TooSogiE Health

VITAMIN E

2010-02-15T11:49:00.000-08:00

VITAMIN E

Other Names:
All Rac-Alpha-Tocopherol, Alpha-Tocopherol, Alpha Tocopherol Acetate, Alpha Tocopheryl Acetate, d-Alpha-Tocopherol, d-alpha Tocopherol, d-Alpha Tocopheryl Acetate, d-Alpha-Tocopheryl Acid Succinate, d-Alpha Tocotrienol, dl-Alpha-Tocopherol, d-Beta-Tocopherol, d-Delta-Tocopherol, d-Gamma-Tocopherol, d-Gamma Tocotrienol, Fat-Soluble Vitamin, Mixed Tocopherols, RRR-Alpha-Tocopherol, Tocopherol, Mixed Tocotrienols, Tocotrienol, Beta-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol, Alpha Tocotrienol, Beta Tocotrienol, Delta Tocotrienol, Gamma Tocotrienol, Palm Tocotrienols, Tocopherol Acetate, Tocopheryl Acetate, Tocotrienols, Vitamin E Acetate, Vitamin E Succinate.

Vitamin E exists in eight different forms ("isomers"): alpha, beta, gamma, and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Dosing and daily allowance recommendations for vitamin E are often provided in Alpha-Tocopherol Equivalents (ATE) to account for the different biological activities of the various forms of vitamin E, or in International Units (IU), which food and supplement labels may use. Vitamin E supplements are available in natural or synthetic forms. The natural forms are usually labeled with the letter "d" (for example, d-gamma-tocopherol), whereas synthetic forms are labeled "dl" (for example, dl-alpha-tocopherol).

Vitamin E is a fat-soluble antioxidant that stops the production of ROS formed when fat undergoes oxidation. [1] Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of the various antioxidants with vitamin E activity, only alpha-tocopherol is preferentially recognized by the alpha-tocopherol transfer protein (alpha-TTP) and is transferred to plasma, while the other vitamin E forms (e.g., gamma-tocopherol or tocotrienols) are removed from the circulation. Hepatic alpha-TTP is required to maintain plasma and tissue alpha-tocopherol concentrations. The liver is the master regulator of the body's vitamin E levels in that it not only controls alpha-tocopherol concentrations, but also appears to be the major site of vitamin E metabolism and excretion. Vitamin Es are metabolized similarly to xenobiotics they are initially omega-oxidized by cytochrome P450s, undergo several rounds of beta-oxidation, and then are conjugated and excreted. As a result of these various mechanisms, liver alpha-tocopherol and other vitamin E concentrations are closely regulated; thus, any potential adverse vitamin E effects are limited. [Traber MG, Annu Rev Nutr. 2007;27:347-62]

Vitamin E is an important component of our antioxidant system. It is considered a master antioxidant because: [Papas AM. The Vitamin E Factor, HarperCollins Publishers, Inc., New York, NY. 1999]

Tocopherols and tocotrienols are chain-breaking antioxidants – they break the chain reaction of lipid peroxidation, the process that turns lipid rancid.
The structure of vitamin E makes it unique and indispensable in protecting cell membranes. Vitamin E, primarily alpha-tocopherol, anchors itself strategically in the membrane with the hydrophobic (water hating) tail in the interior of the membrane. The hydrophilic (water loving) head is in the hydrophilic area of the membrane.
Vitamin E is the master inhibitor of oxidation of the bad cholesterol LDL - which is believed to be the first step in atherosclerosis.

Vitamin E is more than the master antioxidant, it has additional important functions. For example:

Vitamin E inhibits the activity of the enzyme PKC (protein kinase C) which is associated with inflammation.
Vitamin E exhibits anticoagulant properties. Oxidized alpha-tocopherol (called alpha-tocopheryl quinone) is also a powerful anticoagulant.
Vitamin E compounds reduce the production of inflammatory compounds such as prostaglandins.
Tocotrienols and gamma-tocopherol have other unique functions.

The main sources of vitamin E in the diet are vegetable oils (especially safflower oil, sunflower oil, and cottonseed oil), green leafy vegetables, nuts, cereals, meats, egg yolks, wheat germ, and whole wheat products. Vitamin E deficiency is rare and occurs almost exclusively in people with an inherited or acquired condition that impairs their ability to absorb this vitamin.

Table: Recommended Dietary Allowances (RDAs) for Vitamin E (Alpha-Tocopherol) [4]

* Adequate Intake (AI)

Table lists the RDAs for alpha-tocopherol in both mg and IU of the natural form; for example, 15 mg x 1.49 IU/mg = 22.4 IU. The corresponding value for synthetic alpha-tocopherol would be 33.3 IU (15 mg x 2.22 IU/mg).

Symptoms of vitamin E deficiency include muscle weakness, visual problems (especially at night), and a poor sense of balance. Over a long period, vitamin E deficiency may progress to blindness, heart disease, and impaired thinking. Supplements are usually only necessary or recommended for people with vitamin E deficiency or a condition that puts them at risk for this deficiency. [5] Possible Risks of Vitamin E Use include increased bleeding and inhibition of clotting function (if taken in excess of 1,000 mg/day). And, some studies indicate an increase risk of heart problems among people who are taking high doses of vitamin E (more than about 300 mg/day). Vitamin E has no known side effects when taken in moderate doses. It’s rare for anyone to be allergic to Vitamin E. But if you do experience a severe reaction (rash, itching, swelling, severe dizziness, trouble breathing) see a doctor immediately. [6]

Vitamin E, a potent peroxyl radical scavenger, is a chain-breaking antioxidant that prevents the propagation of free radical damage in biological membranes. Scientist consider the evidence for potential sites in cellular metabolism and signal transduction where vitamin E may have a structure-specific role in addition to its antioxidant function. The roles of tocopherol-binding proteins in cellular trafficking of vitamin E, especially the incorporation of RRR-alpha-tocopherol into nascent lipoproteins, and the delivery of RRR-alpha-tocopherol to the nucleus are considered. [7] Scientists are investigating whether, by limiting free-radical production and possibly through other mechanisms, vitamin E might help prevent or delay the chronic diseases associated with free radicals. [8]

Perhaps not surprisingly, vitamin E which has been touted to be potentially beneficial for a variety of disorders, including cancer, heart disease, and Other health benefits of vitamin E, based on its function as an antioxidant. [9] The most reliable studies on this issue are controlled clinical trials, such as a large 1994 study of antioxidant vitamins and cancer conducted by the National Cancer Institute (NCI) and the National Public Health Institute of Finland. The study was designed to find out whether antioxidant vitamins in higher doses than the RDA (50 milligrams) could reduce the incidence of lung cancer, other types of cancer, and other illnesses among 29,000 male smokers. The study found no beneficial effect of vitamin E supplements on lung cancer incidence. It found lower rates of prostate and colorectal cancer among those who received vitamin E, but higher rates of bladder, stomach, and other types of cancer. [10,11]

Vitamin E has been linked to the prevention of cardiovascular disease (CVD) based on the hypothesis that oxidation of LDL initiates the development of atherosclerotic plaque. This hypothesis, although not universally accepted, is supported by studies in vitro, in animals, and in humans. This background in basic science and a number of epidemiological studies, led to the initiation of clinical intervention trials.

G. Oriani et. al. in their study suggest that vitamin E plays an important role in the regulation of serum concentrations of cholesterol and lipoproteins in weanling rabbits. Consequently, the maintenance of an adequate nutritional status of vitamin E in the postweaning period is important to avoid alterations of serum lipid pattern ( J Anim Sci. 1997 Feb;75(2):402-8.) [12].

Support for the role of vitamin E in heart disease prevention has come from observational studies, particularly 2 cohort studies which were published in 1993. In the 1st study, the Nurses' Health Study, the researchers concluded that among 83,234 middle-aged women who participated in the study, there was a 40% reduced risk of coronary artery disease for those who took vitamin E supplements compared to those who did not (New England Journal of Medicine 1993;328: 1444-9). The 2nd study, the Health Professionals Follow-up Study, involved over 39,000 males and showed evidence of a significant association between a high intake of vitamin E from supplements and a lower risk of heart disease (New England Journal of Medicine 1993; 328:1450-1456). [13]

The following is a very brief overview of the role of vitamin E in wellness and disease prevention, Andreas M. Papas, Ph.D in NutriNews, January/February 2008 to explain other health benefits of vitamin E including Alzheimer’s disease, aging and immunity, cataracts, and skin health.

Alzheimer’s disease: A collaborative study at major medical centers across the United States found that in Alzheimer’s patients taking large doses of vitamin E (2,000 IU/day), progression of the memory-robbing disease was delayed by approximately seven months.
Aging and immunity: Studying healthy elderly people, researchers at Tufts University, reported that vitamin E increased the power of disease-fighting T-cells, improved delayed-type hypersensitivity skin response (DTH) by 65 percent and antibody response to hepatitis B six-fold. It also increased significantly the antibody titer to tetanus vaccine. A recent study in Netherlands reported no benefit in acute respiratory tract infections in elderly person from vitamin E supplementation.
Cataracts: A Canadian study compared the consumption of vitamin supplements by 175 cataract patients with that of 175 cataract-free controls. People in the control group were taking significantly more supplements of vitamins C and E than the cataract group.
Skin health: Vitamin E has been shown to reduce the damage to skin from exposure to UV radiation and ozone.

