Prevention is still the best medicine

A scratchy throat and a few sneezes. The day's just beginning, but already you know what's in store for the next week or so. Check the tissue supply - it's another cold.

You can expect to get from 2 to 4 colds in any given year. Yet, as common as colds are, there's still no known cure. Prevention remains your best defense.

Anatomy of a cold

More than 200 different viruses can cause the common cold. Although the cold season generally runs from early September through March or April, Cold viruses are always around. It's just that exposure to a virus is more likely during that time because you're spending more time indoors and in closer contact with people.

"Contact" is the key to how cold viruses spread. You may literally pick up a cold through hand-to-hand contact with another person who has a cold. Once the virus is on your hands it can easily become your next cold if you inadvertently touch your eyes, nose or mouth.

Cold can also be acquired by using shared objects (such as telephone or towels) that are contaminated with a virus. And they can be acquired by inhalaing infectious particles that are briefly airborne following a sneeze or cough.

How susceptible you are to a cold virus depends on several factors :

Your age
Your genetic makeup
Whether you smoke
The intensity and duration of exposure
Whether you already have antibodies to the specific virus

Is it a cold or influenza?

Symptoms Cold Flu
Fever Rare Typical, 102-104F,3 to4
days or more
Headache Rare Prominent
Cough Dry or productive Dry, can become severe

Fatigue,weakness Very mild Can last up up to 2 to 3 Weeks
Extreme exhaustion Almost never Early and prominent
Aches, pains Slight Usual and often severe
Stuffy nose Common Sometimes
Sneezing Usual Sometimes
Sore throat Common Sometimes
Chest discomfort Mild Common

Pass the tissue

When a cold virus strikes, your upper respiratory tract becomes inflamed. Cold symptoms generally develop 2 or 3 days after you've picked up the virus. Typical symptoms may include a runny nose, sneezing, congestion in your nasal passages and sinus, membranes, sore throat and cough.

Colds can last anywhere from 2 to 24 days, but most people recover in a week. During that time, getting extra rest and drinking plenty of warn liquids may help you feel a little more comfortable. In addition, appropriate use of over-the-counter (OTC) cold medications may provide temporary relief, although these products aren't necessary to recover from a cold.

Although there are antiviral medications to help treat influenza (flu), no antiviral medications are on the market to treat colds. Antibiotics aren't useful in treating a cold virus. They're helpful against bacteria, but not viruses. Unnecessary use of them increases the risk of developing antibiotic-resistant bacteria.

Alternative treatments

The hope that there's something but here that will get rid of a cold accounts for alternative treatment you may have heard about.

OTC remedies - it's a jungle out there

Drugstore Shelves are loaded with over-the-counter (OTC) products to help you cope with the common cold. These products won't shorten a cold, but when used appropriately they may help relieve some of its symptoms:

Antihistamines (Such as Benadryl, Chlor-Trimeton, Tavist) - These can decrease nasal secretions and help relieve sneezing and a runny nose. Antihistamines may be most helpful when used early in a cold. However, use them with care as they can make you drowsy.

Antihistamines can make urination more difficult if you have an enlarged prostate (benign prostatic hyperplasia). In addition, they shouldn't be used if of you have certain kinds of glaucoma.

Decongestants (such as Neo-Synephrine, Sudafed) - These relieve congestion and stuffiness by constricting nasal blood vessels. Nasal sprays should be used no more than 3 to 4 days, after which a "rebound" effect is possible - congestion may actually become worse.

Decongestants may increase blood pressure. It's usually best to avoid using a decongestant if you have heart disease or high blood pressure or if you take beta blockers.

Cough medicines - There are two types. Antitussives (suppressants) are products containing dextromethorphan or codeine and its derivatives. They reduce cough frequency for people with a persistent, dry cough. Expectorants - products containing guaifenesin (gwi-FEN-uh-sin) - loosen mucus in the chest and make it easier to cough.

Pain relievers - Generally, acetaminophen (Tylenol) is preferred for aches, pains and fever. Ibuprofen or aspirin may be good choices, too, but may cause bleeding problems if taken in high doses over a long period or if you're also taking blood thinning drugs (and children should avoid aspirin).

Cough/cold combinations - These products are designed to relieve multiple cold symptoms and should not be taken with other OTC medications. Generally, it's best to avoid combination cold medications. And instead use individual products when they'll have the most benefit.

Talk with a pharmacist or your doctor before combining various cold medications or taking them with other prescription medications.

