by the kidney as androsterone. Since androsterone occurs in the urine of normal men, this is presumptive evidence that testosterone, or something very much like it, is in circulation in the body.
Edgar Allen, op, cit.. Chapter XII, "The Biochemistry of Androgens," by F. C. Koch.
Just what cells in the testis are responsible for producing the hormone is an interesting and debatable question. There are two possibilities, the interstitial cells on one hand, and the spermatogenic cells of the tubules on the other. Let us examine the evidence. In the first place the interstitial cells look like endocrine tissue, since they are large cells provided with a rich circulation of blood but obviously not producing an external secretion, for they are not arranged in channels and ducts. Years ago, moreover, Bouin and Ancel called attention to evidence favoring the interstitial cells as the source of the hormone. When the testes fail to descend and therefore do not form sperm cells, the cells lining the tubules are reduced to an inactive state (Plate XXIV, B). They assume a vague, nondescript form as if they were merely surviving without any function. The interstitial cells however remain in place, they look normal, and indeed have even been thought to increase in amount. Although the cryptorchid animal or man bearing such sex glands is sterile, he develops male secondary sexual characters and male sex psychology. With the spermatogenic cells seemingly inactive (as judged by appearances under the microscope) but the interstitial cells in good condition, it is difficult to avoid the assumption that the latter are making the sex hormone. When bits of the testis are grafted successfully into a castrated animal the same cellular state develops in the grafts, and the animal likewise develops male qualities. It was formerly thought that tying off the seminal ducts produced the same effect. The Steinach operation described above was based upon this whole set of considerations. It is now known, however, that blocking the ducts and thus damming up the semen does not stop spermatogenesis. It is also known that cryptorchid (undescended) testes with inactive sperm cell formation do not produce more hormone but considerably less. In short, the two functions of the testis, spermatogenesis and hormone production, run parallel to a certain extent. For this reason some of the soundest of the investigators are not willing to point to one or the other of the constituent tissues of the testis and say "here is the sole source of the hormone." The tubule cells, even if they are inactive in producing sperm cells, may for all we know still be taking part in making the hormone ; or perhaps the two kinds of cells work together. If a time ever comes when the hormone can be recognized in the tissues in very small amounts, say by some sort of super-spectrograph or X-ray analysis, such as the modern magicians of the physics laboratories are using in their easier problems of test tube chemistry, then perhaps we can answer such questions as these.
There is no sharp division between the estrogens, the androgens, and the progestins. Several of these substances give both estrogenic and androgenic effects, and a few have been found even to affect the uterine lining like progesterone, though only in very large doses.
The androgens are usually assayed by testing their effect upon the growth of the comb of the capon. The League of Nations Committee on Standardization of Drugs set up in 1935 an international standard of potency, specified as the equivalent of 0.1 milligram of crystalline androsterone. This is approximately the daily dose required to give a measurable response in a capon's comb in 5 days.
The androgenic hormones are usually injected in oil solution. In recent years the method of implanting pellets under the skin has begun to be tried. The hormones are also effective when applied in suitable ointments. Growth of the cock's comb can be elicited by applying hormone-containing ointments directly to the comb itself (Appendix II, note 19).
Effects and medical use of the androgenic hormones. The effects of the androgenic hormones, as C. R. Moore" neatly puts it, are measured by the difference between a castrated and a normal man. These substances substitute completely, in animal experiments, for the normal internal secretion of the testis. They counteract castrate atrophy of the seminal vesicles and prostate gland ; when given to immature animals they stimulate precocious growth of the accessory sex organs, and they induce sex activity and mating in castrated and immature males. A castrated male, skillfully treated with potent hormones, will resemble a normal animal of his species in all respects except that he will be infertile because he is producing no germ cells.
These effects have been tested quite thoroughly in an experimental way upon human patients who lack the testis hormone. In these men and boys, as in laboratory animals, the injected hormones bring out all the known responses which the bodily tissues normally make to the natural hormones of the testis. It should be recalled here that the symptoms of deprivation of testis hormone may be due to defects in either one of two glands. The testes may themselves be missing or deficient, or the pituitary gland may be furnishing an inadequate supply of gonadotropic hormone (see Chapter VI). In the latter case the testis will not be functional and the patient will show symptoms of testis hormone deficiency exactly as if the testis itself were the seat of the difficulty. At some time in the future, when endocrine treatment has reached a higher state of perfection, it may become possible to treat the pituitary cases with pituitary hormones, reserving the androgenic hormones for cases of deficiency of the testis itself. At present, however, the distinction is more or less academic. In either case the physician finds himself confronted with signs of male hormone deficiency, and the question of immediate importance is how far he can hope to help the patient by treatment with androgenic hormones.
8C. R. Moore, "Physiology of the Testis," in Glandular Phytiology and Therapy , 2d ed., Chicago, 1942.
I write about this subject of the medical use of the androgenic hormones with hesitation, because it is difficult on one hand to avoid raising false hopes without on the other hand underrating the progress that has been made and the future possibilities in this field. To make the problem clearer, let us consider a specific case.® Here is a boy in his middle 'teens who is not exhibiting the usual signs of sexual maturation. We know that if the deficiency persists he will grow to be a eunuchoid man. He will have underdeveloped genital organs, a delicate skin, the childhood type of hair distribution, a highpitched voice; possibly also he will be overfat and he may suffer from muscular and circulatory difficulties causing easy fatigability and inability to do hard muscular work. Another important feature of his general immaturity will show itself in the long bones of the skeleton. The growth zones (epiphyseal junctions) will not close up at the usual time (18 to 20 years), but will go on growing, so that he will develop the long delicate bones of the eunuch and will thus display his defect in the entire configuration of his body. Although the deficiency has nothing to do with intelligence or fundamental character, he is very likely, as he grows up, to suffer from psychological damage due to a sense of defectiveness and of difference from other men.
If this boy could be treated as simply as a guinea pig is treated in the laboratory, we could control all these visible defects by administration of androgenic hormone. The treatment is fairly expensive and must be kept up by frequent injections or inunctions. Administration by pellets buried in the tissues may in time become practical, but is hardly yet ready for use. We are, moreover, not yet free from insecurity about possible danger from long continued administration of the sex hormones through damage to the tissues of various organs. Finally, whatever improvement is gained by treatment will wear off fairly rapidly if the drug is discontinued. In one feature only, so far as known, the improvement is permanent; that is in the skeleton, for the growth of the long bones will be permanently stopped by closure of the epiphyseal junctions. Even this requires care and forethought, for if the treatment is begun too early, the epiphyses may be closed prematurely and growth stopped before the boy reaches full stature.
ej. B. Hamilton, "Testicular Dysfunction," in Glandular Physiology and Therapy, 2d ed., Chicago, 1942.
I have no doubt said enough to make it clear that the use of androgenic hormones to correct testicular hormone deficiency is very decidedly still in the stage of exploration, and that every case so treated is an experiment. This does not mean that the attempt should not be made by properly trained physicians and scientists who are in a position both to guard the welfare of the patient and to study the results with rigid scientific standards for future guidance. We have, of course, been considering an extreme case, one in which there is permanent total deficiency. The androgenic hormones are certainly going to be useful in many disturbances of less intensity and as collateral treatment. To make up for partial deficiencies, to tide over the acute deprivation which follows surgical removal of the testicles, to supplement the treatment in various cases of sexual disability and impotence - for such purposes the androgenic substances will no doubt be helpful in competent medical hands.
At any rate, the contemplation of these distressing deficiencies of the sex hormones must have impressed the reader anew with the thought that the normal processes of reproduction involve a remarkable series of linkages and coordinations within the body. It is indeed a subtle and potent chemistry by which the reproductive glands create the egg and the sperm cell and surround them with all that is needful of nourishment and protection to carry them through their critical journey from conception to birth. In this book we have traced the main outlines of these complex physiological patterns. We have seen the great advance of knowledge that has taken place in less than fifty years, by the efforts of faithful laborious men who worked in peace and quiet, giving their lives to the understanding and improvement of life. When I wrote these closing words, the guns were sounding all over the world. The scientists were dropping their instruments, or turning them perforce to the uses of death and wastage. But life goes on nevertheless, and the problems of life will be studied until the day comes we all dream of, when mankind may everjrwhere seek the truth undaunted by fear of war and oppression. In that day we shall gather the fruits of our labor. The childless wife, the ailing girl, the boy deprived of his birthright of sex by some failure of Nature's process, will call and not in vain for the help that science can bring them, and man shall understand at last the miracle of his birth.
1. For a full account of this subject, see Sex and Internal Secretions, edited by Edgar Allen, 2d ed., Baltimore, 1939; Chapter VII, "Biology of the Testes," by Carl R. Moore.
2. See many, chapters of Edgar Allen, Sex and Internal Secretions.
3. A. A. Berthold, "Transplantation der Hoden," Archiv fur Anatomie, Physiologie, und Wissenschaftliche Medizin, 1849 (Appendix II, note 18).
Hormones in Human Reproduction (1942): 1 Higher Animals | 2 Human Egg and Organs | 3 Ovary as Timepiece | 4 Hormone of Preparation and Maturity | 5 Hormone for Gestation | 6 Menstrual Cycle | 7 Endocrine Arithmetic | 8 Hormones in Pregnancy | 9 Male Hormone | Appendices
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Mem Inst Oswaldo Cruz, Rio de Janeiro, 112(6) June 2017
Original Article
Genome analysis of yellow fever virus of brazil ongoing outbreak reveals polymorphisms
Myrna C. Bonaldo1,+, Mariela Martínez Gómez1, Alexandre A. C. dos Santos1, Filipe Vieira Santos de Abreu2,3, Anielly Ferreira-de-Brito2, Rafaella Moraes de Miranda2, Marcia Gonçalves de Castro2, Ricardo Lourenço-de-Oliveira2
1Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
2Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
3Instituto Federal do Norte de Minas Gerais
Page: 447-451 DOI: 10.1590/0074-02760170134
3621 views 3290 downloads
ABSTRACT
The current yellow fever (YF) outbreak in Brazil is the most severe recently reported in the country. It has rapidly spread to areas where YF viral activity have not been observed for more than seventy years and vaccine coverage is almost null. Here, we sequenced the whole YF genome of two naturally infected howler-monkeys (Alouatta clamitans) from the Municipality of Domingos Martins, State of Espírito Santo, Brazil. The ongoing-outbreak genome sequences are identical. They clustered in 1E sub-clade (South America I genotype) together with recent Brazilian and Venezuelan strains characterized from infections in humans and non-humans primates. However, we detected eight unique amino acid changes in the viral proteins, which are located in the structural capsid protein (1 change), and the components of viral replicase complex, the NS3 (2 changes) and NS5 (5 changes) proteins, suggesting a potential role in the capacity of viral infection to vertebrate and/or invertebrate hosts and spreading in the ongoing outbreak.
Yellow fever virus (YFV) is the prototype member of the genus Flavivirus and family Flaviviridae. It is an arbovirus transmitted by the bite of infected mosquitoes in Africa and Americas, causing a disease with a large spectrum of symptoms, from mild disease to severe and deadly haemorrhagic fever in humans and New World non-human primates (NHP) (Vasconcelos & Monath 2016). Two main YFV cycles are described: the urban cycle involving the domestic mosquito Aedes (Stegomyia) aegypti, currently restricted to Africa, and the wild cycle in which humans are essentially infected by epizooties-affected NHPs, having sylvatic arboreal tree-hole breeding mosquitoes as vectors (species of Aedes, in Africa, and of Haemagogus and Sabethes, in the Americas). A rural or intermediate cycle may also occur in zones of emergence recorded in Africa (Monath & Vasconcelos 2015).
YFV is a single-stranded, positive-sense RNA virus with a genome of approximately 11 kb. Seven lineages have been identified: five in Africa (West Africa I and II, East Africa, East/Central Africa and Angola), and two in the Americas (South America I and II) (Bryant et al. 2007). Phylogenetic analysis provided evidence that the YFV circulating in the Americas is derived from a Western African lineage ancestor that emerged in Africa and was imported into the American East coast from West Africa during the slave trade (Vasconcelos et al. 2004, Bryant et al. 2007, Nunes et al. 2012).
The South American I is the most frequent genotype recorded in Brazil (Nunes et al. 2012, Monath & Vasconcelos 2015). Five lineages have been recognised in the South American genotype I, namely, 1A to 1E, which were associated with epidemics recorded during the cyclic expansions and retractions of YFV circulation in Brazil and other tropical American countries (Vasconcelos et al. 2004, de Souza et al. 2010). Since the turn of the century, the lineages 1D and 1E have been found in Brazil. However, since 2008, only YF viruses from lineage 1E have been detected in Brazil (de Souza et al. 2010, Nunes et al. 2012).
The most severe YFV epidemic recorded in Brazil in the recent decades has been reported since late 2016. Until the 10th epidemiological week of 2017, 1,558 cumulative cases with 137 confirmed YFV deaths were reported (COES 2017). Most importantly, this epidemic has rapidly and alarmingly spread eastward, reaching the most populated Brazilian regions where vaccine coverage is minor. Epizooties in NHPs and humans cases have been diagnosed in states considered YFV-free territories for almost 70 years.
Here, we present the complete genome sequence of two YFV samples collected during the current Brazilian epidemic along with a comparative analysis of recent YFV genome sequences characterised as belonging to the South American genotype I.
Blood samples were obtained from one recently dead and one dying howler-monkey (Alouatta clamitans) found on the Velho Rio farm (20º 17' 08" S 40º 50' 15" W), in Areinha, district of Ponto Alto, Municipality of Domingos Martins, state of Espírito Santo, Brazil, on February 20th and 22nd, 2017, respectively. Following centrifugation (2,000 g for 10 min), plasma samples were immediately frozen and transported to the laboratory in N2. Next, plasma samples were screened through reverse transcriptase polymerase chain reaction (RT-PCR), for which RNA was extracted from 140 ?L of plasma using the QIAamp Viral RNA Mini Kit (Qiagen, Hilden, Germany), according to the manufacturer's recommendations. RNA was eluted in 60 ?L of AVE buffer and stored at -80ºC until use. Viral RNA was reverse transcribed using the High Capacity System (Applied Biosystems) with random hexamers according to the manufacturer's recommendations. The reverse transcription reaction was carried out at 25ºC for 10 min, 37ºC for 120 min and 85ºC for 5 min. Further, the viral RNA was amplified by conventional PCR using PCR Master Mix (Promega), carried out at 95ºC for 2 min, followed by 30 cycles at 95ºC for 1 min, 58ºC for 1 min and 72ºC for 50 s, and then an extension at 72°C for 5 min. The set of primers utilised in this procedure were 5'-CTGTGTGCTAATTGAGGTGCATTG-3' and 5'-ATGTCATCAGGCTCTTCTCT- 3'. The YFV infection of the monkeys was confirmed by the specific detection of a single amplicon with the expected YFV amplicon size of 650 bp (Fig. 1).
To sequence of the full-length YFV genomes from the positive plasma monkey samples, 12 PCR amplicons were obtained (Supplementary data, Table). Viral RNA was reverse transcribed using the Superscript III First-Strand Synthesis System (Invitrogen) with random hexamers. Alternatively, we generated the first strand cDNA with the reverse primer P11R encoding the 3'UTR end (5´-AGTGGTTTTGTGTTTGTCA-3') and further processed it with YF12F and YF12R for the synthesis of the second strand of cDNA. The cDNA was amplified by conventional PCR using GoTaq Green Master Mix (Promega) according to the manufacturer's instructions. The thermocycling program in a Veriti 96-well thermocycler (Applied Biosystems) was used to amplify regions (1) to (11): 1 cycle at 95ºC for 5 min; 30 cycles at 95ºC for 40 s, at 50ºC for 40 s, and at 72ºC for 2 min; and finally 1 cycle at 72ºC for 10 min followed by incubation at 4ºC. For region (12), we applied 1 cycle at 95ºC for 5 min; 40 cycles at 70ºC for 40 s, 65ºC or 70ºC at 40 s, 72ºC at 50 s; and 1 cycle at 72ºC for 10 min and hold of 4ºC. Aliquots (3 µL of 50 µL) of amplified products were detected by electrophoresis on a 1% agarose gel, visualised by ethidium bromide staining and UV illumination, and purified with QIAquick PCR Purification Kit (QIAGEN). The amplicons were nucleotides that were directly sequenced without molecular cloning. Nucleotide sequencing reactions were performed using the ABI BigDye terminator V3.1 Ready Reaction Cycle Sequencing Mixture (Applied Biosystems) according to manufacturer's recommendations. Nucleotide sequence was determined by capillary electrophoresis at the sequencing facility of Fiocruz-RJ (RPT01A - Sequenciamento de DNA - RJ). Raw sequence data were aligned and edited using the SeqMan module of LaserGene (DNASTAR Inc.).
The complete genome sequences of both YF viruses were deposited in the GenBank database under the following accession numbers: KY885000 for strain ES-504/BRA/2017 and KY885001 for strain ES-505/BRA/2017. When we compared these genomes, they displayed 100% identity. The evolutionary relationships of these two YFV strains from the ongoing outbreak with the modern YF sequences, primarily from South American genotype I, was established by phylogenetic analysis. Initially, we selected a set of sequences of the prM/E junction fragment using the Blast tool (https://blast.ncbi.nlm.nih.gov/Blast.cgi). The 666-bp sequence consists of the last 108 nucleotides of the prM gene, including the entire 225 nucleotides of the M gene, and the ?rst 333 nucleotides of the E gene. Nucleotide sequences were aligned using the CLUSTAL W program (Thompson et al. 1994) with selected YF viral sequences available at the GenBank database. A phylogenetic tree was generated by the Neighbour-joining method (Saitou & Nei 1987) using a matrix of genetic distances established under the Kimura-two parameter model (Kimura 1980), by means of the MEGA7 program (Kumar et al. 2016). The robustness of each node was assessed by bootstrap resampling (2,000 replicates) (Felsenstein 1985). The homologous region (prM/E) of a dengue virus strain available at the GenBank database (PaH881/88; Accession number: AF349753) was used as an outgroup. The Asibi prototype yellow fever strain (Accession number: AY640589) and the vaccine strain 17DD-Brazil (Accession number: DQ100292) were also incorporated into the analysis.
The South American YF sequences formed two major clusters: the South America I and the South America II genotypes, supported by 97% and 98% bootstrap values, respectively (Fig. 2). The South America genotype I clade is further divided into sub-clades as described by Vasconcelos et al. (2004) and de Souza et al. (2010). Sequence strains from ES-504/BRA/2017 (GenBank access number: KY885000) and ES-505/BRA/2017 (GenBank access number: KY885000) belonged to the South America genotype I, and grouped within the 1E sub-clade in conjunction with other modern strains detected in Brazil (years: 2002, 2004, 2008) and Venezuela (years: 1998, 2005-2007, 2010). The recent Brazilian and Venezuelan strains that were characterised from infections in humans and NHPs, also clustered in the 1E sub-clade (South America genotype I). Auguste et al. (2015) suggested that Brazil is the major source of YFV introduction into Venezuela. However, our data suggest that the most recent Brazilian YFV strains would have originated from a Venezuelan YFV strain, since the oldest strains in the E1 sub-clade were isolated in Venezuela in 1998 (Fig. 2). The acquisition in phylogenetic studies of additional complete YF genomes from ancestral and present circulating strains from humans, NHPs and mosquitos became necessary.
The comparison of the YFV precursor polyproteins obtained from complete genome sequences with those detected in Brazil and Venezuela since 1980 demonstrated eight unique and semi-conservative amino acid (aa) changes in the C, NS3 and NS5 proteins (Fig. 3). These changes map to the following polyprotein positions: (1) 108 for isoleucine (C protein); (2) 1572 for aspartic acid and 1605 for lysine (NS3 region); and (3) 2607 for arginine, 2644 for isoleucine, 2679 for serine, 3149 for alanine and 3215 for serine (NS5 protein). Interestingly, seven out of eight aa changes are located in the two important proteins of the viral replicase complex-NS3 and NS5 - and are perhaps associated with some selective advantage for viral fitness reflecting the ability of the virus to infect vertebrate and/or invertebrate hosts and spread the infection.
However, it remains to be determined whether these specific aa changes are unique to the strains belonging to the ongoing outbreak. Alternatively, they, or at least some of them, could occur in some ancestral sequences that have not been sequenced so far. Hence, there are relatively very few complete YFV genomes from the Americas available at the GenBank database. On the other hand, this matter will be better clarified with the elucidation of the genomes of other circulating YF viruses in the current outbreak from infected mosquitos, NHPs and human biological samples. A wider understanding of the molecular epidemiology and evolution of YFV and their potential association with viral spreading and infectivity is of utmost relevance to determine the ancestral and modern YFV strains.
ACKNOWLEDGEMENTS
To Marta Pereira Santos and Marcelo Quintela Gomes, for technical assistance; Alessandro Pecego M Romano (Grupo Técnico de Vigilância de Arboviroses) and Roberta Gomes de Carvalho (Programa Nacional de Controle da Dengue), Brazilian Ministry of Health, Gilsa Aparecida P Rodrigues (Secretaria de Saúde do Estado do Espírito Santo), Gilton Luiz Almada (Centro de Informação Estratégica de Vigilância em Saúde-ES) and Roberto da Costa Laterrière Junior (Núcleo Especial de Vigilância Ambiental-ES), for the access to epidemiological data and support for the field work; and Núcleo de Entomologia e Malacologia do Espírito Santo (NEMES), Marilza L Lange (Secretaria Municipal de Saúde, Municipality of Domingos Martins), Vigilância Ambiental and Luciano L Salles (Vigilância em Saúde, Municipality of Ibatiba), for technical support in the field work.
AUTHORS' CONTRIBUTION
MCB and RLO - Conceived the study; FVSA - carried out the collection of biological specimens; RMM, AFB and MGC - carried out viral RNA extraction from the biological specimens and the diagnosis by RT-PCR; AACS - performed rapid viral RNA extraction and genome sequencing; MCB, AACS and MMG - analysed the genome sequences; MMG - performed phylogenetic analysis; and RLO, MCB and MMG - prepared the manuscript. All authors critically read and approved the final version of the manuscript.
REFERENCES
Auguste AJ, Lemey P, Bergren NA, Giambalvo D, Moncada M, Morón D, et al. Enzootic transmission of yellow fever virus, Venezuela. Emerg Infect Dis. 2015; 21(1): 99-102.
Bryant JE, Holmes EC, Barrett AD. Out of Africa: a molecular perspective on the introduction of yellow fever virus into the Americas. PLoS Pathog. 2007; 3(5): e75.
COES - Febre Amarela. Informe 32/2017. 2017. Available from: http://portalarquivos.saude.gov.br/images/pdf/2017/marco/16/COES-FEBRE-AMARELA---INFORME-32---Atualiza----o-em-16mar2017---s-13horas.pdf.
de Souza RP, Foster PG, Sallum MA, Coimbra TL, Maeda AY, Silveira VR, et al. Detection of a new yellow fever virus lineage within the South American genotype I in Brazil. J Med Virol. 2010; 82(1): 175-85.
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Monath TP, Vasconcelos PF. Yellow fever. J Clin Virol. 2015; 64: 160-73.
Nunes MR, Palacios G, Cardoso JF, Martins LC, Sousa Jr EC, de Lima CP, et al. Genomic and phylogenetic characterization of Brazilian yellow fever virus strains. J Virol. 2012; 86(24): 13263-71.
Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987; 4(4): 406-25.
Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994; 22(22): 4673-80.
Vasconcelos PF, Bryant JE, da Rosa TP, Tesh RB, Rodrigues SG, Barrett AD. Genetic divergence and dispersal of yellow fever virus, Brazil. Emerg Infect Dis. 2004; 10(9): 1578-84.
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Financial support: FAPERJ, CNPq, CAPES, FIOCRUZ
+Corresponding author: [email protected]
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Iranian Journal of Medical Sciences
Document Type : Original Article(s)
Authors
1 Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2 Health Human Resources Research Center, Department of Health Economics, School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
3 Emergency Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4 Medical Imaging Research Center, Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5 Department of Epidemiology, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
6 Chemical Injuries Research Ccenter, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
7 Student Research Committee, School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: Reinfection with Coronavirus Diseases 2019 (COVID-19) has raised remarkable public health concerns globally. Therefore, the present retrospective cohort study intended to investigate COVID-19 reinfection in registered patients of Fars province in Iran from February 2020 to
April 2021.
Methods: The patients’ data, including the COVID-19 infection, symptoms, comorbidities, and demographics, were collected using the Health Information Systems (HISs). The patients were divided into three groups in terms of the duration between the initial infection and reinfection, including 28-44, 45-89, and more than 90 days. Following the univariate analysis, logistic regression was used to investigate the factors effective on COVID-19 reinfection.
Results: A total of 213768 patients had a positive Polymerase Chain Reaction (PCR) test. The reinfection rate was 0.97% (2079 patients). Of these re-infected individuals, 14.9%, 18.5%, and 66.6% had their second positive test 28-45, 45-89, and ≥90 days later, respectively. The mean duration between the initial infection and reinfection was 130.56 days (29-370 days). The chance of reinfection was significantly higher in the youths (Odds Ratio (OR)=2.055; P<0.001), men (OR=1.283; P<0.001), urban population (OR=1.313; P<0.001), and healthcare providers (OR=4.453; P<0.001). The patients with chronic pulmonary diseases, chronic kidney diseases, and malignancy were 1.421 (P=0.036), 2.239 (P<0.001), and 3.437 (P<0.001) times, respectively, more likely prone to reinfection.
Conclusion: The results of this study showed that there is a higher risk of reinfection in several vulnerable groups including healthcare providers, young individuals, residents of urban areas, men, and individuals with underlying diseases.
Keywords
What’s Known
There are many pieces of evidence that show people are getting reinfected by COVID-19. The reinfection rate by COVID-19 may differ based on demographic variables.
What’s New
COVID-19 reinfection happened in 0.97% of the people who were infected by COVID-19 in Fars province, Iran. The reinfection rate was higher in the young age group, male patients, inpatients, residents of the urban areas, and healthcare providers.
Introduction
Until November 06, 2022, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as the causative agent of the Coronavirus Diseases 2019 (COVID-19) pandemic, has caused more than 637 million cases of infection and more than 6.6 million deaths globally. Unfortunately,there is a rapid and global spread of the disease due to its extremely high infectivity. 1 It infected almost all global countries in a relatively short time and is currently known as a major threat to global public health. 2 , 3 The related global and rapid spread, high infectivity, and significant mortality of COVID-19 made the World Health Organization (WHO) issue a statement on January 30, 2020, announcing the novel coronavirus as the sixth leading cause of global public health emergency. 4
Besides the primary infection, COVID-19 reinfection has raised further public health concerns. 5 , 6 Another vital question and major global public health concern now exists: Is COVID-19 reinfection possible? Moreover, how strong is the body immunity against this disease in individuals with the previous infection? 7 , 8 The first case of reinfection with a phylogenetically distinct strain of SARS-CoV-2 was reported in the literature on August 25, 2020, 4 with other 70 cases being reported in the following months, along with more than 30,000 cases of suspected reinfections. 8
Herd immunity considerations, vaccination strategies, and general epidemic simulations depend on the effectiveness and duration of immunity against COVID-19. 7 Immunity against COVID-19 reinfection or global vaccination can affect the disease severity and spread. It is believed that lack of immunity due to the lack of the previous infection is the main cause of the rapid and global spread of the disease and epidemic continuation. 9 Therefore, a greater understanding of the immunity against COVID-19 reinfection is essential for better management of the disease, greater knowledge for diagnosis, reinfection prevention, and appropriate intervention strategy modifications. 10
According to the limited evidence available, COVID-19 reinfection is rare and occurs in less than 0.3% of the individuals with previous positive Polymerase Chain Reaction (PCR) for SARS-CoV-2. 11 - 13 A recent study in Qatar reported that the immunity against reinfection continued for at least seven months in about 95% of the individuals with previous positive PCR. 11 Moreover, another study on healthcare providers in the UK showed that the related immunity could continue for at least 5-6 months post-infection. 14 Despite the evidence showing a high level of immunity against COVID-19 reinfection in healthcare providers, the risk of reinfection in the general population is still unknown.
There is limited information on the COVID-19 reinfection due to the extremely limited number of reported cases. 15 Therefore, suspected reinfection documentation is essential to illustrate the natural history of the disease and find the risk factors making the individual susceptible to reinfection. 15 Moreover, understanding the COVID-91 reinfection rate, consequences, and determining factors is also essential to gain a proper insight into the pathophysiology of this novel disease, predict the disease course, and guide the ongoing efforts for vaccine development. 11 Therefore, the present study intended to estimate the COVID-19 reinfection rate in all the hospitalized individuals and outpatients recorded in the Fars province, Iran, from early February 2020 to late April 2021. Besides, this study aimed to find the factors that could be related to the reinfection rate.
Patients and Methods
Study Design and Population
This is a retrospective cohort study including the data of all the patients with COVID-19 infection in the Fars province, Iran. With a population of about five million, Fars province is located in southern Iran and is considered a medical hub in the related geographical region. Annually, many patients from neighboring provinces and countries and evens other parts of Iran come to Fars province to receive medical care. The present study population included all the patients with COVID-19 who presented to the healthcare facilities and hospitals under the coverage of the Universities of Medical Sciences of Shiraz, Fasa, Jahrom, and Larestan from early February 2020 to late April 2021. The study was performed using the census method. Thus, no sampling was needed. The inclusion criterion was having a registered positive PCR test, and there were no exclusion criteria. In addition, the study protocol was approved by the Ethics Committee of Shiraz University of Medical Sciences (Ethics Code: IR.SUMS.REC.1400.040).
Variables and Data
The data included COVID-19 infection, patients’ symptoms, comorbidities, and demographics and was collected from the Health Information Systems (HISs) of the Universities of Medical Sciences located in Fars province. The variables included the demographic variables of age, sex, admission type (inpatient or outpatient), residence location (rural or urban areas), and job (healthcare providers and those with jobs not related to healthcare). According to the WHO guidelines, the patients were classified into four age groups, including 0-14 years old (pediatric group), 15-47 years old (young group), 48-63 years old (middle-aged group), and ≥64 years old (elderly group). 16
The variables related to underlying diseases and conditions included body mass index (BMI), smoking, hypertension, diabetes, cardiovascular diseases, respiratory distress syndrome, mild and severe pneumonia, malignancy, and human immunodeficiency virus (HIV), as well as chronic renal, neurologic, neuromuscular, pulmonary, and hepatic diseases. These variables were described as present or absent.
The clinical presentation variables related to COVID-19 included cough, fever, dyspnea, sputum production, articular, abdominal or chest pain, headache, nausea, diarrhea, rhinorrhea, sore throat, dizziness or irritability, myalgia, fatigue, smell disorder, and taste disorder. These variables were described as present or absent.
The main variable of the present study was reinfection in the study population, which was described as a PCR test positive for SARS-CoV-2 that was taken at least 28 days from the first positive PCR. We considered the cut-off point of 28 days, because previous studies had reported that the related viral load reached its lowest levels after 28 days from the initial infection. 17 , 18 Moreover, the patients were divided into three groups in terms of the duration between the primary infection and reinfection, including 28-44 days, 45-89 days, 7 and more than 90 days. 12
Statistical Analysis
To identify the relation between some categorical risk factors and reinfection, contingency tables were formed. Since the data set included a large number of observations, the Chi squared test was used for preliminary data analysis. Data modeling was performed by logistic regression to estimate the coefficient and effect size of different factors. As the most important and widely used method in categorical response modeling, this method has been increasingly used in a wide variety of applications, especially in biomedical studies, in recent decades. 19
It should be noted that due to the large number of independent variables that were candidates to enter the model, the variable selection was performed in the way that at first simple logistic regression was fitted for each independent variable; then those variables with coefficient P<0.2 were entered the multiple logistic regression. 20 Obviously, variables with missing observations reduce the number of observations that contribute to the analysis, and also the reduction in the number of observations would lead to a decreased analytical power. It is clear that multiple analysis that involves more variables would lead to more lost observations and consequently less power. Therefore, only the variables having <20% of missing observation entered the multiple logistic regression in the present study. Finally, since two sided-tests are more common than one-sided ones, 19 all tests were performed two-sided and at the significance level of 0.05. Moreover, the data analysis was performed using Excel 2016 and STATA software, version 14 (Stata Corp LLC, 1985-2015, USA).
Results
A total of 705,818 PCR tests were performed in Fars province in the study duration. Of all the PCR tests, 218,804 (31%) had positive results, while 487,014 (69%) were negative. The tests were taken from 562,152 individuals, including 56.3% men and 43.7% women. Moreover, each patient had 1.26 PCR tests on average. The duplicated results were omitted, and the number of individuals was calculated using the number of PCR tests. It was found that 213,768 individuals had at least one positive PCR test for SARS-CoV-2.
Table 1 presents the demographics of all the patients with COVID-19 in the Fars province. According to these data, 54% of the patients were men, while 46% were women. Moreover, 89% and 88% of the patients were outpatients and residents of urban areas, respectively. While 11% and 12% were inpatients and residents of rural areas, respectively. Additionally, 6% of the patients were healthcare providers, wherein 94% had jobs unrelated to healthcare. In terms of age, the least number of COVID-19 patients belonged to the pediatric age group (3%), while the young age group (15-47 years) had the highest number of patients (66%). The middle-aged and elderly groups included 20% and 11% of the patients, respectively.