Sjögren's Syndrome

2010-01-23T09:44:00.000-08:00

Sjögren's Syndrome

Other names : Mikulicz syndrome, Sicca syndrome

Sjögren's (pronounced SHOW-grins) syndrome is a chronic autoimmune disease in which a person’s white blood cells attack their moisture-producing glands. Historically, Mikulicz first reported these symptoms in 1898 so this condition was called "Mikulicz syndrome." It is more commonly named for Henrik Sjögren (1899-1986), a Swedish ophthalmologist, who reported the association of severe dry eyes [keratoconjunctivitis sicca (KCS)], dry mouth and rheumatoid arthritis in 1933. Later, it was recognized that patients might have dry eyes and dry mouth but no rheumatoid arthritis.

Today, according to the National Institute of Neurological Disorders and Stroke (NINDS), between 1 and 4 million people in the United States are living with this disease. The condition is found throughout the world and in all ethnic groups. Most people are more than 40 years old at the time of diagnosis. Women are 9 times more likely to have Sjögren's syndrome than men.

This desease is a disorder of your immune system often defined by its two most common symptoms — dry eyes (its medical term is xeropthalmia; your eyes may burn, itch or feel gritty — as if there's sand in them) and a dry mouth (its medical term is xerostomia; your mouth may feel like it's full of cotton, making it difficult to swallow or speak). In addition, Sjogren's syndrome may cause vaginal dryness that can cause dyspareunia, dryness of the trachea and bronchus (the airways) can lead to a dry cough and chest infections, and dry skin can occur. Sjogren's syndrome may affect other organs of the body including the kidneys, blood vessels, lungs, liver, pancreas, and brain.

The risk for passing this disease on to family members is extremely low. There is a slightly increased incidence of autoimmune diseases in siblings and children. Many women with Sjögren's syndrome are interested in the risks of pregnancy and risks to the baby. Obstetrical authorities report slightly higher rates of recurrent fetal death and congenital heart block in those pregnancies complicated by maternal autoimmune disease.

There are two types of Sjogren's syndrome; primary and secondary. Primary Sjögren's syndrome is when Sjögren's syndrome occurs by itself. Secondary Sjögren's syndrome is when Sjögren's syndrome occurs in association with another autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus. (Sjögren's syndrome affects 5 out of 10 people who have rheumatoid arthritis.)

The cause of Sjögren's syndrome is not known, but it is considered an autoimmune disorder. People with this disease have abnormal proteins in their blood suggesting that their immune system, which normally functions to protect the body against cancers and invading infections, is reacting against their own tissue. As note, Sjögren’s syndrome causes increased levels of IL-1RA in CSF suggesting increased activity in the Interleukin 1 system and that this is associated with increased fatigue through cytokine induced sickness behavior.

Sjögrens syndrome is marked by lymphocytic infiltration of the lacrimal and salivary glands. Extra-glandular manifestations are common and result from similar infiltration of various organs. Immunohistologic studies have shown that the lymphocytic infiltrate is comprised predominantly of CD4-positive T cells, primarily of the Th1-type. Unlike normal epithelium, the glandular epithelial cells express MHC class II antigens and B7 co-stimulatory molecules, allowing them to serve as antigen-presenting cells.

Diagnosis of Sjögren's syndrome; The doctor needs to take a good history, seeking out features of dryness. The physical examination is helpful looking at the eyes and the mouth and observing whether they are dry, red and irritated and the skin is dry. A specialist eye examination is valuable and occasionally kidney and lung function tests are needed. Dry mouth and eyes alone may result from aging, medication or a condition known as Amyloidosis. Blood Tests for diagnosis include : ANA (Anti-Nuclear Antibody), SS-A (or Ro) and SS-B (or La) Antibodies to SS-A (or Ro) and SS-B (or La.), RF (Rheumatoid Factor), ESR (Erythrocyte Sedimentation Rate), IGs (Immunoglobulins). The Salivary Gland Tests include: Parotid Gland Flow, Salivary Scintigraphy, Sialography.

Treatment of this disorder is based on the symptoms. Dry eyes are treated with artificial tears, a tear stimulant, or eye lubricant. Dry mouth may be helped by frequent small drinks of water or chewing gum to stimulate saliva production. Arthritis symptoms are treated with anti-inflammatory medicines, such as aspirin, acetaminophen, and other NSAIDs.

These are the medications used to relieve the dryness caused by the Sjögren autoimmune attack on the body’s moisture-producing glands on table below [1].

Treatment of Sjögren's syndrome is aimed at symptomatic relief, at this stage there is no cure [2].

Dry Eyes
A variety of artificial tear preparations can be used to treat dry eyes. The severity of the dryness will determine how frequently you need to use the drops. Some preparations have preservatives - these last longer but may be irritating to the eye. It is a matter of trying one brand and seeing how you go. Lubricating ointments are longer acting preparations that are useful at night whilst sleeping. These tend to be greasy so are not appropriate for daytime use.

Dry Mouth
Dry mouth is harder to treat than dry eyes. There are some artificial oral lubricant preparations available, but none are entirely satisfactory. Some people find chewing sugarless gum is helpful, whilst others prefer simply to spray water into the mouth. Dietary modification using soft or moist foods may be of some assistance. The use of sugar should be avoided as it contributes to the development of dental caries. Good dental hygiene and frequent dental visits are essential.

Dry Skin
Sorbolene cream and moisturisers may be helpful. For dryness of the vagina, lubricating creams or oestrogen creams may be helpful.

Oral Medications
Oral medications are used in a majority of people. Non-steroidal anti-inflammatory drugs, or the anti-malarial drug Plaquenil, may be used to treat joint symptoms. Prednisone and immunosuppressant drugs are seldom used but are useful where there is severe lung or kidney involvement.

In an era of increasing health maintenance organizations (HMO's) and the need for diagnosis codes, it is often necessary for the patient to help their physician or dentist by informing them of currently accepted diagnosis codes. Individuals should consult a qualified health care provider for professional medical advice, diagnoses and treatment of a medical or health condition.

CELIAC DISEASE AND GLUTEN

2009-12-31T09:15:00.000-08:00

CELIAC DISEASE AND GLUTEN

Other names of this disease : cœliac disease (with œ ligature), gluten intolerance, celiac sprue, nontropical sprue, endemic sprue, gluten enteropathy or gluten-sensitive enteropathy.

Celiac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward [1]. For people with celiac disease, a lifelong disorder of the digestive system, these foods aren't always the treats that most people think they are. They usually contain a type of protein called gluten, which causes problems for people with celiac disease. [2]

When people with celiac disease eat foods or use products containing gluten, their immune system responds by damaging or destroying villi—the tiny, fingerlike protrusions lining the small intestine. Villi normally allow nutrients from food to be absorbed through the walls of the small intestine into the bloodstream. Without healthy villi, a person becomes malnourished, no matter how much food one eats. Celiac disease is both a disease of malabsorption—meaning nutrients are not absorbed properly—and an abnormal immune reaction to gluten [3]. Eventually, the decreased absorption of nutrients (malabsorption) that occurs with celiac disease can cause vitamin deficiencies that deprive your brain, peripheral nervous system, bones, liver and other organs of vital nourishment. This can lead to other illnesses and stunted growth in children. [4]

What is gluten ?

Gluten is a composite of the proteins gliadin and glutenin. These exist, conjoined with starch, in the endosperms of some grass-related grains, notably wheat, rye, and barley. Gliadin and glutenin comprise about 80% of the protein contained in wheat seed. Being insoluble in water, they can be purified by washing away the associated starch. Worldwide, gluten is an important source of nutritional protein, both in foods prepared directly from sources containing it, and as an additive to foods otherwise low in protein. [5]

When these proteins are present in the diet of someone with celiac disease, they become toxic and cause damage to the intestine. This damage leads to decreased absorption of essential nutrients and, if left untreated, can lead to nutrient deficiency and subsequent disease (i.e. iron deficiency anemia, decreased bone density, unintentional weight loss, folate and vitamin B12 deficiency). [6]

Gluten is found in most types of cereals and in many types of bread. Not all foods from the grain family, however, contain gluten. Examples of grains that do not have gluten include wild rice, corn, buckwheat, millet, amaranth, quinoa, teff, oats, soybeans, and sunflower seeds.

Gluten can be removed from wheat flour, producing wheat starch. All of the gluten in wheat flour, however, cannot be removed. Gluten helps make bread elastic, providing it with that chewy texture it has when eaten. For this reason, flour that has had most of its gluten removed, produces a sticky dough that feels much like chewing gum. Gluten provides many additional important qualities to bread. For example, gluten keeps the gases that are released during fermentation in the dough, so the bread is able to rise before it is baked. In addition, gluten firms up when it is cooked and, with the help of starch, helps ensure the bread maintains its proper shape.

Gluten also has an absorbent quality, which is why bread is capable of soaking up broth. Because of this feature, gluten is often used by those on a vegetarian diet as an imitation meat. On the downside, gluten is believed to be partly responsible for causing bread to become stale.