Among the possibilities that have been tried and studied (to varying degrees) are:

Vitamin C - This vitamin is a good antioxidant, so it's been suggested that adequate levels may help strengthen resistance to viral infections and even act as a mild antihistamine (which can decrease nasal secretions). However, no good studies exist demonstrating that vitamin C has much impact when it comes to colds. Nonetheless, there's probably no harm in taking a daily vitamin C supplement of up to 500 milligrams (mg)

Echinacea - This herb is thought to stimulate the immune system. Some studies show that Echinacea purpurea and Echinacea pallida probably don't prevent colds or influenza, but they may help shorten their duration. Other studies question those results.

Echinacea, like other dietary and herbal supplements, isn't subject in this country to the same rigorous review standards as drugs are. Product purity and potency are uncertain - "buyer beware" is still the best attitude.

Talk with your doctor before you decide to use this herb. Generally, Echinacea shouldn't be used for more than 4 weeks at a time as overuse has the potential to actually suppress your immune system. Echinacea shouldn't be taken if you have diabetes, immune system diseases (such as rheumatoid arthritis and HIV infection).

Zinc - Debate continues over the value of zinc in reducing the severity and duration of a cold. A study in 1996 created a lot of excitement when cold systems disappeared a full 3 days earlier among study participants who took zinc lozenges at the onset of their cold. However, subsequent studies have had mixed results, with some showing benefit and some not.

Although more research is needed, using zinc to treat a cold isn't likely to harm most people. However, before taking zinc, talk with your doctor. People with stomach or duodenal ulcers shouldn't take it.

In addition, zinc shouldn't be taken for more than a week or so as high doses (150mg/day or more) over an extended time can weaken the body's immune function.

When to see the doctor

Generally, it's not necessary to see your doctor when you have a cold. Sometimes, though, a cold takes a turn for the worse and a secondary infection develops, such as strep throat, pneumonia or a sinus infection.

Call your doctor if you experience any of the following :

• A fever higher than 102 F that lasts beyond the first few days of a cold
• Ear, sinus, tooth or throat pain that is severe or persists for 3 days rash
• A cough lasting more than 2 weeks or that produces blood
• You seem to be getting over your cold but then it comes back or you start feeling worse

You should see a doctor immediately if you experience breathing
problems (such as shortness of breath or wheezing), chest pain or difficulty swallowing.

An ounce of prevention

Washing your hands with soap remains the most effective way to avoid getting a cold. One study indicates that washing your hands with regular dish washing soap might be particularly effective against viruses. In addition, keep unwashed hands off of your face, particularly your eyes, nose and mouth.

After water, tea is the most commonly consumed beverage in the world, and drinking it has been linked to slew of health benefits. Now recent research shows that the billions of people who drink it may be on to something.

Tea and Heart

One area in which tea is supposed to be beneficial is in fighting cardiovascular disease. A recent study published in circulation, the journal of the American Hear Association, found that heart patients who drank copious cups of tea were less likely to die 3 or 4 years after a heart attack.

Researchers at Beth Israel Deaconess Medical Center and the Harvard Medical School interviewed 1900 patients who had been hospitalized following a heart attack. The subjects were asked about their tea consumption over the last year and divided into three groups : Non-drinkers, moderate drinkers (fewer than 14 cups per week), and heavy drinkers (14 or more cups per week). After a follow-up period of almost 14 years, the moderate group was 28% less likely to die, while the heavy use group had a 44% lower death rate, after taking into account differences in lifestyle (such as smoking and exercise) and medical conditions.

"If the true effect of tea in clinical trials is anywhere near what we saw, this will be of great public health importance," says Kenneth Mukamal, MD, assistant professor of medicine at Harvard Medical School and an associate in medicine at Beth Israel Deaconess Medical Center. Additional research needs to be done, but he hopes that this work will spur controlled studies in the future.

What's in those tea leaves?

The curative power of tea may be due to the antioxidants it contains known as flavonoids, which are thought to prevent cardiovascular disease. Flavonoids may help lower LDL ("bad") cholesterol, and studies have shown that they may have an anti-clotting effect as well. They are found naturally in green and black tea, as well other foods such as apples, anions, and broccli.

A recent study appearing in current opinion in Lipidology analyzed previously published research on the health benefits of tea and found that 150 milligrams of flavonoids - the amount found in a cup of brewed tea - was enough to have an immediate antioxidant effect. Consuming higher doses of flavonoids, or additional cups or tea, increased the effect.