Variable No. (%)
Age group (Year) Pediatric (0-14) 6469 (3.03)
Young group (15-47) 140260 (65.62)
Middle age (48-63) 42911 (20.08)
Elderly ( ≥64 years) 24102 (11.28)
Sex Male 115318 (53.95)
Female 98424 (46.05)
Admission type Outpatient 190530 (89.14)
Inpatient 23212 (10.86)
Location Urban 187409 (87.68)
Rural 26.333 (12.32)
Job Other jobs 196939 (93.7)
Health care personnel 13242 (6.3)
Table 1.Demographic characteristics of the population infected with COVID-19 in Fars province
Regarding the reported cases of reinfection, of a total of 213,768 patients, 2079 had another positive test at least 28 days after the initial infection. Therefore, the overall reinfection rate was calculated to be 0.97% (table 2). Of these patients, 310 (14.9%), 385 (18.5%), and 1384 (66.6%) had their second positive test 28-45, 45-89, and ≥90 days later, respectively (figure 1). The mean duration between the initial infection and reinfection was 130.56 days, with a range of 29-370 days.
Variable Reinfection P value
Yes No
Overall 2079 (0.97) 211663 (99.03)
Age group (year) Pediatric (0-14) 28 (0.43) 6441 (99.57) <0.001
Young group (15-47) 1610 (1.15) 138650 (98.85)
Middle age (48-63) 288 (0.67) 42623 (99.33)
Elderly (≥64) 153 (0.63) 23949 (99.37)
Sex Men 1201 (1.04) 114117 (98.96) <0.001
Women 878 (0.89) 97546 (99.11)
Admission type Outpatient 1709 (0.9) 188821 (99.1) <0.001
Inpatient 370 (1.59) 22842 (98.41)
Location Urban 1906 (1.02) 185503 (98.98) <0.001
Rural 173 (0.66) 26160 (99.34)
Job Other jobs 1563 (0.79) 195376 (99.21) <0.001
Health care personnel 498 (3.76) 12744 (96.24)
ICU* hospitalization Yes 24 (1.54) 1536 (98.46) 0.007
No 111 (0.84) 13035 (99.16)
BMI** (Kg/m2) Over 40 8 (0.94) 842 (99.06) 0.863
Below 40 1677 (0.89) 187687 (99.11)
Smoking Yes 24 (0.67) 3584 (99.33) 0.153
No 1661 (0.89) 184945 (99.11)
Hypertension Yes 70 (0.61) 11354 (99.39) 0.001
No 1615 (0.9) 177175 (99.1)
Diabetes Yes 67 (0.63) 10591 (99.37) <0.001
No 2012 (0.99) 201072 (99.01)
Cardiovascular Yes 99 (0.98) 10028 (99.02) 0.959
No 1980 (0.97) 201635 (99.03)
HIV*** Yes 4 (2.2) 178 (97.8) 0.514
No 366 (1.59) 22664 (98.41)
Chronic kidney diseases Yes 38 (1.66) 2246 (98.34) 0.001
No 2017 (0.96) 209125 (99.04)
Chronic neurologic or neuromuscular disease Yes 6 (1.52) 389 (98.48) 0.904
No 364 (1.6) 22453 (98.4)
Chronic pulmonary disease Yes 38 (1.23) 3056 (98.77) 0.128
No 2017 (0.96) 208315 (99.04)
Hepatic disease Yes 4 (2.06) 190 (97.94) 0.601
No 366 (1.59) 22652 (98.41)
Respiratory distress syndrome Yes 1 (0.5) 199 (99.5) 0.215
No 369 (1.6) 22643 (98.4)
Mild pneumonia Yes 3 (0.61) 488 (99.39) 0.079
No 367 (1.62) 22354 (98.38)
Severe pneumonia Yes 7 (0.77) 905 (99.23) 0.042
No 363 (1.63) 21937 (98.37)
Malignancy Yes 20 (2.7) 720 (97.3) <0.001
No 2059 (0.97) 210943 (99.03)
*ICU: Intensive Care Unit; **BMI: Body Mass Index; ***HIV: Human Immunodeficiency Virus; +Pearson Chi square was used for data analysis.
Table 2.COVID-19 reinfection rate in Fars province in terms of demographics and underlying diseases
Figure 1. The highest frequency of reinfection interval with COVID-19, according to the interval time between the first and second-time infection, was more than 90 days.
According to univariate analysis (table 2), the reinfection rate was higher in the young age group (1.15%), male patients (1.04%), inpatients (1.59%), residents of the urban areas (1.02%), and healthcare providers (3.76%) than the individuals of other age groups, female patients, outpatients, residents of rural areas, and those with jobs not related to healthcare, respectively.
Regarding the underlying diseases and conditions, the reinfection rate was shown to be significantly higher in the patients who were admitted to the Intensive Care Unit (ICU) (1.54%; P=0.007), those with chronic kidney diseases (1.66%, P=0.001), and patients with malignancy (2.7%, P<0.001). However, the patients with high BMI (P=0.863), cardiovascular diseases (P=0.514), HIV (P=0.863), chronic pulmonary diseases (P=0.904), and hepatic disease (P=0.601) were not different in the reinfection rate. Moreover, it was different for hypertensive and diabetic patients and those with severe pneumonia. Patients without hypertension, diabetes, and severe pneumonia had reinfection rates of 0.9% (P<0.001), 0.99% (P<0.001), and 1.63% (P=0.042), respectively, which were significantly different. Besides, patients who were smokers (P=0.153) or had a chronic neurologic disease (P=0.904), respiratory distress syndrome (P=0.215), or mild pneumonia (P=0.079) had no significant difference.
According to the regression findings (table 3), the chance of reinfection in the young age group was twice the pediatric age group, which was significant; while it was also insignificantly higher in the middle-aged and elderly groups. Moreover, men and residents of the urban areas had 28% and 30% higher chances of reinfection than women and residents of the rural areas, respectively. Eventually, it was found that healthcare providers were four times more likely to have COVID-19 reinfection than people with jobs not related to healthcare.
Variables Coefficient Odds Ratio (95% Confidence interval) P value
Age group (year) Pediatric (0-14) Reference
Young group (15-47) 0.72 2.055 (1.411-2.9940) <0.001
Middle age (48-63) 0.325 1.384 (0.936-2.045) 0.103
Elderly (≥64) 0.338 1.403 (0.933-2.107) 0.103
Sex Female Reference
Male 1.283 (1.173-1.403) <0.001
Admission type Outpatient Reference
Inpatient 0.07 1.072 (0.941-1.222) 0.292
Location Rural Reference
Urban 0.272 1.313 (1.121-1.537) 0.001
Job Other jobs Reference
Health care personnel 1.493 4.453 (3.948-5.021) <0.001
Diabetes No Reference
Yes -0.155 0.855 (0.664-1.102) 0.228
Chronic kidney diseases No Reference
Yes 0.806 2.239 (1.612-3.110) <0.001
Severe pneumonia No Reference
Yes 0.351 1.421 (1.022-1.975) 0.036
Malignancy No Reference
Yes 1.234 3.437 (2.182-5.416) <0.001
Model significance <0.001
+Logistic regression was used for data analysis.
Table 3.Regression estimates of factors affecting reinfection with COVID-19 in Fars province
Regarding the underlying diseases, patients with chronic pulmonary disease, chronic renal disease, and malignancy were 1.421, 2.239, and 3.437 times more likely to have reinfection, respectively.
According to table 4, the symptom prevalence rates in the initial infection were as follows: cough=29.12%, myalgia=29.04%, fever=25.86%, sore throat=21.68%, fatigue=15.7%, headache=14.72%, dyspnea=11.37%, smell disorders=6.79%, nausea=5.26%, confusion or irritability=4.55%, chest pain=4.16%, rhinorrhea=4.2%, articular pain=3.99%, diarrhea=3.86%, taste disorders=3.68%, abdominal pain=1.98%, and sputum=0.09%.
Symptom Percentage of patients with the related symptoms
Primary infection n (%) N=211663 Reinfection n (%) N=2079
Sputum 190 (0.09) 2 (0.10)
Articular pain 8445 (3.99) 23 (1.11)
Abdominal pain 4191 (1.98) 11 (0.53)
Chest pain 8805 (4.16) 118 (5.72)
Headache 31157 (14.72) 70 (3.37)
Nausea 11133 (5.26) 113 (5.44)
Diarrhea 8170 (3.86) 106 (5.10)
Rhinorrhea 8890 (4.2) 42 (2.02)
Sore throat 45888 (21.68) 533 (25.64)
Confusion or irritability 9631 (4.55) 16 (0.77)
Myalgia 61467 (29.04) 142 (6.83)
Fatigue 33231 (15.7) 353 (16.98)
Dyspnea 24066 (11.37) 268 (12.89)
Cough 61827 (29.21) 611 (29.39)
Fever 54736 (25.86) 471 (22.66)
Smell disorder 14372 (6.79) 83 (3.99)
Taste disorder 7789 (3.68) 47 (2.26)
Table 4.Patients’ symptoms in initial COVID-19 infection and reinfection
Moreover, the symptom prevalence rates in the COVID-19 reinfection were as follows: cough=29.39%, sore throat=25.64%, fever=22.66%, fatigue=16.98%, dyspnea=12.89%, myalgia=6.83%, chest pain=5.72%, nausea=5.44%, diarrhea=5.10%, smell disorders=3.99%, headache=3.37%, taste disorders=2.26%, rhinorrhea=2.02%, articular pain=1.11%, confusion or irritability=0.77%, abdominal pain=0.53%, and sputum=0.1%.
Discussion
The present study found an overall reinfection rate of 0.97%, while previous studies have reported controversial results. For example, some studies in the UK reported different reinfection rates of 0.0%, 0.2%%, 0.057%, and <0.05%, 15 , 21 and Abu-Raddad and colleagues in Qatar reported a reinfection incidence of 0.66% per 10,000 individuals per week. 11 Moreover, Pilz and others reported a reinfection rate of <0.3% during two major disease waves in Austria, which has a population of 8.9 million. 13 Moreover, a study by Zare and colleagues in Shahroud, Iran, found 2.5 cases of reinfection per 1000 patients. 18 The results of the mentioned study were different from our results, which can be due to the fact that Fars province is a referral healthcare center in southern Iran and hosts some patients seeking healthcare from neighboring provinces. In general, these controversial results in different studies can be explained by differences in the definition of reinfection, the duration between the initial infection and reinfection, and the specificity and sensitivity of the diagnostic tests.
Regarding the type of occupation, our results showed a higher chance of reinfection (more than four times) in healthcare providers than individuals with other jobs, which is compatible with other studies. According to different studies on healthcare providers in Denmark, the chance of COVID-19 infection in the frontline healthcare providers who worked in COVID-19 wards was 1.38 times higher than the healthcare providers working in other parts of hospitals. Moreover, the overall infection rate was two times higher among the healthcare providers than in the general population. 12 , 21 Other studies have also reported a higher chance of reinfection with COVID-19 in healthcare providers. 18 , 22 This can be explained by the fact that healthcare providers are at high viral exposure in the healthcare facilities, therefore, they have a higher chance of infection. 12
Given the effect of age, our findings showed a higher chance of reinfection in the young age group (1.15%) than in other age groups. Moreover, this chance was almost two times higher than the pediatric age group, which was significant. This can be explained by inappropriate behaviors in this age group, such as not following social distancing and other health protocols including frequent handwashing and facemask wearing. These behaviors can increase exposure to the virus and subsequent reinfection. 23 Moreover, this age group has a higher rate of social relationships in society. Therefore, our findings were compatible with those of Tillett and colleagues and Azam and others regarding the effect of age on reinfection. These studies showed a higher chance of reinfection in this age group as well. 6 , 24 Moreover, a 25-year-old individual had severe symptoms in his reinfection. 6 However, the studies by Hansen and others in Denmark and Zhao and colleagues in China reported a higher reinfection rate in the elderly with underlying diseases than in the young age group, 12 , 25 which is not compatible with our results.
Regarding the effect of sex on the chance of reinfection, our study showed that men were 28% more likely to have reinfection than women, which is not compatible with other studies. The study by Zare and others in Shahroud showed a higher rate of reinfection in men (2.96 in 1000 individuals) than women (1.98 in 1000 individuals). 18 However, a study by Adrielle and colleagues (2021) in Brazil showed that women included 78.8% of the reinfection cases. 26 Biological differences in the immune systems of women and men can affect their abilities in fighting infections, especially COVID-19. 27 According to studies, women have a more responsible attitude toward the COVID-19 pandemic than men, which can affect their compliance in following the preventive measures, such as frequent handwashing and facemask wearing. 8 Moreover, different lifestyles between the sexes can also affect the reinfection differences. For example, opioid abuse is more frequent in men than women. 28 Another reason can be the prominent role of men as the families’ breadwinners. Therefore, men are much more exposed in society than women due to this financial responsibility. This can affect the chance of reinfection.
In terms of residence location, our findings showed a higher reinfection rate (30% higher) in the residents of urban areas than those in rural areas. However, no study investigating this difference was available. Therefore, a comparison of the results was not possible. This can be due to overcrowding in cities, the widespread use of public transport, especially subways, and crowded markets. All these factors can increase the close contact of people, decreasing social distancing. 29
Regarding the type of admission, our study showed a higher chance of reinfection in the inpatients and ICU-admitted patients than the outpatients. These findings were compatible with those of Yuan and colleagues, who reported a significant positive correlation between hospitalization and the risk of reinfection. This higher risk can be due to the lack of virus clearance from the patients’ bodies after the initial infection. 25 Moreover, some COVID-19 patients are more exposed to bacterial and fungal infections due to prolonged hospital stays. 30 This can increase the chance of reinfection.
Regarding the effect of different underlying diseases on the COVID-19 reinfection, our findings indicated a higher chance of reinfection (two times higher) in patients with chronic kidney disease, which was compatible with the study by Krishna and others that reported a higher chance of reinfection in patients undergoing hemodialysis. 31 This can be due to the frequent encountering of these patients with healthcare providers and facilities, as well as their immunosuppression and poor immune responses against SARS-CoV-2. 32
The present study showed that patients with malignancy were three times more likely to have reinfection, which was compatible with other studies. For example, a study by Kapoor and others in India on patients with hematologic malignancies who developed immunodeficiency after complete recovery from the initial infection, showed that the reinfection in these patients was more severe than the initial infection. 33 Potential reasons include the lack of neutralizing antibodies due to immunosuppression or the phenomenon of virus reactivation, which is observed in immunosuppressive patients and viruses such as the Cytomegalovirus (CMV), herpes viruses, and Epstein Barr Virus (EBV). 33 Additionally, another study by Bellesso and colleagues in Brazil showed a higher chance of reinfection in patients with multiple myeloma. 34 Patients with active multiple myeloma have severe humoral immunodeficiency due to their inability for normal immunoglobulin production and secretion of the monoclonal component. Dysfunctional cellular and innate immune system, as well as high viral exposure due to close contact with healthcare providers, are other possible causes of reinfection in these patients. 35
The present study results showed a 40% higher rate of reinfection in patients with chronic pulmonary disease. However, no study was available on this topic. Therefore, the comparison of results was not possible. Nevertheless, it is evident that in patients with damaged pulmonary parenchyma due to chronic pulmonary disease, the infectivity of the respiratory viruses is enhanced. Thus, the chance of reinfection with COVID-19 is increased. 36
Regarding the different clinical symptoms between the initial infection and reinfection, the present study showed that patients with reinfection had fewer symptoms than their initial infection. The prevalence of most symptoms was decreased in the reinfection, especially the symptoms of confusion, headache, pain, and myalgia that showed significant decreases in the prevalence. This finding is compatible with that of Pan and colleagues (2021), reporting fever (78.6%), cough (71.4%), and fatigue (50.0%) as the most common symptoms in the initial infection, which had a lower prevalence in the reinfection. 37 Some other studies conducted in Hong Kong, 32 Belgium, and the Netherlands 38 had similar results as well. This difference can be due to different immune responses between the initial infection and reinfection. 39 Moreover, the phenomenon of herd immunity can decrease the severity of future infections compared to the initial infection. Moreover, telemedicine can help in alleviating the disease severity and rapid detection of recurrent cases. 32 It is worth noting that the causative agent of the initial infection in the present study was the primary and Chinese variants of the virus, while the reinfection cases were mainly due to Indian and English variants. Additionally, some studies reported several cases of more severe disease in the reinfection. Even some cases of reinfection led to ICU admission and death, 6 , 18 which is not compatible with our results.
The present study was the first to comprehensively investigate the COVID-19 reinfection rate and its relationship with demographics, underlying diseases, and clinical presentations in a large population of inpatients and outpatients in southern Iran. This could be the main advantage of the study. However, the study limitations include the potential errors in editing the data, because a large number of data can lead to errors beyond the control of the researchers. Moreover, our diagnostic criteria for reinfection diagnosis are still limited. It is worth noting that some patients might have a recurrence of a reactivated virus, which cannot be diagnosed without gene sequencing. Another limitation was related to explanatory variables, which were included based on the availability of data. Many other factors could affect reinfection such as vaccination, antibody level, and the time to wear a mask. However, this study was limited to the available data. Future studies are suggested for checking the effects of these factors on reinfection.
Conclusion
There is a risk of COVID-19 reinfection. Despite the related risk is limited, it cannot be ignored. The study found the population groups who are vulnerable to being reinfected by COVID-19. Therefore, the policymakers and authorities should emphasize implementing the related health protocols (social distancing, facemask wearing, and so on), especially in the high-risk groups, including healthcare providers, young individuals, residents of urban areas, men, and individuals with underlying diseases.
Acknowledgment
This study was supported and approved by Shiraz University of Medical Sciences (Code: 1400-01-21-23245). In addition, the authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran.
Authors’ Contribution
A.T: research idea and the data providing; M.L: research idea and acquisition of the data; F.L: the data cleaning and making them ready for analysis. M.B, M.S.E and M.S.A: the data analysis and writing the results section; M.E and S.D: helping in the data cleaning and writing the first draft of the manuscript; K.K: arranging the team and supervising the whole research process. All authors contributed in revising the final version of the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of Interest:
None declared.
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Candida and Staph cooperate to resist antimicrobials
More evidence that multispecies biofilms are a force to be reckoned with. But there is a bright side.
Like Comment
An interesting paper just came out in mBio reiterating the message that multispecies biofilms need to be taken seriously in the clinic. Specifically, they showed that the Candida extracellular matrix protects Staphylococcus aureus cells from antimicrobials like vancomycin (the last line antibiotic for many gram positives).
It's not all doom and gloom though. They also show that using antifungals reverses the protective effect and senstitises the S. aureus cells again. This means that if multispecies biofilms can be identified early enough as the cause of an infection, treatment can be swift and effective.
Rapid diagnostics for Candida and Staph anyone? Read more details below and let me know what you think in the comments.
Abstract
Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted β-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections.
Importance
The fungus Candida albicans and the bacterium Staphylococcus aureus are important microbial pathogens responsible for the majority of infections in hospitalized patients and are often coisolated from a host. In this study, we demonstrated that when grown together, the fungus provides the bacterium with enhanced tolerance to antimicrobial drugs. This process was mediated by polysaccharides secreted by the fungal cell into the environment. The biofilm matrix formed by these polysaccharides prevented penetration by the drugs and provided the bacteria with protection. Importantly, we show that by inhibiting the production of the fungal polysaccharides, a specific antifungal agent indirectly sensitized the bacteria to antimicrobials. Understanding the therapeutic implications of the interactions between these two diverse microbial species will aid in overcoming the limitations of current therapies and in defining new targets for treating complex polymicrobial infections.
Reference
Kong EF, Tsui C, Kucharíková S, Andes D, Van Dijck P, Jabra-Rizk MA. 2016. Commensal protection of Staphylococcus aureus against antimicrobials by Candida albicans biofilm matrix. mBio 7(5):e01365-16. doi:10.1128/mBio.01365-16.
Ben Libberton
Science Communicator, Freelance
I'm a freelance science communicator, formerly a Postdoc in the biofilm field. I'm interested in how bacteria cause disease and look to technology to produce novel tools to study and ultimately prevent infection.
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Me5 | Nursing homework help
In this discussion, we’ll discuss anxiety, effective and ineffective interventions, and stress management. Please include the following in your initial posting:
Describe a client from your clinical setting or work who experienced severe anxiety or panic. Include a brief history and three most pertinent medications.
• Describe the assessment process for this patient.
• Identify at least one effective and one non-effective nursing intervention. Why did they work? What didn’t work?
• Name and describe two stress reduction techniques you have used and whether they were helpful or not in reducing stress.
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Refined Sugar
It’s probably no real surprise to most of you reading this that consuming a lot of refined sugar is bad for your health. The majority of houses in Ireland will have sugar in the kitchen press or a bowl on the table! This sugar comes mainly from sugar cane or to a lesser extent sugar beet. In its raw state, cane sugar is dark coloured, thick syrup better known as black molasses. It is this syrup which is refined to produce the clean looking granulated form we all know but along the way, all of the original goodness, the nutrients contained in its original form are removed in the refining process. This leaves a handy product that is very sweet to the taste but is devoid of any goodness whatsoever.
As someone who wants to improve their health, or maybe lose some weight, there are two main varieties of sugar that you should be aware of. They are:
• Intrinsic Sugars
• Extrinsic Sugars
Intrinsic Sugars are those sugars that occur naturally in fruits and vegetables and are called intrinsic because they reside within the cell structures themselves. The good news is that you do not need to cut back on these sugars if you want to lose weight or get healthy because they are natural. They also come with a variety of wholesome vitamins and minerals plus dietary fibre which are all essential to the body’s normal functioning. Simply put, these are good sugars to include in your diet.
Extrinsic Sugars are those sugars not contained within the cell structures of the above mentioned natural foods. Instead they themselves fall into two main groups. These are:
Milk Extrinsic Sugars: these occur naturally in milk products
Non Milk Extrinsic Sugars (NME): these are added to foods
NME sugars are added to foods for a variety of reasons, but are mainly added to sweeten them, to increase their bulk or to preserve them. From a health and weight loss viewpoint, it is these NME sugars which should be avoided. The reason is they contain no useful nutrients for the body, so are metabolized and stored as fat. The problem for dieters when this happens is the body never gets to use its stored up fat because we never get hungry, so it just keeps piling it on.
That’s the main reason you gain weight when you eat large amounts of NME sugars. However, if you cut down hard on these sugars and exercise regularly, your body will have no choice but to use up the stored fat and then you will start to lose weight.
Negative Health Aspects of Consuming Refined Sugar
What are the negative health aspects of eating refined sugar?
Sucrose in its refined form, when consumed is broken down by the body into glucose and other simpler sugars that are used by the body for producing energy. When this is done in small quantities, there is no real problem, but when sucrose is taken in and broken down into large amounts of simpler sugars, the blood gets a rush of these sugars which causes an imbalance in blood sugar levels.
As a general rule of thumb, the more refined the sugar you eat is, the more likely your body will react in a negative way to it. In this sense, blood sugar levels are constantly rising and falling sharply when you ingest too great a volume of NME sugars. This is countered to some extent by the body’s own regulatory system in the form of insulin. Insulin is a hormone manufactured within the pancreas. Its main job is to regulate blood sugar levels. So when those levels get too high too quickly, insulin is released in large quantities to break those sugars down fast and return the blood sugar levels to equilibrium.
What happens is that you get a fast rush of energy from the sugar as its processed and released into the bloodstream. This is rapidly followed by a rapid drop in energy as the insulin does its work. You then eat more food or drink more liquids that contain high levels of NME sugars and the process begins again.
What this does is put a terrible strain on your pancreas in the constant creation and release of insulin. Eventually, the strain becomes too much and insulin production becomes erratic, meaning that blood sugar levels can no longer be effectively regulated. This leads to the onset of type II diabetes, which if not diagnosed and is allowed to degenerate further can lead to type I diabetes, which means having to manually injecting insulin to stay alive.
The recommended daily allowance of sugar is 90g. Calculate how much you eat daily, you will be surprised. If you would like more information on diet and/or nutritional advice email [email protected]
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What is the Difference Between Butt Augmentation and Brazilian Lift and Which is a Better Route?
Q: I’m 128 pounds height 5’3 I’m looking for the best option, to go. Also what is the difference between the both . Also i was 117. Most of the weight is in the stomach area.
A: A Brazilian Butt lift is a specific type of butt augmentation like a Ford is a specific type of car. The Brazilian butt lift is fat transfer to the butt. I use liposuction to shape the midsection and remove fat from unwanted areas and then inject this fat into the buttocks. The other option for buttock enlargement is a silicone implant. Fat transfer (Brazilian Butt Lift) is my favorite method for a lot of reasons. First, it looks and feels natural. Second, you can customize (with implants you have a set option of sizes/shapes). Third, you get liposuction to slim your midsection, which, in my opinion, is just as important as shapely buttocks.
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Headache in pregnancy: causes and natural remedies
Contents
• 1 Headache in pregnancy: what it looks like
• 2 Causes of headache in pregnancy
• 3 most common types of headaches
• 4 Headaches in pregnancy: when to worry
• 5 Headaches in pregnancy and medications
• 6 Headache in Pregnancy: Natural Remedies
Sometimes it comes slowly, concentrates between the eyes and then squeezes the whole skull. At other times, however, he rises almost silently from the shoulders and takes the neck. Often he is just passing through, but sometimes he is so violent that he is bedridden. In short, in the event of a headache or migraine you only want one thing: that it passes as quickly as possible! Headaches in pregnancy are not uncommon. On the contrary, it can happen to have it often. The reasons are many. Let's see them and, above all, look for the best remedies.
Headache in pregnancy: what it looks like
Different situations occur during gestation. Those who suffered from headaches before getting pregnant very often see tremendous improvements with a drastic decrease in attacks. In the most fortunate cases, the headache becomes just a distant memory for the whole 9 months. It disappears, almost by magic. And it's a great feeling.
Other times, however, the exact opposite happens. A nasty surprise that one would gladly do without. Finally, it could also happen that, with pregnancy, there is no classic "head circle", but different shapes. One of these - rather unpleasant - is migraine with aura. In this case, the headache is preceded or accompanied by visual symptoms, such as flashes of light in front of the eyes. When it happens, tell the gynecologist.
Causes of headache in pregnancy
The main reason why you often have headaches with the belly is to be found in the hormonal variations typical of pregnancy. This happens especially in the first trimester, which is the one in which the headache is generally more frequent. In the following years the situation improves because the hormones (especially estrogen) are much more stable.
In addition to hormonal changes, there are other causes of pregnancy headaches:
fatigue.
Insomnia.
Nausea and vomit.
Eating disorders.
Influenza.
Incorrect posture.
Anxiety and stress.
Changes in blood circulation.
Dehydration.
Fasting and consequent lack of sugar (hypoglycemia).
Iron deficiency.
Deficiency in some vitamins and minerals (for example, folic acid and magnesium).
Hypertension (high blood pressure).
Gestosi.
Most common types of headaches
In general, headaches in pregnancy can be considered a normal event. However, it is always advisable to point this out to the gynecologist, especially if it occurs often or if it is accompanied by other important symptoms, such as vomiting or excessive sensitivity to light.
There are two main forms of headache that can affect during pregnancy:
Migraine. It is a throbbing and annoying type of headache. Usually, it starts slowly, on one side of the head, then spreads to the forehead and up to the temple. Sometimes it involves both sides of the head. The intensity can be quite strong. Migraine is sometimes associated with nausea, vomiting, sensitivity to odors or light.
Muscle-tension headache. Sufferers speak of a typical "head circle". This headache tightens like a vice, but the cause is to be found in the muscles of the neck and shoulders. Stress, for example, tends to accumulate in the muscles. Bad postures (for example when watching TV or working on a computer) also play their part.
There are other types of headaches, such as cluster headaches. Some are secondary, that is, caused by other disorders. A typical case is that of sinusitis, an inflammation of the paranasal sinuses which, among its symptoms, also has an annoying headache concentrated between the eyes. Another example is trigeminal neuralgia. Influenza and parainfluenza viruses also cause more or less intense headaches.
Headaches in pregnancy: when to worry
Sometimes a pregnancy headache becomes a sign of something wrong. When it occurs recurrently and is very strong and if it is associated with high blood pressure, it could be the alarm bell of pre-eclampsia, also called gestosis. It is a late pregnancy complication. Hypertension is also present among the various symptoms.
The consequences of gestosis can be serious. These include fetal growth retardation, but also intrauterine death. Therefore, in case of frequent and very painful headaches it is necessary to contact your doctor immediately to check that it is not an onset of pre-eclampsia.
A violent headache could also be one of the manifestations of eclampsia, which is the next and most severe form. If you experience problems such as abdominal pain, visual symptoms (for example, double vision), confusion, you should go to the hospital immediately.
Headaches in pregnancy and medications
The only person authorized to recommend drugs during pregnancy is the gynecologist. Never go out of your own way or listen to suggestions from friends and relatives. Generally what is prescribed is acetaminophen, which is considered safe for both mother and baby. Non-steroidal anti-inflammatory drugs (NSAIDs) are not recommended.
For advice on medications during pregnancy, you can contact the Red Telephone (06-3050077) or the toll-free number of the Poison Control Center of the Papa Giovanni XXIII hospital in the city. The number is 800-883300 and it is completely free.
Headache in pregnancy: natural remedies
Before thinking about drugs, you can try some other remedies depending on the triggering cause of the headache.
Insomnia. You can look for some remedies to promote sleep.
Stress. To say it is very easy, but really reducing it is another story altogether. Every pregnant woman should try to get pregnant as peacefully as possible. Thoughts (sometimes even negative) are inevitable: a child changes everything. However, eliminating the sources of anxiety can already be a good way to relieve stress and, consequently, headaches.
Muscle tensions. One solution could be a nice decontracting neck or shoulder massage. In these areas of the body they are not forbidden during pregnancy and indeed could give great benefits. However, it is important not to improvise, but to have them done by expert people.
Food causes. Some foods more than others can promote the onset of a headache or make it worse. An example are fatty ones, such as chocolate or some cheeses. Better to avoid them, if possible, and instead prefer healthier foods, such as fruit and vegetables, lean meats and fish, whole grains. They may not solve, but they can help.
Nausea and vomit. They are among the typical pregnancy symptoms. Each mom experiences the most effective method for herself. From car sickness bracelets to ginger, from small sips of water and lemon to mint candies, from crackers to dried fruit, there are many ways to try.
Anemia. It is very common in pregnancy, especially from the second trimester when the fetus absorbs a large part of the mother's iron. Tiredness, fatigue, paleness, headache, difficulty concentrating are some of the symptoms.
Among other remedies for headaches in pregnancy, you can try massaging the forehead and temples with a few drops of Olio 31; rest in a dark, quiet and cool place; put something cool on your head or, if the source is muscle, keep your neck and shoulders warm. And have a little patience: the headache will go away sooner or later.
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Shared Flashcard Set
Details
Trends Test III
Exam Prep for Test III
144
Nursing
Undergraduate 2
04/03/2012
Additional Nursing Flashcards
Cards
Term
How many questions should you have for each interview at a minimum?
Definition
Three
Term
What are appropriate questions to ask?
Definition
May I see the job description?
How many pt's on unit?
How many patients will I be responsible for ?
What will my scheduled shift be ?
Term
Name the four phases of 'Reality Shock'
Definition
Honeymoon phase
Shock or rejection phase
Recovery phase
Resolution phase
Term
Biculturalism
Definition
The merging of school values with those of the workplace.
Term
Compassion fatigue
Definition
The gradual decline of compassion over time as a result of caregivers being exposed to events that have traumatized their patients.
Term
Horizontal hostility (also known as lateral hostility)
Definition
“A consistent (hidden) pattern of behavior designed to control, diminish, or devalue another peer [or group] that creates a risk to health and/or safety”
Term
Mentoring
Definition
A mutual interactive method of learning in which a knowledgeable nurse inspires and encourages a novice nurse.
Term
Novice nurse
Definition
A nurse who is entering the professional workplace for the first time; usually occurs from the point of graduation until competencies required by the profession are achieved.
Term
Preceptor
Definition
An experienced professional nurse who serves as a mentor and assists with socialization of the novice nurse.
Term
Reality shock
Definition
Occurs when a person prepares for a profession, enters the profession, and then finds that he or she is not prepared.
Term
Role model
Definition
A person who serves as an example of what constitutes a competent professional nurse.
Term
Socialization
Definition
The nurturing, acceptance, and integration of a person into the profession of nursing; the identification of a person with the profession of nursing.
Term
Transition
Definition
Moving from one role, setting, or level of competency in nursing to another; change.
Term
Workplace violence
Definition
Sexual harassment and abusive acts from patients that can be physical, verbal, and emotional and lead to a hostile work environment. It has been suggested that identifying workplace violence is difficult due to its subjectivity by the recipient.
Term
REALITY SHOCK
Definition
Reality shock occurs in novice nurses when they become aware of the inconsistency between the actual world of nursing and that of nursing school. As the novice nurse enters the new profession, reality shock begins.
Term
Reality shock
Definition
leads to stress (Bowles and Candela, 2005), which can threaten the well-being of new nurses resulting in physical illness and mental exhaustion, leading to disillusionment with their career (Hertel, 2009) and ultimately absenteeism and turnover (Jennings, 2008). There are four phases of reality shock: honeymoon, shock or rejection, recovery, and resolution.
Term
Name the four phases of reality shock:
Definition
honeymoon, shock or rejection, recovery, and resolution.
Term
Honeymoon Phase
Definition
During the honeymoon phase everything is just as the new graduate imagined. The new nurse is in orientation with former school friends or other new graduates who often share similarities. Many novice nurses in this phase are heard making the following comments: “Just think, now I'll get paid for making all those beds” and “I'm so glad I chose nursing; I will be a part of changing the future of health care.”