According to the Food and Drug Administration (FDA), if a certain amount of the gluten is removed, the food product can be labeled "gluten-free." (This is somewhat similar to food products that can be labeled as 0 Calories even though a serving contains 4 or less Calories) [7]. Standards for "gluten-free" labeling have been set up by the "Codex Alimentarius"; however, these regulations do not apply to "foods which in their normal form do not contain gluten". [1]

The legal definition of the phrase "gluten-free" varies from country to country. Current research suggests that for persons with celiac disease the maximum safe level of gluten in a finished product is probably less than 0.02% (200 parts per million) and possibly as little as 0.002% (20 parts per million).

Prevalence of Celiac Disease

Celiac disease is a serious health issue and challenge for food scientists, because celiac disease can only be treated by strict adherence to a gluten-free diet. The prevalence of celiac disease, an intolerance of gluten, has been reported to be as high as 1 in 200 of the world population [8 : Shih F.F., Daigle K.W., Truong V.; 2006].

The prevalence of clinically diagnosed disease (symptoms prompting diagnostic testing) is 0.05–0.27% in various studies. However, population studies from parts of Europe, India, South America, Australasia and the USA (using serology and biopsy) indicate that the prevalence may be between 0.33 and 1.06% in children (5.66% in one study of Sahrawi children) and 0.18–1.2% in adults. People of African, Japanese and Chinese descent are rarely diagnosed; this reflects a much lower prevalence of the genetic risk factors. Population studies also indicate that a large proportion of celiacs (coeliacs) remain undiagnosed; this is due to many clinicians being unfamiliar with the condition. [1, accessed Dec. 2009]

Principal Features of This Disorder

It's important to diagnose celiac disease early before it causes damage to the intestine. But because it's easy to confuse the symptoms with other intestinal disorders, such as irritable bowel syndrome or lactose intolerance, teens with celiac disease may not know they have it.

Symptoms of Celiac Disease may include one or more of the following : Recurring bloating; gas or abdominal pain, Chronic diarrhea or constipation or both, Unexplained weight loss or weight gain, Pale; foul-smelling stool, Unexplained anemia, Bone or joint pain, Behavior changes / depression / irritability, Vitamin K Deficiency, Fatigue; weakness or lack of energy, Delayed growth or onset of puberty, Failure to thrive (in infants), Missed menstrual periods, Infertility male and female, Spontaneous miscarriages, Canker sores inside the mouth, Tooth discoloration or loss of enamel.

Symptoms include chronic diarrhea, failure to thrive (in children), and fatigue, but these may be absent, and symptoms in other organ systems have been described. Someone with the disease may feel tired and could be irritable or depressed. Some have skin rashes and mouth sores. Teens with undiagnosed celiac disease may go through puberty late. Someone might not show any symptoms until going through an emotionally or physically stressful event, such as going away to college, illness, or an injury or pregnancy. [1,2]

Sometimes people with celiac disease may have no gastrointestinal symptoms at all. Celiac disease symptoms can also mimic those of other conditions, such as irritable bowel syndrome, gastric ulcers, Crohn's disease, parasite infections, anemia, skin disorders or a nervous condition. [9]

People at higher risk for celiac disease are those that have type 1 diabetes, autoimmune, thyroid disease, dermatitis, herpetiformis, Down syndrome, Turner syndrome, Williams syndrome, or have a relative with celiac disease. You may still have celiac disease even though you are not in a group at higher risk.

Causes

The disease has some genetic background, which means that it may run in families. Just like eye or hair color, people inherit the genes that make them more likely to get celiac disease from their parents and grandparents. If an immediate family member (such as a parent or a sibling) has celiac disease, there's about a 5% to 10% chance that you could have it, too. Celiac disease affects people of all heritages and backgrounds. [2]

A growing portion of diagnoses are being made in asymptomatic persons as a result of increased screening. Celiac disease is caused by a reaction to gliadin, a prolamin (gluten protein) found in wheat, and similar proteins found in the crops of the tribe Triticeae (which includes other cultivars such as barley and rye). Upon exposure to gliadin, and certain other prolamins, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the small-bowel tissue, causing an inflammatory reaction. That leads to a truncating of the villi lining the small intestine (called villous atrophy). This interferes with the absorption of nutrients, because the intestinal villi are responsible for absorption. [1]

Treatment

The only known effective treatment is a lifelong gluten-free diet. While the disease is caused by a reaction to wheat proteins, it is not the same as wheat allergy.

If your nutritional deficiencies are severe, you may need to take vitamin and mineral supplements recommended by your doctor or dietitian to help correct these deficiencies. Complete healing and regrowth of the villi may take several months in younger people and as long as two to three years in older people.

If you notice or experience any of the signs or symptoms common to celiac disease, see your doctor. If someone in your family is known to have celiac disease, you may need to be tested.

ALZHEIMER’S DISEASE

2009-12-23T10:25:00.000-08:00

ALZHEIMER’S DISEASE

General Description of Alzheimer’s Disease

Other names : Alzheimer’s presenile and senile dementia, senile dementia (Alzheimer type)
Alzheimer’s disease is a brain disorder named for German physician Alois Alzheimer, who first described it in 1906. Scientists have learned a great deal about Alzheimer’s disease in the century since Dr. Alois Alzheimer first drew attention to it.

Alzheimer's disease is the most common cause of dementia — the loss of intellectual and social abilities severe enough to interfere with daily functioning. In Alzheimer's disease, healthy brain tissue degenerates, causing a steady decline in memory and mental abilities. Alzheimer's disease is not a part of normal aging, but the risk of the disorder increases with age. About 5 percent of people between the ages of 65 and 74 have Alzheimer's disease, while nearly half the people over the age of 85 have Alzheimer's. Although there's no cure, treatments may improve the quality of life for people with Alzheimer's disease. Those with Alzheimer's — as well as those who care for them — need support and affe. [definition by Mayo Clinic]

Alzheimer's disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception. Many scientists believe that Alzheimer's disease results from an increase in the production or accumulation of a specific protein (beta-amyloid protein) in the brain that leads to nerve cell death; called amyloid plaque.

Other major hallmarks in the brain that are associated with the disease processes of AD are Neurofibrillary tangles (NFTs) and Loss of connections between neurons responsible for memory and learning.

Neurofibrillary tangles (NFTs), found inside neurons, are abnormal collections of a protein called tau. Normal tau is required for healthy neurons. However, in AD, tau clumps together. As a result, neurons fail to function normally and eventually die.
Loss of connections between neurons responsible for memory and learning. Neurons can't survive when they lose their connections to other neurons. As neurons die throughout the brain, the affected regions begin to atrophy, or shrink. By the final stage of AD, damage is widespread and brain tissue has shrunk significantly.

Prevalence

Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in the year 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group. Prevalence rates in less developed regions are lower. The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030. Other studies have reached similar conclusions. Another study estimated that in 2006, 0.40% of the world population (range 0.17–0.89%; absolute number 26.6 million, range 11.4–59.4 million) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by the year 2050. As of September 2009, this number is reported to be 35 million-plus worldwide. The prevalence of Alzheimer's is thought to reach approximately 107 million people by 2050. [Wikipedia, December 24, 2009]

Principal Features

Insidious onset leading to progressive and permanent decline of all intellectual functions. Mood changes apathy, depression, irritability, anxiety, paranoia. Loss of recent memory, inability to recall facts of common knowledge, disorientation, confusion, all worse at night. Impaired attention, understanding, judgment. Loss of ability to think abstractly, to use language correctly, to calculate. Eventual gait disturbances, incoordination of movements. Social skills may be retained until late in course of disease. Course is from 3 to 20 years, with mean duration of 7 years.

Causes

Degeneration of nerve cell in the areas of the brain that control intellectual functions. Actual cause of degeneration in unknown. Scientists are not absolutely sure what role plaques and tangles play in Alzheimer’s disease. Most experts believe they somehow block communication among nerve cells and disrupt activities that cells need to survive.

Genetic predisposition appears probable; Alzheimer type dementia is four times more frequent among family members than in the general population. There is a history of previous head injury in 15% to 20% of cases. One common feature is a marked deficiency of the nerve transmitter acetyl-choline.

Drugs That Can Cause This Disease

No drugs cause true Alzheimer’s dementia. However, 3% of all dementias are drug induced. The following drugs can cause symptoms in the elderly that resemble Alzheimer’s disease : antidepressants, atropinelike drugs, barbiturates, benzodiazepines, butyrophenones, cortisonelike drugs, digitalis preparations, MAO inhibitors.

Drugs Used to Treat This Disease

No specific or truly effective drug treatment is available at this time. Ergoloid mesylates (Deapril-ST, Hydergine) are tried during the early stages to relieve symptoms; benefits are infrequent, negligible and fleeting.
Experimental drugs : choline, lecithin, physostigmine (none re curative or significantly beneficial). Nimodipine, a calcium channel blocking drug, is currently under study for human use. It has been shown to accelerate learning in aged rabbits.

Goals of Drug Treatment

Temporary improvement of alertness and memory. Relief of confusion, depression and behavioral disturbances.