Drinking tea may fight cancer

Tea's benefits may derive from more than just flavonoids, however. It also contains catechins, another powerful antioxidant belonging to a group of chemicals known as polyphenols. Green tea, which is the least fermented type of tea, contains the most catechins, followed by oolong and black teas. Research has shown that catechins may halt tumor cell growth and protect healthy cells from damage.

At a recent meeting of the American Association for Cancer Research, researchers at the Keck School of Medicine at the University of Southern California presented a study conducted with colleagues at the Shanghai Cancer Institute in China that showed tea drinkers were about half as likely to develop stomach or esophageal cancer as nontea drinkers.

Over 18,000 men in Shanghai, China were followed and the 232 subjects who developed one of these types of cancers were compared to 772 similar subjects without cancer. Researchers measured epigallocatechin (EGC), a substance that's produced when catechins break down, and found that subjects who had more EGC in their urine had a lower cancer risk.

This was the first study that used a biomarker to measure substances found form drinking tea, as "I'm not sure our study means people should fill up their cupboards with tea," Says Mukamal, "but it points to the possible health benefits." Considering there are no risks to drinking tea - if you don't load it up with sugar and high fat milk - he says it may make sense to discuss it with your doctor and add it to whatever you're already doing.

Sources :

• Beth Israel Deaconess Medical Center/Harvard
• Medical School
• USC Keck School of Medicine
• Beltsville Human Nutrition Research Center
• Current Opinion in Lipidology
• General Dentistry
• University of Chicago, Tang Center for Herbal
• Medicine Research

Every one is talking about antioxidants ! A major pharmaceutical company runs full-page ads in newsmagazines pointing out the dangers of oxidative stress while mentioning that three of their multivitamins products can protect you from excess oxidation. Sales of vitamins have been increasing by 20 to 30 percent per year, and much of the growth can be credited to antioxidant formulas. Animal studies and several large controlled human trials point to the wisdom of taking antioxidant supplements, especially vitamin E to help prevent heart disease and cancer.

It is useful to know what oxidative stress is and which compounds normally found in our bodies protect us from the damaging effects of oxygen. This demonstrate how antioxidants can be protective, and it can also help you decide what might be the most important antioxidant for you to take.

This chapter explains antioxidant in the context of a regimen for good health.

OXYGEN RADICALS

Only some microorganisms (and plants), known as anaerobes, can live without oxygen; most, including humans, need oxygen. Anaerobes make energy by breaking down preformed carbohydrates and proteins, but energy-wise this process is inefficient. Most microorganisms and all animals (including humans) use oxygen to "burn" or oxidize foods into carbon dioxide and water. A great deal of energy is produced as a result of this process. Metabolizing one molecule of glucose with oxygen produces about four times as much energy as could produced if the same molecule were to be metabolized without oxygen. In our bodies, carbon from food is oxidized to carbon dioxide. Oxygen superoxide grabs electrons from a neighboring source and combines with hydrogen to form water. The reduction of oxygen is accomplished in special structures inside body cells called mitochondria. Carbon dioxide that results from this process is eliminated in our breath, urine, and sweat. Plants use the carbon dioxide we produce to make oxygen. This is a very nice ecosystem, and one we need to be careful not to disrupt.

But the system isn't perfect. Did you ever notice how rubber or plastic becomes brittle and cracks after some time has passed? This happens when these materials react with oxygen in the air to produce a modified plastic or rubber that is not as soft and flexible as the original. We live in an environment filled with oxygen, and this is exactly what happens to our bodies as we age. Our skin loses flexibility and starts to wrinkle; our organs don't work as well; our blood vessels get clogged with plaque, putting us at risk at a heart attack or stroke; and we are at a higher risk for cancer. Oxygen is not the only reason that our bodies deteriorate, but it is part of the picture.

Oxygen damage body tissues after long periods of exposure because tiny amounts of chemically reactive oxygen are produced in the everyday reduction of oxygen in the mitochondria. This reaction sometimes occur in other parts of our bodies as well. Reactive oxygen molecules that cause the problems described above are called free radicals. They will reach out to whatever is close by and attach to it. Let's say, for example, that the free radical combines with a lipid molecule in a kidney cell membrane. The lipid molecule is now a reactive radical itself and can react with another oxygen molecule to form a lipid peroxide radical. Meanwhile, a neighboring radical reacts with oxygen in the same process. This can continue until the kidney cell is permanently damaged. In theory, a single radical could destroy us with this chain reaction!