Term
Shock (Rejection) Phase
Definition
Then orientation is over, and the novice nurse begins work on his or her assigned unit. This nurse receives daily assignments and begins the tasks. “But wait. I've only observed other nurses hanging blood. Where is my instructor?” Now the shock or rejection phase comes into play. The nurse comes into contact with conflicting viewpoints and different ways of performing skills, but lacks the security of having an expert available to explain uncertain or gray areas. The security of saying, “I am just the student nurse,” is no longer valid. During this phase, the novice nurse may be frightened or react by forming a hard, cold shell around him or herself. Vague feelings of discomfort are experienced, and the inexperienced nurse often wonders whether the other nurses care about the patients. After going home from a shift, the new nurse may experience feelings of rejection and a sense of lack of accomplishment. The novice nurse may reject the new environment and have a preoccupation with the past when he or she was in school. A need to contact former instructors, call schoolmates, or visit the nursing school may occur. Others may reject their school values and adopt the values of the organization. In this way, they may experience less conflict (Kramer, 1974); however, there are drawbacks to this approach as well.
Term
Name eight of the negative responses to the 'Shock' or 'Rejection' phase:
Definition
Natives, Runaways, Rutters, Burned Out, Compassion Fatigue, Loners,New Nurse on the Block, Change Agents
Term
What is usually the first sign of the 'Recovery Phase' ?
Definition
The return of humor usually is the first sign of the recovery phase. The novice nurse begins to understand the new culture to a certain degree. There is less tension and anxiety, and healing begins. The nurse in this phase may comment, “I'll hang that blood, and I'll bet I can infuse it before 8 hours this time.”
Term
Natives
Definition
Many nurses choose to go “native” (Kramer, 1974, p. 161). That is, they decide they cannot fight the experienced nurses or the administration, thus they adopt the ways of least resistance. These nurses may mimic other nurses on the unit and take shortcuts, such as administering medications without knowing their action and side effects and the associated nursing responsibilities.
Term
Runaways
Definition
Others choose to “run away.” They find the real world too difficult. These new nurses may choose another occupation or return to graduate school to prepare for a career in nursing education to teach others their “values in nursing.”
Term
Rutters
Definition
Some adopt the attitude that “I'll just do what I have to do to get by,” or “I'm just working until I can buy some new furniture.” These nurses are called “rutters.” They consider nursing just a job.
Term
Burned Out
Definition
These nurses bottle up conflict until they become burned out. Kramer (1974) describes the appearance of these nurses as having the look of being chronically constipated. In this situation, patients may feel compelled to nurse their nurse. Inexperienced nurses may become burned out because they assume too many responsibilities in a short period of time (Domrose, 2000). Some common symptoms of burnout include extreme fatigue, headaches, difficulty sleeping, mood swings, anxiety, poor work quality, depression, and anger (Larsen, 2000). The more intelligent, hard-working nurses are the most prone for burnout, but if you exhibit these symptoms; remember that they can be reduced.
Term
Compassion Fatigue
Definition
Not to be confused with burnout or transference, compassion fatigue is the gradual decline of compassion over time as a result of caregivers being exposed to events that have traumatized their patients (Figley, 2001). Even experienced nurses, who commonly have a great deal of empathy, working in environments in which patients have suffered trauma, may develop a reaction in which they have a decrease in compassion. Exposure to traumatic events experienced by their patients may result in compassion fatigue. Nurses who work in emotionally charged environments, such as hospice, emergency departments, and mental health settings, are likely to experience this reaction. The compassion fatigue process is depicted in Figure 24-1.
Term
Loners
Definition
These nurses create their own reality. They adopt the attitude of “just do the job and keep quiet.” These nurses may prefer night shifts, during which they often are “left alone.”
Term
New Nurse on the Block
Definition
These nurses change jobs frequently. They go from the hospital setting to community health to the physician's office. They are always new in their setting and therefore adopt the attitude of “teach me what you want; I'm new here.”
Term
Change Agents
Definition
These are the nurses who care enough to work within the system to elicit change. They frequently visit the nurse manager or head nurse to suggest change or a better way. They keep the welfare of the patient at the forefront. Unfortunately, Kramer refers to these nurses as “bicultural troublemakers” (1974, pp. 91–93).
Term
Resolution Phase
Definition
The resolution phase is the result of the shock phase combined with the novice nurse's ability to adjust to the new environment. If the nurse is able to positively work through the rejection phase, he or she grows more fully as a person and a professional nurse during the resolution phase. Work expectations are more easily met, and the nurse will have developed the ability to elicit change.
Term
VIOLENCE AT WORK
Definition
However, nursing is four times more dangerous than most other occupations (Gallant-Roman, 2008), second only to law enforcement in violence at work.
Term
Nurse Recruiting and interviewing
Definition
Appropriate job choice is critically important and can be costly to the new graduate. Accordingly, an ineffective hiring decision can also be expensive for the employer. Some estimate the cost of recruiting, placing, and orienting a new nurse to be from two to two and one half times the average RN salary—but the costs are more than financial (Donna Herrin, personal communication, 2009). Critical to effective selection is high-level nurse leader competency in resource management processes and attention to creation of an effective healthful practice environment. A great decision on the part of the new graduate and the nurse leader will have better outcomes for the individual nurse in areas of job satisfaction and retention and overall organizational outcomes, employee engagement and retention, and patient outcomes.
Term
Nurse Interviewing
Definition
When interviewing for their first positions, novice nurses should determine philosophies of the agencies and how orientation programs assist new nurses to enter the profession. There are many opinions on the best way to accomplish a smooth transition, and each nurse should evaluate orientation options available.
Term
Biculturalism
Definition
Biculturalism is the joining of two contradictory value systems, in this context, those of school values with those of the workplace. Biculturalism is designed to enhance a positive self-image and help novice nurses set realistic goals for practice. This strategy, if accepted in the workplace, allows the new nurse to introduce ideas or values brought from nursing school and integrate them into the work environment. Kramer (1974) suggests that the novice nurse apprise both sides of an issue, determine how his or her behavior will have an effect on other members of the interprofessional health care team, and single out accessible objectives.
Term
Biculturalism
Definition
The merging of school values with those of the workplace.
Term
Reality shock
Definition
Occurs when a person prepares for a profession, enters the profession, and then finds that he or she is not prepared.
Term
Shock (Rejection) Phase
Definition
Then orientation is over, and the novice nurse begins work on his or her assigned unit. This nurse receives daily assignments and begins the tasks. “But wait. I've only observed other nurses hanging blood. Where is my instructor?” Now the shock or rejection phase comes into play. The nurse comes into contact with conflicting viewpoints and different ways of performing skills, but lacks the security of having an expert available to explain uncertain or gray areas. The security of saying, “I am just the student nurse,” is no longer valid. During this phase, the novice nurse may be frightened or react by forming a hard, cold shell around him or herself. Vague feelings of discomfort are experienced, and the inexperienced nurse often wonders whether the other nurses care about the patients. After going home from a shift, the new nurse may experience feelings of rejection and a sense of lack of accomplishment. The novice nurse may reject the new environment and have a preoccupation with the past when he or she was in school. A need to contact former instructors, call schoolmates, or visit the nursing school may occur. Others may reject their school values and adopt the values of the organization. In this way, they may experience less conflict (Kramer, 1974); however, there are drawbacks to this approach as well.
Term
Recovery Phase
Definition
The return of humor usually is the first sign of the recovery phase. The novice nurse begins to understand the new culture to a certain degree. There is less tension and anxiety, and healing begins. The nurse in this phase may comment, “I'll hang that blood, and I'll bet I can infuse it before 8 hours this time.”
Term
Change Agents
Definition
These are the nurses who care enough to work within the system to elicit change. They frequently visit the nurse manager or head nurse to suggest change or a better way. They keep the welfare of the patient at the forefront. Unfortunately, Kramer refers to these nurses as “bicultural troublemakers” (1974, pp. 91–93).
Term
Resolution Phase
Definition
The resolution phase is the result of the shock phase combined with the novice nurse's ability to adjust to the new environment. If the nurse is able to positively work through the rejection phase, he or she grows more fully as a person and a professional nurse during the resolution phase. Work expectations are more easily met, and the nurse will have developed the ability to elicit change.
Term
Personal protective equipment (PPE)
Definition
Equipment designed to shield or isolate individuals from chemical, physical, and biologic hazards.
Term
Preparedness
Definition
Activities that build capability and capacity to address potential needs identified by the threat and vulnerability study.
Term
Recovery
Definition
Activities designed to return responders and the facility to full normal operational status and to restore fully the capability to respond to future emergencies and disasters; activities traditionally associated with providing federal supplemental disaster relief assistance under a presidential major disaster declaration. These activities usually begin within days after the event and continue after response activity ceases. Recovery includes individual and public assistance programs that provide temporary housing assistance, in addition to grants and loans to eligible individuals and government entities to recover from the effects of a disaster.
Term
Level A PPE
Definition
Level A provides a totally encapsulated chemical resistant suit, including supplied air. As a result, maximum respiratory and skin protection is provided. In addition, this level of equipment is used to provide protection against liquid splashes or in situations in which agents are still unidentified.
Term
Level B PPE
Definition
Level B provides a chemical splash–resistant suit with hood and self-contained breathing apparatus (SCBA). It provides maximum respiratory protection but less skin protection than level A equipment.
Term
Level C PPE
Definition
Level C equipment is chemical-resistant clothing with a hood and an air-purifying respirator. The respirator can remove all anticipated contaminants and concentrations of chemical materials, thus providing adequate protection against airborne biologic agents and radiologic materials.
Term
Level D PPE
Definition
Level D protection may consist of a uniform or scrubs and is appropriate when it has been determined that no respiratory or skin hazard is present.
Term
GINKGO BILOBA
Definition
Use: Increases circulation to brain, which may improve cognitive performance in persons with dementia
Cautions: Close monitoring necessary if taken by person using anticoagulant because it can prolong bleeding time; can reduce effectiveness of anticonvulsants. Should not be used by people who have fragile blood vessels and a tendency to easily bleed.
Term
Complementary and alternative medicine (CAM)
Definition
Healing philosophies, practices, and products that are outside of what Western society considers mainstream medicine and are not typically taught in the educational programs of physicians, nurses, and other health professionals.
Term
Conventional medicine
Definition
Western style of medicine practiced in the United States; also called allopathic.
Term
Energy therapies
Definition
Qi gong, Reiki, therapeutic touch, healing touch, bioelectromagnetic-based therapies.
Term
Containment
Definition
Limitation of an emergency situation within a well-defined area.
Term
Decontamination
Definition
The physical process of removing harmful substances from personnel, equipment, and supplies.
Term
Scene assessment
Definition
The act of reviewing the location of an event to look for information that might help to determine treatment options.
Term
Triage
Definition
Process of prioritizing which patients are to be treated first; first action in any disaster response (Veenema, 2007).
Term
Telephone Triage Nurse
Definition
Another career option is that of telephone triage nurse. In this practice, nurses interact with clients on the telephone to assess needs, intervene, and evaluate. This position requires excellent communication and assessment skills, in addition to problem-solving skills. Telephone triage is used in a variety of settings, including emergency departments and physician practices.
Term
Time management
Definition
The development of processes and tools that increase efficiency and productivity within the set standard of time.
Term
External Time and Energy Distractions
Definition
Interruptions, Socializing or Visitors, Meetings, excessive paperwork, understaffing, lack of information, inneffective communication, lack of feedback, travel, inadequate policies and procedures, incompetent or uncooperative coworkers, poor filing system, looking for misplaced files etc., personnel or coworkers with problems, lack of teamwork, duplicating efforts, (confusing lines of authority, responsibility, and communication), bureaucratic red tape, Junk Mail, waiting, meeting delays.
Term
Internal Time and Energy Distractions
Definition
Procrastination, inadequate planning, ineffective delegation, failure to set goals and priorities, a cluttered desk or mind, personal disorganization, inability to say no, lack of self discipline, responding to crises, haste, indecisiveness, an 'open door' policy, shifting priorities without sound rationale, leaving tasks unfinished, not setting time limits, daydreaming, attempting too much at once, overinvolvement in routine details, making numerous errors, surfing the internet, not listening.
Term
Time management
Definition
The development of processes and tools that increase efficiency and productivity within the set standard of time.
Term
Physical Energy
Definition
This scenario is not uncommon as novice professionals begin the rigors of full-time work after spending time in college and working part time. Key components of successful transition to a productive, highly energizing experience include paying attention to physical energy through a routine of proper eating, adequate sleep and exercise, frequent breaks during long shifts (about every 90 minutes), drinking plenty of water, and focusing on one activity while collecting thoughts about what to prioritize next. Once the physical capacity of your holistic self is working well, then attention can be paid to your mental, spiritual, and emotional capacities.
Term
Mental Energy
Definition
The mental energy that is most potent in ensuring full engagement and high performance is that of realistic optimism. Realistic optimism is seeing the world as it is, but always working toward an optimal solution or goal. Mental energy is the ability to maintain sustained concentration on a task, move flexibly between broad and narrow issues, and be internally and externally focused as needed by the situation. It includes mental preparation, visualization, positive self-talk, effective time management, and creativity. Susan has begun to identify this mental energy in her desire to get back on track. She realizes that change is necessary. To move in this direction Susan needs to spend some time to reflect on the following: (1) What are my major goals in life, and (2) what is my purpose?
Term
Spiritual Energy
Definition
Often we do not take the time to reflect about what is important to us. Being in a quiet place helps us identify our vision of life—our purpose and direction in life. Susan has yet to determine her life vision given her frequent job changes and her lack of clarity about how she wants to spend her personal time. Having direction and purpose is the key factor in one's spiritual capacity.
Peter Senge (1999) has identified “personal mastery” as the discipline of continually clarifying and deepening one's personal vision, focusing one's energies, developing patience, and seeing reality objectively. People with a high level of personal mastery live in a continual learning mode, uncovering their personal growth areas.
Term
Time Management Truisms
Definition
♦“Nothing changes if nothing changes.”
♦“We train people how to treat us.”
♦“Everything you own owns you.”
Term
What is the most important step in time management ?
Definition
Planning is the most important step in time management.
Term
Unclear Goals and Priorities.
Definition
Within a particular work shift or within your life as a whole, if you lack clarity about purpose and expected outcomes, the ability to manage time to meet your desires becomes a futile task.
Term
Conquistador of Chaos.
Definition
If you are constantly overburdened with tasks, events, urgent requests, and last-minute cancellations, you are a better crisis manager than manager of time.
Term
Fear of Downtime.
Definition
Some individuals fear the possibility of standing still too long. They feel guilty with timeouts or time off. Often this is a result of not wanting to address the larger issues in life. Staying too busy to think keeps long-term planning and personal introspection at bay.
Term
Need to be a Caretaker.
Definition
Need to be a Caretaker. In professions such as nursing the need to be a caretaker is a common devotion and can be very gratifying. However, when this need becomes unbalanced, it can cause you to feel resentful, unappreciated, and overwhelmed.
Term
Fear of Failure.
Definition
When you are unable to get to the things that are important to you and are unable to meet your personal goals, it may mean you are afraid of failure. It can be very upsetting to go after your dreams and find out you cannot reach them. Sometimes it is easier to avoid making the effort. Take time to understand what your fears are and to openly address them.
Term
Fear of Success.
Definition
You may have been given a message somewhere in your life that you do not deserve to be a success. Therefore, it can be anxiety provoking to garner success and stand apart from others who may distance themselves from you. Take time to think through whether or not this is playing out in your life.
Term
Fear of Disrupting the Status Quo.
Definition
Not pursuing your goals for fear of the reactions of those around you is very common. Your family, coworkers, or supervisors may be critical of what you want to pursue. Gradually approaching changes gives you and those around you time to acclimate.
Term
Fear of Completion.
Definition
If you are afraid of completing a project that is creative and fun because you are fearful that another similar project will not find its way to you or the project may no longer be important to you, take the time to understand why you are not completing a routine task or a major project that has been with you for some time.
Term
Need for Perfection.
Definition
If you are a perfectionist and feel that everything should be completed with the same level of excellence, you are not keeping things in perspective. If you demand extremely high standards for every single task you undertake, you simply will not get everything done.
Term
Fear of Losing Creativity.
Definition
Many creative people think that by creating an organized time management structure or approach to life their creative natures or tendencies will be squelched. However, creating a framework to manage priorities will allow more freedom and time to enhance one's creative juices.
Term
What is the fundamental currency of high performance ?
Definition
“Energy, not time, is the fundamental currency of high performance”
Term
Mental Energy
Definition
The mental energy that is most potent in ensuring full engagement and high performance is that of realistic optimism. Realistic optimism is seeing the world as it is, but always working toward an optimal solution or goal. Mental energy is the ability to maintain sustained concentration on a task, move flexibly between broad and narrow issues, and be internally and externally focused as needed by the situation. It includes mental preparation, visualization, positive self-talk, effective time management, and creativity.
Term
Spiritual Energy
Definition
Peter Senge (1999) has identified “personal mastery” as the discipline of continually clarifying and deepening one's personal vision, focusing one's energies, developing patience, and seeing reality objectively. People with a high level of personal mastery live in a continual learning mode, uncovering their personal growth areas.
Term
Emotional Energy
Definition
Physical, mental, and spiritual energy provide fuel for building our emotional capacity. Managing emotions skillfully in the service of high positive energy and full engagement is called emotional intelligence. Goleman (1999) suggests that self-confidence, self-control, and interpersonal effectiveness are all key to emotional intelligence. Striving to increase one's emotional capacity—which includes improving one's self-confidence, self-control, self-regulation, social skills, interpersonal effectiveness, empathy, patience, openness, trust, and enjoyment—will result in a more positive, invigorating work experience and personal life.
Term
Interprofessional team
Definition
Health care team composed of professionals from different disciplines including chaplains, nurses, dietitians, pharmacists, physical therapists, physicians, respiratory therapists, social workers, and speech language pathologists who cooperate, collaborate, communicate, and integrate care to ensure that care is continuous and reliable.
Term
Nursing roles
Definition
(1) Traditional duties and responsibilities of the professional nurse, regardless of practice area or setting, such as the roles of care provider, educator, counselor, client advocate, change agent, leader and manager, researcher, and coordinator of the interprofessional health care team. (2) Duties and responsibilities of the professional nurse that are guided by specific professional standards of practice and usually are carried out in a distinct practice area (e.g., flight nurse, forensic nurse, and occupational nurse).
Term
Name 7 Professional Nursing Roles
Definition
Care provider
Educator and counselor
Client advocate
Change agent
Leader and manager
Researcher
Coordinator of the interprofessional health care team
Term
Care Provider
Definition
The role of care provider is basic to the nursing profession. As the provider of care the nurse assesses client resources, strengths and weaknesses, coping behaviors, and the environment to optimize the problem-solving and self-care abilities of the client and family. The nurse plans therapeutic interventions in collaboration with the client, physician, and other health care providers. In addition, the nurse takes responsibility for coordination of care that involves other health professionals or resources, providing continuity and helping the client deal effectively with the health care system. As part of this role, caring is always central to nursing interventions and is an essential attribute of the expert nurse.
Term
Change Agent
Definition
When nurses first adopted the role of “change agent,” few individuals anticipated to what extent nurses would fulfill this role. However, nurses have expanded their role as change agents in many ways. The profession continues to identify client, patient safety, and health care delivery problems; to assess individual and organizational motivation and capacity for change; to determine alternatives; to explore possible outcomes of the alternatives; and to assess cost-effective resources in infinite health-related situations.
Term
Leader and Manager
Definition
The leadership role of the professional nurse is paramount to the health care system. Nursing leadership varies according to the level of application and includes:
♦Improving the health status and potential of individuals or families
♦Ensuring that safe, high-quality care is provided across all health care settings
♦Increasing the effectiveness and level of satisfaction among professional colleagues providing care
♦Managing multiple resources in a health care facility
♦Raising citizens’ and legislators’ attitudes toward and expectations of the nursing profession and the health care system
There is little doubt that the management role of the nurse has become more important. Nursing management includes planning, giving direction, and monitoring and evaluating nursing care of individuals, groups, families, and communities.
Term
Coordinator of the Interprofessional Health Care Team
Definition
Interprofessional teams consist of collaborative practice relationships among several disciplines of health care professionals. These disciplines may include nursing, medicine, pharmacy, nutrition, social work, case management, and other allied health professionals, such as physical therapists, respiratory therapists, occupational therapists, and speech therapists. Chaplains or pastoral care representatives also serve a valuable role on the interprofessional health care team. These teams are found in all health care delivery settings and function most effectively when their focus revolves around the needs of the client.
Term
Infection Control
Definition
The infection control nurse assesses the total incidence of infections within the hospital. Clients who suffer an infection while in the hospital are comprehensively reviewed to ensure prompt and accurate treatment and timely containment of the client's infection so that it is not passed to other clients or staff. The infection control nurse must also conduct a thorough analysis to determine the source of the infection and its onset. If the infection is determined to have been contracted during hospitalization, an investigation is initiated to assess the sequence of events leading up to the infection, and an action plan is developed to prevent future occurrences. A position such as this enables the nurse to have hospital-wide interactions and functioning. Knowledge of epidemiology and outstanding interpersonal skills foster full participation in the infection assessment process. Infection control nurses may work in community settings and hospitals.
Term
Quality Management
Definition
Although the parameters of a position in quality management may vary from setting to setting, the basic premise is to ensure that outcomes in client care services are consistent with established standards. Benchmarking activities to establish such standards have been under way on a national level for the past few decades. Quality management nurses assess the compliance of the agency or institution with established standards and explore variations from these established standards. Chart reviews and ongoing interaction with the staff of the agency are integral components of a quality management position. Chapter 20 provides a more in-depth overview of the quality management process.
Term
Coordinator Positions
Definition
Some hospitals have various coordinator positions, such as trauma nurse coordinator. The nurse in this position is responsible for the coordination and integration of the clinical and administrative requirements of the trauma victim. Consisting of equal parts of program and case management, the trauma nurse coordinator role involves overseeing the care of the client from the point of injury through acute care to rehabilitation and back to society. Maintenance of a comprehensive database on the management of trauma victims is an important part of this position. Another example of a coordinator position for a highly specialized area is the organ donor coordinator, who procures organs and oversees the transplantation program. Coordinators require considerable experience in the specialty in which they practice.
Term
Occupational Health Opportunities
Definition
Nursing within the framework of specific occupational groups (e.g., automobile manufacturing, textile plants, etc.) has long been a career option for nurses. Within these settings the nurse designs and implements a program of health promotion and disease prevention for employees and assists with immediate health needs as necessary. In this primary care milieu, the nurse assesses the need for programs about specific topics of importance to the health of the employees. Some examples of these might be breast-screening programs for female employees and information on early identification of prostate cancer for male employees. Other programs might revolve around the management of developmental events, such as empty nest syndrome, menopause, care for aging parents, or retirement.
In addition to services related to maintaining the health of employees, the occupational nurse is responsible for the assessment of the work environment to ensure the safety of the employees. Examples of significant environmental improvements in the health of U.S. workers are clean air programs, antismoking-on-the-job campaigns, and eliminating the use of asbestos in heating or insulation of buildings. All these activities pose special challenges to the occupational health nurse. The nurse in this setting develops procedures to be followed in the event of illness at work, including the management of health care emergencies.
Opportunities also exist in specific industries. For example, within the airline industry the nurse is responsible for airline safety through maintaining the health of employees. Protection of the employee's health is a component of the role, as is the effect of the health of the employee on the safety of the airline and its passengers. The nurse must be vigilant in the assessment of employee health problems that could affect overall airline safety. An obvious function is alcohol and drug screening. Protocols for the maintenance of employee health programs in the airline industry must be strictly followed and enforced, as required by government regulation.
Nonetheless, the heart of this nursing position still lies with providing care to people, which sometimes can place the nurse in a difficult position. In the ongoing monitoring of the health of the employees, the nurse often is the first to spot a deviation from health that could affect the career and livelihood of an employee. Such an example is hypertension. If an employee is developing high blood pressure, which will affect his or her employment status, that employee may encourage the nurse to “hear” the blood pressure in the qualifying range.
Occupational health and employment screening activities are entwined with urgent care and travel assistance for passengers. Although occasionally an emergency situation develops with a passenger or an employee, most of the client problems are travel related. For example, international travel to some countries requires comprehensive precautions regarding immunizations and inoculations. Airport nurses were critical in screening passengers on international flights during such times as with the severe acute respiratory syndrome (SARS) crisis in 2003. Also passengers may forget prescribed medications, or medications may be lost in baggage. Short-term problems, such as fear of flying, are also managed.
Another form of transportation provides a career opportunity: cruise ship nurse. Generally when people think of taking a cruise, they do not plan on getting sick—nor do nurses usually consider career possibilities in the industry. However, many cruise ships are as large as small cities. The role of the nurse in this setting is similar to that of the airline nurse with respect to the health of the employees and the safety of the passengers. The unique elements of the ship relate to special sanitation requirements, such as testing and culturing the water supply, and managing the total health needs of the passengers. The nurse is responsible for instructing the staff on the basic elements of emergency care and transport. Primary patient care needs are similar to those found in an emergency department.
Term
Quality Manager
Definition
Another role that is attractive to nurses is that of quality manager. This reflects the need for health care providers to assess opportunities for process improvement, implement changes, measure outcomes, and then start the improvement process over again. Quality management nurses research and describe findings and look for opportunities to improve care. The result of quality assessment studies may produce critical pathways or algorithms defining care and expected client outcomes. Basic and advanced knowledge of quality management tools is essential, although practice may vary from setting to setting. For instance in the inpatient setting, the quality management nurse needs strong clinical skills, such as those that might be acquired in medical-surgical practice, intensive care units, or the operating room. Experience in home care would be an advantage for a quality management nurse if employed in that setting. Interpersonal skills are important because to be successful in this role, the nurse must build relationships and rapport with people and groups across the organization. The role of quality manager is one that promotes improved care for health care recipients in a variety of settings.
Term
Case Manager
Definition
This role has had a rich tradition in community and public health nursing and now has gained more prominence in acute care. Case managers coordinate resources to achieve health care outcomes based on quality, access, and cost. The complexity of case management practice is obvious in the era of chaotic systems caused by recent changes in the health care market, in which providers, services, and coverage details are constantly changing. Case managers identify the best resources at the lowest cost to achieve the optimal health outcome for the client. Case managers are often nurses, but can also be other professionals, such as medical social workers.
Term
Recovery
Definition
Activities designed to return responders and the facility to full normal operational status and to restore fully the capability to respond to future emergencies and disasters; activities traditionally associated with providing federal supplemental disaster relief assistance under a presidential major disaster declaration. These activities usually begin within days after the event and continue after response activity ceases. Recovery includes individual and public assistance programs that provide temporary housing assistance, in addition to grants and loans to eligible individuals and government entities to recover from the effects of a disaster.
Term
CBRNE
Definition
stands for chemical, biologic, radiologic, nuclear, and explosive.
Term
STAGES OF DISASTER
Definition
three phases of the disaster continuum: preimpact, impact, and postimpact. In the preimpact phase, activities are focused on planning, preparedness, prevention, and warning. In the impact phase, all efforts are directed to responding to the disaster, initiating the emergency management system, and mitigating the effects of the hazard. During the postimpact phase, which usually begins 72 hours after the disaster and may continue for 2 to 3 years, a network of activities is designed to enhance recovery, rehabilitation, and reconstruction. Evaluation of the disaster preparedness and response plan is a major activity that needs to be included in the postimpact phase.
Term
Impact Phase
Definition
Response activities are first initiated during the impact phase of disasters. These activities begin at the time of the event and are focused on providing the first emergency response to victims of the disaster, stabilizing the situation, and providing adequate treatment for the victims. This phase requires the interaction of emergency responders from fire and police departments, emergency medical services, hazardous materials teams, health care agencies, health departments, and other agencies to be able to triage and provide assistance to the victims and stabilize the scene. Usually the first unit responding establishes an incident command post from which to coordinate the activities. However, as other units arrive and as the cause of the incident becomes known, one of the law enforcement agencies may assume control if there is suspicion of a crime before the establishment of a community-based emergency operations center (EOC).
Term
MMRS
Definition
Metropolitan Medical Response System
The MMRS builds a cadre of specialty trained responders and equipment. The system is coordinated with area and statewide planning systems and integrates the efforts of all of the emergency response teams. The MMRS includes plans for expanding hospital-based care, enhancing emergency medical transport and emergency department capabilities, locating specialized pharmaceuticals to respond to a mass casualty event, managing mass fatalities, and providing mental health care for the community, victims, and health care providers. Scenarios designed to test the effectiveness of the MMRS in the community in providing an integrated response to an MCI are conducted on a regular basis.
Term
Biculturalism
Definition
The merging of school values with those of the workplace.
Term
Biculturalism
Definition
Biculturalism is the joining of two contradictory value systems, in this context, those of school values with those of the workplace. Biculturalism is designed to enhance a positive self-image and help novice nurses set realistic goals for practice. This strategy, if accepted in the workplace, allows the new nurse to introduce ideas or values brought from nursing school and integrate them into the work environment. Kramer (1974) suggests that the novice nurse apprise both sides of an issue, determine how his or her behavior will have an effect on other members of the interprofessional health care team, and single out accessible objectives.
Term
Role Models and Mentors
Definition
Mentoring and role modeling are often considered to be the same, but in fact they are different. Mentoring is an interactive, mutual, and personal experience (Sullivan and Decker, 2009), whereas role modeling is usually not an interactive process (Stone, 2000). Sullivan and Decker (2009) suggest that choosing the correct mentor is one of the most important tasks for the novice nurse.
Term
Mentors
Definition
Mentors are experienced nurses who must be willing to commit to a relationship with novice nurses to help them recognize their weaknesses and strengths. Mentors help novice nurses set and reach realistic goals by reinforcing and recommending appropriate courses of action. Mentors help novice nurses build self-confidence and gain professional satisfaction while helping novice nurses develop as nurses and individuals (Blakeney, 2005). The benefactor of mentoring is termed a protégé. A skilled mentor can be a role model, but also serves as the student advocate (Blakeney, 2005) opening not only the novice's eyes to the profession but also hopefully a few professional doors and career opportunities.
Term
Socialization
Definition
Networking with other male nurses helps with the socialization and integration of men into the profession.
Term
Violence Prevention
Definition
Because new graduates are frequently victims of horizontal violence in their first year of practice, preceptors with zero tolerance for such activities are invaluable. It is also suggested that having nurses on the unit describe their first year may deflect the desire to continue the violence cycle with the new hires (Baltimore, 2006; Longo and Sherman, 2007). Novices who practiced responses to horizontal violence during orientation were better equipped to successfully defend against horizontal violence (Longo and Sherman, 2007). Baltimore (2006) also suggests that nurses should devise a plan to increase socialization of novice nurses with staff; make assignments realistic, role modeling professional behavior, check egos, evaluate attitudes of staff, resist gossiping, and should conflict arise address it directly with the individual. Should incompetence of the novice be apparent, leave this to management to resolve. Perhaps most important is making horizontal violence transparent. DeRung (2004), herself a novice nurse, suggested finding intra and interprofessional coworkers who exhibit healthy working relationships and not dwell on the negative but refuse to accept abusive behaviors. Novice nurses entering the workforce will find the Occupational Safety and Health Administration (OSHA) book Guidelines for Preventing Workplace Violence for Health Care and Social Service Workers helpful (www.osha.gov/SLTC/etools/hospital/hazards/workplaceviolence/viol.html) along with the Framework Guidelines for Addressing Workplace Violence in the Health Sector (www.osha.gov/SLTC/etools/hospital/hazards/workplaceviolence/viol.html#violenceprevention). In fact, OSHA has called for zero tolerance of workplace violence. “The incidence of lateral violence and bullying in the workplace is on the rise”
Term
key to stopping the cycle of horizontal violence
Definition
Novice nurses are key to stopping the cycle of horizontal violence by being aware of its existence and refusing to accept it as part of the hazing of new nurses. Novice nurses must report any behavior that undermines them on their job; this may be horizontal violence
Term
Delegation Skills
Definition
Another important skill that novice nurses need to learn is delegating. First, nurses should consider how others have delegated to them. Body language is important when delegating. Look at the person, be pleasant, and leave room for suggestions from the delegatee; however, do not allow the delegatee to resist or intimidate you so that you end up completing the task yourself. After communicating face to face, give a list of tasks in writing or post it at the nurses’ station. This leaves little room for misunderstanding. Be willing to change the assignment if there are changes in a patient's condition, new patients are admitted, or you realize that the time needed to perform a task was underestimated. If time allows, it is always good to help those to whom you have delegated tasks. For example, if a nurse passes by a door and the attendant is trying to turn a very large patient, she should enter the room and ask, “How can I best help you turn the patient?” Always take time to give sincere positive reinforcement and say thank you.
Term
Priority-Setting Skills
Definition
Now consider the best way to prioritize. How did you prioritize in nursing school? What worked then will probably work now with a few modifications. Remember: if it is not written down, it probably will be forgotten. Keep a notepad and pen in your pocket. Jot down reminders of things to be done and place a number indicating their importance.
Term
Priority-Setting Skills
Definition
Now consider the best way to prioritize. How did you prioritize in nursing school? What worked then will probably work now with a few modifications. Remember: if it is not written down, it probably will be forgotten. Keep a notepad and pen in your pocket. Jot down reminders of things to be done and place a number indicating their importance.
Term
Priority-Setting Skills
Definition
Now consider the best way to prioritize. How did you prioritize in nursing school? What worked then will probably work now with a few modifications. Remember: if it is not written down, it probably will be forgotten. Keep a notepad and pen in your pocket. Jot down reminders of things to be done and place a number indicating their importance.
Term
Transition
Definition
Experienced RNs should consider the following to help ease the transition of the novice nurse to the profession of nursing: The novice nurse should not be expected to enter the work environment and be as productive as experienced staff members. It is important for experienced nurses serving on agency committees to serve as advocates for novice nurses by reminding nurse managers and administrators that it is not possible for nursing students to learn everything necessary for professional practice during school. Also remind other members of the nursing unit about this fact. If a novice nurse develops initiative, autonomy, and a desire to become a team member, he or she will succeed.
Term
role modeling
Definition
role modeling is usually not an interactive process
Term
Collective bargaining
Definition
The process whereby workers organize under the representation of a union in order to share a degree of power with management to determine selected aspects of the conditions of employment.