CROHN’S DISEASE

2009-12-20T22:56:00.000-08:00

CROHN’S DISEASE

Other Names of This Disease
Regional enteritis, regional ileitis, granulomatous colitis, inflammatory bowel disease.

Incidence of Crohn’s Disease

The incidence of Crohn's disease has been ascertained from population studies in Norway and the United States and is similar at 6 to 7.1:100,000. Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country. The incidence of Crohn's disease is thought to be similar in Europe but lower in Asia and Africa. It also has a higher incidence in Ashkenazi Jews.

The incidences of Crohn’s disease based on age group; onset from infacy to 25 years of age, 15% to 30% have onset before puberty. Peak incidence is from 10 to 25 years of age. It slightly more common in females. [Long J W, 1993]

What is Crohn's Disease ?

Crohn's disease is a chronic inflammatory disease of the intestines. Crohn's disease is one type of inflammatory bowel disease (IBD). Inflammatory bowel diseases were described by Giovanni Battista Morgagni (1682-1771), by Polish surgeon Antoni Leśniowski in 1904 (leading to the use of the eponym "Leśniowski-Crohn disease" in Poland) and by Scottish physician T. Kennedy Dalziel in 1913.

Burrill Bernard Crohn, an American gastroenterologist at New York City's Mount Sinai Hospital, described fourteen cases in 1932, and submitted them to the American Medical Association under the rubric of "Terminal ileitis: A new clinical entity". Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer published the case series as "Regional ileitis: a pathologic and clinical entity".

Crohn's disease invariably affects the gastrointestinal tract, and most gastroenterologists categorize the presenting disease by the affected areas.
Ileocolic Crohn's disease, which affects both the ileum (the last part of the small intestine that connects to the large intestine) and the large intestine, accounts for fifty percent of cases. Crohn's ileitis, affecting the ileum only, accounts for thirty percent of cases, and Crohn's colitis, affecting the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from ulcerative colitis. The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, being affected in other parts of the gastrointestinal tract such as the stomach and esophagus.

IBD and Colon Cancer

Having Crohn's disease increases your risk of colon cancer. Despite this increased risk, more than 90 percent of people with inflammatory bowel disease (IBD) never develop cancer. Your risk is greatest if you've had inflammatory bowel disease for at least eight years and if it has spread through your entire colon. The longer you've had the disease and the larger the area affected, the greater your risk of colon cancer. The risk of other cancers also is increased, including cancer of the anus.

Principal Features of Crohn’s Disease

An intermittent to chronic disorders of the small intestine and colon; one third of cases occur in the lower segment of the small intestine (the ileum), one third in the colon and one third in both. Less than 50% of cases involve the rectum. The onset is usually insidious, but may be rapid and resemble acute appendicitis. Symptoms include loss of appetite, fatigue, fever, loss of weight, abdominal cramps and pain after eating, nausea, vomiting, diarrhea (occasionally bloody), anal sores and retarded growth in children. There may also be inflammatory disorders in the skin, eyes, mouth and large joints. Children may experience fever and joint pains before any indications of disease in the intestine or colon. Adults may have a higher incidence of gallstones or kidney stones. This disorders often recurs throughout life.
Caution: The early manifestations of Crohn’s disease may vary. Loss of appetite and weight may lead to the mistaken diagnosis of anorexia nervosa.

Causes of Crohn’s Disease

The primary cause in unknown. There is a familial clustering in 15% to 20% of cases. It is thought that an inherited susceptibility may predispose to unknown environmental factors capable of inducing the disorder.

Drugs That Can Cause This Disease

By altering the normal balance of bacteria in the intestine, several antibiotics can cause a form of enteritis that might resemble crohn’s disease. These include some of the tetracyclines, penicillin and chloramphenicol. Antibiotic-induced enteritis is transient and easily corrected; no permanent damage occurs. The vitamin A derivative etretinate (Tegison) has been reported to cause Crohn’s disease.

Drugs Used to Treat This Disease

Sulfasalazine, cortisonelike streroids, principally prednisone, azathioprine; 6-mercaptopurine, metronidazole, antidiarrheals (diphenoxylate, loperamide), antispasmodics (belladonna, dicyclomine), antibiotics (ampicillin, tetracycline; used when appropriate for bacterial infections of intestine).

Alternative Medicine

Many people with either Crohn's disease or ulcerative colitis have used some form of complementary or alternative therapy. Some commonly used therapies include:
• Herbal and nutritional supplements
• Probiotics
• Fish oil
• Acupuncture

Treatment Goals of Crohn’s Disease

1. Induction of remission (return to normal) during the active phase of the disease.
2. Relief of symptoms.
3. Protection of bowel, avoidance of complications.
4. Maintenance of general nutrition.

Classification and external resources

The three most common sites of intestinal involvement in Crohn's disease are ileal, ileocolic and colonic

KAWASAKI SYNDROME

2009-12-13T01:22:00.000-08:00

KAWASAKI SYNDROME

Introduction

Kawasaki syndrome (KS) was first described by Tomisaku Kawasaki in the Japanese-language medical literature in 1967. At that time, he reported his experience with 50 children who presented from 1961 to 1967 with symptoms distinct from other known childhood illnesses. He termed the condition “mucocutaneous lymph node syndrome” and originally thought that the syndrome represented a benign childhood illness. [Rowley A H and Shulman S T, 1998]

Kawasaki syndrome (KS) is the most common cause of acquired heart disease in children. This acute, self-limited vasculitis results in permanent coronary artery damage in up to 25% of untreated children. High dose intravenous gamma globulin reduces the risk of coronary artery aneurysm to 3-5% if administered early in the course of disease. However, without a specific diagnostic test, affected children may be difficult to recognize, and delayed diagnosis and treatment continue to result in potentially preventable morbidity and mortality. The etiology of Kawasaki syndrome (KS) remains unknown despite 30 years of intensive search for an agent. [Pediatr Infect Dis J. 2008;27(11):981-985)]

Incidences of Kawasaki Syndrome

In the continental United States, population-based and hospitalization studies have estimated an incidence of KS ranging from 9 to 19 per 100,000 children younger than 5 years of age. Approximately 4248 hospitalizations with KS, of which 3277 (77%) were for children under 5 years of age, were estimated among children younger than 18 years of age in the United States in the year 2000. In 2006, the number of hospitalizations with KS was 5523 (standard error [SE] 289) and the percentage of children under 5 years of age remained the same (unpublished data).

Outside the United States, the disease is most frequently observed in Japan, Taiwan, and Korea. The prevalence of Kawasaki disease increased from 1967 to the mid 1980s and has leveled out at 5000-6000 cases per year. Several epidemics occurred in Japan during the years 1979, 1982, and 1985. The current Japanese incidence is approximately 112 cases per 100,000 population.

In Indonesia, an investigation of KS on January 2005 found 100 cases, generally in children 3 months of age to 4 years of age. In the report, that wasn’t much of an accidence in children under 3 months of age or in children older than 8 years of age. Statistic-based; estimated that in Indonesia will be found 6000 – 7000 cases per year.

Causes

Kawasaki disease is a poorly understood illness. The cause has not been determined. Although, some now believe that many factors (viruses, staphylococci "super antigens") are capable of triggering a final common pathway that results in immune activation. It may be an autoimmune disorder. The disorder affects the mucus membranes, lymph nodes, walls of the blood vessels, and the heart.
Kawasaki disease can cause inflammation of blood vessels in the arteries, especially the coronary arteries. This inflammation can lead to aneurysms. An aneurysm can lead to a heart attack, even in young children, although this is rare.

Symptoms

1. High-grade fever (greater than 39 °C or 102 °F; often as high as 40 °C or 104 °F) that normally lasts for more than 5 days if left untreated.
2. Red eyes (conjunctivitis) without pus or drainage, also known as "conjunctival injection"
3. Bright red, chapped, or cracked lips
4. Red mucous membranes in the mouth
5. Strawberry tongue, white coating on the tongue or prominent red bumps (papillae) on the back of the tongue
6. Red palms of the hands and the soles of the feet
7. Rash which may take many forms, but not vesicular (blister-like), on the trunk
8. Swollen lymph nodes (frequently only one lymph node is swollen), particularly in the neck area
9. Joint pain (arthralgia) and swelling, frequently symmetrical
10. Irritability
11. Tachycardia (rapid heart beat)
12. Peeling (desquamation) palms and soles (later in the illness); peeling may begin around the nails
13. Beau's lines (transverse grooves on nails)
14. Increased peeling on palms of the hand
15. may find breathing difficult.

Additional symptoms may include: diarrhea, vomiting, abdominal pain, cough and runny nose.

Complications

The main complication of Kawasaki disease is development and rupture of coronary artery aneurysms. These aneurysms may also cause heart problems in later life. Other complications include dehydration and limited mobility from joint inflammation.

Prevention

There are no known measures that will prevent this disorder.

Treatment

Children with Kawasaki disease are admitted to the hospital. Treatment must be started as soon as the diagnosis is made to prevent damage to the coronary arteries and heart.
Intravenous gamma globulin is the standard treatment. It is given in high doses. The child's condition usually greatly improves within 24 hours of treatment with IV gamma globulin.
High-dose aspirin is often given along with IV gamma globulin.
Even when they're treated with aspirin and IVIG, up to 25% of children may still develop problems in their coronary arteries. Some research has suggested that adding steroids to the usual treatment routine may improve a child's outcome, but more research is needed.