Actually, there are many different kinds of oxygen radicals. The most important are superoxides, hydroxy radicals, and perhydroxy radicals. These are extremely reactive and will combine immediately with anything nearby. There is another reactive from of oxygen as well, called singlet oxygen.

Oxidative injury is implicated in a long list of disease. Following are some of the more important examples.

DISEASES RELATED TO OXYGEN RADICALS

Hardening of the Arteries (Atherosclerosis)

We have "good cholesterol" and "bad cholesterol" in our bodies. Good cholesterol is attached to lipids called HDL (high-density lipoproteins). Bad cholesterol is attached to LDL (low-density lipoproteins). One reason that the LDL cholesterol is bad is that it can from plaques in our arteries. When a plaque cracks or is otherwise activated, a blood clot can from that blocks blood flow through the artery. If the clot is in an artery that supplies heart muscle, the blood supply to part of the heart is blocked. This lead to chest pain or a heart attack. If the clogged arteries carries blood to the brain, a stroke or TIA can develop. If the clogged artery is in the leg, pain develops on exercise, and in very severe cases leg amputation may be needed.

In the past decade it has become apparent that the free 0 radical oxidation of LDL is important to the process of plaque formation. This is one of the most important findings for heart disease and stroke prevention to date and provides many ways for people to help decrease their risk of heart disease.

Unmodified LDL does not begin the process of plaque formation. It can be inappropriately oxidized in the artery wall, though. Once LDL reacts with an oxygen radical, it is seen as a foreign substance by body defense systems and is attacked by protective cells called macrophages. Unfortunately, the process can be destructive, and the oxidized LDL sets up an inflammation in the outer layer of the artery that leads to a "fatty streak" and, later, a plaque deposit. Both can start the process of blood clotting. Chemicals, including antioxidant vitamins, that neutralize free radicals can help block plaque formation and may reduce the risk of heart attack and stroke.

The Complications of Diabetes

High glucose levels in blood and tissues that result from diabetes lead to increased LDL oxidation. Diabetes have an increased incidence of coronary and vascular diseases, and antioxidants have the potential of decreasing some of the LDL oxidation associated with diabetes.

Cancer

Exposing DNA in our cell nuclei to free radicals may result in DNA strand breaks and mutations, leading to cancer. Chronic inflammation and injury generate free radicals as part of the process, which helps explain why these conditions increase the risk for the development of cancers. For example, the hepatitis viruses often cause a chronic liver infection that sharply increases the risk of liver cancer. The inflammation caused by inhaled asbestos results in high risk of lung cancer. Antioxidants have the potential to decrease cancer risks by neutralizing the free radicals causing damage.

Inflammation

Body cells whose job is to engulf and destroy bacteria and damaged tissue particles accomplish this by producing short bursts of hydrogen peroxide and superoxide. For reasons that are not well understood, the process can get out of hand and these chemicals set off reactions like the one outlined earlier, leading to tissue injury. The reaction products of free radicals are detected in synovial fluid. The chain reaction sequence described earlier is probably important is spreading the inflammation and damage. Arthritis is one example of this situation, and antioxidants have the potential to help prevent inflammation.

Reperfusion Injury

If blood flow to an organ or tissue is temporarily shut off and then restarted, the influx of oxygenated blood causes injury over and above that caused by the temporary oxygen loss. Apparently, a lack of oxygen reduces the ability of body tissues to neutralize radicals. When radicals are generated with the influx of oxygen, damage results. This is a problem in organ transplantation and heart surgery, where blood supply is temporarily interrupted during the procedure. Antioxidants have the potential to reduce this injury.

Aging

Radical reactions certainly play a role in declining body function as we age. The immune system weakens, blood vessels get stiff and clogged, and organ function begins to decline. DNA strand breaks result in mutations that may start cancers. Cigarette smoke, ionizing radiation, and certain chemicals all increase the amount of free radicals and accelerate the aging process. For example, the wrinkled facial skin of the longtime smoker is due to free radical damage to the fabric to the skin by way of reactions discussed here. Antioxidants have the potential to minimize some aspects of the aging process.