Term
Industrial unionism
Definition
Occurs when there is a single union for all workers in a corporation. For example, all people who work in an automobile manufacturing company may be grouped together under the United Auto Workers (UAW). It is possible that the industrial union, with its massive numbers of union members, is the strongest possible collective group.
Term
Grievance
Definition
A term associated with a negative workplace event that results in an allegation by an employee that he or she has not been treated fairly and equitably. Grievances can occur in union and nonunion settings. In a union setting, a grievance generally arises when two parties, such as an employee and a manager, interpret contract provisions differently. Grievances often involve job security or safety, which is a union priority, or job performance or discipline, which is a management priority.
Term
Mediation
Definition
A form of settling disputes that involves a trained person who listens to all parties and makes recommendations. Such mediation is generally not legally binding.
Term
Occupational unionism
Definition
Each occupation within a given company has separate unions; these occupational groups might join others of like work across boundaries and across the country. White-collar workers coming from a background of higher education and some measure of job security tend to prefer occupational unionism and organizing with like-minded professionals. In general, nurses prefer occupational unionism.
Term
In general nurses prefer what type of unionism ?
Definition
In general, nurses prefer occupational unionism.
Term
Collective bargaining
Definition
Collective bargaining is a method for achieving power-sharing in the workplace.
Term
Union shop
Definition
Refers to a worksite that requires all new employees in a specific work group to join the union. Dues will be deducted automatically from employees’ paychecks as defined in the facility's contract.
Term
NLRA
Definition
As a result of these early efforts at unionization, Congress passed the National Labor Relations Act (NLRA) in 1935. Under the terms of the NLRA, employees were given the right to self-organize, to form labor unions, and to bargain collectively. As part of the 1935 NLRA, the National Labor Relations Board (NLRB) was established to implement provisions of the NLRA. The NLRB continues to play a vital role in labor-management relations and, working through 52 regional and field offices in major U.S. cities, they conduct union elections and prosecute unfair labor practices.
Term
Nursing & NLRA
Definition
employees of nonprofit hospitals such as nurses were not protected under the NLRA and therefore were not legally protected for participation in collective bargaining activities. Hospitals’ employees may have been excluded from protection by the NLRA because it was believed that services provided were so essential that organizing activities would be contrary to the public's interest. Eventually in 1974 legislation allowed for the inclusion of nonprofit hospitals in coverage under provisions of the NLRA. Nurses could form collective bargaining units. The 1974 amendments also included the requirement for a 10-day written notice of the intent to picket or to strike. This notice would allow the health care facility time to prepare and would protect the relative health and safety of the public.
Term
Taft-Hartley
Definition
Formal unionization in nursing began in 1946 when the American Nurses Association (ANA) endorsed collective bargaining as a way to gain economic security and influence other employment issues. Its efforts were dealt a serious blow, however, when Congress passed the 1947 Taft-Hartley Act, exempting charitable institutions, including nonprofit hospitals, from the 1935 NLRA Act. The ANA immediately began efforts to get the Taft-Hartley provisions related to charitable institutions repealed. As noted, legislation enacted in 1974 finally allowed for the inclusion of nonprofit hospitals in coverage under the NLRA.
Term
UAN/NLA
Definition
in 1999, a national nurses union, the United American Nurses (UAN), was established as an ANA affiliate to create an independent voice for union nurses. UAN is also affiliated with the American Federation of Labor and Congress of Industrial Organizations (AFL-CIO), which is the largest federation of unions in the United States. The mission of UAN is to “shape the future of all staff nurses and the health care system for the better by improving the economic and general welfare of nurses, providing a quality work environment, protecting nurse and patient safety and influencing nursing practice standards” (UAN, 2009, p. 1). Today, UAN represents a significant number of the estimated 200,000 unionized nurses, but virtually all major unions now represent nurses at some level.
Term
Collective bargaining
Definition
Collective bargaining is a method of equalizing power. As such, it involves negotiation and administrative agreements between employees and employers. Because the individual employee, or even a small group of employees, has limited power to bargain with the employer, the idea of banding together in a union enhances the position of employees in situations calling for negotiation. The goals of collective bargaining are achieved by imposing rules regarding how employers must treat employees represented by a union. The union movement in the United States is involved with strengthening a worker's position in the relationship between management and labor.
Term
DEVELOPMENT OF COLLECTIVE BARGAINING IN AMERICA
Definition
During the late nineteenth century, when the Industrial Revolution was a force throughout North America, a cadre of thinkers arose who believed that to protect workers from circumstances such as long work hours, child labor, and unhealthy factory conditions, there needed to be collectivization of workers. These early groups sought such basic conditions as safety in work situations, adequate pay for hours worked, and the right not to be arbitrarily dismissed. This banding together of workers to accomplish goals was termed trade unionism. This technique was successful in many instances and remains with us today.
Term
Arbitration
Definition
The process of negotiation sanctioned in the United States by the National Labor Relations Board. It is the method used for formal talks between management and labor within modern business, industry, or service organizations. Binding arbitration means that all parties must obey the arbitrator's recommendations.
Term
Orientation
Definition
Activities that enhance adaptation to a new environment.
Term
REFLEXOLOGY
Definition
Application of pressure to pressure points on the hands and feet that correspond to various parts of the body
Term
REIKI
Definition
A therapy that uses techniques to direct universal life energy to specific sites
Term
Reiki
Definition
Reiki is a practice in which the Reiki practitioner (of which there are several levels) channels energy to others using a series of hand positions. It is believed that healing energy flows through the hands without the need for any special skills. Like other forms of energy work, Reiki is believed to be useful for pain management, wound healing, stroke rehabilitation, and general relaxation
Term
ROLFING (STRUCTURAL INTEGRATION)
Definition
Use of manual manipulation and stretching of body's fascial tissues to establish balance and symmetry
Term
Ayurveda
Definition
Although it recently has gained popularity because of the writings and lectures of Deepak Chopra, Ayurveda has existed in India for more than 5000 years. Ayurveda means “the science of life” and is a system of care that promotes spiritual, mental, and physical balance. Noninvasive approaches are used to achieve balance and include yoga, massage, diet, purification regimens, breathing exercises, meditation, and herbs.Currently there is no process for licensing or certifying Ayurvedic practitioners. Because some of the treatments have the potential to cause complications (e.g., dehydration from cleansing enemas, herb-drug interactions), finding a reputable trained practitioner is important. The Ayurveda websites listed in Box 11-2 can assist in locating qualified practitioners.
Term
Mind-body interventions
Definition
Aromatherapy, art therapy, biofeedback, dance therapy, hypnosis, imagery, meditation, music therapy, prayer, relaxation, self-help support groups, tai chi, yoga.
Term
Mind-body interventions
Definition
biofeedback
Term
Biofeedback
Definition
Biofeedback is a technique in which the client is taught to alter specific bodily functions (e.g., heart rate, blood pressure, muscle tension). The client uses various relaxation and imagery exercises to affect desired responses. Machinery, such as electroencephalograms, electromyelograms, and thermistors, are used to measure and offer feedback about the function that the client is trying to alter. As the client becomes familiar with ways to successfully alter bodily responses, the equipment may no longer be necessary.
There are many conditions for which biofeedback can offer benefit, including urinary incontinence, anxiety, stress, irritable bowel syndrome, neck and back pain, and cardiac arrhythmias.
Term
Doshas
Definition
Individuals are believed to have distinct metabolic body types called doshas, which are vata, pitta, and kapha (Table 11-1). Signs of illness occur when the delicate balance of the doshas is disturbed.
Term
Homeopathy
Definition
Homeopathy is a branch of medicine developed in the late eighteenth century by Samuel Hahnemann. It was widely practiced in the United States until the early 1900s, when modern (i.e., conventional) medicine discredited it as being unscientific and ineffective. Homeopathy remained popular in other parts of the world, however, and recently has regained popularity in our country.
The origin of the word homeopathy helps in understanding this therapy. In Greek the word homos means “similar,” and pathos means “suffering.” The foundation of homeopathy are the laws of similars, the minimum dose, and cure Box 11-4.
Although the reason for their effectiveness is not fully understood, homeopathic remedies have been shown to be effective for a variety of conditions. People use homeopathy for a range of health concerns, from wellness promotion and disease prevention to the treatment of diseases and conditions such as allergies, asthma, chronic fatigue syndrome, depression, digestive disorders, ear infections, headaches, and skin rashes (NCCAM, 2009b).
The ideal way to use homeopathic remedies is to have a homeopath prescribe a customized remedy based on individual characteristics and symptoms. However, homeopathic practitioners are not plentiful, so the next best thing is to buy over-the-counter preparations that are labeled for their intended purpose (e.g., arthritis, headache, hay fever, cold).
Term
burnout
Definition
Some common symptoms of burnout include extreme fatigue, headaches, difficulty sleeping, mood swings, anxiety, poor work quality, depression, and anger (Larsen, 2000). The more intelligent, hard-working nurses are the most prone for burnout, but if you exhibit these symptoms; remember that they can be reduced.
Term
Dirty bomb
Definition
Dirty bomb causes immediate effects (radiation burns, acute poisoning) and long-term effects (cancer, contamination of drinking water); decontamination must occur before patient care can be safely provided by the health care worker
Term
Chemical
Definition
Agents injure or kill through variety of means: vesicant, nerve, blood, respiratory
Spread easily through air; cause immediate effects; require decontamination
Less toxic than biologic agents; need to be used in large quantities; subject to dispersion by wind; terrorists need to protect themselves; require trained HAZMAT teams
Dependent on agent used; in some cases have agent-specific medications; require decontamination; require use of personal protective equipment by personnel
Term
Radiologic
Definition
Ionizing radiation able to strip electrons from atoms, causing chemical changes in molecules; expression may be delayed; radiation depends on time, distance, shielding, and quantity of radioactive material
Available; psychologic effect likely to be substantial; often used in conjunction with explosive devices (“dirty bomb”)
Delayed effects of radiation materials; difficult to shield against
Dirty bomb causes immediate effects (radiation burns, acute poisoning) and long-term effects (cancer, contamination of drinking water); decontamination must occur before patient care can be safely provided by the health care worker
Term
Explosive
Definition
Most common method for terrorists; capable of violent decomposition; pressure, temperature changes and propellants cause injury and/or death
Easy to find materials to construct explosive device; large devices can be placed in abandoned vehicles; smaller devices can be placed on bodies of persons willing to commit suicide by igniting the device
Volatile ingredients could cause premature explosion of device, thus creating danger for terrorists; government agencies have improved training and processes for identifying incendiary devices
Symptomatic; often requires treatment for burns
Term
Nuclear
Definition
Depends on yield of nuclear weapon, but consists of blast range effects, thermal radiation, nuclear radiation, and radioactive fallout
Requires decontamination; contamination can remain for many years; psychologic effect likely to be substantial
Large, heavy, and dangerous weapons; hazardous to terrorist; expensive and difficult to make weapons of this type
Symptomatic treatment of thermal burns, shrapnel injuries, and radioactive fallout; depends on distance from source and time of exposure
Term
Imagery
Definition
Imagery is the process of creating a “picture” (image) in the mind that can cause a specific bodily response. Although hypnosis uses imagery, in hypnosis an image and suggestion are presented to the person, whereas in imagery the person creates an image on his or her own. The process of imagery begins by the client establishing a desired outcome (e.g., to relieve stress, enhance circulation, reduce blood pressure). The nurse or other practitioner assists the client in creating an image that helps to achieve the outcome (e.g., the nurse may describe how the blood circulates through the body, help the client develop an image of how cancer cells can be eliminated, or suggest that the client think of a peaceful place where cares can “melt away”) and guides the client in reaching a relaxed state. As an alternative to having someone guide him or her through an imagery exercise, a client can learn the process from books or use commercially prepared audiotapes.
Imagery is not a difficult mind-body healing therapy to master and can be easily implemented in virtually every practice setting.
Term
Hypnotherapy
Definition
Although the use of trance states for healing purposes dates back to primitive cultures, hypnotherapy was not approved as a valid medical treatment until the 1950s. This mind-body therapy is now widely and successfully used for a wide range of conditions, including chronic pain, migraines, asthma, smoking cessation, and irritable bowel syndrome.
The process of hypnosis begins by the therapist guiding the client into a relaxed state and then creating an image that focuses attention to the specific symptom or problem that needs to be improved. The client must be in a state of deep relaxation to be receptive to a posthypnotic suggestion. Most people are capable of being hypnotized if they are willing.
Supporting users have an ad free experience!
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Ïðèìåðû èøåìèè ìèîêàðäà. Ìàêðîñêîïèÿ è ìèêðîñêîïèÿ ñåðäöà ïðè îñòðîé èøåìèè
Áîëüíîé Ñ, 66 ëåò, â ïðîäîëæåíèå ïîñëåäíèõ 10 ëåò ñòðàäàë ãèïåðòîíè÷åñêîé áîëåçíüþ, îñëîæíåííîé ñíà÷àëà ñòåíîêàðäèåé íàïðÿæåíèè, à ïîòîì ïîêîÿ. Çà ãîä äî ñìåðòè ïåðåíåñ òÿæåëûé èíôàðêò ìèîêàðäà, ïîñëå êîòîðîãî ñòåíîêàðäèòè÷åñêèå ïðèñòóïû ó÷àñòèëèñü è óñèëèëèñü. Çà 10 äíåé äî ñìåðòè èìåë ìåñòî î÷åíü òÿæåëûé ïðèñòóï ñæèìàþùèõ áîëåé â îáëàñòè ñåðäöà, ïðîäîëæèâøèéñÿ îêîëî 1,5 ÷àñîâ. Óìåð áîëüíîé âíåçàïíî, íà óëèöå, äî ïðèáûòèÿ âðà÷à ñêîðîé ìåäèöèíñêîé ïîìîùè.
Ìàêðîñêîïè÷åñêîå èññëåäîâàíèå ñåðäöà. Ðàçìåð ñåðäöà 13,5 X 13,5 X 7 ñì, âåñ 500 ã. Íà ïåðåäíåé ïîâåðõíîñòè ñåðäöà, áëèæå ê âåðõóøêå, îòìå÷àåòñÿ çàèàäåíèå äèàìîòðîì 2 ñì.  àíåâðèçìàòè÷åñêîì âûïÿ÷èâàíèè, îáðàçîâàííîì ïåðåäíåé ñòåíêîé ëåâîãî æåëóäî÷êà, îáíàðóæåí ðîçîâàòîãî öâåòà êðîøàùèéñÿ òðîìá, ñïàÿííûé ñî ñòåíêîé æåëóäî÷êà.  ïðèëåãàþùåé ê ëåâîìó æåëóäî÷êó ÷àñòè ïåðåãîðîäêè îáíàðóæåí ðóáåö ðàçìåðîì 9 X 3,5 ñì. D ìåææåëóäî÷êîâîé ïåðåãîðîäêå, ðÿäîì ñ ðóáöîì, îòìå÷àþòñÿ ó÷àñòêè íåðàâíîìåðíîãî êðîâåíàïîëíåíèÿ ñåðäå÷íîé ìûøöû. Ñòåíêè âåíå÷íûõ ñîñóäîâ óòîëùåíû, ïðîñâåò èõ íåðåçêî ñóæåí.
Ìèêðîñêîïè÷åñêîå èññëåäîâàíèå ñåðäöà.  ìûøöå ñåðäöà îïðåäåëÿþòñÿ êðóïíûå è ìåëêèå íîëÿ ãðóáîâîëîêèèñòîé ðóáöîâîé òêàíè. Ìûøå÷íûå âîëîêíà íåðàâíîìåðíî ãèïåðòðîôèðîâàíû, ìåñòàìè ôðàãìåíòèðîâàíû, îòìå÷àåòñÿ èíòåðñòèöíàëüíûè îòåê. Ñòåíêè âåíå÷íûõ àðòåðèè ðåçêî óòîëùåíû íà ñ÷åò êðóïíûõ ñòåíîçèðóþùèõ áëÿøåê. Îòäåëüíûå àòåðîñêëåðîòï÷åñêïå áëÿøêè íîñÿò ñëîèñòûé õàðàêòåð, ñîäåðæàò ìíîãî èàâåñòêîâûõ îòëîæåíèè.
Ïàòîëîãîàíàòîìè÷åñêèé äèàãíîç. Ãèïåðòîíè÷åñêàÿ áîëåçíü è îáùèé àòåðîñêëåðîç. Àòåðîñêëåðîç àîðòû è âåíå÷íûõ ñîñóäîâ. Ãèïåðòðîôèÿ ìûøöû ëåâîãî æåëóäî÷êà ñåðäöà. Ðóáåö ïåðåäíåé ñòåíêè è ïåðåãîðîäêè ëåâîãî æåëóäî÷êà, àíåâðèçìà ïîðõóøêè ñåðäöà ñ ïðèñòåíî÷íûé òðîìáîì â åå ïîëîñòè. Î÷àãà íåðàâíîìåðíîãî êðîâåíàïîëíåíèè è îáëàñòè ìåææåëóäî÷êîâîé ïåðåãîðîäêè. Ìåëêèå êèñòû â ïîëóøàðèÿõ ãîëîâíîãî ìîçãà. Ïîëíîêðîâèå âíóòðåííèõ îðãàíîâ.
Çàêëþ÷åíèå. Áîëüíîé Ñ. â òå÷åíèå 10 ëåò ñòðàäàë ãèïåðòîíè÷åñêîé áîëåçíüþ, îñëîæíåííîé ñòåíîêàðäèåé íàïðÿæåíèÿ è ïîêîÿ. Çà ãîä äî ñìåðòè ïåðåíåñ èíôàðêò ìèîêàðäà, çàêîí÷èâøèéñÿ îáðàçîâàíèåì àíåâðèçìû ïåðåäíåé ñòåíêè ëåâîãî æåëóäî÷êà. Çàáîëåâàíèå íîñèëî ïðîãðåññèâíûé õàðàêòåð. Ïî ìåðå åãî ðàçâèòèÿ ïðèñòóïû ãðóäíîé æàáû ó÷àñòèëèñü è óñèëèëèñü; îäèí èç íèõ çàêîí÷èëñÿ âíåçàïíîé ñìåðòüþ áîëüíîãî.
Íà âñêðûòèè îòìå÷åí ñèëüíî âûðàæåííûé àòåðîñêëåðîç âåíå÷íûõ ñîñóäîâ ñåðäöà, îñîáåííî íèñõîäÿùåé âåòâè òâîé âåíå÷íîé àðòåðèè, è î÷àãè íåðàâíîìåðíîãî êðîâåíàïîëíåíèÿ â îáëàñòè ðóáöà è ìåææåëóäî÷êîâîé ïåðåãîðîäêè.
Ñìåðòü ïîñëåäîâàëà â ðåçóëüòàòå îñòðîãî ôóíêöèîíàëüíîãî íàðóøåíèÿ âåíå÷íîãî êðîâîîáðàùåíèÿ ïðè íàëè÷èè ñèëüíî âûðàæåííîãî àòåðîñêëåðîçà ñîñóäîâ ñåðäöà.
èøåìèÿ ìèîêàðäà
Áîëüíîé Ï., 55 ëåò, â êðàéíå òÿæåëîì ñîñòîÿíèè è èç-çà îñòðîãî ïðèñòóïà áîëåé â îáëàñòè ñåðäöà áûë äîñòàâëåí â ïðèåìíîå îòäåëåíèå Èíñòèòóòà èìåíè Ñêëèôîñîâñêîãî. Ïðè ïîñòóïëåíèè îòìå÷àëèñü áëåäíîñòü êîæíûõ ïîêðîâîâ, öèàíîç ëèöà, õîëîäíûé íîò. Ïóëüñ åëå ïðîùóïûâàëñÿ, îïðåäåëÿëñÿ òîëüêî ïî ñåðäå÷íûì ñîêðàùåíèÿì, ðàâíÿëñÿ 62 óäàðàì â ìèíóòó. Òîïû ñåðäöà ãëóõèå. Ïðèåì áîëüíûì äâóõ êàïåëü 1% ðàñòâîðà íèòðîãëèöåðèíà íå îêàçàë ïîëîæèòåëüíîãî äåéñòâèÿ. Âñêîðå ïî ïðèáûòèÿ â ïðèåìíîå îòäåëåíèå, ïðè íàðàñòàþùèõ ÿâëåíèÿõ ñåðäå÷íî-ñîñóäèñòîé íåäîñòàòî÷íîñòè, áîëüíîé óìåð.
Ìàêðîñêîïè÷åñêîå èññëåäîâàíèå ñåðäöà. Ðàçìåð ñåðäöà 10,5 õ 10,5 õ 6 ñì, âåñ 420 ã. Ìûøöà ñåðäöà íà ðàçðåçå êðàñíî-áóðîãî öâåòà. Íà çàäíåé ñòåíêå ëåâîãî æåëóäî÷êà îòìå÷åíû áåëåñîâàòûå ðóáöû ðàçìåðîì 4x2 ñì, âîêðóã íèõ — ó÷àñòêè ìèîêàðäà ñ íåðàâíîìåðíûì êðîâåíàïîëíåíèåì.
Ïðîñâåò íèñõîäÿùåé âåòâè ëåâîé âåíå÷íîé àðòåðèè íà ïðîòÿæåíèè 3 ñì ðåçêî ñóæåí ñòåíîçèðóþùèìè æåëòîèàòî-áåëûìí áëÿøêàìè. Ïðîñâåò îãèáàþùåé âåòâè ëåâîé âåíå÷íîé àðòåðèè íà 1,5 ñì íèæå óñòüÿ ïîëíîñòüþ çàêðûò èçâåñòêîâûìè ñåðîâàòî-áóðûìè ìàññàìè.
Ìèêðîñêîïè÷åñêîå èññëåäîâàíèå ñåðäöà. Óìåðåííàÿ ãèïåðòðîôèÿ ìûøå÷íûõ âîëîêîí è íåðåçêî âûðàæåííûé ïåðèâàñêóëÿðíûé ñêëåðîç.  îáëàñòè çàäíåé ñòåíêè ëåâîãî æåëóäî÷êà ðóáåö, ïðåäñòàâëåííûé êîëëàãåíîâîé òêàíüþ, ìûøå÷íûå âîëîêíà â ðàéîíå ðóáöà èñòîí÷åíû, íåêîòîðûå èç íèõ ôðàãìåíòèðîâàíû.  ïåðåäíåé íèñõîäÿùåé àðòåðèè ñòåíîçèðóþùèå áëÿøêè, çíà÷èòåëüíî ñóæèâàþùèå ïðîñâåò ñîñóäà.
 îäíîé èç áëÿøåê îáíàðóæåíî ñâåæåå êðîâîèçëèÿíèå, â äðóãèõ — îòëîæåíèå ãåìîñèäåðèíà.  îãèáàþùåé âåòâè ëåâîé âåíå÷íîé àðòåðèè àòåðîìàòîçïûå áëÿøêè ñîäåðæàò êðóïíûå êðèñòàëëû èçâåñòè.
Ïàòîëîãîàíàòîìè÷åñêèé äèàãíîç. Àðòåðèîêàðäèîñêëåðîç: çàêðûòèå ëåâîé âåíå÷íîé àðòåðèè èçâåñòêîâûìè ìàññàìè. Ðóáöû çàäíåé ñòåíêè ëåâîãî æåëóäî÷êà, íåðàâíîìåðíîå êðîâåíàïîëíåíèå âîêðóã ðóáöà.
Çàêëþ÷åíèå. Áîëüíîé Ï. áûë äîñòàâëåí â ïðèåìíîå îòäåëåíèå Èíñòèòóòà èìåíè Ñêëèôîñîâñêîãî â êðàéíå òÿæåëîì ñîñòîÿíèè ñ æàëîáàìè íà ðåçêèå áîëè ï îáëàñòè ñåðäöà è ÿâëåíèÿìè îñòðîé ñåðäå÷íî-ñîñóäèñòîé íåäîñòàòî÷íîñòè.
Áîëüíîé ïîãèá ïðè íàðàñòàþùèõ ÿâëåíèÿõ ñåðäå÷íî-ñîñóäèñòîé íåäîñòàòî÷íîñòè. Íà âñêðûòèè îáíàðóæåíû ñëåäû ðàíåå ïåðåíåñåííîãî èíôàðêòà çàäíåé ñòåíêè ëåâîãî æåëóäî÷êà ñåðäöà è ïðèçíàêè íîâîãî îñòðîãî íàðóøåíèÿ êîðîíàðíîãî êðîâîîáðàùåíèÿ.
- ×èòàòü "Âëèÿíèå íèòðîãëèöåðèíà íà ñòåíîêàðäèòè÷åñêîå ñåðäöå. Âëèÿíèå ýóôèëëèíà íà ñåðäöå ïðè ñòåíîêàðäèè"
Îãëàâëåíèå òåìû "Ìèîêàðä è êîðîíàðíûå ñîñóäû ïðè ãèïîêñèè":
1. Ìèêðîýëåìåíòû ïðè èíôàðêòå ìèîêàðäà. Ðîëü êàòåõîëàìèíîâ ïðè èíôàðêòå ìèîêàðäà
2. Ãîðìîíû íàäïî÷å÷íèêîâ ïðè èíôàðêòå ìèîêàðäà. Áåëêîâî-æèðîâîé îáìåí ïðè èíôàðêòå ìèîêàðäà
3. Ñîäåðæàíèå òèàìèíà ïðè èíôàðêòå ìèîêàðäà. Ôàêòîðû ïðèâîäÿùèå ê áûñòðîìó íåêðîçó ìèîêàðäà
4. Âëèÿíèå ãèïîêñèè íà ðåàêòèâíîñòü ñåðäöà è ñîñóäîâ. Ãèïîêñèÿ ìèîêàðäà
5. Ïîñëåäîâàòåëüíîñòü ãèïîêñè÷åñêèõ èçìåíåíèé ìèîêàðäà. Ìåòàáîëèçì ìèîêàðäà ïðè ãèïîêñèè
6. Ìèîçèí ïîä äåéñòâèåì ãèïîêñèè. Ðåàêòèâíîñòü ñîñóäîâ ñåðäöà íà ôîíå ñòåíîêàðäèè
7. Ïðèìåðû èøåìèè ìèîêàðäà. Ìàêðîñêîïèÿ è ìèêðîñêîïèÿ ñåðäöà ïðè îñòðîé èøåìèè
8. Âëèÿíèå íèòðîãëèöåðèíà íà ñòåíîêàðäèòè÷åñêîå ñåðäöå. Âëèÿíèå ýóôèëëèíà íà ñåðäöå ïðè ñòåíîêàðäèè
9. Âëèÿíèå ñòðîôàíòèíà íà ñòåíîêàðäèòè÷åñêîå ñåðäöå. Âëèÿíèå àäîíèçèäà, äèãèòàëèñà íà ñåðäöå ïðè ñòåíîêàðäèè
10. Ñîñóäû ñåðäöà ïðè èíôàðêòå ìèîêàðäà. Ðåàêòèâíîñòü êîðîíàðíûõ ñîñóäîâ ïîñëå èíôàðêòà
Î ñàéòå:
1. Êîíòàêòû è ïîëüçîâàòåëüñêîå ñîãëàøåíèå
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Vitality
4 Tips to Stay Healthy this Holiday Season
While the holidays are full of family, friends and good food, our health habits often fall by the wayside. Between large portions, fancy drinks and plenty of dessert, the holidays are a season of indulgence. To help you find balance...
The Need to Know on Potassium
Despite the pivotal roles it plays, potassium often does not receive the attention it deserves. We all know that potassium is an electrolyte that can be found in bananas and that it’s good for our health, but very few of...
How to Solve Acid Reflux with 7 Effective Home Remedies
If you have ever left a meal with a sore throat or an unsettled stomach, it could be more than the chef’s cooking that leaves a bad taste in your mouth. Chest pain, a burning sensation, and difficulty swallowing are...
Moroccan Alkaline Stuffed Squash
If you’re looking for fall and winter alkaline meal inspiration, you’ve come to the right place. This tasty Moroccan Alkaline Stuffed Squash delivers the warmth of a comfort meal without cutting any corners on nutrients. Quinoa, lentils and squash provide...
GERD: Symptoms, Causes, and Natural Remedies
If you’ve ever burped, experienced an acidic taste in your mouth or experienced heartburn, then you have likely suffered from gastroesophageal reflux. These are the common symptoms of gastroesophageal reflux disease, or GERD. While these mild symptoms are almost universal,...
The Ultimate Alkaline Water Guide
Since 75% of your body is made of water, it is essential to drink the right amount every day in order to ensure the proper functioning of your organs and tissues. Drinking an adequate amount of water, however, is not...
Iced Alkaline Green Tea Lemonade
Switch up your hydration game with this refreshing iced alkaline green tea lemonade. It packs a little punch with turmeric and a hint of sweet maple balances out the flavour beautifully. The mix of tea, lemon, alkaline water and turmeric...
10 Amazing Benefits Of Mineralized Alkaline Water
Every day, our body strives to maintain a balance between acid and alkaline. Stress, poor sleep, an imbalanced diet, alcohol, tobacco, and the lack of physical activity all cause acidity and force the body to work harder in order to...
Types of Water: Ionized, Zero, Mineral, Spring, Distilled, Alkaline
Other than the air we breathe, water is the most essential component for human survival. Our bodies are made up of 70% water, and as we live, we deplete our body’s resources – which is why it is crucial to...
Nutrients in Drinking Water
Most people assume that water is just water. They know it is essential in order to survive, but they aren’t really aware of its nutritional value. But why is it essential to drink water? Water keeps our body at a...
Is it Safe for Toddlers to Drink Alkaline Water?
Can Toddlers Drink Alkaline Water? Water is essential for toddlers, just as it is for all life on earth. But is there a significant difference between giving your child tap water and alkaline water? A developing body, like that of...
How Does Zinc Affect the Human Body?
While zinc might not be the first nutrient you prioritize on your trip to the grocery store, its importance should not be discounted. The essential trace mineral aids your body with many daily functions, including the promotion of a healthy...
The Need to Know on Magnesium
Magnesium is an abundant mineral in the body and is - luckily - present in most foods. It is required for over 300 metabolic reactions in the human body and is crucial for maintaining bone health and proper muscle function....
The Need to Know on Calcium
Calcium is an essential nutrient that our body uses to strengthen bones and teeth, to regulate muscle function - including the heart - and for transmissions of the nervous system. A calcium deficiency, or hypocalcemia, occurs when one doesn’t consume...
Top Alkaline Foods and Drinks
Navigating the aisles of a grocery store has become a kind of quasi-obstacle course, where processed sugars, trans-fats, and unpronounceable chemicals threaten to invade your shopping basket. But in a society where convenience is key, it can be challenging to...
How does Hydrogen Affect the Human Body?
Hydrogen is the most abundant element in the universe, meaning that at any given time, hydrogen molecules are surrounding you. Not surprisingly then, Hydrogen molecules are found inside your body. What does this mean for your health? Hydrogen is a name...
5 Basic Needs to Survive and Thrive
In extreme conditions, a human can survive three minutes without air, three hours without shelter, three days without water, and three weeks without food. Your body has certain physiological needs that are required for survival. While there are other factors...
4 Benefits of Staying Hydrated
Water, our trusty friend. Day in, day out, we loyally sip water. At our desk. In our car. At the gym. But, what’s the magic? What does water offer beyond quenching our thirst? The benefits of water are numerous for...
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-5,930,744,451,526,194,000
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Skip to main content
All CollectionsFAQ
What is 4-ACO-DMT?
What is 4-ACO-DMT?
Updated over a week ago
A legal substitute to the classical psychedelic. 4-ACO-DMT offers benefits when taken as a microdose.
4-ACO-DMT is a compound that produces effects very similar to the classical psychedelic, Psilocybin. 4-ACO-DMT, converts into Psilocin in your body after being ingested. The effects of 4-ACO-DMT lasts up to 7 hours.
Many reports of 4-ACO-DMT compare it favorably, describing it as more euphoric, gentle, warm, and colorful. It has also been described as less less likely to produce nausea as there is less material to consume.
Did this answer your question?
|
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Exercise and health:
A guide on what type of exercise is best for you
You can’t outrun a bad diet. We’ve heard it time and time again. And for the most part, it’s true.
But hold on. That doesn’t mean exercise has no role in health and weight loss. On the contrary, exercise can have a profound impact on overall health and body composition, especially when combined with healthy eating. The key is understanding how to incorporate different forms of exercise into a healthy lifestyle.
In this guide, we hope to answer all of your questions about exercise and its impact on your health.
First, define your goals
Would you be interested in losing weight while also increasing insulin sensitivity, lowering blood pressure, improving HDL, reducing abdominal fat, building lean body mass, relieving symptoms of depression and anxiety, and enhancing feelings of wellbeing?
If all of that was in a pill, who wouldn’t want to take it? But it’s not in a pill; rather, it’s what you can accomplish through exercise.1 As you read the following sections, consider your goals, priorities, and current fitness level in order to determine what type of exercise would be best.
Different types of exercise: the basics
Just as recommending a nutritious diet is too vague, saying exercise can help with health and weight loss makes sense but tells us nothing.
Different types of food may impact our bodies in different ways; the same is true for exercise. The key is understanding the different benefits of specific forms of exercise and knowing how to best use them for success.
In addition, both diet and exercise only work if you stick with them. You may have heard the saying, “The best exercise is the one you will do long term.” While this is true, it still helps to understand the different modes of exercise, because you may find you enjoy one more than you thought!
The main exercise categories we’ll discuss in this guide are resistance training, moderate cardio, and high-intensity interval training (HIIT). Keep in mind, however, that many classes, videos, and popular exercise routines combine elements from all three categories.
Resistance training
Time to pump that iron.
Resistance training does not require lifting weights or a gym membership. Exercise bands, body weight exercises, and chair exercises done at home qualify as resistance training as long as you stress your muscles enough so they fatigue and eventually become stronger.