See more informations : kidshealth, americanheart, emedicine, cdc

MEASUREMENT OF BLOOD PRESSURE WITH SPHYGMOMANOMETERS

2009-12-04T23:02:00.000-08:00

MEASUREMENT OF BLOOD PRESSURE WITH SPHYGMOMANOMETERS

Brief History of Sphygmomanometer

Hypertension is a 20th century diseases only, because measurement of the arterial blood pressure became conveniently possible when Scipione Rivarocci (1863-1973) perfected an early version of the modern sphygmomanometer in 1896. Stephen Hales, an English clergymen, was the first to measure blood pressure directly – in a mare, in 1733 - and investigators utilizing mercury manometers had measured blood pressure in various ways in the 19th century. Richard Bright ((1789-1858), during the course of his classic studies of the diseases that bears his name, concluded that the thick left ventricle, dilated aorta, and arterial disease could be due to increased resistance to the flow of blood in the blood vessels, but Bright had no method of measuring blood pressure.

At the turn of the century, Rechklinghausen noted the falsely high levels of blood pressure (especially in the obese) that could be obtained with narrow cuffs such as those used by Riva-Rocci; the standard 12.5 cm cuff used today owes its origin to Recklinghausen’s research. Korotkoff in 1905 described the 5 sounds heard over the brachial artery, distal to the cuff, as the pressure in the sphygmomanometer is reduced: Phase I, the abrupt sharp sound as the pressure is reduced just below systolic pressure. Phase II, a prolonged, louder murmuring sound. Phase III, a load clear with only a slight murmur. Phase IV, an abrupt muffling of sounds, thought by some to represent the diastolic pressure. Phase V, the total disappearance of sounds, used usually in the USA to reflect the diastolic pressure.
Mahomed (about 1879) was the first to demonstrate that renal and cardiac disease were complications of hypertension in some patients (and not the reverse, as had been suggested by Bright and by Allbutt).

Types of Sphygmomanometers

At the modern era, there are three types of sphygmomanometers:
A. Digital with manual or automatic inflation. These are electronic, easy to operate, and practical in noisy environments. Many have not been validated for all patient groups, and they can give very inaccurate readings. They measure mean arterial pressure (MAP) and use algorithm to calculate systolic and diastolic values. In this sense, they do not actually measure the blood pressure, but rather derive the readings. Digital oscillometric monitors are also confronted with "special conditions" for which they are not designed to be used: arteriosclerosis; arrhythmia; preeclampsia; pulsus alternans; and pulsus paradoxus. Some wrist cuff blood pressure monitors have been found to be quite accurate, but the monitor has to be at the level of the heart when the reading is taken.

B. Digital portable finger blood pressure monitors with automatic inflation. These are more portable and easy to operate, although less accurate. They are the smallest blood pressure monitors.

C. Manual. Should be operated by a trained person. Mercury manometers are considered to be the "gold standard" of measurement because their measurement is absolute and does not require re-calibration. For this reason they are often required in clinical trials of pharmaceuticals and for clinical evaluations of determining blood pressure for high risk patients including pregnant women. Aneroid, mechanical types are in common use, but they should be calibrated against a mercury manometer. The unit of measurement of blood pressure is millimeters of mercury (mmHg). Blood pressures are usually given as an even number. Manual sphygmomanometers require a stethoscope for auscultation.

Regular Maintenance and Calibration of Sphygmomanometers

The Sphygmomanometer is an essential piece of equipment used daily in general medical practice, and plays a role in many routine consultations. Without regular maintenance and calibration, however, both mercury and aneroid sphygmomanometers are at risk of becoming inaccurate over time. A significant level of inaccuracy may lead to misdiagnosis of hypertension and inhibit its control, thus placing patients at unnecessary risk.

Raouse A and Marshal T (2001) in their study [1]; a researcher trained in the calibration of sphygmomanometers visited 231 general practices in the Birmingham area and calibrated 1462 mercury and aneroid sphygmomanometers. The Practices in Birmingham were asked about what arrangement had been made for maintenance and calibration of their instruments, and, in a small telephone survey, 54 practices across the country were asked the same question. Almost one in 10 of the sphygmomanometers checked gave readings that were inaccurate by more than 5 mmHg (9.2%). None of the practices visited had arrangements in place for the maintenance and calibration of their Sphygmomanometers. Of the 54 practices questioned by telephone, only one had such arrangements in place. The finding has implication for public health, primary care, and medical ethics. Inaccurate sphygmomanometers may result in the prescription of treatment to patient who do not require it.

In the other study by Mion D and Pierin AMG, 1998 [2]; was to assess the accuracy and reliability of mercury and aneroid sphygmomanometers. Measurement of accuracy of calibration and evaluation of physical conditions were carried out in 524 sphygmomanometers, 351 from a hospital setting, and 173 from private medical offices. Mercury sphygmomanometers were considered inaccurate if the meniscus was not ‘0’ at rest. Aneroid sphygmomanometers were tested against a properly calibrated mercury manometer, and were considered calibrated when the error was <3 mm Hg. Both types of sphygmomanometers were evaluated for conditions of cuff/bladder, bulb, pump and valve.

In this study; of the mercury sphygmomanometers tested 21% were found to be inaccurate. Of this group, unreliability was noted due to: excessive bouncing (14%), illegibility of the gauge (7%), blockage of the filter (6%), and lack of mercury in the reservoir (3%). Bladder damage was noted in 10% of the hospital devices and in 6% of private medical practices. Rubber aging occurred in 34% and 25%, leaks/holes in 19% and 18%, and leaks in the pump bulb in 16% and 30% of hospital devices and private practice devices, respectively. Of the aneroid sphygmomanometers tested, 44% in the hospital setting and 61% in private medical practices were found to be inaccurate. Of these, the magnitude of inaccuracy was 4–6 mm Hg in 32%, 7–12 mm Hg in 19% and . 13 mm Hg in 7%. In summary, most of the mercury and aneroid sphygmomanometers showed inaccuracy (21% vs 58%) and unreliability (64% vs 70%).

Additionally, home blood pressure readings may be more representative than those obtained in the clinicians's office. The prevalence of home sphygmomanometers in the general population is currently undocumented. The prevalence of ownership (7.5 per cent) and the accuracy of home sphygmomanometers were determined in a population-based survey in the Minneapolis-St. Paul metropolitan area. A study by Hahn LP and Folsom AR (1987) [3]; Prevalence and Accuracy of Home Sphygmomanometers
in an Urban Population. Sixty-four per cent of home sphygmomanometers were accurate within ±2 mm Hg of a calibrating sphygmomanometer; another 26 per cent were within ±3-6 mm Hg. These results suggest that although many home sphygmomanometers are accurate, some are very inaccurate. Health care providers should advise regular calibration when home sphygmomanometers are used for therapeutic self-management of hypertension.

As conclusion, the present studies showed a high incidence of inaccuracy in both aneroid and mercury sphygmomanometers, and in both hospital and private medical practice based settings. These results reinforce the recommendations made by The American Heart Association and The British Hypertension Society that aneroid and mercury sphygmomanometers must be checked regularly in order to avoid errors in blood pressure measurement and consequently the diagnosis and treatment of hypertension.

Andi Surya Amal
email : suryaamal88@gmail.com

References :
1. Rouse A, Marshal T (2001), The Extent and Implication of Sphygmomanometer Calibration Error in Primary Care, Journal of Human Hypertension; 15[9]:587-591
2. Mion D and Pierin AMG (1998), How accurate are sphygmomanometers?, Journal of Human Hypertension; 12, 245–248
3. Hahn LP and Folsom AR et al (1987), Prevalence and Accuracy of Home Sphygmomanometers in an Urban Population, American Journal of Public Health, Vol. 77, No. 11, 77:1459-1461
4. Markandu NK, Whitcher F, Arnold A, Carney C (2000), The Mercury sphygmomanometer should be abandoned before it is prescribed. Journal of Human Hypertension 14(1): 31-6.
5.Sokolow M and Mcllroy MB (1979), Clinical Cardiology, 2nd Ed., Lange Medical Publications, 208-209
6.Jones DW, Frohlich ED (2001), Mercury Sphygmomanometers Should Not be Abandoned: An Advisory Statement From the Council for High Blood Pressure Research, American Heart Association, Hypertension;37:185

PROCESSES OF ANTIMICROBIAL RESISTANCE

2009-11-29T03:08:00.000-08:00

PROCESSES OF ANTIMICROBIAL RESISTANCE

Over eighty years ago Alexander Flemming discovered penicillin, and since then a multitude of natural and synthetic agents have been developed in our humankind fight against microorganisms, which comprise three main groups: bacteria, fungi and viruses. Antibiotic or antibacterial agents are selective poisons with activity only against bacteria, not viruses or fungi, since other specific agents kill these microbes selectively.

Antibiotics are the naturally occurring entities such as penicillins, while the term antimicrobial encompasses a range of synthetic agents like quinolon, as well as naturally derived ones. The key consideration of antimicrobial agents is their mode of action against bacteria. A typical bacterial cell antimicrobial and identify which sites certain antimicrobial agents act upon. Irrespective of their shape or size, this fundamental cellular structure permits certain generalizations.