Eye Disease

Premature infants who receive life-saving oxygen sometimes suffer damage to the retina of their eyes because the protective systems that neutralize oxygen free radicals are not yet in place. Degeneration of the retina, common in the elderly, is thought to be due in part to the inability of eye tissue to neutralize free radicals. Antioxidants have the potential to help prevent certain eye diseases.

Other Diseases

We could cite many other examples of conditions where oxygen radicals are thought to play an important role. If oxygen radical reactions could be blocked or minimized by drug or vitamin treatment, we might not cure disease, but we would certainly have a valuable treatment and prevention strategy.

THE BODY'S DEFENSES AGAINST FREE RADICALS

If radical reactions went unchecked, we would all have a very short lifespan. Fortunately, we are well equipped to survive in an oxygen - rich atmosphere. The burning questions are : Can we further enhance these protective mechanisms with dietary supplements? If we accomplish this, will it result in better health? We believe the answer to both questions is a resounding yes.

First let us consider our natural protective mechanisms and then see how several vitamins fit in. The most direct way to block free-radical-induced damage is to neutralize the radical where it is generated. A critically important nutrient, vitamin E, is well poised to do this. The chemistry of vitamin E is nearly perfect for its task. It dissolves in fat, so it can move in and through the lipidlike cell membranes. It can pick up that lone unpaired electron from a carbon-centered or oxygen radical to form a less reactive vitamin E radical.

Vitamin E is considered a chain-breaking free-radical scavenger because it removes the radical and stabilizes it. The vitamin E radical is chemically much more stable than other radicals. As such, it doesn't do damage to neighboring molecules. Eventually, however, we need to regenerate the E and to neutralize the vitamin E radical. This is done with the help of another remarkable vitamin, vitamin C. Unlike vitamin E, vitamin C dissolves in water and can accept the unpaired electron from E sitting in the lipid membrane. Now the radical is the vitamin C in the fluid outside the cell membrane. The vitamin C by enzymes with the aid of NADH, a coenzyme form of niacin. Now we are out of danger thanks to three vitamins.

More protective modalities exist as well. An enzyme called superoxide dismutase is also very important. This enzyme causes the inactivation of superoxide to form less reactive hydrogen peroxide and oxygen. There are two superoxide dismutase enzymes. One is in cell mitochondria and contains manganese. The other is found in fluid outside the cell and contains copper and zinc.

Hydrogen peroxide, generated by the breakdown of superoxide, requires either of two other enzymes, glutathione peroxidase or catalase, to convert the reactive hydrogen peroxide molecule to water and oxygen. You may have seen catalase in action if you have ever put hydrogen peroxide liquid on an a open wound. The "fizz" is the oxygen released by the action of catalase in the wound on the added hydrogen peroxide.

Earlier we mentioned singlet oxygen as another reactive molecule. The carotenoids, precursors of vitamin A, are chemically designed to neutralize singlet oxygen. Beta carotene is the most well known carotenoid, but there are many others. Other chemicals in the body can also react with radicals to render them harmless. These includes melatonin, coenzyme Q10, bioflavonoids, lycopene, and uric acid, but their exact roles are less well established.

Table 1. Antioxidant Vitamins and Minerals

And there are yet more protective mechanisms. Earlier we said that lipid peroxides are dangerous because they undergo complex reactions that can damage a cell or membrane. Several vitamins and one mineral are involved in stopping this dangerous reaction. An enzyme called glutathione peroxidase stimulates the conversion of organic peroxides to relatively harmless organic alcohols. This critical enzyme requires selenium to function. In the reaction, glutathione is oxidized to glutathione disulfide. In order to regenerate glutathione, a series of enzymatic reactions occurs involving thiamin, riboflavin, and niacin.

Oxidative stress is the term used to describe a risk for damage from oxygen radical reactions due to an imbalance between oxidants and antioxidants. Oxidative stress can lead to damage and disease. Table 1 present a summary of the antioxidants vitamins and minerals and their role in protection from the damage of oxidative stress.

CAN ANTIOXIDANT SUPPLEMENTS PREVENT CANCER AND HEART DISEASE?

Cancer and heart disease kill more people than any other disease. Basic research indicates that oxidative stress plays a role in these diseases, and animal research has indicated potential for antioxidant vitamins to help in preventing them. Here we will focus on studies of the potential effects of antioxidant vitamins in heart disease and cancer. Radicals may be involved in the development of other diseases, but they will be discussed only briefly because evidence for their effect is more limited.