Important tips:
• Stay in control and use good form. Keep your movements slow and do only as much as you can with good form to reduce your risk of injury.
• Engage your gluteal (glutes) and abdominal (abs) muscles – also known as your “core” – with every movement. This helps maintain good form, creates a more functional workout, and decreases your risk of injury.
• Stress the working muscle group until it fatigues. Whether you do 5 or 35 repetitions, you want your muscles to be at or near complete failure when you finish. Your body will respond by adding more muscle.2
Moderate cardio or Zone 2 training
Close up of unrecognizable athlete running on a treadmill in a gym.
Moderate cardio refers to a steady pace activity — like walking, jogging, or biking — that you maintain for an extended period of time, potentially hours. It usually involves keeping your heart rate between 60-80% of your predicted maximum.3
Tips:
• Keep it fun. Moderate cardio doesn’t have to be 30 minutes on a treadmill. Mix it up by taking a dance class, walking outside, riding a bike or jumping in the pool.
• Keep it social. One benefit of Zone 2 training is that you can still have a conversation while exercising. (It’s much harder to converse during HIIT). A walk with friends is a healthy way to socialize; when you can, choose active time with others rather than meeting in a bar or coffee shop.
• Start with at least 30 minutes. Since the intensity of moderate cardio is lower than other forms of exercise, the time required to see benefits is higher. You should aim for a minimum of 30 minutes per session, and you’ll benefit further from 150 minutes or more each week.4
High-intensity interval training (HIIT)
Cross training and rowing on the machine in gym
As the name implies, HIIT involves a cyclical high effort combined with an active rest period. It is meant to be uncomfortable as you push your heart rate beyond its anaerobic threshold (usually above 81% of your predicted maximum heart rate) for brief periods of time (anywhere from 10 seconds to 3 minutes) with adequate “active rest” to recover. Then you repeat the high intensity surge again and again.
A major benefit to HIIT is its efficiency. You tend to burn more calories and improve cardiopulmonary fitness more (per minute of training) compared to other forms of exercise.5
Tips:
• Start with a bike, elliptical or rower, or even a jump rope or running in place to reduce injury risk. Running and circuit training are excellent HIIT options but should be reserved for those more experienced with exercise and HIIT.
• Start with short intervals of 10-30 seconds and longer rest periods of 60 seconds. As you gain more experience, gradually lengthen the intervals. You may eventually do 60-second intervals with 60-second rest periods.
• Recover between intervals, but stay active (known as “active rest”). If you are using a heart rate monitor, use your recovery time to get your heart rate below 85%. Decrease your intensity, keep moving, and see how long it takes to get your heart rate below 85%.
What type of exercise is right for you?
Depending on your goals, different forms of exercise may be best for you. Let’s look at the specific benefits offered by each type.
What type of exercise is best for blood sugar and insulin control?
Fortunately, all forms of exercise can improve blood sugar control.6
HIIT is the “new kid on the block” for metabolic health, with a surge of research over the past decade showing that it can increase insulin sensitivity and reduce waist circumference, body fat, and blood pressure in as little as 12 weeks.7In addition, HIIT can give you the so-called “afterburn effect.” After 12 minutes of high-intensity work, your body will continue to burn more energy even at rest for the next 24 hours.8
However, resistance training and cardio exercise are also great for blood glucose control.9 Muscles do not require insulin to burn glucose.10So even severely insulin-resistant individuals can benefit from building muscle. The more muscle you have, the more glucose you burn.
In addition, resistance training improves resting metabolic rate — the amount of energy you burn at rest — which can help promote healthy weight loss.11 Moderate cardio, especially after eating, helps your body use glucose more efficiently, which may prevent post-meal glucose spikes.12 And even medium intensity interval training can improve metabolic health.13
What does it mean if your blood sugar increases with exercise? For many, this is a normal response to HIIT and resistance training that resolves shortly after exercise.14 But if you’re more insulin resistant, blood sugar increases from exercise can take longer to resolve. The good news is that the longer you stick to your exercise regimen, the better it should get as your insulin resistance improves!
You can also consider experimenting with fasted exercise vs. eating a small snack before exercise to see how your blood sugar responds. Some people have reported seeing a smaller exercise-induced rise if they eat prior to exercise.15 The biggest thing to remember, however, is that you don’t even have to check your glucose with exercise. Chances are it is a small contributor to your daily glucose, and rest assured you are likely doing much more benefit with consistent exercise.
Winner — A combination of HIIT, resistance training, and zone 2 training may be the best approach for controlling blood sugar and insulin levels.
What type of exercise is best for improving cholesterol levels?
First, exercise’s effect on lipids is small, especially when compared to nutrition. But it’s not insignificant.
With LDL cholesterol, most research suggests aerobic exercise can help lower it, but only when accompanied by weight loss, and even then only slightly.16 Resistance training, on the other hand, may independently lower LDL. One study showed a 5% reduction in LDL cholesterol in people who followed a twice-weekly resistance training program for 24 weeks.17
Additionally, exercise may affect the size of LDL particles. Kraus and colleagues found that jogging 20 miles per week at moderate intensity significantly increased the size of LDL particles, along with improving other heart disease risk factors.18
Less is known about HIIT and its effect on LDL levels. One might assume that it would produce similar results to a combination of cardio and resistance training, but we need more studies before reaching conclusions.
Regarding HDL cholesterol, studies show aerobic exercise can increase HDL cholesterol levels by 5%.19 Resistance training appears to have no significant HDL effect.20 Again, less is known about HIIT.
Winner — Mix it up with resistance training and moderate cardio to improve HDL, LDL and LDL particle size.
What type of exercise helps control blood pressure?
A large meta-analysis of randomized, controlled trials (RCTs) found that all three forms of exercise can reduce systolic blood pressure.21 Moderate cardio exercise is likely the most studied version, and blood-pressure lowering effects are fairly consistent. Interval training also appears to be beneficial.22
Keep in mind that blood pressure can briefly go up during both HIIT and resistance training but these exercise regimens will likely have long-term positive impacts on blood pressure and heart health.23
Winner — Pick your favorite and just do it!
What type of exercise promotes better body composition?
Resistance training appears to have the edge for promoting lean body mass, whereas aerobic training may be more beneficial for fat loss.24 HIIT, on the other hand, may be the best combination for both effects in the most time-efficient manner.25
We need more comparative trials to know for sure, but once again a combination of resistance training, cardio, and HIIT seems to be most promising for fat loss and muscle building. Just remember the tips mentioned above:
• Stress your muscles to failure for maximal results with resistance training.
• Perform aerobic exercise for at least 30 minutes per session.
Winner — Resistance training for muscle building, moderate cardio for fat loss, and HIIT for both.
What type of exercise improves bone health?
To improve bone mineral density and reduce fracture risk, bones should be exposed to a greater mechanical load than they get during daily living activities. Resistance training seems to do this best.26
While weight-bearing cardio exercise, like walking and running help with bone mineral density in the lower body, a well-designed resistance training program stresses your entire musculoskeletal system and can improve overall bone strength.27
Winner — Resistance training first, with weight-bearing cardio second.
What type of exercise helps with frailty and age-related muscle loss?
A systematic review of 121 resistance training RCTs found that this form of exercise improves strength and function in older adults.28
Although comparative studies do not exist, it appears resistance training is the most beneficial. It makes sense since strong muscles can help prevent falls or help us get up off the floor if we do fall. Wall pushups, sit-to-stand repetitions, partial squats, and upper-body band exercises are all effective ways for older people to remain fit and strong.
Winner — Resistance training.
What type of exercise helps with mental health?
Large systematic reviews show exercise can reduce depression symptoms as well as, or possibly even better than, antidepressants.29
Most of these studies do not differentiate between specific types of exercise, so the type you enjoy the most may be the right one for you.
But what if you aren’t depressed and just want to feel a natural high from exercise? Although some people experience a “runner’s high,” others absolutely hate the way running makes them feel.
Clearly, individual preference plays a role. If an activity moves your body, provides at least a mild physical stress, and you enjoy doing it, then that activity will likely benefit your mood.30
Winner — Do what you enjoy!
Remembering to rest
The side effects of exercise are mostly good ones: more energy, better sleep, and improved body composition. But there’s such a thing as overdoing it. This can mean soreness, fatigue, injury, and ultimately giving up.
The key to success is simple: rest is as important as movement. In exercise lingo, this is called “recovery time.” Make sure your body has time to recover by having one or two rest or “easy movement” days between your challenging days.
You can use your rest days for walking, gardening, or focusing on mobility work. Light yoga and stretching are great ways to stay active on your rest days and help promote better movement patterns that should help with injury prevention.
For instance, if you do a hard HIIT workout on Monday, then take Tuesday off, go for a social walk with friends and do light stretching on Wednesday, and get back at it with a hard resistance training session on Thursday.
If you want to get technical, you can follow trends in your resting heart rate or heart rate variability. A higher than usual resting pulse or a lower than usual heart rate variability may be a sign that you need more rest. Or you can simply go by how you feel. Isn’t it amazing how we ever survived before tech?
Getting started: Sample workout plans
Ideally, a balanced exercise routine involves a combination of all three forms of exercise. Depending on your level of experience and your goals, you may want to emphasize one type more than the others.
Here are a few sample workout schedules to give you an idea of where you can start.
Beginners:
• 2 days of 30+ minutes of moderate cardio
• 2 days of 20 minutes of light resistance training, gradually increasing the degree of resistance
• 1 day of 10 minutes of stretching or mobility work like light yoga
• 1 day of 10-15 minutes of interval training (a bicycle or rower is usually safest to start with, or even jumping jacks or burpees if you don’t have any equipment)
• For beginners, each workout day should include only one type of exercise
Intermediate:
• 3 days of 20+ minutes of resistance training,
• 2 days of 30+ minutes of moderate cardio
• 1-2 days of 15 minutes of HIIT.
• 2 days of 10 minutes of stretching or mobility work. This can be combined with any of the other days.
• In the intermediate phase, you can start to include multiple forms of exercise on a single day. For instance, 20 minutes of resistance training with 30 minutes of cardio.
Advanced:
• 3 days of 20 minutes or more of resistance training
• 2 days of 20-30 minutes of HIIT
• 2 days of 45 minutes of moderate cardio
• 2 days of 10 minutes of stretching or mobility work. This can be combined with any of the other days.
• As with the intermediate group, feel free to include different forms of exercise in a single day.
Now it’s your turn. Go out there and get started!
/ Dr. Bret Scher
Exercise
1. British Journal of Pharmacology 2012: Exercise acts as a drug; the pharmacological benefits of exercise [overview article; ungraded]
BMC Public Health 2013: Long-term health benefits of physical activity–a systematic review of longitudinal studies
[overview article; ungraded]
2. Journal of Strength and Conditioning Research 2005: Training leading to repetition failure enhances bench press strength gains in elite junior athletes. [observational study, weak evidence]
3. The most basic formula to estimate your maximum heart rate is 220-your age. While this is not 100% accurate, it is a reasonable, rough estimate. Another way to target 60-80% of your max heart rate is the “conversation test.” When you are in zone 2 you should still be able to carry on a conversation albeit with heavier breathing than normal. Once you pass 80% of your maximum heart rate, conversations become much more challenging. The “gold standard” way to test one’s max heart rate is with a cardiometabolic test done in a specialized lab setting, but of course many people will not have access to that.
4. Journal of the American College of Cardiology 2014: Leisure-time running reduces all-cause and cardiovascular mortality risk [observational study, weak evidence]
5. PLoS One 2016: Comparison of high-intensity interval training and moderate-to-vigorous continuous training for cardiometabolic health and exercise enjoyment in obese young women: A randomized controlled trial. [randomized trial; moderate evidence]
6. Diabetes Care 2006: Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients [systematic review of randomized trials; strong evidence]
7. British Journal of Sports Medicine 2017: Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies [systematic review of randomized trials; strong evidence]
Obesity Reviews 2015: The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis. [systematic review of randomized trials; strong evidence]
8. Sports Medicine Open 2015: The acute effect of exercise modality and nutrition manipulations on post-exercise resting energy expenditure and respiratory exchange ratio in women: a randomized trial. [randomized trial; moderate evidence]
9. Diabetes Care 2010: Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement.
[overview article; ungraded]
10. Journal of Physiology 2001: Glucose, exercise and insulin: emerging concepts [overview article; ungraded]
11. Medicine Science Sports and Exercise 2009: Minimal resistance training improves daily energy expenditure and fat oxidation. [randomized trial; moderate evidence]
12. Scientifica 2016: Exercising tactically for taming post-meal glucose surges [overview article; ungraded]
13. The following RCT reported an improved overall metabolic health score in both the HIIT and medium intensity interval training groups compared to a sedentary control group.
Scientific Reports 2021: Effects of very low volume high intensity versus moderate intensity interval training in obese metabolic syndrome patients: a randomized controlled study[moderate evidence]
14. During exercise, the liver increases glycogenolysis (breaking down glycogen to glucose) as well as gluconeogenesis (creating glucose from amino acids and other substances), which causes a rise in blood glucose. The body regulates this by increasing the muscles’ use of glucose and adjusting glucagon and insulin release as needed. However, for those who are insulin resistant, the regulation may be incomplete.
Diabetes, Metabolic Syndrome and Obesity 2013: The impact of brief high-intensity exercise on blood glucose levels [review or randomized and non randomized trials; moderate evidence]
Journal of Diabetes Science and Technology 2010: Blood glucose regulation during prolonged, submaximal, continuous exercise: A guide for clinicians [overview article; ungraded]
15. [anecdotal report; very weak evidence]
16. International Journal of Obesity 2005: Aerobic exercise, lipids and lipoproteins in overweight and obese adults: a meta-analysis of randomized controlled trials [strong evidence]
17. Prevention Medicine 2009: Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. [strong evidence]
18. NEJM 2002: Effects of the amount and intensity of exercise on plasma lipoproteins
[randomized trial; moderate evidence]
19. Archives of Internal Medicine 2007: Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. [systematic review of randomized trials; strong evidence]
20. Prevention Medicine 2009: Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials.
[systematic review of randomized trials; strong evidence]
21. Journal of the American Heart Association 2013: Exercise training for blood pressure: a systematic review and meta-analysis [systematic review of randomized trials; strong evidence]
22. Medicine 2017: Reducing effect of aerobic exercise on blood pressure of essential hypertensive patients [systematic review of randomized trials; strong evidence]
Physician and Sportsmedicine 2016: The effect of low volume interval training on resting blood pressure in pre-hypertensive subjects: A preliminary study [randomized trial; moderate evidence]
23. European Journal of Preventive Cardiology 2012: Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients [randomized trial; moderate evidence]
British Journal of Sports Medicine 2015: Resistance training reduces systolic blood pressure in metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials
[strong evidence]
24. Journal of Applied Physiology 2012: Effects of aerobic and/or resistance training on body mass and fat mass in overweight or obese adults [randomized trial; moderate evidence]
25. British Journal of Sports Medicine 2017: Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies [systematic review of randomized trials; strong evidence]
Journal of Obesity 2012: The effect of high-intensity intermittent exercise on body composition of overweight young males [randomized trial;moderate evidence]
26. Endocrinology and Metabolism 2018: Effects of resistance exercise on bone health [overview article; ungraded]
27. Journal of Family Community Medicine 2014: The impact of adding weight-bearing exercise versus nonweight bearing programs to the medical treatment of elderly patients with osteoporosis [randomized trial; moderate evidence]
28. Cochrane Database Systemic Reviews 2009: Progressive resistance strength training for improving physical function in older adults [systematic review of randomized trials; strong evidence]
29. Cochrane Database Systemic Reviews 2012: Exercise for depression
[systematic review of randomized trials; strong evidence]
DFronteir in Pharmacology 2017: Is the comparison between exercise and pharmacologic treatment of depression in the clinical practice guideline of the American College of Physicians evidence-based?
[overview article; ungraded]
30. Archives of Physical Medicine and Rehabilitation 2008: Exercisers achieve greater acute exercise-induced mood enhancement than nonexercisers [non-controlled study, weak evidence]
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header dental restorations
Dental restorations
The majority of the world’s population are affected; children as well as adults. According to a study by the World Health Organization, 60-90% of school-age children and the vast majority of adults have, or have had, cavities at one point. The decay may start as soon as the baby teeth first appear.
The professionals at the Centre Dentaire Anjou concur that both regular exams as well as professional cleanings are an essential complement to daily oral home care. Additionally, reducing the consumption of sugary, sticky and acidic foods will help to prevent tooth decay and therefore maintain optimal oral health.
The cavity process
There are millions of bacteria in the mouth. These bacteria will coalesce and form a sticky biofilm called dental plaque. The risk of developing a cavity is increased by the amount of time the plaque remains in contact with the tooth enamel. Bacteria in the plaque ferment the sugars of the dietary carbohydrates and transform them into acid. It is this acidic environment that is conducive to the development of cavities. The acids attack and destroy the hard tissues of the tooth (enamel and dentin).
Many people believe that cavities always causes pain. The early stages of a cavity however, are symptomless. It is only when the cavity pierces through the enamel and reaches the dentin that the person may feel discomfort to hot, cold or sugary foods. Some people never experience any pain.
A cavity is an active process and if not treated early enough, it will continues until it eventually reaches the nerve of the tooth. Once the nerve is affected, an infection ensues. The tooth then becomes very painful, swelling can occur and prompt intervention should be sought.
In addition to pain and throbbing, the following symptoms may be experienced:
• Redness and swelling of the gums or cheek
• Pain on chewing
• Headaches
• Fever
Plus la carie est extensive, plus la dent s’affaiblit et risque de se fracturer.
The more extensive the decay, the weaker the tooth becomes which will lead to an increased risk of tooth fracture. Do not underestimate an early cavity as the repercussions can be serious. A diagnosis of a cavity that requires a basic filling can very quickly turn into a major event that could require a root canal, a crown or even an extraction.
Our teeth play an important role in the digestive process. They are constantly taxed in order to withstand the forces of mastication. It is important to maintain and keep them healthy for as long as possible.
Possible treatments
Possible treatments
The professionals at centre dentaire anjou have our best interest at heart. For this reason, several treatment options will be presented to you that will take into account your health, your needs and your budget. Furthermore at Centre Dentaire Anjou we will facilitate accessibility to Dental care bu offering you numerous payment options.
When a tooth is decayed, the dentist removes the affected part of the tooth and replaces it with a filling.
They are numerous treatment options and material choices available to restore the affected tooth. They all have the same purpose; to seal the tooth in order to prevent bacteria from re-entering and thus stop the carious process. Even on a tooth that has already been treated a new cavity may still develop, hence the importance of maintaining optimal oral hygiene at all times and adopting healthy eating habits.
Certain restorations offer superior advantages in terms of durability, longevity and esthetics. The dentist has the professional ability to inform you of all the available options as well as discuss with you the particularities of each one so that you are able to make an informed choice.
Material currently used
Amalgam
Dental amalgam (otherwise known as a silver filling) is a very common material used to fill cavities. It has been used for over a century and consists of a powdered alloy of silver (50% to 70%), tin and copper that is combined with liquid (elemental) mercury whose role is to bind these components so that they become a hard, safe and stable putty. Amalgam may not be very esthetic but it is very durable and is extremely resistant to wear.
Amalgam is a safe and excellent material for the posterior teeth. With time, it also seals the tooth. It is economical and durable under the forces of mastication. Its main disadvantage is its silver colour. It also tends to expand which in in turn creates additional stress on the tooth that can sometimes cause fractures. Dental amalgam has been studied extensively and has been deemed safe. The small amount of mercury released when placing or removing amalgam has not been shown to cause any adverse health effects.
Composites
Compared with amalgam, the composite resin is a more recent material. Due to the availability of numerous colours they are more esthetic and the fillings may even appear invisible. Composites were initially used only for anterior teeth, but the development of more wear-resistant composites has allowed them to be used for the restoration of posterior teeth as well. They are better than amalgam when conservative preparation is recommended as an amalgam requires the removal of more sound tooth structure.
A composite resin (white filling) is a tooth coloured filling material composed of a resin based matrix and an inorganic filler such as silica. The soft putty is placed in the cavity and molded, it is hardened when a polymerization light is applied to it. Polymerization is a chemical reaction that causes the composite to harden. Before the composite can adhere to the tooth, an acid gel is applied, followed by a glue to hold it all in place.
Some of the advantages of a composite are esthetic as a range of shades are available so that the colour of your tooth can be matched closely and less tooth structure needs to be removed due to the adhesiveness of the composite.
Composite fillings can be used for both anterior and posterior restorations. In use for over 30 years they are a modern restorative material that respect both health and the environment. Composites, however, do have drawbacks. It is important to know that the life of a composite is less than that of an amalgam or ceramic restoration. The insertion technique is more technique sensitive and the restorations take more time to do which is why they are more expensive. The lifespan of a composite is less than 10 years and all composites experience polymerization shrinkage. This can lead to open margins which in turn leads to an increased risk of re-decay. For these reasons, the composite restorations may need to be replaced more often than amalgam.
Ceramic Inlay
Ceramic inlays are also an option for restoring teeth. They are as durable as amalgam and just as esthetic as a composite because there are many colours available. Closer to the strength of enamel, they restore the original tooth strength. Studies have shown that a tooth restored with a porcelain inlay can recover up to 98% of its original strength. For this reason, ceramic inlays are recommended for teeth with deep cavities, or when many margins of the tooth are damaged and the integrity of the tooth is compromised.
Ceramic inlays are now considered to be one of the most effective restorations for the long term. They allow us to fabricate restorations with unmatched resistance and esthetics. An inlay is therefore recommended when at least one cusp of the tooth is damaged and the remainder of the tooth is intact.
The ceramic inlay is fabricated by a professional dental laboratory and is permanently cemented onto the tooth by a dentist. It can be used to non-invasively repair teeth that have large fillings or are damaged by cavities or trauma. Porcelain inlays are an excellent alternative to traditional fillings be it amalgam, composite resin or in some cases even a full crown.Porcelain inlays are very resistant and will remain in place for many years, ensuring a lasting and functional smile.
Below are some of the indications for an inlay:
• Broken or fractured teeth
• Esthetic improvement
• Deep / extensive cavities
• Fractured fillings
Inlay procedure:
An inlay generally requires two appointments. During the first appointment, the dentist will remove any cavities and / or old fillings. Your tooth may need to be frozen beforehand. The tooth will then be carefully cleaned and prepared in order to enable the inlay to be well seated. An impression of the prepared tooth will be taken and sent to the laboratory. A temporary filling will be placed until the next appointment.
During your second appointment, your new restoration will be carefully and precisely seated on the tooth. Some adjustments may be necessary to ensure proper fit and a comfortable occlusion. You will receive post-op instructions following the installation of your inlay. Good oral hygiene along with good eating habits and regular visits to your dentist will help preserve your new restoration.
Online appointment booking
Are you a patient of Centre Dentaire Anjou?
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Search
How Does Cryotherapy Relieve Jet Lag?
Are you enjoying a long Spring Break to a great vacation locale? If so, you are likely to experience the phenomenon of jet lag, a condition resulting from an imbalance in your body's natural "biological clock" caused by traveling to different time zones.
According to the National Sleep Foundation, "simple behavioral adjustments before, during and after arrival at your destination can help minimize some of the side effects of jet lag:
Anticipate the time change for trips by getting up and going to bed earlier several days prior to an eastward trip and later for a westward trip.Upon boarding the plane, change your watch to the destination time zone.Avoid alcohol or caffeine at least three to four hours before bedtime.Avoid any heavy exercise close to bedtime. (Light exercise earlier in the day is fine.)Bring earplugs and blindfolds to help dampen noise and block out unwanted light while sleeping.Try to get outside in the sunlight whenever possible. Daylight is a powerful stimulant for regulating the biological clock.
Cryotherapy and Jet Lag
So, how does Whole Body Cryotherapy help relieve jet lag? When you undergo a 3-minute cryotherapy session, your body responds to the cold air by releasing a substantial amount of nor-epinephrine and acetylcholine, two endorphins vital to the activation of REM sleep. As you may know, REM sleep is the deeper, high-quality sleep state our bodies require to function optimally.
Web MD states: “Endorphins act as analgesics . . . and also act as sedatives. They are manufactured in your brain, spinal cord, and many other parts of your body and are released in response to brain chemicals called neurotransmitters. The neuron receptors endorphins bind to are the same ones that bind some pain medicines . . . Endorphins also trigger a positive feeling in the body . . . the feeling that follows a run or workout is often described as “euphoric.”
Thus, those endorphins help you relax to enter more--and more complete--sleep cycles. Wouldn't you like to sleep well again--to wake up fully rejuvenated? If so, consider trying cryotherapy!
Sources:
https://sleepfoundation.org/how-sleep-works/how-much-sleep-do-we-really-need
https://sleepfoundation.org/sleep-topics/jet-lag-and-sleep
http://www.bakadesuyo.com/2015/06/get-better-sleep/
https://www.ted.com/talks/jeff_iliff_one_more_reason_to_get_a_good_night_s_sleep#t-1601
http://www.helpguide.org/articles/sleep/how-to-sleep-better.htm
http://www.bakadesuyo.com/2013/01/sleeping-well/
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Memories: Which Sense is the Strongest?
Memories: Which Sense is the Strongest?
Unless you’re the little boy from the Sixth sense, you’re like the rest of us five sense people. And in case you’re a little rusty on your grade school science, your five senses are taste, smell, sight, touch and sound. Each one used to get through daily functions and recall memories.
But with five senses all working both together and separately, which one trumps the rest?
Well, first let’s get a little more familiar with each – how they work, what part of the brain they stimulate and how they affect our memory.
Sight
Our eyes are incredible perceivers. Using a lens at the front of the eyeball, we can focus the images that we see onto the retina at the back of the eye, like the organic version of a mechanical camera. Our retinas are covered with two light sensitive cells – cones and rods. Cones allow us to see color and rods help with seeing when its dark and peripheral vision. All this happens in the blink of an eye (literally), as it sends the information to the brain via the optic nerve. Which is good because if it wasn’t for the brain, we’d be seeing everything upside down.
Part of the brain worked: The occipital lobe in the back of the brain and the temporal lobes, which are responsible for short-term memory, speech and music are the biggest receptors of sight.
Type of memory: Iconic memory
Fun fact: We can see between 2-7 million different colors
Touch
The feeling of touch is spread throughout the entire body via the largest organ in our body, our skin. So it must be the strongest sense, right? Not quite. While it is powerful due to our nerve endings shooting information into our brains (particularly when it comes to pain), it’s not the top sense. As humans, we can experience four touch sensations: cold, heat, contact and pain. Furthermore, the hair on our skin can almost act as a type of Spidey sense, like the web slinging superhero, increasing the sensitivity like the body’s own early warning system.
Part of the brain worked: The parietal lobe is the main receptor for touch, as it processes the primary somatic sensory cortex. It gives you that sense of ‘me.’
Type of memory: Haptic memory
Sound
Hearing is much more than just sounds. It aids in our equilibrium, keeping us balanced and focused. But sorry ears, you’re still not the top sense. Our ears are made of two separate parts – outer and inner (pretty simple, right?). The outer works like a satellite, catching sound and funneling it into the inner ear, which contains the three smallest bones in your body. As the spiral-like inner ear sends the vibrations that the outer ear captured via the auditory nerve to the brain, it processes these vibrations into the sounds we know as well as the direction from which they came.
Part of the brain worked: The auditory nerve connects your inner ear directly to the auditory cortex (which has three parts: primary, secondary and tertiary) on both the right and left side of the brain.
Type of memory: Echoic memory.
Research has shown that hearing words associated with sounds, rather than just the sounds alone, can aid memory. Music is also a huge proponent in nostalgia and memory recall, like those songs that transports you back in time.
We can hear approximately 350,00 different tones
Taste
What would the world be like if we couldn’t enjoy every savory bite of a pizza? A bad, bad place that’s what. But while taste is largely responsible for our enjoyment of food, it’s still doesn’t take the top spot. In fact, if it weren’t for our sense of smell, most of what we tasted would be simply bland textures. As one of the strongest muscles in the body, our tongues are responsible for gauging temperatures, ensuring that we don’t torch our mouths on that hot, fresh out of the oven mozzarella cheese.
Part of the brain worked: Just like touch, the parietal lobe is responsible for our mealtime escapades in taste.
Type of memory: N/A
Oddly, there isn’t a memory term specially coined for taste, but that doesn’t mean there isn’t a connection. However, that memory recall isn’t because of your taste buds, it’s because of your sense of smell …
Smell
If you didn’t sniff this answer coming by now, then you need your nose checked. Smell is in fact the strongest human sense, and contrary to popular belief, may be just as powerful as the snout sniffers in dogs and rodents (to certain degrees). Our olfactory receptor neurons, which are located behind your sinuses and are the only neurons in your body that are exposed to air, make physical contact with whatever molecules compose an odor. Then they instantly send that info straight to the brain. Our sense of smell is so strong that it aides dramatically in how we perceive taste – even going as far as affecting our behavior, emotions, perceptions and memories, more so than any other of our sense.
Think of it this way: Seeing vomit might make you want to throw up but smelling vomit is what ultimately triggers your gag reflex.
Part of the brain worked: The piriform cortex, which is a collection of neurons located behind the olfactory bulb, works to identify smell.
Type of memory: Olfactory memory
Because the olfactory bulb and cortex are so close physically to the hippocampus and amygdala (huge factors in memory retention), smell is considered the strongest and quickest memory inducer. Smell is also in cahoots with the brain’s limbic system, which controls emotion, making smell the biggest nostalgia and behavior catalyst of the sensory bunch.
We can detect 1 trillion different smell stimuli
So your smell may be the strongest of your senses, especially when it comes to memory recollection, but that doesn’t mean your other senses deserve any less credit for your moments of nostalgic bliss. After all, you can’t smell a picture … well, you can but that’s just weird. And speaking of pictures, if you’ve got a collection of old family photos and film, now’s the perfect time to digitize those analog memories before they fade away with father time.
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» » Ñëèâû âêóñíûå è ïîëåçíûå
Ñëèâû âêóñíûå è ïîëåçíûå
Ñëèâû âêóñíûå è ïîëåçíûåÏðåäïîëàãàåòñÿ, ÷òî ñëèâû áûëè îäíèì èç ïåðâûõ ïëîäîâ, êîòîðûå íà÷àë ñïåöèàëüíî âûðàùèâàòü ÷åëîâåê. Ïðè ðàñêîïêàõ âðåìåí íåîëèòà áûëè íàéäåíû ñëåäû âèíîãðàäà, ñëèâû è èíæèðà.
Ñëèâû î÷åíü ïîëåçíû ïî÷òè âñåì. Ïðè ìèíèìàëüíîé êàëîðèéíîñòè ïåðåêóñ ñëèâàìè äàåò ÷óâñòâî íàñûùåíèÿ, à çíà÷èò, ïîçâîëèò ìåíüøå ñúåñòü ïèùè â ïîñëåäóþùèé ïðèåì, âû íå áóäåòå «ìåòàòü» âñå ïîäðÿä. Òàêèì îáðàçîì, îòïàäàåò óãðîçà îæèðåíèÿ, äèàáåòà è ïðîáëåì ñ ñåðäå÷íî-ñîñóäèñòîé ñèñòåìîé. È õîòÿ ÷åðíîñëèâ ñëàäêèé íà âêóñ, îí íå âûçûâàåò ñóùåñòâåííîãî ïîâûøåíèÿ óðîâíÿ ãëþêîçû â êðîâè è èíñóëèíà. ×åðíîñëèâ ïðåäîòâðàùàåò âîçìîæíûå çàïîðû, à çíà÷èò, ñïîñîáñòâóåò ðåãóëÿðíîìó îïîðîæíåíèþ òîëñòîé êèøêè, òî åñòü ëèêâèäèðóþòñÿ ïðåäïîñûëêè ðàêà òîëñòîé êèøêè – îäíîé èç íàèáîëåå ðàñïðîñòðàíåííûõ ôîðì ðàêà.
×òî ñîäåðæèòñÿ â ïëîäàõ ñëèâû? Â 100 ãðàììàõ ñëèâû íåò æèðîâ, âñåãî 76 êêàë, óãëåâîäîâ 19 ãðàìì, ïèùåâûõ âîëîêîí 2 ãðàììà, ñàõàðà 16 ãðàìì, 1 ãðàìì áåëêîâ.
Ïðè ýòîì ñîäåðæàòñÿ âèòàìèíû Ñ, Ê, À, Å, Â6, ôîëèåâàÿ êèñëîòà, ïàíòîòåíîâàÿ êèñëîòà, òèàìèí, ðèáîôëàâèí, íèàíöèí. Êðîìå òîãî ñîäåðæàòñÿ ìèêðîýëåìåíòû ìåäü, ìàðãàíåö, æåëåçî, ìàãíèé, ôîñôîð. Âñå ýòî â óäîáíîì äëÿ óñâîåíèÿ âèäå è õîðîøåì ñîîòíîøåíèè.
Ñëèâû ñîäåðæàò ìîùíûå àíòèîêñèäàíòû, êîòîðûå ñïîñîáíû ïðåäîòâðàòèòü ìíîãèå âèäû ïîâðåæäåíèÿ êëåòîê, êîòîðûå âûçûâàåòñÿ ïðåèìóùåñòâåííî èõ îêèñëåíèåì. Àíòèîêñèäàíòû çàìåäëÿþò ïðîöåññ ñòàðåíèÿ, ñíèæàþò ðèñê âîçíèêíîâåíèÿ ðàêà.
