Friday June 23, 2017

Articles:225


5

November 23

Cytokines

Cytokines are not usually stored as preformed molecules, and their synthesis is initiated by new gene transcription as a result of cellular activation. Such transcriptional activation is transient, and the messenger RNAs encoding most cytokines are unstable and often rapidly degraded, so cytokine synthesis is also transient. Once synthesized, cytokines are rapidly secreted, resulting in a burst of release when needed… Cytokines share many other general properties. One cytokine can act on diverse cell types and have multiple biologic effects, a property that is referred to as pleiotropism… Most cytokines act close to where they are produced, either on the same cell that secretes the cytokine (autocrine action) or on a nearby cell (paracrine action). When produced in large amounts, cytokines may enter the circulation and act at a distance from the site of production (endocrine action). Tumor necrosis factor (TNF) is an example of a cytokine that has important local and distant (systemic) effects. 


November 13

US Pharmacopeia Council of Experts

United States Pharmacopeia Development of the Medicare Model Formulary Guidelines

Leonard Bielory, M.D. - Member of U.S. Pharmacopeia Council of Experts

Prescription drug formularies are a key element in prescription drug benefit management. The use of formularies can both increase the quality of prescribing and reduce the costs of prescription drug therapy. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 specified that an external agency, the United States Pharmacopeial Convention, Inc. (USP) through the Secretary of the United States Department of Health and Human Services develop model formulary guidelines for prescription drug plans. The model formulary guidelines are to assist individual drug plans in developing formularies that would qualify for participation in the Medicare Part D prescription program. The guidelines were developed through a Model Guidelines Expert Committee assisted by USP staff and following input from patient advocate groups, health care organizations, and pharmaceutical organizations over a period of 8 months (April 2004 to December 2004). The USP Model Formulary Guidelines organize prescription medications into 41 therapeutic categories (32 with associated pharmacologic classes and nine with no associated pharmacologic classes), 137 pharmacologic classes, and 146 unique therapeutic categories and pharmacologic classes.

United States Pharmacopeia Development of the Medicare Model Formulary Guidelines (pages 301–307)

Leonard Bielory


November 12

Raynaudís Disease or Phenomenon

A 43-year-old woman reports that her fingers turn blue and tingly when they are exposed to cold temperatures. She also has had recent complaints of fatigue and joint pain (arthralgia).

 

The clinical problem

In 1862, Maurice Raynaud recognized that some people who were exposed to cold temperatures had transient digital ischemia, temporary lack of blood flow to the fingers, that he had described as an exaggerated response of the central nervous system. The term “Raynaud’s phenomenon” (RP) is now used to describe these episodic events that represent constriction of the blood vessels supplying the arteries, precapillary arterioles, and cutaneous arteriovenous shunts in the fingers.

The ischemic phase of the attack is evidenced by the appearance of a demarcated pale or cyanotic skin, limited to the digits. It typically starts in one or several digits after exposure to the cold, such as getting something out of the freezer or walking outside in the winter, or during a stressful situation. The involvement of several fingers typically spreads to all fingers of both hands. The attack usually ends with a rapid reflow of blood into the digit(s), which is manifested by erythematous skin (reactive hyperemia). In general, the prevalence of RP is less than 5%. Geographic variations in the prevalence reflect differences in climate with the frequency and severity of the attacks proportionately related to the daily ambient temperature. Clear exacerbations occur during the winter season. Approximately 80% of patients with RP who are seen by an internist are found simply to have an exaggerated physiologic response to cold temperatures. In a community-based survey that we distributed, more than 10% of participants responded affirmatively to the question: “Are either your fingertips or toes unusually sensitive to cold temperatures?” Cool skin and nondemarcated mottling of the skin of the digits, hands, and limbs are considered a normal response to exposure to the cold. RP should be distinguished from acrocyanosis, a condition characterized by continuous cyanosis of the hands or feet that is aggravated by cold temperatures, but is not pathologic. However, there is a small percentage of patients with RP that indicates a clinical manifestation of a serious underlying autoimmune disease such as scleroderma that may lead to critical ischemia of a digit or limb. This depends on the severity of the insult and the size of the blood vessel, and can result in just a superficial ulceration or a more problematic deep-tissue necrosis with gangrene, resulting in amputation.

The diagnosis of RP is made through a history of cold sensitivity with episodic pallor or cyanosis of the distal portions of the digits (or both). Photographs of the hands taken during an attack can be used to confirm the history (as seen in figures 1 and 2). Laboratory-based techniques to measure digital and cutaneous blood flow after a cold challenge can be used to distinguish patients with RP from cold-sensitive persons. These tests are complex and are generally not used clinically since they require a carefully controlled ambient temperature to provide meaningful data. Clinical criteria are used to distinguish patients with uncomplicated or primary RP from those with secondary RP – associated with various autoimmune disorders. The suggested criteria for primary RP are: symmetric attacks; the absence of tissue necrosis, ulceration, or gangrene; the absence of a secondary cause on the basis of a patient’s history and general physical examination; normal nail-fold capillaries; a negative test for antinuclear antibody; and a normal erythrocyte sedimentation rate.