Epidemiological or population studies show generally that dietary antioxidant vitamins have value in preventing heart disease and cancer. In recent years several placebo-controlled human studies targeting this effect have been completed. The results of these specific studies are encouraging but not in uniform agreement; two large studies of the preventive benefit of beta carotene that produced negative results have caused considerable on this tissue.

Dietary Studies

Early epidemiological studies of dietary habits supported the idea the antioxidants from dietary sources were associated with a reduced risk of heart disease and some cancers, especially lung cancer. These studies rely on huge data collections from several study populations. The Framingham Study is an example. Here a large segment of the population of Framingham, Massachusetts, has been followed for many years. Blood samples have been periodically taken, questionnaires completed, diets monitored, and the volunteers watched for changes in health status. This study and many similar studies from around the world consistently find that vegetable and fruit consumption is related to the risk for coronary heart disease and some cancers. That is, the more fruits and vegetables you eat, the lower your risk. At the high end of fruit and vegetable consumption is related to the risk for coronary heart disease and some cancers. That is the more fruits and vegetables you eat, the lower your risk. At the high end of fruit and vegetable intake, risk decreased by more than 50 percent compared to those eating the fewest fruits and vegetables.

What is it in the fruits and vegetables that may be protective? When the diets are analyzed, intake of Vitamin E, vitamin C, beta carotene, flavonoids, and the mineral selenium are related to disease risk, that is, the smaller the intake, the higher the risk. While these studies suggest a strong benefit for antioxidant vitamin intake, in one of their limitations that is impossible to control for all confounding variables. For example, it is possible that people eating a diet high in vitamin E have a lower risk for heart disease because they live a healthier lifestyle in general.

Population Studies of Vitamin Supplement Use

Several more recent large-scale human studies have looked not only at diet but also at vitamin supplements taken by the populations being studied. These results address the issue of antioxidant vitamin supplement value more directly, but there is still the question of whether people who take supplements also have other healthy lifestyle practices, which may account for some of the observed results. Nevertheless, the value of vitamin E supplements over and above the amount obtained from a standard multivitamin now seems apparent for help in the prevention of coronary disease.

For example, the Health Professionals Follow-up Study has followed 51,529 male health professionals since 1986. Participants filled out detailed questionnaires on their diet and supplement use. Based on the results of four years of observation, and after controlling for other risk factors, a lower risk of heart disease was noted with increasing vitamin E dietary intake in 39,910 men. Those at the high end of dietary intake had a 36 percent smaller chance of developing heart disease. Of special interest is the observation that people taking vitamin E capsules in daily doses between 100 and 250 IU per day had a 46 percent lower risk of heart disease compared to people who did not take a supplement. Supplements had to be taken for at least two years in order for them to have a protective effect. Dietary carotene intake did not have a protective effect, except in smokers and former smokers, nor did total vitamin C intake. Multivitamin use was only modestly protective and only in people who took multivitamins for more than ten years.

The Nurses Health Study of 89,245 nurses followed from 1980 to 1988 and showed that vitamin E had a similarly strong protective effect against heart disease. The greatest effect, a decrease in risk of almost 50 percent, was found in women who took more than 100 IU per day for at least two years, compared to those who took no vitamin E supplement. Vitamin C supplements and beta carotene intake were not protective. Again, taking a multivitamin was only modestly protective.

The final example is a study of 11.178 elderly people, ages 67 to 105 years, over a period of about ten years. In this population, at high risk for death from heart disease and cancer, vitamin E supplements had a striking effect. People who took vitamin E supplements separate from a multivitamin had a 37 percent lower risk of death due to heart disease. The risk for death due to cancer was 41 percent less in vitamin E users. Those who used both vitamin E and vitamin C supplements were somewhat better protected, with a 52 percent smaller risk of disease.

There was a trend for people to benefit from the combination of vitamins C and E in reducing cancer death, but vitamin C use alone did not protect against death from heart disease, cancer, or other causes. This study is the best one to demonstrate an advantage of taking both vitamin E and vitamin C. Multivitamin use was not shown to be protective in this study.

Primary Prevention Studies

The previous studies provide reasonable evidence that antioxidant vitamins, especially vitamin E, are useful to help prevent heart disease. The evidence for protection against cancer is weaker. More definitive proof of protection is obtained from studies in which healthy people without any evidence of disease take a placebo or an antioxidant vitamin and are followed for a sufficient length of time or until disease develops. These studies are called primary prevention trials. As you might imagine, primary prevention trials are expensive are very difficult to conduct. As a result, these large vitamin studies are generally funded by government health agencies.