Ïèùåâûå âîëîêíà, ïðèñóòñòâóþùèå â ñëèâàõ, ïîìîãàþò ðåãóëèðîâàòü ñèñòåìó ïèùåâàðåíèÿ.  ïóëüïå ñëèâû ñîäåðæèòñÿ ðàñòâîðèìîå âîëîêíî, îíî â ñîñòàâå êëåéêîé ìàññû ïðèòÿãèâàåò è âûâîäèò èç îðãàíèçìà ëèøíèå ñàõàðà, æèðû, òîêñèíû è ìèêðîîðãàíèçìû, ñíèæàåò óðîâåíü «ïëîõîãî» õîëåñòåðèíà, ÷òî ïîëåçíî äëÿ ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû. Íåðàñòâîðèìàÿ êëåò÷àòêà ðàáîòàåò êàê íàæäàê, óäàëÿÿ èç æåëóäî÷íî-êèøå÷íîãî òðàêòà íàêîïëåííûå îòðàáîòàííûå ìàòåðèàëû è òîêñèíû. Òàê ÷òî ñëèâà ÿâëÿåòñÿ ïðåêðàñíûì ñðåäñòâîì äëÿ î÷èùåíèÿ îðãàíèçìà, ñòàáèëèçàöèè óðîâíÿ ñàõàðà â êðîâè.
Ôåíîëüíûå êîìïîíåíòû è ôëàâîíîèäû, ñîäåðæàùèåñÿ â ñëèâàõ, îêàçûâàþò ïðîòèâîâîñïàëèòåëüíîå äåéñòâèå íà êëåòêè îðãàíèçìà. Ôèòîíóòðèåíòû, ñîäåðæàùèåñÿ â ñëèâàõ, ñïîñîáñòâóþò óìåíüøåíèþ âîñïàëåíèÿ â íåâðîëîãè÷åñêèõ îáëàñòÿõ, óëó÷øàþò ñïîñîáíîñòü óñâàèâàòü è ñîõðàíÿòü èíôîðìàöèþ. Òàê ÷òî ñëèâû ïîìîãàþò ïðåäîòâðàòèòü íåéðîäåãåíåðàòèâíûå ðàññòðîéñòâà, ÿâëÿþùèåñÿ íåîòúåìëåìîé ÷åðòîé ñòàð÷åñêîé äåìåíöèè, áîëåçíåé Ïàðêèíñîíà è Àëüöãåéìåðà. Îíè î÷åíü ïîëåçíû äëÿ ìîçãà. Âèòàìèíû îðãàíèçìó íåîáõîäèìû, îá ýòîì çíàþò âñå. Ïðè÷åì èç îâîùåé è ôðóêòîâ îíè óñâàèâàþòñÿ ëó÷øå, äà è ïðèñóòñòâóþò îíè â äîçàõ, íå ñïîñîáíûõ íàíåñòè âðåä.
 íàñòîÿùèé áè÷ â íàøè äíè ïðåâðàòèëñÿ äèàáåò. Íî ñëèâû èìåþò íèçêèé ãëèêåìè÷åñêèé èíäåêñ, ýêñòðàêò ñëèâû ïîìîãàåò ñíèæàòü óðîâåíü ãëþêîçû â êðîâè è óðîâåíü òðèãëèöåðèäîâ â îðãàíèçìå. Áîëåå òîãî, ôëàâîíîèäû, î êîòîðûõ ãîâîðèëîñü âûøå, çàùèùàþò îðãàíèçì îò ðåçèñòåíòíîñòè ê èíñóëèíó. Ðàñòâîðèìàÿ êëåò÷àòêà ñëèâ òîæå íîðìàëèçóåò óðîâåíü ñàõàðà â êðîâè. Òàê ÷òî ñëèâû è äèàáåò ëå÷àò.
Ïîëèôåíîëû è êàëèé, ïðèñóòñòâóþùèå â ñëèâàõ, ïîëåçíû äëÿ êîñòåé, òàê êàê ïîâûøàþò ïëîòíîñòü òêàíåé, ïðåäîòâðàùàþò ïîòåðþ êîñòíîé ìàññû. Ýòî îñîáåííî âàæíî äëÿ ëþäåé ñ îñòåîïîðîçîì, ê êîòîðîìó ñêëîííû ìíîãèå æåíùèíû ïîñëå 50 ëåò.
Òàê ÷òî â öåëîì ñëèâû î÷åíü ïîëåçíû, íî åñòü è íåêîòîðûå îãðàíè÷åíèÿ. Èõ íå ðåêîìåíäóåòñÿ óïîòðåáëÿòü ëþäÿì, ñêëîííûì ê äèàðåå.  ñëèâàõ ñîäåðæàòñÿ îêñàëàòû, êîòîðûå ìîãóò ñïîñîáñòâîâàòü îáðàçîâàíèþ êàìíåé â ïî÷êàõ. Ïîýòîìó ïðè íàëè÷èè êàìíåé â ïî÷êàõ óïîòðåáëÿòü ñëèâû ìîæíî, íî î÷åíü ïîíåìíîãó.óíèêàëüíûå øàáëîíû è ìîäóëè äëÿ dle
Óâàæàåìûé ïîñåòèòåëü, Âû çàøëè íà ñàéò êàê íåçàðåãèñòðèðîâàííûé ïîëüçîâàòåëü. Ìû ðåêîìåíäóåì Âàì çàðåãèñòðèðîâàòüñÿ ëèáî çàéòè íà ñàéò ïîä ñâîèì èìåíåì.
êîììåíòàðèåâ
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The Open Clinical Cancer Journal
(Discontinued)
ISSN: 1874-1894 ― Volume 5, 2011
Expression of Nuclear β-Catenin in Rectal Versus Colonic Cancers
Rolf Aamodt*, 1, Johan Bondi1, Solveig Norheim Andersen2, Geir Bukholm3 , Ida R.K. Bukholm1
1 Department of Surgery
2 Department of Pathology, Akershus University Hospital, 1478 Loerenskog, Norway,
3 EpiGen Institute, University of Oslo, Norway
Abstract
Rectal cancers have more local relapses than colonic cancers. Since nuclear β-catenin plays an important role for the proliferation capacity of cells, we wanted to evaluate whether there may be differences in the expression pattern of nuclear β-catenin between rectal and colonic adenocarcinomas, explaining the observations made in clinical practice. Sec- tions from 235 rectal adenocarcinomas treated surgically in the years 1992 - 2000 were immunohistochemically stained for β-catenin. Nuclear immunopositivity was recorded. The results were compared to the results of a similar examination performed earlier on 162 colonic cancers. We found a higher protein expression of nuclear β-catenin in rectal cancers than in colonic cancers. No statistically significant correlation was observed between nuclear expression of β-catenin in rectal cancers and cancer specific survival. Our findings indicate that rectal cancers and colonic cancers are biologically different. The results might partly explain the clinical difference observed between rectal cancers and colonic cancers.
Keywords : Colorectal neoplasms, beta catenin, immunohistochemistry.
Article Information
Identifiers and Pagination:
Year: 2008
Volume: 2
First Page: 13
Last Page: 17
Publisher Id: TOCCJ-2-13
DOI: 10.2174/1874189400802010013
Article History:
Received Date: 5/12/2007
Revision Received Date: 7/12/2007
Acceptance Date: 28/1/2008
Electronic publication date: 18/3/2008
Collection year: 2008
Bentham Science Publishers Ltd.
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
* Address correspondence to this author at the Department of Surgery, Akershus University Hospital, 1478 Loerenskog, Norway; E-mail: [email protected]
INTRODUCTION
Adenocarcinomas of the rectum and colon can be different with regard to the cellular biological basis for cancer development.
This view is in conflict with the readily observable fact that adenocarcinomas of the colon and the rectum have the same appearance both macroscopically and microscopically. The location of the border between the two organs is not obvious. It is therefore usually defined either by a fixed length from the anal verge regardless of body size, or by its relation to the promontory of the sacrum. These facts support the traditional view that adenocarcinoma of the rectum and colon is in fact the same disease that has just happened to strike at different anatomical level.
However, clinical observations indicate that there can be biological differences between these two localizations. Adenocarcinomas located within the rectal cavity have a higher local recurrence rate and a lower rate of distant and peritoneal metastases than colonic cancers [1-5]. The incidence of lymph node metastasis has been shown to be higher in rectal tumors than in colonic tumors [6,7] and the risk of lymph node metastases increases from proximal to distal direction of the rectal cavity [8]. The beneficial effect of adjuvant chemotherapy is larger in colonic cancers than in rectal cancers [9]. The effect of radiotherapy also differs between colonic and rectal adenocarcinomas [10].
Local relapse, distant metastases, the effect of treatment and the prognosis of cancer patients depend on the biology of the tumor. Hence, we hypothesize that molecular biological differences are responsible for the differences in clinical behavior between colonic and rectal adenocarcinomas. There are few studies where the molecular biological differences between colonic and rectal adenocarcinomas have been investigated [4, 11, 12].
Abnormally located β-catenin plays a central role in colorectal tumorigenesis [13] by being part of the signalling cascade of the Wnt pathway [14]. β-catenin plays its key role in tumorigenesis in association with APC [15,16]. Mutations in either β-catenin or APC can distort the normal tumor suppressive effect of APC [15]. Somatic mutations of the APC gene causes malfunctioning APC in 80 % of colorectal cancers [13]. This malfunctioning APC fails to reduce the level of cytoplasmic β-catenin [13,17]. The resulting increased level of cytoplasmic β-catenin induces transcription through the TCF/LEF pathway [13], leading to increased proliferation rate of the cancer cells.
Many studies have been performed on different aspects of the relation between β-catenin and colorectal tumors, but few have investigated the expression patterns of β-catenin in rectal carcinomas and made comparison to the findings in colonic cancers [3,18].
The aim of the study was to compare the expression pattern of β-catenin between colonic and rectal adenocarcinomas.
MATERIALS AND METHODOLOGY
All available tumor samples from a consecutive series of 274 paraffin-embedded rectal adenocarcinomas removed surgically at Akershus University Hospital in the years 1992 – 2000 were scrutinized for inclusion into the survey. These surgical treatments were all primary operations. We decided to include solely tumors at a level of 15 centimeters (5.9 inches) or less from the anal verge (i.e. the outer border of the anus). This level was chosen partly because this is a commonly used definition of the border between the rectum and the colon. We wanted a restrictive border in order to avoid unintentional inclusion of sigmoid tumors.
This material of rectal carcinomas was compared to a material by Bondi et al. of 162 colon carcinomas operated on at Akershus University Hospital during the years 1988, 1990 and 1997-2000 [19].
Immunohistochemistry
Sections (3 - 4 micrometers) from formalin fixed, paraffin wax embedded archive tumor tissue were applied to coated slides. After antigen retrieval by microwaving (20 min at 100 degrees Celsius), immunostaining with anti-β-catenin (Novocastra Laboratories, Newcastle upon Tyne, UK, dilution 1:300) was performed in Autostainer (Dako Corporation, Carpentaria, USA), according to the operation protocol. The antibody was visualized for light microscopy with Envision Plus-System and diaminobenzidine (DAB). Counter-staining was done with Hagen’s haematoxylin for visualization of tissue structures. Positive control was a test block with multiple colonic adenocarcinomas with diverse differentiation.
We counted the percentage of positive nuclei semi quantitatively by applying four grades of immunopositivity, 0, 1, 2 and 3. Only nuclear staining was recorded. When 60 % or more of the nuclei were stained, we scored the tumor as grade 3 (Fig. 3). Staining of 30 % up to 60 % of the nuclei was classified as grade 2 (Fig. 2). When nuclear staining was less than 30 %, the score was grade 1 (Fig. 1). No nuclear immunostaining at all qualified for grade 0 (Fig. 4). Only clearly nuclear staining was recorded as positive. Almost all slides contained normal adjacent mucosa in addition to the cancer. The normal mucosa served as an internal control. The slides were judged independently by three investigators (RAa, IRKB and JB). At least 100, usually more than 1000 cells were examined in each slide.
Fig. (1)
Grade 1 immunostaining of nuclear β-catenin in rectal adenocarcinoma. Original magnification 40 X.
Fig. (2)
Grade 2 immunostaining of nuclear β-catenin in rectal adenocarcinoma. Original magnification 40 X.
Fig. (3)
Grade 3 immunostaining of nuclear β-catenin in rectal adenocarcinoma. Original magnification 40 X.
Fig. (4)
Grade 0 immunostaining of nuclear β-catenin in rectal adenocarcinoma. Original magnification 40 X.
The slides of the colonic material of Bondi et al. were produced and classified in the same way [19].
Statistical Analyses
Statistical analyses were performed by SPSS version 14.0 running on Windows XP. Binary logistic regression analysis was used to evaluate the levels of β-catenin expression in rectal cancers compared to colonic cancers. This comparison was also done by means of one-way ANOVA. Survival analyses were carried out by Cox regression. Test plot for proportional hazard was performed. We chose an alpha level of statistical significance of p<0.05.
RESULTS
Table 1 shows the main characteristics of the rectal cancers.
Table 1
Rectal Cancers Characteristics. Numbers. Percentages in Parentheses (%)
The tumors were classified according to Dukes’ classification of 1932 with the addition of a class D introduced by Turnbull et al. in 1967 [20] in such a way that the Dukes A, B, C and D classes correlate to the stages I, II, III and IV based on the TNM-classification [21]. The TNM classification of each cancer was also recorded. Patients were followed up according to the Norwegian guidelines for colorectal patients for five years after surgery.
Mean follow-up time for the rectal cancers was 6.01 years, median 6.09, ranging from 0.01 to 14.53 years, standard deviation 4.16. One hundred and thirty-two patients (56.2 %) died during follow-up. Out of these, 53 (40.2 %) died from rectal cancer. Twenty-three cancers (9.8 %) recurred locally. In 47 patients (20.0 %), distant metastasis was discovered during follow-up, at a later time than surgery. Mean time from surgery till local relapse was 2.26 years. Mean time from surgery till distant metastasis was 2.32 years. Mean time from surgery till local relapse and/or distant metastasis was 2.11 years.
In the colon material, 4 cancers (2.5 %) were T1, 24 (14.7 %) T2, 126 (77.3 %) T3 and 8 (4.9 %) T4. I.e. there was a tendency towards lower T stages in the rectal cancers. The percentage of Dukes’ A cancers was three times higher in the rectal material than in the colon material. A slight majority of the colon cancer patients were females while the opposite was true for the rectal cancers. The rectal patients were slightly younger than the colon patients.
From a total of 274 rectal carcinomas, 235 were available for evaluation of β-catenin protein expression.
The results of the immunostaining of nuclear β-catenin are shown in Table 2.
Table 2
Nuclear β-Catenin Expression in Rectal and Colonic Cancers
When comparing the expression level of nuclear β-catenin between colonic and rectal adenocarcinomas by means of one-way ANOVA analysis, we observed a highly significant difference between rectal adenocarcinomas and colonic adenocarcinomas (p < 0.00001). The post hoc tests of the ANOVA analysis indicated that the difference between colon and rectum was larger when β-catenin had an immunopositivity of grade 0 or 1 than when the grade was 2 and 3.
The same comparison was also performed by means of binary logistic regression analysis. In this analysis we adjusted for Dukes stage, patient age, T-stage, and tumor differentiation grade. This analysis also showed a highly significant difference between rectal and colonic cancers concerning the expression level of nuclear β-catenin (p< 0.00001. OR=31.7, 95 % CI for OR [16.8; 59.9]). The nuclear expression of β-catenin was higher in rectal compared to colonic adenocarcinomas. None of the other parameters included in the analyses, except T-stage, showed any statistical difference between colonic and rectal adenocarcinomas. The T-stage was higher in the colonic adenocarcinomas than in the rectal adenocarcinomas (p=0.009, OR=0.452, 95 % CI for OR [0.250; 0.818]).
No statistically significant correlation was observed between nuclear expression of β-catenin in rectal cancer and cancer specific survival, distant metastasis nor local relapse of the cancer.
DISCUSSION
We found a higher protein expression of nuclear β-catenin in rectal cancers than in colonic cancers. The difference was highly significant.
The percentage of nuclear β-catenin expression was higher in the present study than in previously published data. We observed nuclear β-catenin expression in 94.9 % of the tumors, which is higher than observed in studies performed by Gunther et al. [18] and Kapiteijn et al. [3]. The reason for this discrepancy is difficult to explain exactly, but it is possible that the composition of patient groups between these studies may have been different regarding tumor stage.
The lack of association between rectal nuclear β-catenin expression and clinical outcome observed in the present study is in concordance with the observations of Gunther et al. [18]. In contrary, Cheach et al. [22] found a significant relation between nuclear β-catenin expression and higher mortality rates. Their patients were colorectal cancer patients, i.e. a mixture of colonic and rectal cancers. Bondi et al. [19] found a borderline association between the same parameters in their examination of exclusively colonic cancers. We believe that a relationship between nuclear β-catenin expression and mortality seems to exist for some colonic cancers. This relation appears to be lacking in rectal cancers.
Increased translocation of β-catenin to the nucleus of tumor cells is usually the result of reduced degradation of cytosolic β-catenin. The APC gene plays an important role in the degradation of β-catenin [13,17], and mutation in either the APC gene or in the β-catenin gene itself may lead to reduced degradation and increased translocation to the nucleus. Dimberg et al. detected higher prevalence of mutations in the mutation cluster region of the APC gene in rectal cancers than in colonic cancers. Their investigation also indicated a relation between APC mutations in human colorectal cancers and nuclear translocation of β-catenin [23]. From this, one might suspect a higher prevalence of nuclear β-catenin in rectal cancers than in colonic cancers, as observed in the present study.
Translocated β-catenin leads to increased expression of cyclin D1 [24] and c-Myc [25], which may turn up the proliferation capacity of the tumor cells. Tumor cells with high proliferation rate may expand locally fast, escaping from the immune system. This can cause a local recurrence that is of clinical significance. The results from the present study support, and in part explain why local relapse may be a more pronounced problem in rectal cancer. The results may also partly explain the necessity of not leaving any cancer behind when doing surgery. A few rectal cancer cells left behind can multiply rapidly because of the high proliferation rate of the tumor cells, leading to clinically significant local recurrence.
Local relapse was a major problem before the introduction of TME (total mesorectal excision) as a standard procedure. After the introduction of TME the local relapse frequency of rectal cancer is declining [26], probably because of better salvage of tumor cells by the TME procedure.
A more rapid growth of a localized tumor does not necessarily lead to more distant metastases. This may be why there is no significant association between nuclear expression of β-catenin and cancer specific survival. Rectal cancer patients die from distant metastasis and not from a localized tumor in the pelvic cavity alone. If handled correctly, a local relapse need not necessarily lead to mortality, but is associated with high morbidity.
CONCLUSION
We have in the present study observed a highly significant difference in nuclear expressed β-catenin between colonic and rectal adenocarcinomas, even when adjusted for other histopathological and clinical parameters. This difference in the cellular biology between these two localizations may in part explain the differences observed in clinical practice.
ACKNOWLEDGEMENTS
The study and the manuscript preparation were funded by the South-Eastern Norway Regional Health Authority and the University of Oslo.
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Forceps
Page history last edited by Anna Laycock 7 years, 6 months ago
Forceps
Author and Researcher - Anna Katherine Laycock
Forceps are defined by the Oxford English Dictionary as "An instrument of the pincers kind, used for seizing and holding objects, esp. in surgical and obstetric operations." (OED). The use of forceps for obstetric purposes became prominent in the eighteenth century, with the rise of man-midwifery. However, the introduction of the instrument did cause some controversy, with opponents of the forceps deeming them unnatural and dangerous. Major players in the forceps debate included Edmund Chapman, William Smellie, John Burton, William Hunter and William Douglas, who all published essays, treatises and midwifery manuals stating their opinions on the best way to practice midwifery and criticising the methods of others.
Obstetric forceps seldom appear in literature of the eighteenth
A pair of 18th century forceps designed by William Smellie.(1)century, which is unsurprising due to their specific purpose and association with the most intimate parts of a woman's body. However, in Laurence Sterne's Tristram Shandy, forceps play a central role in the birth of Tristram and the forceps debate is discussed in the narrative. As I will explore further,Tristram Shandy engages with the arguments for and against forceps advocated by the leading obstetricians of the day in their publications.
Overall, by investigating the use of forceps in the eighteenth century, one can explore the changing societal customs and perceptions of childbirth throughout the century; particularly how midwifery changed from a predominantly collective female practice to a medicalised male one.
A pair of 18th century forceps designed by William Smellie.(Image 1)
Contents
A brief history of the obstetrical forceps
Historically, the invention of the obstetrical forceps has been attributed to the Chamberlen family in the early seventeenth century. The Chamberlen family were Huguenot refugees who settled in London during the late sixteenth century. The eldest son, Peter Chamberlen (1560-1631) was a surgeon to Queen Anne and served as an accoucheur to Queen Henrietta Maria, being present at the birth of Charles II in 1630. It is thought that Peter was the original inventor of the forceps. The Chamberlens managed to keep their invention a secret within the family, passing the instrument down through three generations of Chamberlen obstetricians. However, at the beginning of the eighteenth century the secret had leaked with the first written accounts of similar but improved obstetrical tools appearing, such as from Chapman and Pugh who significantly both lived only a few miles away from the Chamberlens in Essex. By 1720, a similar instrument to the Chamberlen forceps was being demonstrated in Paris and there are accounts of at least two London obstetrician practitioners using a type of tool resembling the forceps. Yet, it was not until the 1730’s when the secret of the forceps at last truly became public. Edmund Chapman published his Essay Towards the Improvement of Midwifery in 1733 which included the first account of the obstetrical forceps and gave the instrument their name. As soon as the instrument was in the public domain, it was adopted by many other leading obstetricians such as Alexander Butter and William Giffard who also published works detailing the benefits of using forceps. However, the forceps were a controversial instrument which instigated debates as to whether interventionist equipment was necessary and safe during labour among obstetricians and midwives throughout the eighteenth century.
The Chamberlen forceps which were discovered at their home at Woodham Mortimer Hall in Essex. They are now displayed at the Royal College of Obstretricians and Gynaecologists. (Image 2)
Forceps and the rise of Man-Midwifery
This caricature(Image 3),drawn by Scottish illustrator Isaac Cruikshank, for a 1793 pamphlet written by Samuel William Fores arguing against man-midwifery, ridicules the role of the man-midwife. It highlights the man's reliance on instruments such as forceps, hooks and perforators, compared to the woman's more simplistic and natural techniques. The image depicts how men have been intruding into the traditional female occupation of the midwife, and thus illustrates this new hybrid Man-Midwife to be a monster. The text underneath the image reads "A Man-mid-wife, or a newly discover'd animal, not known in Buffon's time; for a more full description of this Monster , see, an ingenious book, lately published, price 3/6, entitled, Man-Midwifery dissected, containing a Variety of well-authenticated cases, elucidating this animal's Propensities to cruelty & indecency, sold by the publisher of this print, who has presented the Author with the Above for a Frontispiece to his Book".
In William Hunter and the Eighteenth Century Medical World, Adrian Wilson describes forceps as the “key to the lying-in room” for man-midwives. (343) The invention of the forceps can be attributed as one of the main factors for the sharp rise in man-midwifery during the eighteenth century. Midwifery was traditionally a female occupation, the expectant mother would be assisted by the local midwife and a number of female ‘gossips’ who were most likely neighbours and friends. Men were prohibited from the delivery room and for the preceding lying-in month. Before the invention of forceps and the rise of man-midwifery, childbirth was a communal female custom, therefore it is not surprising that there was opposition to the medicalisation of childbirth and the entrance of men into the lying-in room.
The use of forceps by man-midwives enabled men to gain access to the most intimate parts of the female body. Philip Rhodes, a historian of London’s first Lying-In Hospital states; “when the forceps became available to accoucheurs for the first time, it must have seemed as if there were a sudden flood of light cast in dark places!” (qtd. in Blackwell 78). Indeed, it can be seen that forceps allowed men to exert control over women’s bodies. Interestingly Bonnie Blackwell describes the “mechanical mother"; a life sized model of the pregnant female body, that was used in student lecture halls to demonstrate forceps (see Dolls for further information about artificial substitutes for the human body). Blackwell points out;
The medical theater brought the capricious womb and its fragile contents under the controlled setting of a university hall, and offered to obstetric students the promise of a total, visual mastery of the female body: a mastery so complete that their profession did not even need live women, because it could manufacture new and improved female bodies which were suited to its specifications. The innovations of eighteenth-century man-midwifery engendered a new perception of birth as theater, for doctors trained in surgeries and hospitals emerged with expectations about the female body, labor, and time which were premised on dramatic convention; they left universities convinced that labor, like all plots, could conform to the Aristotelian unities. (82)
With forceps as the principal prop, childbirth became a theatrical event in these student lectures. Labour was a dramatic plot, with the man-midwife as the hero, stepping in with his forceps to save the unborn child. This image of the ‘heroic’ man-midwife is satirised in Laurence Sterne’s Tristram Shandy, as I will explore later. Forceps enabled men to power over the female body; whereas before the unpredictable mother’s body was in control of the birth of her child, the forceps allowed men to intervene and speed up the process.
Indeed, after the introduction of forceps, many midwifes and obstetricians publicly expressed their opposition to the instrument. They deemed the use of instruments and the intervention of man unnatural during childbirth. In her famous work, A Treatise on the Art of Midwifery, staunch forceps opposer and midwife, Elizabeth Nihell, posits; “Nature, if her expulsive efforts are but, in due time, and when requisite, gently and skilfully seconded by the hands alone, will do more, and with less pain than all the art of the instrumentarians, with their whole armoury of deadly weapons” (454). Nihell argues that Nature should be in charge of childbirth, not man, and that the “natural hand” is the “best instrument” (454). Nihell was firmly against man-midwifery, believing that they threatened the wellbeing of the woman and child.
Nihell’s views were widely supported as can be seen from arguments against man-midwifery and the use of forceps in this article from the Hicky’s Bengal Gazette, published on the 20th of October 1781:
I take for granted I need instance no more Cases, to convince an unprejudiced Reader of the Danger of these abominable Forceps.Their very Nature, not only enables a Man—but in the Language of Doctor Smellie, tempts him to exert his Force, inconsistent with Safety.—Hands, are the best, and most natural Instruments. Is a Child to be torn thus from the Womb? —Horrible Idea—Satisfied that I have transcribed enough to convince any reasonable Person of the Danger of Instruments, I shall shock my Readers with no more such inhuman Relations—but refer whoever can remain unconvinced, to Doctor Sentelise's two Volumes. If it be said that these Passages should not be read by Women, because they will frighten them—I answer, that there is no occasion for their being read by those Women who do not intend to employ a Man Midwife, wantouly, before they know that their Case is site of many thou-sands. But if a Woman does intend to employ a Man, notwithstanding the Custom is so indecent, and unnatural —it is better she should be frightened, by reading this Book—that risk being injured, perhaps irreparable, in parts of the most expensive Sensibility. (Hicky’s Bengal Gazette)
Using passionate language, rhetorical questions and hyperbole, the author of this article attempts to shock the reader and discourage them from employing a male-midwife.
It is noteworthy that the article mentions Dr William Smellie, the leading man-midwife of the eighteenth century, as his use of forceps caused much anger among forceps opponents. Controversially, in his most famous work, A Treatise on the Theory and Practice of Midwifery, Smellie advocates that “the forceps be unlocked, and the blades disposed cautiously under the cloths so as not to be discovered” (272). Unsurprisingly, Smellie’s suggestion that the forceps be used secretly led to shock and outrage. It promoted the violation of women’s bodies by men, and depicted how forceps and the medicalisation of childbirth had allowed men direct and open access to women’s most intimate areas for the first time. Women in the eighteenth century were often dressed from head to toe in artificial adornments - clothing, wigs, make-up…etc (see Stockings, Swift’s A Beautiful Young Nymph Going to Bed and Pope’s The Rape of the Lock for information about the literary representation of women's dress) - therefore with the forceps, male-midwives were able to get under the many layers of clothing and have direct access to the physical body. Consequently, with the invention of the forceps and the rise of male-midwifery, the protection of women’s modesty and dignity was called into question.
"Doctor Forceps" satirical cartoon. This illustration depicts a blind and senile forceps practitioner.
This type of cartoon would have been widely distributed among the public through cheap prints.(Image 4)
Forceps in Midwifery Manuals, Treatises and Essays
Above are images from two eighteenth century books concerning midwifery.(Image 5) (Image 6) The forceps debate was played out through essays, treatises, manuals and letters in which the authors argued their points and sought to persuade their readership. Bonnie Blackwell argues that “obstetric writing and fiction were, in the eighteenth century, far more prone to collision than has yet been acknowledged by either medical or literary historians” (85). Indeed, many eighteenth century books and documents regarding midwifery and the use of forceps can be seen as having similarities to fictional literary texts.
Obstetricians, such as Edmund Chapman, included first person accounts of some of the cases they attended to in their publications. Chapman’s An essay on the improvement of midwifery includes narratives about fifty of Chapman’s cases, often detailing his use of forceps. He can be seen as casting himself as the hero in these narratives; he describes the midwives’ “endeavours of no service”, and by stepping in and using his forceps Chapman successfully “delivered [the woman] of a Son, who with his Mother is now living” (76;71). The cases are told like a story. Each has a dramatic title which summarises the case, such as; “Two children extracted by the Feet after the Membranes were broke”, “A Head separated and left behind in the Womb, extracted with the Crotchet” or “Of a Woman that was delivered at the Anus.” (80; 82; 87). These dramatic and shocking titles are similar to newspaper headlines, they compel the reader to read the following narratives out of curiosity.
Significantly, some writers of midwifery books present their arguments through a series of letters. The form of these books resembles the popular epistolary novels of the eighteenth century. S.W Fores’s Man-Midwifery dissected uses the epistolary form. He presents his argument against man-midwifery and opinions about the use of forceps in fourteen letters addressed to Alex Hamilton, in response to Hamilton’s published letters to Dr W Osborn. There is a dichotomy in the use of the private and personal form of the letter in a public, open format of a published book. By using the epistolary form, the writers enhance their arguments by directly positioning themselves against another’s viewpoint. William Douglas’s Letter to Dr. Smellie (pictured above) ridicules Smellie’s newly invented wooden forceps and criticises the way he teaches and practices midwifery. Through the epistolary form, the forceps debate was played out clearly through writing; the arguments between obstetricians of differing opinions were staged in a public format.
Obstetric writing and The Diary of Thomas Turner
It is interesting to compare eighteenth century obstetric writing to Thomas Turner’s account of the death and post-mortem of a pregnant woman from his parish in his diary. Turner writes on the 13th July 1756; “This day died Elizabeth Elless, and immediately after she was dead, Mr Adams told me Mr French and I would be fined on account of her death. The reason was because we carried her before a justice and asked her to swear the father” (50). It is insinuated in this short entry that it was believed to be a possibility that Elless committed suicide due to the pressure she was being put under from Turner and French to declare who the father of her child was. However, despite Turner’s personal involvement in the case and the probable grief it would have caused him, in the diary entries of the next two days Turner displays great emotional distance from the events. Indeed, Turner’s account of the post-mortem has many similarities to medical writing.
On the 14th of July, Turner recounts the series of events leading up to Elizabeth Elless’s death, listing precisely the times that her symptoms appeared and using medical terminology. The next diary entry details the post-mortem itself. Turner gives a factual account of the operation, including a diagram of the incision made into Elless’ abdomen and presents the findings of the post-mortem in his diary;
They also opened the uterus where they found a perfect fine female child, which lay in the right position and would, as they imagined, have been born in about 48 hours. And as the membranes were all entirely whole, and the mob full of the water common on such occasions, there was convincing proof she was never in travail. The ilea were all very much inflamed, as was the duodenum, but they both declared they could see no room to suspect poison. But if anything else had been administered, it had been carried off by her violent vomiting and purging. (53)
At the end of his diary entry Turner concludes that the most likely cause of Elizabeth Elless’ death was bilious colic. Significantly, the structure of the diary entry is comparable to a medical case study. Similar to William Smellie,Turner outlines the patient’s history, details the examination of the patient, relates the findings and presents a diagnosis. In this entry Turner adopts a medical discourse for his personal diary. It could be assumed that he was familiar with medical writing and modelled his narration on their format. Indeed, he does mention reading medical treatises in his diary such as "Mead On Poisons"and "the 5th volume of Medical Essays and Observations, published at Edinburgh by a society of physicians" (61; 113). It is notable that for Turner reading for pleasure included medical writing as well as fiction. Ultimately Turner's diary highlights that there are interesting similarities between medical writing and other forms of literature in the eighteenth century which can be researched further.
For more information about the role and influence of medical literature in a different context during the eighteenth century, see Smelling Salts .
Smellie's drawing of straight and curved forceps, as illustrated in one of his midwifery manuals. (Image 7)
Forceps and Politics
Adrian Wilson in The Making of Man-Midwifery (1995) highlights how during the first few decades of forceps practice the use of forceps was split along party lines. On the whole, Tory obstetricians were in favour of forceps and used them in their practice, whereas the Whigs were opposed to the instrument and favoured the style of an alternative midwifery promoted by Dutch obstetric surgeon, Hendrik van Deventer. England in the eighteenth century was a polarised political country, therefore it is not surprising that the forceps debate had a political element.
Wilson points out that Hugh Chamberlen II was a Tory supporter and he sold his family’s invented forceps under an oath of secrecy to other Tories. Their shared political allegiance helped keep the instrument a secret. Significantly, it was not until after the death of Hugh Chamberlen and many of his exclusive circle of Tory obstetricians that the use of forceps became more widespread; firstly among other Tories and then much later in the century among Whigs as well.
Whig supporters in the early eighteenth century followed a much different, less interventionist style of midwifery. Hendrik van Deventer (1651-1724) rejected the use of manual instruments, and instead endorsed a style of childbirth based on adjusting the position of the mother. He published The art of midwifery improv’d in 1716 which became the most influential midwifery manual among his English supporters, or ‘Deventerians’. Wilson summarises Deventer’s theory, stating that;“the presentation of the child - on which previous authors had concentrated - Deventer reconceptualised as an aspect of total bodily posture or ‘turning’. The uterus could be oriented ‘directly’ which favoured a natural birth” (81). Also, the ‘Deventer’s Manoeuvre’ became popular among the Whig Deventerians. Wilson writes that the move involved “forcing the coccyx to bend backwards (as it does naturally in normal labour) thereby slightly enlarging the diameter of the passage” (82). Therefore by adjusting the mother’s posture to encourage delivery, instruments such as forceps would become practically unnecessary.