Additionally the structure and composition of the cell wall, i.e. whether it is gram positive or gram negative, has a bearing on how effectively an antimicrobial agents can penetrate the bacterial cell. One way of viewing the role of antimicrobial agents and their selective responses to bacteria is by way of comparison to battlefield. In essence there are :
(1) The bacterial soft spots, or targets; key targets are cell wall, protein and DNA synthesis, substituent biosynthetic pathways.
(2) Our weapons, or antimicrobial agents; the various antimicrobial agents attack the different key target sites.
(3) The enemy’s response, or the ways of bacterial defense.

What processes of antimicrobial resistance are expressed by these gene sequences ? Basically there are four main mechanisms by which these processes occur; 1. Drug inactivation (enzyme inactivation), 2. Cellular access (decreased permeability), 3. Site modification (altered target site), 4. Biochemical Feedback (by pass). The main mechanisms of antimicrobial resistance processes are illustrated on the figure below; modified from Schentag JJ, 1999, (Operation Resistance 2000; The Terrain, Dynamics and Defense of Antimicrobial Resistance, Sheffield Dawson Publisher Ltd, 3-16).

A. DRUG INACTIVATION (enzyme inactivation)
The mechanism is a process by which bacterial enzymes either completely destroy the antimicrobial, or modify the drug by adding a molecule to it and rendering it incapable of specific activity. Examples of these two activities are β-lactamase; which destroy the β-lactam ring, the acetylation of chloramphenicol, the modification of aminoglycoside by acetylation or other additions.

B. CELLULAR ACCESS (decreased permeability)
The mechanism is controlled in terms of allowing entry to the bacterial cell, or an active process of ejecting drugs via an efflux pump. Coincidental with these processes is intrinsic resistance due to physical barriers – e.q. Gram-negative outer membrane provides resistance to some β-lactams.
Efflux pump mechanisms are increasingly recognized as a common method by which bacteria can remove a wide range of antimicrobials, from tetracyclines to quinolones.

C. SITE MODIFICATION (altered target site)
Site modification – involves alteration of the target site of an antimicrobial agent so that the fit is no longer sufficient to exert activity. Analogous to a lock and key situation, wherein a small change in the lock can render the key useless; a good example would be the alteration of the 23s ribosome to prevent macrolides, such as clarithromycin, from binding to the ribosome.

D. BIOCHEMICAL FEEDBACK (by pass)
Biochemical feedback – via target hyperproduction is best represented by the folic acids pathway in which an organism may deliberately over-produce an enzyme so as to saturate all the sulfonamide or trimethoprim present and still be able to catalyze the biosynthetic pathway.

See other contains :
1. Antimicrobial Resistance
2. Resistance Mechanism and Their Genetic Bases
3. Factors That Encourage the Spread of (Antimicrobial) Resistance

RESISTANCE MECHANISM AND THEIR GENETIC BASES

2009-11-26T04:23:00.000-08:00

Resistance Mechanism and Their Genetic Bases

Genetic of Resistance
Bacteria posses a remarkable number of genetic mechanisms for resistance to microbials. They can undergo chromosomal mutations, express a latent chromosomal resistance gene, or acquire new genetic resistance material through direct exchange of DNA (by conjugation), through a bacteriophage (transduction), through extrachromosomal plasmid DNA via transformation. The information encoded in this genetic material enables a bacterium to develop resistance through three major mechanisms: production of an enzyme that will inactivate or destroy the antibiotic; alteration of the antibiotic target site to evade action of the antibiotic; or prevention of antibiotic access to the target site.

Examples of organisms that are known to possess resistance mechanisms of the various types are shown in tables, together with the genetic mechanism for the resistance. It is not unusual for a single bacterial strain found in a hospital to possess several of these resistance mechanisms simultaneously.

Modified from : Neu HC. The Crisis in antibiotic resistance. Science 1992;257

Factors That Encourage the Spread of (Antimocrobial) Resistance

2009-11-17T19:04:00.000-08:00

Factors That Encourage the Spread of (Antimicrobial) Resistance

The emergence and spread of antimicrobial resistance are complex problems driven by numerous interconnected factors, many of which are linked to the misuse of antimicrobials and thus amenable to change. In turn, antimicrobial use is influenced by an interplay of the knowledge, expectations, and interactions of prescribers and patients, economic incentives, characteristics of a country's health system, and the regulatory environment.

Patient-related factors are major drivers of inappropriate antimicrobial use. For example, many patients believe that new and expensive medications are more efficacious than older agents. In addition to causing unnecessary health care expenditure, this perception encourages the selection of resistance to these newer agents as well as to older agents in their class.

Self-medication with antimicrobials is another major factor contributing to resistance. Self-medicated antimicrobials may be unnecessary, are often inadequately dosed, or may not contain adequate amounts of active drug, especially if they are counterfeit drugs. In many developing countries, antimicrobials are purchased in single doses and taken only until the patient feels better, which may occur before the pathogen has been eliminated. Inappropriate demand can also be stimulated by marketing practices. Direct-to-consumer advertising allows pharmaceutical manufacturers to market medicines directly to the public via television, radio, print media, and the Internet. In particular, advertising on the Internet is gaining market penetration, yet it is difficult to control with legislation due to poor enforceability.

Prescribers' perceptions regarding patient expectations and demands substantially influence prescribing practice. Physicians can be pressured by patient expectations to prescribe antimicrobials even in the absence of appropriate indications. In some cultural settings, antimicrobials given by injection are considered more efficacious than oral formulations. Such perceptions tend to be associated with the over-prescribing of broad-spectrum injectable agents when a narrow-spectrum oral agent would be more appropriate. Prescribing “just to be on the safe side" increases when there is diagnostic uncertainty, lack of prescriber knowledge regarding optimal diagnostic approaches, lack of opportunity for patient follow-up, or fear of possible litigation. In many countries, antimicrobials can be easily obtained in pharmacies and markets without a prescription.

Patient compliance with recommended treatment is another major problem. Patients forget to take medication, interrupt their treatment when they begin to feel better, or may be unable to afford a full course, thereby creating an ideal environment for microbes to adapt rather than be killed. In some countries, low quality antibiotics (poorly formulated or manufactured, counterfeited or expired) are still sold and used for self-medication or prophylaxis.

Hospitals are a critical component of the antimicrobial resistance problem worldwide. The combination of highly susceptible patients, intensive and prolonged antimicrobial use, and cross-infection has resulted in nosocomial infections with highly resistant bacterial pathogens. Resistant hospital-acquired infections are expensive to control and extremely difficult to eradicate. Failure to implement simple infection control practices, such as handwashing and changing gloves before and after contact with patients, is a common cause of infection spread in hospitals throughout the world. Hospitals are also the eventual site of treatment for many patients with severe infections due to resistant pathogens acquired in the community. In the wake of the AIDS epidemic, the prevalence of such infections can be expected to increase.

Veterinary prescription of antimicrobials also contributes to the problem of resistance. In North America and Europe, an estimated 50% in tonnage of all antimicrobial production is used in food-producing animals and poultry. The largest quantities are used as regular supplements for prophylaxis or growth promotion, thus exposing a large number of animals, irrespective of their health status, to frequently subtherapeutic concentrations of antimicrobials. Such widespread use of antimicrobials for disease control and growth promotion in animals has been paralleled by an increase in resistance in those bacteria (such as Salmonella and Campylobacter) that can spread from animals, often through food, to cause infections in humans.

Source : WHO Media Center (November 17 2009)

Antimicrobial Resistance

2009-11-11T17:38:00.000-08:00

ANTIMICROBIAL RESISTANCE

Antimicrobial resistance results in increased morbidity, mortality, and cost of health care. Prevention of the emergence of resistance and the dissemination of resistant microorganisms will reduce these adverse effects and their attendant costs. Appropriate antimicrobial stewardship that includes optimal selection, dose, and duration of treatment, as well as control of antibiotic use, will prevent or slow the emergence of resistance among microorganisms. A comprehensively applied infection control program will interdict the dissemination of resistant strains.

Stuart Levy, MD proposed a provocative hypothesis: the intensity of antibiotic use in a population may be the most important factor in selection of resistance. Moreover, there may be a “threshold” for such selection that may differ for an individual, as compared to a population, and from one population to another. This may explain why, in intensive-care units, where there is usually a small population undergoing intensive antibiotic therapy or prophylaxis, resistance tend to be more common, pathogens are more often multiply resistant, and spread within the population is more likely. The same concept might explain resistance problems in the poultry manufacturing industry and in other setting where antibiotic use is intensive within a small and confined population. [1]

The Prevention of Antimicrobial Resistance In Hospital

The 1990s is the era of multidrug resistance. Some bacteria causing several kinds of human infectious diseases are resistant to multiple antibiotics and are continuing to increase. Resistant infections confront and thwart the treatment of some patients in the community as well as in the hospital. Major resistant hospital organisms include Staphylococcus aureus, enterococcus, Klebsiella, Enterobacter, Escherichia coli, Pseudomonas and more recently Acinetobacter. Multidrug resistant bacteria causing community acquired infections include pneumococcus, gonococcus, Mycobacterium tuberculosis, group A streptococci and E. coli. [See : NFID]

It therefore is recommended that hospitals, large and small, with and without perceived problems of bacterial resistance to antimicrobials, do the following :
1. Establish a system for monitoring bacterial resistance and antibiotic usage.
2. Establish practice guidelines and other institutional policies to control the use of antibiotics, and respond to data from the monitoring system.
3. Adopt the recommendations of the Centers for Disease Control and Prevention’s (CDC) “guidelines for Isolation Precautions in Hospitals” as concerns the isolation of patients colonized or infected with resistant microorganisms.
4. Utilize hospital committees to develop local policies and to evaluate and adopt, as appropriate, guidelines from state advisory boards and national societies.
5. Recognize that the financial well-being of the institution and the health of its patients are at stake be accountable for the implementation and enforcement of policies adopted by hospital committees.
6. By measuring outcomes, evaluate the effectiveness of the policies that are put in place.