The median age at the onset of primary RP is 14 years, and only 27% begin at 40 years or later. If a patient meets the criteria for primary RP and is followed for a two-year period without the development of clinical or laboratory signs, then secondary disease is highly unlikely (less than 15%).

The NIH Raynaud’s Treatment Trial that was led by Dr. Bielory and conducted at various sites throughout the United states including the New Jersey Medical School, Wayne State University, University of Pittsburgh, and Medical University of South Carolina in patients with primary Raynaud’s phenomenon (history of two or more attacks per day during the previous cold season) involved a randomized, controlled clinical trial, double-masked for drug and placebo but not masked for temperature and control biofeedback. Participants were randomized to one of four treatment groups: (1) sustained-release nifedipine; (2) pill placebo; (3) temperature biofeedback; or (4) control (electromyographic) biofeedback. Nifedipine is produced by Pfizer, Inc. The primary outcome measure – color chart-verified primary RP attacks during one winter month approximately one year after initiation of treatment – was self-reported. Secondary outcome measures included verified attacks at two months, all attacks at two months and one year, and quality of life.

The eight-year study concluded that temperature biofeedback is not better than its control treatment and is inferior to sustained-release nifedipine for treating primary RP. Sustained-release nifedipine (30 to 60 mg once daily) showed a 66 percent reduction in attacks and was a safe and effective treatment for this disease. Side effects resulted in the discontinuation of nifedipine in 15 percent of participants, and those who continued vasodilator therapy reported sustained benefit during the one-year follow-up. In addition, the study showed that stress was not a significant predictor of RP attack characteristics. Higher anxiety was related to more frequent attacks above 60º F and to greater attack severity at all temperatures, but no greater pain above 60º F, and between 40º and 49.9º F, was noted. A more detailed evaluation of specific cooling temperature effects showed that at the 15º C and 10º C local cooling temperatures, the patients in the nifedipine group had a higher mean digital systolic blood pressure, a higher relative digital systolic blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a smaller proportion of subjects with a zero reopening pressure than the patients in the three other treatment groups. These results were statistically significant at 10º C. The nifedipine group was significantly different from all others (p < 0.05). No significant difference was found between the three other treatment groups, suggesting that the use of the calcium channel blocker was able to maintain arterial pressure in the digital arteries to keep them open at lower temperatures. The ability to learn the desired physiological response was seen in only 35% of the temperature biofeedback group, and 55% of the EMG biofeedback group while 67% of a normal temperature biofeedback group were capable of learning hand warming, suggesting that the ability to warm hands decreased the incidence of RP.

The patient described at the beginning of this article most likely has primary RP and would probably do quite well using a chronic treatment plan with a long acting calcium channel blocker. She may develop a secondary autoimmune disease process associated with Raynaud’s phenomenon.

 

 

November 11

Rice source of Human Protein

The highly sought-after plasma protein, human serum albumin (HSA), can now be produced at high yield and purity in rice, according to a report published (October 31) in Proceedings of the National Academy of Sciences. Using the rice-derived protein in place of its blood-derived counterpart will not only ease demand but also eliminate the risk of spreading diseases.

HSA is used for a variety of clinical applications such as the treatment of blood loss, serious burns, and abdominal fluid retention caused by cirrhosis (scarring) of the liver. In addition, HSA has served as a vehicle for vaccine and drug delivery, and as a cell culture supplement in the production of vaccines and pharmaceuticals.


November 10

Allergy Free Recipes- Chocalate Strawberry pancakes

Chocolate Strawberry Pancakes

M, E, P, N

Ingredients:
1 cup whole wheat
1 T sugar
1 tsp. baking soda
1/4 tsp. salt
1/2 cup non-dairy semisweet chocolate chips (check labels for nuts)
1 cup soymilk
1 T canola oil
1 tsp. vanilla extract
3 strawberries, chopped

Directions:
Combine dry ingredients and chocolate chips. In separate bowl, combine soymilk, oil and vanilla extract. Add to dry mixture. Add strawberries; mix only until large lumps are gone. Pour 1/4 cup portions of batter onto hot, non-stick griddle or lightly oiled pan. Cook until bottom is light brown and bubbles form on surface. Flip and cook for an additional 1-2 minutes or until light brown on bottom.

Key:
M=Milk-free; E=Egg-free; W=Wheat-free; P=Peanut-free; S=Soy-free; N=Nut-free


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Location: Springfield, NJ
Today's Date: June 23, 2017
Station Director: Leonard Bielory, M.D
Site Administrator: info@nynjpollen.com