When the forceps were brought into the public in the 1730’s, the opponents of the new-invented instrument were Court Whigs who followed Deventer. Deventer’s method was the principal alternative to the forceps during the period as it favoured a more natural, less interventionist approach which forceps opponents approved of.
A diagram of foetal positions, the birthing chair and three clyster pipes by Hendrik van Deventer for his book, The art of midwifery improved. Clyster pipes were used to inject herbal remedies into the mother's gut in order to clear it to allow a clearer passage for the baby. The birthing chair enabled the midwife assisting the birth easier access to the baby.(Image 8)
Forceps in Tristram Shandy
Illustration of the aftermath of the birth of Tristram Shandy by H.W Bunbury. It depicts baby Tristram with a broken nose caused by Dr Slop's forceps. (Image 9)
The forceps debate is prominent in the novel Tristram Shandy by Laurence Sterne. Protagonist, Tristram, is the victim of the misuse of the instrument as his delivery by forceps causes him to have a broken nose. Tristram’s disdain for the forceps is evident throughout his narrative. His broken nose causes great grief for him and his family. Mr Shandy throws himself on the bed in despair as he believes Tristram’s flattened nose will mean he will be unsuccessful in life, remembering the family history associating small noses with financial instability. Whilst Mr Shandy’s reaction is no doubt hyperbolic, the novel undoubtedly promotes the arguments against the use of obstetric forceps as I will go on to explore.
Firstly, the difference in descriptions of the midwife and Dr Slop, the clumsy forceps practitioner must be noted. The midwife is given an introduction early in the novel, Tristram describes her as a “motherly, notable, good old body of a midwife, who, with the help of a little plain good sense, and some years full employment in her business, in which she had trusted little to her own efforts, and a great deal to those of a dame nature, - had acquired, in her way, no small degree of reputation in the world” (12). Tristram goes onto relate how the midwife, a widow with young children, obtained her position after Yorick sets her up with a licence. Before the midwife enters, she is illustrated to be a caring, motherly figure - the sort of person you would want your child to be delivered by. In contrast the initial description of Dr Slop paints him as a comic ungainly figure. Tristram states; “Imagine to yourself a little, squat, uncourtly figure of a Doctor Slop, of about four feet and a half perpendicular height, with a breadth of back, and a sesquipedality of belly, which might have done honour to a Serjeant in the Horse-Guards” (93). Before the forceps are even used, the reader is compelled to favour the traditional figure of the midwife over the ridiculous forceps practitioner.
Significantly, forceps are frequently described using military language in the narrative, highlighting that the instrument is the weapon in the battle between the traditional female midwives and the new male-midwives, or accoucheurs. When Dr Slop forgets his bag of instruments he is described as having “come forth unarm’d” as he has left his “new-invented forceps” at home (97). The forceps were commonly described in the eighteenth century as the man’s ‘key to the lying in room’, thus without this vital instrument Dr Slop is useless. Consequently, Obadiah is sent to bring the forceps to Dr Slop “with all speed” despite the fact that they may be unnecessary as the labour has not yet encountered any difficulties (97). It is ironic that just before the delivery of Tristram by the forceps, they are described as the “armour” Dr Slop “had proved” to be “the safest instrument of deliverance”(136). Armour is used as a means of protection for the body, however the forceps do the opposite by directly harming the small and vulnerable body of the baby. Ultimately, the forceps are the weapon that triumphs over the female midwife. As Gerald MacLean states; “steel swords, steel scissors, steel forceps: Walter Shandy does anything but resist the steel forceps of the ‘man of science’, but Mrs Shandy resists them adamantly. They eventually triumph over her” (540). The feminine space of the lying-in room and the female practice of midwifery is defeated by the male invention of the forceps.
It has been suggested that Dr Slop is a parody of Dr Burton, a well known forceps practitioner and author of An Essay Towards a Complete System of Midwifery (1751), who practised in and around York, close to where Sterne lived. Notably, Burton was an enemy of the Sterne family as Laurence Sterne’s uncle, Dr Jaques Sterne was the Justice of Peace and had a say in Burton’s arrest during the Jacobite risings of 1745. In his writings, Burton promotes the use of forceps and particularly his own invented “new Sort of Forceps, the use of which is far less prejudicial, either to the Woman or Child, and is much more commodious for the Operator” (383-384). Rene Bosch argues that “Slop’s forceps looks in all details like the improved medical instrument that Burton claimed he invented” (208). Therefore, it can be seen that as well as generally mocking forceps practitioners, the character of Dr Slop is a more personal attack on one male obstetrician.
Dr Burton's "Lobster Claw" forceps.(Image 10)
Interestingly, the forceps become a metaphor for the child they are going to deliver when they become stuck in Dr Slop’s bag and he pulls them out with considerable difficulty. After a debate with Toby about the value of his newly-invented forceps, Dr Slop “thrust his hand into the bag” and “fumbled so vilely in pulling them out, it took off the whole effect (for they seldom come alone in this life) in pulling out his forceps, his forceps unfortunately drew out the squirt along with it” (168). The squirt is a foreboding instrument as it was used to baptise unborn infants when it was clear they were not going to survive, thus the object’s mention further insinuates that Tristram’s birth will not go smoothly. Also, if the bag can be seen as representing Mrs Shandy’s abdomen and the forceps baby Tristram, the unintentional removal of the squirt could be seen as symbolising the danger of perforation of the bladder which was associated with misuse of forceps. Therefore, the ungainly removal of the forceps from the bag highlights the danger Mrs Shandy and her baby are in from the instrument and its incompetent practitioner.
Like the bag, Toby becomes a surrogate for Mrs Shandy in the narrative. Significantly the actual birth scene happens offstage, the reader is not given access to it. Instead we see Toby being injured by the forceps. Dr Slop demonstrates his forceps on Toby’s hands, leading Toby to cry out; “Upon my honour, Sir, you have tore every bit of the skin quite off the back of both my hands with your forceps…and you have crush’d all my knuckles into the bargain with them, to a jelly” (169). Bonnie Blackwell points out that Sterne uses “language of conception and delivery” to describe Toby as “he is ‘confined’ (T, 1:84) as a woman is and is “full two months gone” (T, 1:94) at one point” (118). Toby’s body becomes the substitute mother. Therefore, the pain inflicted on Toby’s hands by the forceps symbolises the pain inflicted offstage on the silenced Mrs Shandy by the controversial instrument.
Furthermore, the brutality of the forceps is further suggested by the threat they make to Tristram’s genitals. Dr Slop tells Mr Shandy “if the hip is mistaken for the head there is a possibility (if it is a boy) that the forceps **************************.” (169). Thus when we are told that Dr Slop “in bringing [Tristram] into the world with his vile instruments, he has crush’d his nose…as flat as a pancake to his face” (193). The nose becomes synonymous with the penis even though Tristram himself denies this. The size of the nose and the penis represent masculinity - the bigger, the better - consequently, Sterne emphasises that Tristram’s masculinity has been damaged by the forceps.
The narrative of Tristram Shandy with its frequent long digressions and loose plot can be seen as a narrative that defies the clock. From the first chapter it is clear that the measurement of time will be a prominent theme as Mrs Shandy interrupts the act of sexual intercourse with her husband asking; “Pray, my dear…have you not forgot to wind up the clock”(6). Her seemingly insignificant and inappropriate comment sets forth a narrative that attempts to thwart the clock. Notably, the clock enters into the forceps debate. After Mr Shandy has seen the effect the forceps had on Toby’s hand he begins to become uncertain about the safety of the instrument. Yet, instead of criticising the forceps he criticises the clock, stating that “in our computations of time, we are so used to minutes, hours, weeks, and months, — and of clocks (I wish there was not a clock in the kingdom) to measure out their several portions to us, and to those who belong to us” (172). If life was not measured by the clock there would be no need for forceps as nature would take its own time in delivering a child without human intervention. Interestingly, Elizabeth Nihell argues in A Treatise on the Art of Midwifery (1760), that "art should aim at imitating Nature: now Nature proceeds leisurely instead of which the forceps goes too quick to work" (415). Tristram Shandy imitates Nature; the narrative can be seen as symbolising a woman’s body, with the birth of the story like the birth of the child; unpredictable and takes a long time.
Overall, despite the light-hearted comic tone, forceps are presented as a dangerous and unnecessary instrument in Tristram Shandy. The novel implies that nature, not man should be in charge of childbirth and intervention can do more harm than good. The arguments Sterne advocates against the forceps relate to many of the arguments put forward by the anti-forceps obstetricians in their treatises, essays and midwifery manuals. Consequently, Sterne enters this debate through the use of comedy and caricature to mock the arrogant men-midwives and their key to women’s bodies; the forceps.
Ten diagrams illustrating different methods of delivering a baby using forceps, 1791. (Image 11)
Links to relevant websites
A Demonstration of some Eighteenth Century Obstetric Forceps - Journal of the Royal Society of Medicine
Extracts from William Smellie's A Treatise on the Theory and Practice of Midwifery
Milestones in the evolution of obstetric forceps by Bryan Hibbard
A set of 18th Century obstetric forceps - Wellcome Library
The start of life: a history of obstetrics by J. Drife - Postgraduate Medical Journal
A Treatise on the Art of Midwifery by Elizabeth Nihell
Annotated Bibliography
Primary (18th Century Sources)
Burton, John. An Essay towards a Complete New System of Midwifry, Theoretical and Practical: Together with the Descriptions, Causes, and Methods of Removing, or Relieving the Disorders Peculiar to Pregnant and Lying-in Women, and New Born Infants ; Interspersed with Several New Improvements ; Whereby Women May Be Delivered, in the Most Dangerous Cases, with More Ease, Safety, and Expedition, than by Any Other Method Heretofore Practised ; Part of Which Has Been Laid before the Royal Society at London, and the Medical Society at Edinburgh ; after Having Been Perused by Many of the Most Eminent of Their Profession, Both in Great Britain and Ireland ; by Whom They Were Greatly Approved of ; All Drawn up and Illustrated with Several Curious Observations, and Eighteen Copper-plates ; in Four Parts. London: Printed for J. Hodges, 1751. ECCO. Web. 6 Feb. 2014.
Dr Burton’s essay promotes his views on how midwifery should be practised. He criticises Dr Smellie’s methods, particularly his leather covered forceps, and presents his own improved design of the forceps. As Dr Slop in Tristram Shandy is thought to be a parody of Dr Burton, I used this source to compare the two figures.
Chapman, Edmund. An Essay on the Improvement of Midwifery Chiefly with Regard to the Operation. To Which Are Added Fifty Cases, Selected from Upwards of Twenty-five Years Practice. By Edmund Chapman, Surgeon. London: Printed by A. Blackwell, for A. Bettesworth and C. Hitch, J. Walthoe; and Sold by T. Cowper, 1733. ECCO. Web. 15 Jan. 2014.
Edmund Chapman’s essay was the first account of the obstetrical forceps. He essay details in what sort of cases require forceps and how to use them. He details fifty different cases of labours he worked on. I found the style of writing in this source is comparable to that of fictional literary texts. I used this source to look at the similarities between obstetric writing and fiction.
Deventer, Hendrik Van. The Art of Midwifery Improv'd Fully and Plainly Laying down Whatever Instructions Are Requisite to Make a Compleat Midwife. ... Illustrated with 38 Cuts ... Written in Latin by Henry à Daventer. London: Printed for E. Curll, J. Pemberton, and W. Taylor, 1716. ECCO. Web. 9 Feb. 2014.
Deventer’s book promotes a non-interventionist midwifery that was an alternative to forceps practice. I looked at how Deventer’s methods were taken up by Whig obstetricians who opposed forceps.
Douglas, William. A Letter to Dr. Smellie Shewing the Impropriety of His New-invented Wooden Forceps ; as Also, the Absurdity of His Method of Teaching and Practising Midwifry. By William Douglas. London: Printed for J. Roberts, 1748. ECCO. Web. 16 Jan. 2014.
William Douglas’s letter ridicules Dr Smellie’s use of wooden forceps and his midwifery methods. I found this source interesting as it is written in the epistolary style, and I used it to analysis the effect of the letter form in obstetric writing.
Fores, Samuel William. Man-midwifery Dissected; Or, The Obstetric Family-instructor. For the Use of Married Couples, and Single Adults of Both Sexes. Containing a Display of the Management of Every Class of Labours by Men and Boy-midwives; Also of Their Cunning, Indecent, and Cruel Practices. Instructions to Husbands How to Counteract Them. A Plan for the Complete Instruction of Women Who Possess Promising Talents, in Order to Supercede Male-practice. Various Arguments and Quotations, Proving, That Man-midwifery Is a Personal, a Domestic, and a National Evil. In Fourteen Letters. Addressed to Alex. Hamilton ... Occasioned by Certain Doctrines Contained in His Letters to Dr. W. Osborn. London: Published for the Author, by S.W. Fores; and to Be Had of All the ellers in Town and Country, 1793. ECCO. Web. 4 Feb. 2014.
This source criticises the practice of male-midwives, deeming them unnatural. I used this source to examine the opposition to man-midwives, as well as analysing the letter format Fores uses.
Nihell, Elizabeth. An Answer to the Author of the Critical Review, for March, 1760. Upon the Article of Mrs. Nihell's Treatise on the Art of Midwifery. By Mrs. Elizabeth Nihell, Professed Midwife. London: A.Morley, 1760. ECCO. Web. 2 Feb. 2014.
Elizabeth Nihell addresses a letter to the author of the Critical Review in response to an article criticising her A Treatise on the Art of Midwifery. This source demonstrates how the forceps debate was played out on the public stage through written publications.
---. A Treatise on the Art of Midwifery: Setting Forth Various Abuses Therein, Especially as to the Practice with Instruments: The Whole Serving to Put All Rational Inquirers in a Fair Way of Very Safely Forming Their Own Judgment upon the Question, Which It Is Best to Employ, in Cases of Pregnancy and Lying-in, a Man-midwife, Or, a Midwife. London: Printed for A. Morley ..., 1760. Medical Heritage Library. Web. 5 Feb. 2014.
Nihell’s famous treatise criticises man-midwifery and the use of forceps. She puts forward a number of arguments against the use of forceps and highlights the use of instruments to be unnatural. Many of the arguments in her work are similar to those advocated in Tristram Shandy. I used this source to analysis the opposition to forceps and man-midwives.
Smellie, William. A Collection of Cases and Observations in Midwifery By William Smellie, M.D. To Illustrate His Former Treatise, or First Volume, on That Subject. Vol. II. London: Printed for D. Wilson and G. Nicol, and T. Durham, 1768. ECCO. Web. 2 Feb. 2014.
In this book, Smellie illustrates what he believes is the best way to use forceps. He his experiences of obstetrics through narrating a series of cases. I read this source alongside Smellie’s Treatise to analysis the way Smellie promotes forceps.
---. A Treatise on the Theory and Practice of Midwifery. London: Printed for D.Wilson, 1752. Google Books. Web. 4 Feb. 2014.
Smellie’s Treatise was one of the most influential and controversial books concerning forceps in the eighteenth century. Smellie was a prominent forceps practitioner and in his Treatise he promotes the use of the instrument. I used this source to examine the debate between obstetricians about forceps and how they should be used.
Sterne, Laurence. Tristram Shandy. London: Penguin Classics, 2012. Print.
Sterne’s novel is one of the only pieces of literature from the eighteenth century that mentions the use of forceps, and can be seen as the only work to do so in any detail. I used Tristram Shandy extensively to analyse the presentation of forceps in literature.
Turner, Thomas. The Diary of Thomas Turner, 1754-1765. Ed. David Vaisey. Oxford: Oxford UP, 1984. Print.
Thomas Turner's diary provides an account of mid eighteenth century rural life. Turner held a number of important positions in East Hoathly including; the shopkeeper, schoolmaster, undertaker, surveyor, and overseer of the poor. I found the description of the death and post-mortem of the Elizabeth Elless particularly interesting as Turner's narrative is comparable to medical discourse.
Unknown. "Vol. II Pages 465 and 466." Hicky's Bengal Gazette [Calcutta] 20 Oct. 1781, 39th ed.: n. pag. Eighteenth Century Journals. Web. 3 Feb. 2014. http://0-www.18thcjournals.amdigital.co.uk.pugwash.lib.warwick.ac.uk/transcript.aspx?imageid=261087,261089&searchmode=true&previous=0
This author of this article staunchly opposes the use of forceps. He uses persuasive language to discourage his readers from employing a man-midwife and warns them of the horrors of forceps. I used this article to look at how forceps were presented in the press.
Secondary Sources
Blackwell, Bonnie. "Tristram Shandy and the Theater of the Mechanical Mother." Elh 68.1 (2001): 81-133. Project MUSE. Web. 10 Jan. 2014.
Blackwell discusses the rise of the medicalisation of midwifery in relation to Tristram Shandy. She describes the ‘mechanical mother’, a model of a woman’s body used to demonstrate forceps in student lecture theatres. I found this source particularly useful when exploring the representation of forceps in Tristram Shandy, as well as providing socio-historical information about the rise of man-midwifery.
Landry, Donna, and Gerald Maclean. "Of Forceps, Patents and Paternity: Tristram Shandy." Eighteenth Century Studies 23.4 (1990): 522-43. JSTOR. Web. 15 Jan. 2014.
This article analyses the depiction of childbirth in Tristram Shandy. I used this article when analysing the portrayal of forceps in the novel.
Wilson, Adrian. The Making of Man-midwifery: Childbirth in England, 1660-1770. Cambridge, MA: Harvard UP, 1995. Print.
Wilson’s book is a historical study into the rise of man-midwifery in the eighteenth century. This source was extremely useful for providing background information about the changes childbirth underwent during the eighteenth century. This source was particularly useful for providing information regarding the political debate around forceps.
---. "William Hunter and the Varieties of Man-midwifery." William Hunter and the Eighteenth-century Medical World. Ed. W. F. Bynum and Roy Porter. Cambridge: Cambridge UP, 1985. 343-69. Print.
This chapter by Wilson examines the rise of man-midwifery in the eighteenth century, with particular reference to William Hunter, a leading man-midwife who opposed the use of forceps. This source was useful in examining the opposition to forceps by leading obstetricians.
Images
1. Smellie's Obstetrical Forceps. 2010. Photograph. Science Museum, London.Science Museum. Web. 01 Feb. 2014. <http://www.sciencemuseum.org.uk/objects/obstetrics_gynaecology_and_contraception/A500206.aspx>
2. The Chamberlen Forceps. N.d. Photograph. Royal College of Obstetricians and Gynaecologists., London. Liverpool Medical Institution. Web. 10 Jan. 2014. <http://www.lmi.org.uk/Data/10/Docs/18/18Hibbard.pdf>.
3. Cruikshank, Isaac. A Man-Midwife. 1793. Wellcome Library, London. Wellcome Library. Web. 12 Feb. 2014. <http://blog.wellcomelibrary.org/2012/12/man-midwife/>.
4. Darly, M. Dr Forceps. 1773. Black and white line engraving. Colonial Williamsburg, Williamsburg. Colonial Williamsburg. Web. 27 Feb. 2014. <http://www.history.org/Foundation/journal/Winter03-04/cartoons.cfm?showSite=mobile>.
5. Nihell, Elizabeth. An Answer to the Author of the Critical Review, for March, 1760. Upon the Article of Mrs. Nihell's Treatise on the Art of Midwifery. By Mrs. Elizabeth Nihell, Professed Midwife. London: A.Morley, 1760. ECCO. Web. 2 Feb. 2014. http://find.galegroup.com/ecco/retrieve.do?sgHitCountType=None&sort=Author&tabID=T001&prodId=ECCO&resultListType=RESULT_LIST&searchId=R3&searchType=BasicSearchForm¤tPosition=3&qrySerId=Locale%28en%2C%2C%29%3AFQE%3D%280X%2CNone%2C16%29elizabeth+nihell%3AAnd%3ALQE%3D%28BA%2CNone%2C124%292NEF+Or+0LRH+Or+2NEK+Or+0LRL+Or+2NEI+Or+0LRI+Or+2NEJ+Or+0LRK+Or+2NEG+Or+0LRF+Or+2NEH+Or+0LRJ+Or+2NEM+Or+0LRN+Or+2NEL+Or+0LRM%24&retrieveFormat=MULTIPAGE_DOCUMENT&userGroupName=warwick&inPS=true&contentSet=ECCOArticles&&docId=CW3308555063&retrieveFormat=MULTIPAGE_DOCUMENT&docLevel=FASCIMILE&workId=CW3308555063&relevancePageBatch=CW108555063&showLOI=&contentSet=&callistoContentSet=ECLL&docPage=article&hilite=y
6. Douglas, William. A Letter to Dr. Smellie Shewing the Impropriety of His New-invented Wooden Forceps ; as Also, the Absurdity of His Method of Teaching and Practising Midwifry. By William Douglas. London: Printed for J. Roberts, 1748. ECCO. Web. 16 Jan. 2014.http://find.galegroup.com/ecco/retrieve.do?sgHitCountType=None&sort=Author&tabID=T001&prodId=ECCO&resultListType=RESULT_LIST&searchId=R2&searchType=BasicSearchForm¤tPosition=21&qrySerId=Locale%28en%2C%2C%29%3AFQE%3D%280X%2CNone%2C15%29william+douglas%3AAnd%3ALQE%3D%28BA%2CNone%2C13%29+2NEL+Or+0LRM%24&retrieveFormat=MULTIPAGE_DOCUMENT&userGroupName=warwick&inPS=true&contentSet=ECCOArticles&&docId=CW3307276864&retrieveFormat=MULTIPAGE_DOCUMENT&docLevel=FASCIMILE&workId=CW3307276864&relevancePageBatch=CW107276864&showLOI=&contentSet=&callistoContentSet=ECLL&docPage=article&hilite=y
7. Smellie, William. A Sett of Anatomical tables, with Explanations, and an Abridgement, of the Practice of Midwifery, with a View to Illustrate a Treatise on That Subject, and Collection of Cases. London: Published for the author, 1754.http://find.galegroup.com/ecco/retrieve.do?sgHitCountType=None&sort=Author&tabID=T001&prodId=ECCO&resultListType=RESULT_LIST&searchId=R6&searchType=BasicSearchForm¤tPosition=113&qrySerId=Locale%28en%2C%2C%29%3AFQE%3D%280X%2CNone%2C7%29smellie%3AAnd%3AFQE%3D%280X%2CNone%2C7%29forceps%3AAnd%3ALQE%3D%28BA%2CNone%2C13%29+2NEL+Or+0LRM%24&retrieveFormat=MULTIPAGE_DOCUMENT&userGroupName=warwick&inPS=true&contentSet=ECCOArticles&&docId=CW3307563929&retrieveFormat=MULTIPAGE_DOCUMENT&docLevel=FASCIMILE&workId=CW3307563929&relevancePageBatch=CW107563929&showLOI=Yes&contentSet=&callistoContentSet=ECLL&docPage=article&hilite=y
8. Deventer, Hendrik Van. The Art of Midwifery Improv'd Fully and Plainly Laying down Whatever Instructions Are Requisite to Make a Compleat Midwife. ... Illustrated with 38 Cuts ... Written in Latin by Henry à Daventer. London: Printed for E. Curll, J. Pemberton, and W. Taylor, 1716. ECCO. Web. 9 Feb. 2014. http://ihm.nlm.nih.gov/luna/servlet/detail/NLMNLM~1~1~101434228~139734:-Various-positions-of-fetus-in-uter
9. Bunbury, H. W. An Episode in Tristram Shandy: Dr. Slop with His Wig on Fire Angrily Gesticulating to Susannah Who Holds Her Nose near the Wounded Baby Tristram Shandy. 1773. Wellcome Library, London. Wellcome Library. Web. 13 Feb. 2014. <http://blog.wellcomelibrary.org/2012/12/man-midwife/>.
10. Burton's Lobster Claw Forceps. N.d. Photograph. Department of Obstetrics, University of Edinburgh, Edinburgh. The Obstetrician's Armamentarium. San Anselmo: Norman, 2000. 38. Google Books. Web. 17 Feb. 2014.http://books.google.co.uk/books?id=NkLYuno1QDIC&printsec=frontcover&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false
11Unknown. Ten Diagrams Illustrating Various Methods of Delivering a Baby Using Forceps. 1791. Etching. Wellcome Library, London .http://catalogue.wellcomelibrary.org/record=b1174960
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5eff3d1f6f98e57329caed0ceb9053d3
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7,761,727,877,218,122,000
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Pleural Friction Rub
A 45-year-old woman with a history of systemic lupus erythematosus (SLE) presents to the Emergency Room (ER) with complaints of sharp retrosternal chest pain that worsens with deep breathing or lying down. She reports a 3-day history of low-grade fever, listlessness and says she feels like she had the flu. A physical exam reveals tachycardia and a pleural friction rub. She was diagnosed with acute pericarditis.
Question:
What does the Advanced Practice Registered Nurse (APRN) recognize as the result of the pleural friction rub?
The post Pleural Friction Rub first appeared on COMPLIANT PAPERS.
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Alternative Uses of the Common Cold
Mostly one would be inclined to feel that having a cold, being under the weather - as the saying goes, is not an optimal state. Sneezing, for example, can be both tiring and disorientating. Headaches can take the edge off getting on with things. But there is something nearly narcotic and indulgent about that sleepy euphoria of a cold, a pleasant disconnection with the pace of what is going on. One slips from being a protagonist to being an observer, albeit one that has things to do. Some people take drugs to get this effect, and while I would not want to be wrapped in rhinovirus euphoria often, sometimes one might sit back and enjoy being under the weather.
Share this:
CONVERSATION
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Monday, September 26, 2022
How To Treat Anxiety Stomach Pains
Does My Child Have Anxiety Stomach Aches
How to manage anxiety related stomach pain? – Dr. Sanjay Gupta
It may surprise many parents to know that anxiety or stress can often cause a belly ache in kids. In fact, approximately 8-25 percent of children experience ongoing stomach pain that cant be chalked up to illness or digestion. However, this pain is very real and can be a symptom of lifes stresses, which then makes belly aches worse. Whether theyre experiencing issues at home or school, nervous stomach can be the bodys coping mechanism. Long term stomach pain can lead to issues with anxiety and depression. Thats why its so important to deal with them head-on.
Effects Of Stress And Anxiety On Your Stomach
Stress and anxiety can trigger lots of different symptoms, in your mind and also on the rest of your body. Stress, for example can cause headaches, chest pain and problems concentrating. And anxiety can cause things like feeling nervous, sweating and problems sleeping.
But both stress and anxiety can also impact your gut. Experiencing a stressful situation can cause short-term problems in the digestive system, including:
In addition, you might find that stress affects your appetite, causing you to eat more or less than you would normally.
Medical Causes Of Anxiety: Anxiety As A Symptom
Anxiety is rarely just about biology or psychology. Except when it is.
We humans are chemistry, and nothing could make this clearer than the chilling story of an old family friend who suffered lifelong anxiety and panic attacks.After of living with this curse, he was diagnosed with a rare genetic disorder. One of the consequences of this genetic disorder are small tumours on the adrenal glands that cause spikes in adrenalin production. He had one on his adrenal gland. The gland was excised, and he was cured or perhaps set free would be a better description.
Thats an exceptionally rare cause of anxiety, of course. But dont neglect the possibility of a medical explanation or complication. Some of them are much, much more common. In fact, there are at least several insidious or underestimated medical causes of anxiety, which may explain an awful lot of allegedly free floating anxiety and symptoms of anxiety disorder in people who do not seem like a good psychological fit for it.
Chronic pain is extremely common, and can be both a cause and consequence of anxiety sometimes equally, sometimes slanted much more one way than the other, but each always influencing the other to some degree. For many people with both anxiety and pain, solving the pain is the best possible treatment for the anxiety. Others must solve both at once. And a few will find that pain is just one of many ways that they are haunted by anxiety demons.
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Did You Know That Stress Can Cause Stomach Pain With Cramps
When the body is under stress due to work pressures or other concerns, you may experience cramping in the stomach and bowel muscles as your digestive system cannot relax. The first thing we recommend for a stress-free life is organising your time sensibly and avoid setting unattainable goals. The philosophy you apply to solving problems is also important. Approaching problems with confidence, assessing the possibilities for practical implementation, and promising yourself not to complain will enhance your effectiveness at achieving a stress-free life while reducing anxiety.
Here are some relaxation techniques:
Identification Of School Stressors
Natural Ways To Reduce Back Pain
Explore whether any significant threats at school or inappropriate classroom placement contribute to the childs school refusal. Children often cannot articulate why they feel bad at school, and often there are no real threats at school it is just their symptoms of autonomic arousal associated with anxiety.
Also Check: How To Help Anxious Stomach
Eat Properly To Help Your Digestion
It’s very easy to spend our working lives eating on the move or at our desks, gulping down food between meetings and then crashing out in front of the TV with a takeaway in the evenings.
But eating this way can play havoc with our digestive system.
Follow some basic rules to prevent problems:
• Do not rush your food. Take the time to eat slowly. Try putting your fork down between bites and chew each mouthful well.
• Do not overeat. Reduce the size of your portions at mealtimes, or try eating 4 to 5 small meals instead of 3 large ones.
• Eat regularly and try not to skip meals.
• Avoid eating a big meal just before you go to bed. Eat your last meal at least 2 to 3 hours before lying down.
• Make sure you have plenty of water to drink.
What Is The Connection Between Anxiety And Stomach Pain
The connection between anxiety and stomach pain is not always clear. However, it is believed that anxiety and stomach pain are closely related because of the mind-body connection. This means that the brain and the gut are connected and can influence each other.
For example, when someone is feeling anxious, they may experience stomach pain. This is because anxiety can cause changes in the digestive system, including increased acid production and muscle tension. These changes can lead to stomach pain.
Conversely, stomach pain can also cause anxiety. This is because the pain can be a source of stress and worry. It can also trigger memories of past experiences of pain or other negative emotions.
So, the connection between anxiety and stomach pain is bidirectional. This means that one can cause the other, and vice versa.
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Why Does Stress Or Anxiety Impact Your Gut
Theres increasing evidence showing that theres an important relationship between the brain and the digestive system. This is sometimes called the brain-gut or gut-brain axis.
Communication between the two can affect activity in the brain and in the digestive system. This is why stress can cause symptoms in the stomach and the gut, and why the reverse is also true having digestive problems can make us feel very stressed and anxious.
When were in a stressful situation, our bodies tend to have a fight or flight reaction. Hormones are released which prepare us to act, by keeping us alert and energised.
The theory is that when these stress hormones are released, digestion slows down or even stops altogether so that the body can divert its energy to managing the perceived threat. This slowing down of the digestive process causes the symptoms of bloating, constipation, and pain.
We also know that in some people, stress can cause the opposite problem, speeding up the digestive process and causing diarrhoea.
Find Space For Yourself To Relax
Anxiety Stomach Pain Relief (Meditation for Anxiety) MIND GUT MEDITATION
Ultimately, find time and space for yourself to clear your head and take control of your nervousness, even if it must be total alone time. Dont be afraid to excuse yourself, even from an important event.
If talking to a friend, family member, or loved one helps, do so during this time. Talking with someone you trust can help you overcome anxiety.
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How To Reduce Stress
Aside from managing the physical symptoms of stress, the only way to truly make a difference is to address the root of the problem the mind. Whilst its true that stress is not a physical condition, there are ways of managing it and improving your physical health.
Experts have suggested that good ways to reduce stress are meditating, breathing exercises and calming exercise such as yoga. Try to take some relaxing walks outdoors as exercise, combined with fresh air and sunlight, are fantastic natural mood-boosters.
You should also consider your work life are you staying late, or continually worrying about deadlines? Some people may find that their stomach pain or similar symptoms worsen while at work. If this sounds like you, take steps to address this work stress. Speak to someone at work and tell them how you are feeling. They should be able to point you in the right direction.
Some individuals also find that therapy or counselling can really help their stress, which subsequently will hopefully lead to fewer stomach problems.
When Is Stomach Pain Most Likely To Occur
If you have anxiety, stomach pain can occur anytime even when no anxiety is present. However, many people experience stomach pain during panic attacks.
The exact link between an anxiety attack and stomach pain is not clear, other than the fact that during a panic attack, your body is under a considerable amount of stress, and your hormones are often on overdrive. Also, those with anxiety attacks are prone to hyperventilation, which may lead to symptoms that create stomach pain.
Read Also: How To Get Rid Of Lower Stomach Fat Female
Activities For When Pain Strikes
When you feel stomach cramps, any steady rhythmic exercise loosens muscles and decreases discomfort. Walking may be all you feel up to, but thats exactly what you need. Swimming is also an excellent gentle way to relieve cramps. In addition to loosening cramping muscles, exercise releases tension that can aggravate pain. Other tension relieving activities you can do include deep breathing exercises and meditation.
How To Stop Anxiety Stomach Pain
Stomach Pains
Anxiety-related stomach pain usually does not result from something you ate or poor lifestyle choices, even though these factors may increase the risk of anxiety in many circumstances. There are no specific dietary changes that can stop anxiety-induced stomach issues.
It is essential to understand that people with panic attacks are more prone to experiencing severe stomach discomfort even when they do not suffer from anxiety. Simply put, it is possible to have stomach pain even without a panic attack. Also, people with anxiety attacks and severe stress could be suffering from over-sensitization. It means they are more likely to notice and feel smaller, even regular changes in the body that can trigger anxiety attacks.