The Joint Commission on the Accreditation of Healthcare Organizations, or a similar review organization skilled in oversight functions, should take into account the priority hospitals give to antimicrobial resistance; policies, procedures, and measurements hospitals put into place; and evidence of ongoing review of data to judge the effectiveness of the plan.

Recommendations for future studies to examine. Means to prevent and reduce the development and dissemination of antimicrobial resistance :
1. The development and testing of protocols for measuring the effect of a variety of antimicrobial usage controls is recommended for use in multiple hospitals to determine the most effective ways to prevent and reduce antimicrobial resistance in specific species to specific antimicrobial.
2. Pharmaceutical industry and governmental support for such studies is recommended and encouraged.
3. It is recommended that educational methods, including those that are interactive and computer-based, be developed to improve the appropriateness of antimicrobial prescribing.
4. It is recommended that protocols to evaluate antimicrobial resistance include the ability to relate resistance rates to the “defined drug density” (the amount of antimicrobial used per geographyc area per unit time).
5. The transfer of resistance determinants in situ in a patient population is very poorly understood. First, the genetics of resistance transfer, the construction of composite transposons, and the actual mechanism of dissemination of these elements in situ, especially intergeneric transfer within the gram-positive bacteria, all should be studied further.
6. Method for interdicting transfer of resistance requires further study, especially in the behavioral area. Novel approaches to this area are needed.
7. The efficacy of various levels of infection control precaution should be documented by controlled trials.
8. Controlled studies of behavior modification, including novel approaches, to permit the efficient application of recommended guidelines within hospitals are recommended.
9. The efficacy of quality improvement approaches to control resistance should be studied.

Microbiologic Diagnostic Tests
[Minimum Bactericidal Concentration (MBC) and Minimum Inhibitory Concentration (MIC)]

Descriptions :
Varying concentrations of an antimicrobial are prepared in liquid growth medium or on solid medium. A standard number of organisms are added to each test tube or agar plate in incubated. After the appropriate incubation period, the test tubes or agar plate that contains the lowest concentration of antibiotic that prevents visible growth is considered the MIC. The tubes that demonstrate no growth are then placed onto an antibiotic free agar an incubated for 24 hours. The MBC is the lowest concentration of drug that results in a 99,9 % reductions in the initial bacterial count.

The MIC is quantitative measure of particular drug’s activity against identified bacteria. This allows the comparison of antibiotics in order to choose the antibiotic with the lowest MICs for likely eradication of infection by use of usual doses of an antimicrobial agent. The MBC can determine if the antibiotic will kill the organism (i.e., bactericidal).

Clinical implication :
1. Although useful in selecting the antimicrobial agent, MICs are not reliable predictors of success or failure of drug therapy.
2. Susceptible organism are those with the lowest MICs that will be effectively treated by the antimicrobial.
3. Moderately susceptible organism are those less likely to be effectively treated and should therefore be treated with maximum doses of the antimicrobial.
4. Resistant organism are those with high MICs to the tested antimicrobial suggesting probable failure of treatment.

Guidelines for Testing Bacterial Pathogens for Antimicrobial Resistance

A major role of the clinical microbiology laboratory is to provide antimicrobial susceptibility testing data on bacterial isolates to guide clinicians in their choice of anti-infective therapy. Susceptibility testing data can serve both as guide to therapy and, in some instances, as an initial means of strain typing for investigations of potential outbreaks of infection.
The guidelines for testing bacterial pathogens for antimicrobial resistance are shown in table. This guide is adapted from The National Committee for Clinical Laboratory Standards Document M100S6 for initial susceptibility testing and reporting of antimicrobial agents for several bacterial pathogen groups . (Not all drugs should be reported routinely).

)*Laboratories may screen for penicillin resistance in pneumococci by using a 1 μg oxacillin disk. Organisms with zone diameters of ≥20 mm are considered susceptible to all β-lactam drugs. Isolates with zona diameters of ≤19mm should be tested by minimum inhibitory concentration method against both penicillin and cefotaxime or ceftriaxone, especially if the organism is causing invasive disease.

by Andi Surya Amal,SSi,Apt,MKes
e.mail : suryaamal88@gmail.com

References :
1. Shlaes DM. et al. “Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: Guidelines for the Prevention of Antimicrobial Resistance in Hospitals”. Infection Control and Hospital Epidemiology, Vol. 18 No. 4, 1997, 275-291
2. Boh LE. Clinical Clerkship Manual. Applied Therapeutics, Inc, Vancouver, Washington, 1996, 5-57,
3. National Committee for Clinical Laboratory Standards Document M100S6 for initial susceptibility testing and reporting of antimicrobial agents for several bacterial pathogen groups.
4. National Foundation for Infectious Diseases

(Please see on the video below; why antimicrobial resistance is a serious problem in both the hospital and community settings. And then, do we have any solution ?)

Clinical Laboratory Test of Lipoprotein Panel

2009-11-09T06:14:00.000-08:00

CLINICAL LABORATORY TEST OF LIPOPROTEIN PANEL

Include cholesterol, low density lipoprotein (LDL) cholesterol, trigliserides, and hight density lipoprotein (HDL) cholesterol.

CHOLESTEROL

Normal Values :
Desirable : 0 – 199 mg/dL [SI = 0-5.17 mmol/L]
Borderline : 200 – 239 mg/dL [SI = 5.2-6.21 mmol/L]
High Risk : ≥ 240 mg/dL [SI = ≥6.22 mmol/L]

Description :
Cholesterol exists in muscle, RBCs, and cell membranes. It is used by the body to form steroid hormones, bile acids, and cell membranes. Elevated cholesterol concentrations are associated with atherosclerosis and an increased risk of coronary artery disease.

Clinical Implication :
1.Increased levels of > 200 mg/dL are considered to be high and require a triglyceride evaluation. Associated conditions include cardiovascular disease, atherosclerosis, Type II familial hypercholesterolemia, and obstructive jaundice.
2.Decreased levels are associated with malabsorption, liver disease, sepsis, and pernicious anemia.
3.A patient must fast for 12 hours before blood is obtained to measure the serum concentration of cholesterol, and should maintain a “normal” diet for 7 days prior. Alcohol should not be consumed 24 hours before testing and all lipid-lowering drugs should be withheld.

LOW DENSITY LIPOPROTEINS (LDL)

Normal Values (Adult) :
Desirable : < 130 mg/dL [SI = <3.36 mmol/L]
Borderline : 130-159 mg/dL [SI = 3.36-3.11 mmol/L]
High Risk : ≥ 160 mg/dL [SI = >4.13 mmol/L]

Description :
LDL are beta cholesterol esters

clinical Implication :
High LDL values are associated with coronary vascular disease or familial hyperlipidemia. Levels may also be elevated samples taken from non fasting subjects. Levels may also be elevated in types IIa and IIb hyperliproteinemia, diabetes mellitus, hypothyroidism, obstructive jaundice, nephrotic syndrome, familial and idiopathic hyperlipidemia, and with the use of estrogens or estrogens-containing oral contraceptives.
Decreased LDL levels may occur in patients with hypoproteinemia.

HIGH DENSITY LIPOPROTEINS (HDL)

Normal Values : Adult : 30-70 mg/dL [SI = 0.78-1.18 mmol/L]
Description : HDL are the products of liver and intestinal synthesis and triglyceride catabolism.

Clinical Implication :
1.There is an inverse relationship between HDL-cholesterol levels and the incidence of coronary artery disease.
2.Increased HDL cam occur in chronic alcoholism, primary biliary cirrhosis, and subsequent to exposure to industrial toxins or polychlorinated hydrocarbons. Patients taking clofibrate, estrogens, nicotinic acids, oral contraceptives, and phenytoin may have increased HDL levels.
3.Decreased HDL can occur in patients with cystic fibrosis, severe hepatic cirrhosis, diabetes mellitus, Hodgkin’s disease, nephritic syndrome, malaria, and some acute infections. Patients receiving probucal, hydrochlorothiazide, progestins, and prolonged parenteral nutrition may have decresed HDL levels.