If your diet contains foods that cause gas, bloating, stomach discomfort, or mild indigestion, it is best to avoid them, as even slight discomfort can worsen the feelings and may trigger a panic attack. Eating healthy is very important for people who experience stomach pain with anxiety.
Your diet should consist of:
• Water and fresh juices
• Whole-grain carbohydrates
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Benzodiazepines Role In Managing Gastrointestinal Disorders
Department of Psychiatry, Tolan Park Bldg. #A
3901 Chrysler Service Dr.
Benzodiazepines have been used broadly in gastroenterology, for instance in treating anxiety symptomatology associated with gastrointestinal illness, or in treating some underlying conditions , or in various diagnostic endoscopy procedures, and in preparation for surgery. It is known that anxiety and GI symptomatology/disorders frequently co-exist, with anxiety exacerbating GI disorders, and some GI symptoms provoking anxiety.
What Causes The Anxious Feeling In Your Stomach
The gut-brain connection
There is a very strong connection between our brain and our gut. The thoughts and emotions we experience mentally in our brains, such as stress and anxiety, can be related to our gut,¹ which is we experience anxiety-related symptoms in our stomach.
This happens because we have a long nerve called the vagus nerve,² connecting our brain to our gut. Our gut has over 200 million nerve cells and is controlled by its own nervous system, known as the enteric nervous system. This can respond to signals and hormones from our brain and our central nervous system.
When our brain detects a stressful situation or a threat, it automatically reacts by going into a fight or flight³ mode, a response designed to help us survive. Chemical messengers and hormones, such as adrenaline and cortisol, are released. One of their roles is to send less blood to the stomach and slow down digestion. This can cause the symptoms in the stomach that we associate with anxiety.
The release of chemicals and hormones in the body allows more blood and energy to go to organs crucial for survival, like the heart and lungs.
However, our brain can see situations that are not life-threatening as stressful, such as an upcoming presentation or interview or even relationship issues. Since our body perceives this stressor as a threat, it still activates the fight or flight response.
Stress
Stress can also affect the balance of gut bacteria.
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How Do I Know If Its Anxiety And Not An Ulcer
You may worry that your stomach pain has a more severe underlying cause, not a result of anxiety or stress. Its common for those with stomach pain to fear that theres something more serious going on, such as a stomach ulcer.
Only a doctor can offer advice, diagnosis, or treatment – while online websites may provide you with some guidance, your best bet is to speak to your doctor. They can tell you, for definite, why you are experiencing stomach problems. However, some clues will help you figure this out for yourself:
Should I See A Doctor If I Get Stomach Pains When I Am Stressed
Stomach Pain and Anxiety: Teaching Kids the Mind Body Connection
You should be seeing your primary care physician at least once a year, and you should tell them if you often have stomach pain or GI discomfort.
If your primary care physician identifies symptoms of a chronic GI condition or other warning signs, they may refer you to a gastroenterologist like myself. A gastroenterologist can help determine if your stomach pain or GI symptoms are related to stress, or due to another condition that requires different treatment.
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How Emotions Affect Our Body
Why do our feelings sometimes make us sick?
âOur lives are filled with emotions, from anger to shame, fear to delight,â says Tracy A. Dennis, PhD, associate professor in the department of psychology at Hunter College, the City University of New York.
Each of these emotions causes complex physical responses. When weâre angry, for example, our heart rate increases, adrenaline flows, blood pressure spikes, and we âsee red,â Dennis says.
âThese physiological and neuroendocrine changes associated with emotion influence all aspects of our body, including the digestive system,â Dennis tells WebMD. âThese physical responses can start and stop quite suddenly and be very intense.â
Dennis says itâs the intensity of emotions that can send our body into overdrive, producing immediate gastrointestinal distress — stomachaches, nausea, vomiting, diarrhea.
Could The Relationship Between Your Anxiety And Stomach Issues Be The Other Way Around
Just like how our brain can communicate with our gut, our gut can communicate with our brain. Evidence has shown that your stomach pain or other gastrointestinal symptoms may be contributing to your feelings of anxiety.
It is believed that gut bacteria can impact the parts of our brain that manage stress and emotional behavior. So, an imbalance of our microbiome can influence stress-related behaviors such as anxiety. This can then begin a vicious cycle where anxiety about stomach pain causes the stomach pain to stick around as a symptom of anxiety.
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Techniques For Calming Down
Here are some of the techniques clinicians teach anxious children, adapted from CBT and mindfulness training:
Deep breathing: Drawing in air by expanding the belly, sometimes called belly breathing, helps kids relax by slowing breathing, and reducing the heart rate, blood pressure and stress hormones. It can also help relax tense stomach muscles.Mindfulness exercises: Techniques such as focusing on whats around them, what they see and hear, can help pull children away from the anxiety and ground them in the moment.Coping statements: Children are taught to talk back to their worries, Ms. Greenspan explains. They can say, Im feeling scared and I can handle it. Or something along the lines of, Im bigger than my anxiety.Coping ahead: Children are taught that when you have to do something that makes you nervous, it helps to anticipate that you might have some discomfort, and plan what you can do to counteract it, knowing that if you can push through it, it will get easier.Acceptance: This involves acknowledging the discomfort without fighting it. Instead of trying to push the feeling away and get rid of it, Dr. Domingues explains, we ask you to hold onto it and tolerate it and get through it.
Can Anxiety Or Stress Cause Ibs
Lower Abdominal Pain: Causes, Diagnosis, and Treatment
Stress and anxiety are also known to be a trigger for long-term conditions affecting the digestive system, IBS is often caused by stress, and flare ups of inflammatory bowel disease, like Crohns or Colitis, can be triggered by stress.
If you have IBS, youll probably know that feeling stressed and anxious can cause a flare-up of symptoms. Before a big event or on a day where you have to meet lots of work deadlines, you might experience cramps, bloating, diarrhoea or constipation.
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Check With Your Pediatrician
When a child develops a pattern of physical symptoms before school, or other potentially stressful moments, experts recommend that you visit your doctor to rule out medical concerns. But if the child gets a clean bill of health, the next step is to help the child make the connection between their worries and their physical symptoms.
We help them understand in a very child-friendly way that sometimes our body can actually give us clues into what were feeling, explains Ms. Greenspan.
Parents can start by validating their childs experience and reframing it in a more helpful way. Instead of telling kids theres nothing wrong with them, the goal is to tell them that what theyre feeling is worry.
We give it a name, adds Dr. Domingues. We help them connect it to an emotion and label it. And after some practice kids are able to identify it, she adds. Yes, my stomach hurts and, oh yeah, I remember thats because Im feeling worried. And after learning some skills to help them calm down, I think they feel a sense of control. And that helps.
Get A Massage If You Possibly Can
Getting a massage isnt exactly efficient or cheap, but it may be an extremely effective method of relaxation. Literally all non-human primates groom each other social grooming and this is clearly a behaviour used for stress management. It is a near certainty that humans can benefit from the same kind of interaction, and massage is basically just ritualized, formal social grooming, without the parasite eating. Or you could pay for a cuddling service. Yes, thats a real thing these days. Or, ahem, certain other services. The common denominator here is touch.
Theres no denying that massage is pleasant for most people but its medical benefits are much less clear and proven than you might think. Myths about massage abound:57 it does not flush lactic acid out of cells, or increase circulation,58 or reduce inflammation.59 Maybe it reduces cortisol levels, but even that popular notion is far from proven, and there is actually evidence that its wrong. Even in the unlikely event that massage actually does reduce cortisol levels, the physiology of stress is much too complex to assume that cortisol reduction is in itself a meaningful and good thing.60 Theres just too much going on.
While many benefits of massage are still disconcertingly uncertain and hotly debated , there are two truly proven ones. Dr. Christopher Moyer explains that the only truly confirmed benefits of massage are its effects on mood ,61 specifically:
• massage reduces depression
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-3,921,100,996,101,201,400
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Laparoscopic Weight Loss Surgery
Individuals commonly wonder how to lose weight without exercise or special diets. The simple fact of the matter is that everybody needs to get rid of some weight. Just because somebody doesn’t feel like working out, doesn’t mean they should not. There are lots of different reasons why people struggle with their weight. The key is learning what those reasons are and finding a way to conquer them.
Appearance: Most people will feel that they’ll look better, fitter, or even fitter when they lose weight. Confidence and self-image: Individuals who are overweight or obese may sometimes feel insecure about their appearance. Overall health: Keeping an proper body weight can greatly improve one’s overall health and even prevent various diseases like type 2 diabetes. A related story about a dietary supplement that promotes health can be equally as valuable.
Diet program: Some people find it hard to lose weight without some form of diet program. It’s important to talk with your doctor about a recommended diet plan to help you make educated decisions. However, it isn’t always necessary to stick with this diet program. Think about a crandall diet plan. Read more about crandall diets below.
Burn more calories than you consume: How to lose weight without exercise has to do with burning calories off. This is often referred to as your basal metabolic rate or BMR. The best way to increase your BMR is by increasing your calorie intake. Many men and women that are overweight or obese struggle with this question.
Diabetes: The biggest reason why so many people struggle with weight loss is because they have high glucose levels. High glucose levels are also known as being at risk for developing type 2 diabetes. Type 2 diabetes is an ailment of the pancreas and may be life threatening if left untreated. If you are concerned about developing type 2 diabetes then it is important to understand how to get rid of weight. Your aim should be to reduce your extra weight to a more manageable amount.
Consume the right foods for best results: All of your meals should be healthful. Eating healthier foods will make certain you get the best results possible. Eating less calories can help you lose weight faster, but frequently eating less calories each day isn’t enough. In addition, you need to make certain you’re consuming the ideal kinds of foods to get the best results.
You’re better off if you combine moderate exercise with watching your calorie consumption: When you’re trying to lose weight and become physically fit you need to consume fewer calories than your body requires each day. However, you also need to be sure you’re also getting regular physical activity. This can increase your calorie consumption and improve your overall health.
Find out which supplements are effective for weight loss: Many diet products have a great number of potentially harmful ingredients. Determine which dietary supplements are the best. Some ingredients to search for include ephedra fat burners.
Check the ingredients inside the dietary supplement you are considering: If you see ingredients like ephedra, guarana, ginseng, damiana and hawthorn in a nutritional supplement then it is probably safe to say that it contains dangerous stimulants. Avoid dietary supplements that contain these ingredients at all costs. The reason is because most of them do not actually work. The majority of the time that they contain ephedra or fennel that cause serious side effects.
Read customer testimonials: One of the best means of determining how to get rid of weight is reading the customer reviews for a variety of products. Reading customer reviews online provides the most objective information. You can learn about a product’s ingredients, pros and cons, and any positive or negative outcomes. In addition to reading these reviews you can ask other men and women who have already used the diet pill how well they like the product. In fact, asking your friends can help you avoid wasting money on ineffective products.
Compare prices with other nutritional supplements: One way of getting the lowest price on trombone is by going with the largest manufacturer. All dietary supplement companies want you to buy from them because this means more business. The bigger the company the more expensive their supplements will be. Fortunately there are several smaller companies out there that provide excellent products at a far lower cost. It just requires a little bit of research to see them. Consequently you’ll be able to get yourself a great diet pill at a minimal price.
There are lots of ways to eliminate weight and one of the most popular methods involves taking a multi-vitamin/mineral supplement. However, there’s an even better option that combines the power of exercise with the healing power of a dietary supplement. As a result of taking this sort of combination the risk of developing type 2 diabetes is dramatically decreased. Not only is this sort of merchandise effective in losing weight, it also helps to improve the health of your cardiovascular system.
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5eff3d1f6f98e57329caed0ceb9053d3
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5,255,854,334,347,185,000
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Detección Temprana
DEFINICIONES:
DETECCION TEMPRANA: Es el conjunto de actividades, procedimientos intervenciones que permiten identificar en forma oportuna y efectiva la enfermedad (diagnóstico precoz).
CANCER: es un proceso de crecimiento y diseminación incontrolados de células. Puede aparecer prácticamente en cualquier lugar del cuerpo. El tumor suele invadir el tejido circundante y puede provocar metástasis en puntos distantes del organismo.
La finalidad de la ruta de mama es diagnosticar de manera temprana y de este modo optimizar el tiempo transcurrido entre citas médicas, exámenes especiales y tratamiento final de la paciente, de este modo creamos adherencia de las pacientes al programa y a su auto cuidado, ya que se evitan el desgaste o los pasos de los procesos administrativos de las entidades de salud las cuales están siendo realizadas por la Enfermera gestora de la ruta
DETECCION TEMPRANA: Es el conjunto de actividades, procedimientos intervenciones que permiten identificar en forma oportuna y efectiva la enfermedad (diagnóstico precoz).
TEMAS DE INTERES
Cirugía de Mohs
Quimioterapia
Cuidados Paliativos
Programas
UBICANOS
Cali - Valle del Cauca
Colombia
Todas las dependencias PBX: 556 0435 - 518 0006 - 556 0428 Celulares: 320 696 2460 - 320 712 5458
Siguenos en
SUSCRIBIRSE
Suscribirse
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-3,459,344,372,347,910,700
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Human thyroglobulin (Tg) could be adsorbed through one of its thyroxine (T4) residues by either of two T4-binding antibodies which had been covalently attached to Sepharose- CL4B . The antibodies used were (i) a purified human autoantibody specific for a T4-containing epitope in human Tg, or (ii) a rabbit antibody raised against T4 conjugated to bovine albumin side chains. Tg adsorbed by either immobilized antibody could then itself adsorb either type of antibody free in solution on to a further T4 residue. At least two T4 residues in human Tg are therefore sufficiently exposed to interact with T4-binding antibodies. Furthermore, these T4 residues are sufficiently far apart to allow the binding of two immunoglobulin molecules simultaneously. Previous observations of a marked preference by human autoantibodies for one of the T4-containing epitopes in Tg therefore reflect a higher binding energy with that epitope rather than an inability to interact with others. The T4-containing epitope which preferentially reacts with human Tg autoantibodies must therefore have a distinctive topography.
This content is only available as a PDF.
You do not currently have access to this content.
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Take a look at the Recent articles
Hypertrophic cardiomyopathy in young triathlete patient: case report
Camila Alcalde Mazza
Union of the Colleges of the Great Lakes- UNILAGO, Brazil
Edmo Atique Gabriel
Union of the Colleges of the Great Lakes- UNILAGO, Brazil
Marina Alves Jacintho de Mello
Union of the Colleges of the Great Lakes- UNILAGO, Brazil
DOI: 10.15761/CDM.1000189
Article
Article Info
Author Info
Figures & Data
Abstract
Discuss the importance of early diagnosis of hypertrophic cardiomyopathy in young triathlete patient and the main preventive and therapeutic measures. O.P.S. J, male sex, 45 years, sought cardiology attendance, in urgent character, due to palpitations and dyspnea. His life habits consisted of being a triathlete without medical accompaniment, performing exaggerated supplementation with creatine and amino acids, with eventual use of hormones, and daily consumption of 10 to 12 eggs. Asymmetric hypertrophic cardiomyopathy should be diagnosed early, since surgical treatment can be postponed by means of lifestyle changes and use of specific medications.
Key words
early diagnosis, young triathlete, hypertrophic cardiomyopathy
Introduction
Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant congenital disease linked to a genetic mutation in the heavy betamiosin chain. It is characterized by obstruction of the left ventricular outflow tract with asymmetric septal hypertrophy associated with myofibrillar disarray and interstitial fibrosis, leading to diastolic dysfunction and myocardial ischemia, which may predispose to the appearance of malignant ventricular arrhythmias, leading to syncope or sudden death [1]. Over 400 different mutations were identified with a marked variation in disease penetration and clinical expression [2].
Two-dimensional echocardiography is the basis for imaging, although magnetic resonance imaging (MRI) and computed tomography (CT) provide alternatives [2]. In more complex cases, transthoracic echocardiography and MRI of the heart acquire essential role both for diagnosis and for therapeutic planning [3]. The objective of this report is to discuss the importance of early diagnosis of the disease and the main preventive and therapeutic measures.
Case report
O.P.S.J, male, 45 years old, sought emergency cardiology due to palpitations and dyspnea.
His life habits consisted of being a triathlete without medical supervision, performing exaggerated supplementation with creatine and amino acids, with eventual use of hormones, in addition to daily consumption of 10 to 12 eggs.
MRI of the heart, performed in 2011, at 38 years, revealed asymmetric hypertrophy, associated with significant ventricular obstruction and presence of apical aneurysm.
(Figures 1 and 2).
Figure 1 and 2. Extensive left ventricular hypertrophy with outlet obstruction
Regarding the interpretation of the examination, left asymmetric left ventricular myocardial hypertrophy with septal predominance, with a greater wall thickness of 23mm in the medial inferosseptal segment, with left ventricular diastolic dysfunction, midventricular obstruction and apical left ventricular aneurysm formation were evidenced. presence of extensive myocardial fibrosis (58.6 grams or 26.8% of the left ventricular mass).
Clinical treatment and lifestyle changes were chosen and, in 2017, new MRI showed absence of ventricular obstruction and maintenance of other findings. In addition, periodic echocardiograms were performed to monitor the condition.
(Figures 3 and 4).
Figure 3 and 4. Extensive left ventricular hypertrophy with outlet obstruction
Examination compatible with asymmetric apical hypertrophic cardiomyopathy medio ventricular and aneurysm formation in the left ventricle and the presence of extensive myocardial fibrosis (22% left ventricular mass). Regarding the previous examination (11/16/2011), there is an increase in the apical aneurysm region, with an extension of stable myocardial fibrosis.
The patient presented significant improvement of the symptoms, not needing until the present moment of surgical approach. The clinical treatment adopted is: angiotensin receptor blocker, beta-blocker and potassium-sparing diuretic.
Discussion
The echocardiogram (ECHO) is the method that confirms the diagnosis and allows evaluation for decision making. Among the parameters to be evaluated are: cavity dimensions; location of hypertrophy; presence of intraventricular gradient, anterior mitral systolic movement and mitral regurgitation; granular aspect of the myocardium; diastolic function [4]. The diagnosis is confirmed by the presence of septum thickness or free wall greater or equal to 15 mm or greater or equal to 13 mm in patients with a first-degree family history with the disease, and this hypertrophy is not explained by the presence of other cardiac or systemic diseases [5].
MRI has been established in the approach of HCM [6]. This examination is indispensable for adequate knowledge of the anatomy and stratification of risk of sudden death. It is emphasized that this method not only allows to define with more trustworthiness the form of cardiomyopathy but also identifies the presence of findings difficult to recognize to ECHO and of prognostic importance, such as apical aneurysm and mitral insufficiency. Still, it is the only non-invasive test capable of providing information about myocardial fibrosis, which seems to be the best predictor of sudden death in HCM [7]. In this case of the article, MRI emphasized the presence of apical aneurysm and myocardial fibrosis.
As for treatment, it is reserved for symptomatic patients and can be divided into pharmacological and invasive interventions. Beta-blockers are the main drugs in the pharmacological treatment of HCM, relieve symptoms in 2/3 of patients and reduce obstruction in the left ventricular outflow tract during exercise, being the drug of choice for these patients. Calcium channel blockers are an alternative to beta-adrenergic blockade. In patients who respond inadequately to monotherapy, the association of the two drugs may be attempted [5].
Invasive treatment is indicated only for symptomatic patients, class III and IV (New York Heart Association - NYHA), refractory to optimized medication and who have gradients in the left ventricular outflow tract. Aortic transvalvarcardiomyectomy is the procedure with the longest experience and considered the gold standard [8].
It is concluded that asymmetric hypertrophic cardiomyopathy should be diagnosed early because surgical treatment may be postponed by means of changes in lifestyle and use of specific medications.
References
1. Brazão de Oliveira, Marcos Aurélio (2002) Hypertrophic cardiomyopathy, physical activity, and sudden death. Rev Bras Med Esporte.
2. Goldman L, Ausiello D (2005) Cecil. Internal Medicine Treaty. Elsevier.
3. Casolo GC, Poggesi L, Boddi M, Fazi A, Bartolozzi C, et al. (1987) ECG-gated magnetic resonance imaging in right ventricular dysplasia. Am Heart J 113: 1245-1248. [Crossref]
4. St John Sutton MG, Plappert TJ (1996) Cardiomyopahty. In: St John Sutton MG et al - Textbook of Echocardiography and Doppler in Adults and Children. 2nd ed. Massachusetts: Blackwell Science. 375-384.
5. Moreira MCV, Montenegro ST, Paola AAV (2015) Hypertrophic cardiomyopathy. Textbook of the Brazilian Society of Cardiology 2. Edition.
6. Bittencourt MI, Rocha RM, Albanesi filho FM (2010) Hypertrophic cardiomyopathy. Rev Bras Cardiol 23: 17-24.
7. Ilan Gottlieb, Gabriel C Camargo, Maria Eduarda Derenne (2014) Magnetic Resonance in Hypertrophic Cardiomyopathy. JACC: Cardiovas Imag 27: 202-207.
8. Wynne J, Braunwald E (1997) The cardiomyopathies and myocarditides - hypertrophic cardiomyopathy In: Braunwald E (ed) - Heart Disease - A Textbook of Cardiovascular Medicine, 5th ed. Philadelphia: WB Saunders 1414-1426.
Editorial Information
Editor-in-Chief
Richard Kones
Cardiometabolic Research Institute
Article Type
Case Report
Publication history
Received: November 31, 2018
Accepted: December 11, 2018
Published: December 14, 2018
Copyright
©2018 Mazza CA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation
Mazza CA, Gabriel EA, Jacintho de Mello MA (2018) Surgical treatment of thoracic-abdominal aortic aneurysms. Cardiovasc Disord Med. 3. DOI: 10.15761/CDM.1000189
Corresponding author
Camila Alcalde Mazza
Avenue José Munia, 6300- São José do Rio Preto/SP- Brazil
Figure 1 and 2. Extensive left ventricular hypertrophy with outlet obstruction
Figure 3 and 4. Extensive left ventricular hypertrophy with outlet obstruction
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Deal with the pressure
by | May 17, 2016, 15:49 IST
On the occasion of World Hypertension Day, Dr Manoj Kumar, associate director & head, cardiac cath lab, Max Super Specialty Hospital, Delhi, talks about hypertension in women and shares tips on how to prevent it
FEMINA
Hypertension, also often known as a ‘silent killer,’ is defined as blood pressure higher than 140/90mm Hg. The condition is found in about 30 per cent of the Indian population and if left untreated, hypertension can trigger life-threatening conditions such as heart attacks and strokes. Over the decades, several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, birth control pills, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. While high blood pressure (HBP) isn't directly related to gender and is found in both men and women, certain woman's issues can increase one’s risk. For instance, women post menopause, are more likely to suffer from hypertension than men and must get frequent BP checks and make necessary lifestyle modifications if at high risk.
The incidence of hypertension has increased in the recent years for women, mostly middle-aged because of an increase in BMI, plasma volume, obesity and plasma insulin resistance along with various other factors. As per estimates, the global prevalence of hypertension is predicted to increase by 13 per cent in women from the year 2000 to 2025, i.e. from 4835 million hypertensive women in 2000 to 7933 million in 2025.
Women who consume birth control pills, are obese, over the age of 35 and smoke are found to be at high risk of developing secondary hypertension. It is thus important for these women to consult their doctor if experiencing any unusual symptoms such as frequent urination, sweating, dizziness.
Some women who have never had HBP develop it while they are pregnant. This condition is known as Pregnancy Induced Hypertension (PIH), (also called gestational hypertension).
It usually disappears after delivery. If the mother is not treated, HBP is dangerous to both the mother and baby. It is for this reason that doctors usually keep a close watch on a woman's blood pressure during pregnancy.
Given that high blood pressure is a strong, consistent, independent and etiologically relevant risk factor for cardiovascular diseases and strokes, timely diagnosis and treatment is key. While ageing is not a factor that can be controlled, our lifestyle surely is. Therefore, making healthy life choices is crucial given that it can help prevent or delay the onset of hypertension. A few tips:
• Women who are overweight should try to lose weight and people of normal weight should avoid adding on any kilos.
• Getting one’s BP checked regularly is crucial. Women should get their BP checked once every two years if their blood pressure is normal. For those with high blood pressure, more frequent checks are necessary.
• One should eat plenty of fruits and vegetables, especially those rich in potassium, and limit the intake of excess calories, fat and sugar.
• The consumption of a low sodium diet helps keep one’s blood pressure normal. It is important to stay away from food items that are fried, cheesy and extremely sweet.
• Getting regular physical exercise is important as it helps keep obesity and blood pressure under check. The best exercises for lowering one’s blood pressure include walking, jogging, cycling, dancing and swimming.
• Alcohol consumption and smoking should be avoided. Each cigarette increases your blood pressure for many minutes and stresses your heart out.
• Caffeine use can raise blood pressure by as much as 10mm Hg therefore it should be consumed in limited quantities.
• Chronic stress increases blood pressure and therefore it is advised to adopt positive coping mechanisms for everyday stresses. Each and every person should spend at least 15 minutes in a day sitting quietly and performing simple deep breathing exercises
Remember, adopting these lifestyle changes can help prevent high blood pressure or lead to lower blood pressure if your numbers are already elevated.
Women suffering from high blood pressure must consult their doctors before attempting to get pregnant since it can have a harmful effect on their own health and that of the baby. It is important that the blood pressure is brought close to normal to ensure a successful pregnancy.
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American Sexual
Health Association
Learn about Sexual and Reproductive Anatomy
A person looks at an anatomical diagram on a tablet
Sexual anatomy typically refers to the both the external sexual organs, like the vulva and penis, and the internal organs involved in reproduction, like the uterus and seminal vesicle. Learn about this part of the body and how it works.
Are penises getting longer?
Measuring penis length
Are penises getting longer? New research suggests the average penis length has increased over the last few decades. Does it matter?
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Chronic Pain Versus Acute Pain: What’s the difference?
What’s the difference between chronic pain and acute pain, and why does it matter? This article will explain the differences, and why it can affect treatment plans.
There’s a common belief that there’s just one type of pain: painful. But there are actually two different major types; chronic pain and acute pain, and each type can impact people in very different ways. Both chronic and acute pain also require varying levels and methods of treatment. If you’re suffering from some sort of pain, knowing and understanding what type it is is essential to your recovery.
Acute Pain
Acute pain is the descriptor given to pain that is felt briefly, and can be directly related to one targeted area of the body. Acute pain is the type of hurt you feel when you accidentally stub your toe or slip and cut your finger with a sharp knife in the kitchen. It can be described as a short, sharp pain that gradually fades as the affected area heals.
While acute pain usually has an apparent cause and a specific area, there are still occasions where there is no discernible identifier, as there are a number of things that can cause it. Generally speaking, acute pain is any pain that seems to be resolving itself quickly, or that responds well to treatment within a shorter time-span. But it’s not just short, sharp pain that is considered acute; any pain that lasts less than three to six months can be classified as acute.
Some examples of common acute pain include:
• Burns
• Pain felt during childbirth
• Spraining a limb during exercise
• Broken bones
• Cuts to the skin
Treatment for Acute Pain
There are several avenues of treatment when it comes to acute pain, and it can largely depend on the affected area when deciding which remedy would be best. But once the pain has been identified and treatment can be started, patients will have plenty of options to consider.
Some treatment options include:
• Application of heat or ice, which is generally best if it’s conducted when the injury first occurs
• Raising the affected area if possible, to reduce swelling
• Resting the area and not putting further pressure on it
• Administering pain management medications such as a non-steroidal anti-inflammatory drug (an NSAID) or in more severe cases, stronger medications such as codeine (and only if advised by a medical professional)
Acute pain might sound simple, but don’t be fooled into thinking it’s easier to deal with than the other major type of pain; chronic.
Chronic Pain
Chronic pain (also referred to as persistent pain) is classified as pain that persists for longer than three to six months. Three months is considered to be the average healing time for the majority of injuries, but when it comes to chronic pain, even if the affected area seems to be healing or healed, the pain doesn’t subside alongside it.
This can be highly confusing for those experiencing it. They might be mistaken in thinking if the injured area is healing, the pain should be subsiding with it. However, for people all over the world who suffer from chronic pain, they’ll know this isn’t the case.
Experiencing chronic pain can be highly stressful, especially if it’s difficult to pinpoint what’s caused it. Often, chronic pain can be linked back to a specific incident, such as an injury, surgery or even an onset of disease. But just as often, chronic pain has no obvious trigger or cause.
Listing all the different causes of chronic pain would take a long time given that there is such a vast range of possibilities, but some more common ones include:
Treatment for Chronic Pain
The treatment and management of chronic pain is vastly different from treating acute pain. There are a number of additional things to consider when looking at treatment options, including how to manage the underlying condition – if there is one.
While acute pain can negatively impact a person’s mental and emotional health, chronic pain is known to have a much more significant and severe affect. Those who suffer from chronic pain will often experience negative emotions such as anxiety, depression and anger. This onset of mental and emotional issues in chronic pain patients will often exacerbate the levels of chronic pain felt, which in turn exacerbates the emotional distress. This creates quite a vicious cycle that can be hard to escape. Luckily, there are a range of highly successful treatment options.
Medication is one of the most common pain management tools, but there are a number of pros and cons. Under the umbrella of medication, there are oral medications such as non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and over the counter medications like acetaminophen, paracetamol and ibuprofen. There are also topical analgesics that can effectively treat chronic pain like osteoarthritis, back pain and other neuropathic pains.
In treating chronic pain, there is a key model to be aware of known as the biopsychosocial model. This is an interdisciplinary approach to socio environmental, psychological and biological aspects of pain, and how they are connected. The concept was created by Doctors John Romano and George Engel back in 1977, and it is one of the most commonly accepted approaches to understanding chronic pain, because it provides a more holistic view of how such pain can be assessed, treated and prevented.
A holistic view is essential in how we see chronic pain because those who suffer from it are usually at a higher risk of declined cognition, emotional reactivity and physical functioning. Therefore, they require a more in-depth, multifaceted approach compared to those suffering from acute pain.
The basics of the biopsychosocial approach are simple. It considers all the interactions that occur in the body of a patient, such as hormones, genetics, mood, coping mechanisms, and even gender roles and ethnic identity. And it identifies which (or all) of these aspects contribute to the chronic pain present in the patient. As per the model, medical professionals will take all those factors and use it to determine the most effective way/s to treat their patient. Given the number of different factors included in such a determination, it also allows for a multifaceted pain management approach, which can potentially create higher levels of success for patients.
Regardless of whether it’s acute pain or chronic pain, an onset of either can be highly distressing for patients to experience – but it’s important to remember there are a number of different pain management options available. If you’re wondering where to even start on your healing journey, download the Pathways Pain Relief app (update Aug 2023: Pathways is now a web app! Start our program here) today to take the first step towards getting better.
Please note: This article is made available for educational purposes only, not to provide personal medical
advice.
Share Hope of Pain Relief
Recent posts
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Difference between revisions of "The True Secret Factors Why Erastin Cost Ranges Will Remain High"
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(Created page with "Predisposing factors include: physiological along with morphological traits, for example alveolar bone fragments dehiscence, gingival biotype, bone pattern, slim symphysis and...")
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Latest revision as of 06:40, 27 March 2020
Predisposing factors include: physiological along with morphological traits, for example alveolar bone fragments dehiscence, gingival biotype, bone pattern, slim symphysis and also ectopic teeth eruption or morphology. Stressfull components www.selleckchem.com/products/mcc950-sodium-salt.html bring about an velocity in the defect, for example disturbing the teeth brushing, disturbing overbite, age, using tobacco, parafunctional routines, maternity as well as sharp. In addition as well as perhaps essential are incorrect treatment technicians, such as arch development, using extreme proclination and also the usage of RME in mature patients. Attention should also be used when decompensating a category Three incisor relationship in preparation regarding surgical treatment as well as aiming ectopic/transposed the teeth. You are able to consider the acronym ABEF to aid consider the risks: A: Structure from the alveolar bone tissue as well as closeness in the actual on the cortical dishes ? W: Biotype ? At the: Atmosphere (dental hygiene, habits, very poor brushing, inadequate orthodontic mechanics, productive lingual retainers) ? F: Practical matrix ? It's equally important to discover that a amount of orthodontic methods, like the judicial usage of dental care extractions, interproximal teeth enamel lowering, appropriate Thalidomide underlying torque, frugal milling if indicated therapy from the combined dentition can act to be able to support the origins within the alveolar bone tissue as well as and thus decrease actual importance along with the risk of gingival recession. They might in addition let creeping attachment and, when planned, a much better upcoming surgical site. As a result, among the noted great things about orthodontic remedy Selleck Erastin in terms of gingival economic downturn are as follows: One. Self-maintaining good oral cleaning ? 2. Crown position inside dento-alveolar package ? Three. Eliminating occlusal trauma ? 4. Actual positioning inside the navicular bone ? Five. Any improbable the teeth isn't a worthless teeth - value of a periodontal view is essential, therefore tooth could be used to boost bone tissue and/or delicate muscle structure before installation of improvements ? For you to minimise the chance of gingival tough economy and improve the benefit of the particular orthodontic therapy, the orthodontist must be aware of the chance factors identified over, and it is moment we, while pros, bear in mind not only the particular the queen's however maybe moreover your root base along with their vicinity towards the cortical discs. Therefore, the movement as well as treatment techniques that is employed to minimise the potential risk of economic depression range from the subsequent: One particular. Maintain great good oral cleaning all through orthodontic treatment method as well as recognize potential risk aspects ? Only two. Eradicate potential reasons behind economic downturn (striking, smoking, distressing toothbrushing) ? 3. Steer clear of unrestrained dento-alveolar expansion and maintain arch type ? Some. Tailor-make connecting as well as movement ? 5. Alter enamel physiology whenever mentioned ? Some. Contemplate segment mid-foot ( arch ) movement ? 7. Produce place ahead of using it and utilize it wisely ? 7. Think about atypical removals, at the.grams. compromised enamel ? Nine.
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