TRIGLYCERIDES

Normal Values (desirable adult) :
Male : 40-160 mg/dL [SI = 0.44-1.88 mmol/L]
Female : 35-135 mg/dL [SI = 0.4-1.53 mmol/L]
Description :
Triglycerides are found in plasma lipids are chylomicrons and very low density lipoproteins (VLDL)

Clinical Implications :
1.Triglycerides are increased in patients with alcoholic cirrhosis, alcoholism, anorexia nervosa, biliary cirrhosis, biliary obstruction, cerebral thrombosis, chronic renal failure, diabetes mellitus, Down’s syndrome, hypertension, idiopathic hypercalcemia, hyperlipoproteinemia (type I, IIb, III, IV and V), gout, ischemic heart disease, hypothyroidism, pregnancy, acute intermittent porphyria, respiratory distress syndrome, thalassemia major, viral hepatitis, and Werner’s syndrome.
2.Cholestyramine, corticosteroids, estrogens, ethanol, high carbohydrate diets, intravenous miconazole, oral contraceptives, and spironolactone can increase triglycerides.
3.Decreased triglycerides may be seen with chronic obstructive lung disease, hyperparathyroidism, intestinal lymphangiectasia, severe parenchymal liver disease, malabsorption, and malnutrition.
4.Ascorbic acid, asparaginase, clofibrate, and heparin can decrease triglyceride serum concentrations.

Source : Boh, L.E. 1996. Clinical Clerkship Manual. Applied Threpuetics, Inc. Washington, 5-33, 5-34, 5-36

Oral Glucose Tolerance Test (OGTT)

2009-11-09T05:57:00.000-08:00

ORAL GLUCOSE TOLERANCE TEST (OGTT)

DESCRIPTION
A blood sample to determine the fasting (baseline) blood glucose for the patient is drawn first. Then, the patient drinks a highly concentrated glucose solution (75 gm/300 mL for nonpregnant adults and 100 gm/300 mL for pregnant women). Subsequently, a timed series of blood glucose tests is performed at 30, 60, 90, and 120 minutes for nonpregnant adults and 1,2, and 3 hours for pregnant women to determine the rate of removal of glucose from the bloodstream. This test is not performed if the fasting blood sugar is > 140 mg/dL since virtually all patients will have blood glucose determinations that meet or exceed the diagnostic criteria for diabetes mellitus.

PURPOSE
OGTT is used to diagnose [or rule (R/O)] overt diabetes, glucose intolerance, cushing’s syndrome, and acromegaly.

FINDINGS

A.Normal
Adult, Non-pregnant :
Fasting blood glucose 115 < mg/dL
After 75 gm of oral glucose : [30 min < 200 mg/dL], [60 min < 200 mg/dL], [90 min < 200 mg/dL], [120 min < 140 mg/dL]

B.Abnormal
Adult :

a.Diabetes Mellitus
Sustained elevated blood glucose levels during at least 2 OGTTs.
The 2 hour sample and at least one other between 0 and 2 hr > 200 mg/dL.

b.Impaired Glucose Tolerance :
[2 hr OGTT blood glucose level of 140 to 200 mg/dL],
[0 to 2 hr OGTT blood glucose level > 200 mg/dL]

c.Gestational Diabetes
This diagnosis may be made if 2 blood glucose values equal or exceed : [Fasting : 105 mg/dL], [1 hr : 190 mg/dL], [2 hr : 165 mg/dL], [3 hr : 145 mg/dL]

PHARMACY IMPLICATIONS
1.Patient should be instructed to fast overmight (12 hr)
2.75 gm glucose (Glucola) is given to nonpregnant women on morning of the test.
3.Insulin or oral hypoglicemics should not be given until after test is completed.
4.The following drugs should be discontinued at least 3 days before the test: hormones (including oral contraceptives), alcohol, salicylates, indomethacin, diuretics (especially thiazide), guanathidine, hypoglycemic agents, propranolol, corticosteroids, MAOIs, lithium, nicotinic acid, phenothiazines, and ascorbic acid.

Source : Boh, L,E (ed), 1996, Clinical Clerkship Manual, Applied Therapeutics,Inc. Washington, 6-19

GENETIC ASPECT OF LGI CANCER

2009-11-09T05:49:00.000-08:00

GENETIC ASPECT OF LGI CANCER

The development of colorectal cancer from normal ephithelium is a multistep process. The process had been proven to be a sequence of genetical changes including activation of protooncogens as well as inactivation of tumor suppressor genes. Numbers of these genes, which involved in complex process of colorectal tumorigenesis, are inactivation of APC gene on chromosome 5q (80% of colorectal cancer), activation of ras oncogene on chromosome 5q, 17p and 18q (50% of colon cancer), inactivation of p53 tumor suppressor gene on chromosome 17p, deleted in colon cancer (DCC) gene at chromosome 18q22 (70% of colorectal cancer) and the presence of microsatelite instability (MSI) on chromosome 2p, 2q, 3p, and 7p in Hereditary Nonpolyposis Colon Cancer (HNPCC).

A colon cancer progression model is initiated by mutation of APC gene and abnormal methylation of DNA which cause hyperproliperative epithelium followed by mutation on K-ras gene which cause the progress of the hyperproliperative epithelium to be adenoma and DC LOH and LOH on chromosome 18q which cause the progress of adenoma to be carcinoma. Finally, the mutation of p53 gene lead to the end of carcinogenesis process as invasive cancer. The model show a significant relation between molecular changes and morphological features of colorectal tomurigenesis.

(By Syarifuddin Wahid, Division of Clinical Pathology Department of Hasanuddin University of Medicines, Indonesia)

Your Responsibilities to Yourself as a Patient

2009-10-21T19:58:00.000-07:00

Your Responsibilities to Yourself as a Patient

We are still to need the data about consideration by the patients to their prescription medications in Indonesia. Studies of medication usage in USA performed over the past 15 years have shown that more than 50 % of patients take their prescription drugs incorrectly. There are a variety of reasons that contribute to this wasteful and sometimes hazardous practice.

James W. Long,M.D. was writing six points for consideration by the patient in his book : Essential Guide to Prescription Drugs, 1993. I want to quote four points of them that important followed if you are a patient. The information you need to know for safe and effective drug use. The following suggestions are offered to reduce confusion and misunderstanding and to increase the likelihood that you take the right drug for the right reason at the right time and the right way.

If you are being treated for a recurrent or chronic disorder (such as asthma or diabetes), learn as much as you can about the nature and medical management of your condition. Ask your physician and pharmacist for written information they may have available for distribution; visit your local libraries and book stores for pertinent publications; consult local chapters of national organization that provide educational materials for specific disorders. The more you know about your disorder and its treatment, the more able you will be to use your prescribed medications safely and effectively.
Cooperate fully with your physician and pharmacist to ensure that the diagnosis of your disorder is as accurate as possible and that treatment prescribed is the most appropriate for you. It is incumbent upon you to share the responsibility for obtaining safe and effective drug treatment.
Do not be unduly influenced by seductive advertising of prescription drug products to the public through television commercials, magazine displays, celebrity endorsements, etc. Ask your physician and pharmacist for unbiased, objective information regarding the drug’s benefits and risks-and its appropriateness for you.
Your responsibilities – to yourself – as a patient:

Know both the generic and brand name of all drugs prescribed for you.
If you are taking more than one drug, be sure that the label of each container includes the name of the drug and the condition it treats.
If you do not clearly understand the directions for using a drug, consult your physician or pharmacist before taking it.
Follow all dosing instructions carefully and completely. Comply fully to obtain the maximal benefit the drug can provide. If you have trouble remembering to take your medications “on time”, ask your pharmacist for a dosing calendar or a weekly medication box.
If you are taking medications prescribed by more than one physician, check the generic names of all prescriptions to ensure that you are not taking duplicate drugs with different brand names. This could cause serious 'overdosage'.
Nonprescription drugs can interact unfavorably with prescription medications. Ask your physician or pharmacist before you begin taking any new over-the-counter preparations.
Be certain all drugs you take are “in date”-have not expired according to the dating on the label.

General practice prescribing is a co-operative exercise between the patient/client, physician and pharmacist. Good communications between all three leads to a successful outcome. The physician often however, and studies show that pharmacist spend more time explaining drug treatments to patients than physicians do. Similarly, a patient's first request for help may be to a pharmacist who may suggest that a physician’s advice or prescription is needed.

The physician and pharmacist thus work together, with the pharmacist sometimes providing a safety net for errors arising out of a physician’s and book stores for pertinent publications haste or inexperience. Naturally if a patient already has a clear idea on the medical condition outcome is much more likely to be assured.

The criteria for selection of a drug include the following :

The drug is used to treat a serious or significant disease or disorder.
The drug is recognized by experts to be among ‘the best choices’ within its class.
The benefits of the drug equal or exceed its risks.
The safe and effective use of the drug requires special information and guidance for both the health care practitioner (physician, dentist, pharmacist, nurse) and the health care consumer (patient and family).
The drug is suitable (safe and practical) for use in an outpatient setting – usually self administered in a nonmedical environment (home, work, site, school, etc.).

Andi Surya Amal, SSi,Apt,M.Kes

References :
1 Long,J.W.,1993, The Essential Guide to Prescription Drugs, Harper Perennial, A Division of Harper Collins Publisher.
2 ………., 1993, Medicines; A Comprehensive Guide, Parragon.