For example, the ATBC study followed 29, 133 Finnish smokers for five to seven years. The volunteers received either 20mg of beta carotene, 50 mg of vitamin E, both vitamins, or an inactive placebo. Neither vitamin alone nor the combination had a protective effect against lung cancer. In fact, more lung cancers were found in the beta carotene group. This study has been criticized because of the low dose of vitamin E, because of the fact that synthetic beta carotene was employed, and because the smokers tested may have already had cancer before they entered the study.

A second study (CARET) gave 18,314 smokers , former smokers, or people exposed to asbestos either a combination of 30 mg of beta carotene and 25,000 IU of vitamin A or placebo. The study was stopped after four years because, as with the ATBC study, a significant increase in deaths due to lung cancer was seen in the beta carotene/vitamin A group.

A third study, the Physicians' Health Study, was remarkable in that 22,071 healthy physicians took either 50 mg of beta carotene or placebo every other day and were followed for twelve years. This study lasted longer and studied a healthier population than the other two. Beta carotene had neither a beneficial nor harmful effect in this study.

Another study, published by the same group of Finnish investigators who did the ATBC trial, looked at the effect of 50mg of vitamin E on prostate cancer in male smokers studies in ATBC. The researchers found that men who took 50 mg of vitamin E for five to eight years had a 23 percent smaller risk of developing prostate cancer, and those who did get prostate cancer were 41 percent less likely to die.

These large studies were disappointing for beta carotene proponents. We cannot say much about vitamin E from these studies because either it was not tested, the dose used was too low, or the results, as in the prostate cancer study, need to be confirmed.

Secondary Prevention Trials

A secondary prevention trials looks at whether the treatment will prevent a second occurrence of the disease being studied in a group of people who have already experienced the disease or who are at proven risk of the disease. Vitamin E has been shown to provide a benefit in several of these secondary prevention studies.

For example, 2,002 patients with heart disease were given a placebo or 400 IU per day of vitamin E for seventeen months. The vitamin E group had about 80 percent fewer nonfatal heart attacks, but the number of fatal heart attacks was about the same for both the E-treated and placebo groups.

Another study followed 156 men who had previous coronary bypass surgery. Vitamin E, at doses over 100 IU per day, reduced the worsening of heart disease compared to placebo. No benefit was seen for vitamin C, for multivitamin use, or for increased intake of dietary vitamin E.

In another study, patients with a previous colorectal adenoma who had had their polyps removed received either 400 IU of vitamin E with 1 gram of vitamin C per day or an inactive placebo. There was no difference between the placebo and vitamin E groups in the number of patients who needed surgery to remove adenomas after one year of treatment.

EVIDENCE OF ANTIOXIDANT SUPPLEMENT BENEFIT IN OTHER DISEASES

In older placebo-controlled studies, vitamin E has also been shown to be of some help in people with intermittent claudication, a painful condition due to poor circulation in the limbs. The origin of this disease is the same as a heart attack or stroke, atherosclerotic narrowing of the arteries, so it is not surprising that vitamin E can be helpful by virtue of its ability to reduce plaque formation and to decrease platelet stickiness.

An exciting finding was that vitamin E treatment somewhat slowed the rate of progression of Alzheimer's disease. A total of 341 patients received a drug called slegiline, a very high dose of vitamin, both or placebo. People taking vitamin E experienced a greater delay in disease progression than those taking selegiline alone or placebo. More recently, a study at New York's Memorial Sloan - Kettering Cancer Center found that one form of vitamin C, dehydroascorbic acid, can get through the blood-brain barrier, allowing large amounts of vitamin C directly into brain tissue. The researchers conclude that this technique may prove to be an important therapeutic advance in treating Alzheimer's disease and other conditions that result from damaged brain cells. Clearly, more studies of vitamins E and C in Alzheimer's disease are needed.

The final example has to do with the signs of aging. Free-radical reactions progressively damage the immune system as we get older. Investigators in Boston gave doses of 60, 200, or 800 IU of vitamin E per day or placebo to eighty0eight elderly subjects for four months. Tests of immune function and antibody response to vaccinations showed that vitamin E improved immune function. The effect was generally better in the group receiving 200 mg per day.

RECOMMENDATIONS FOR TAKING ANTIOXIDANTS VITAMINS

Taking antioxidant vitamins is a modest and inexpensive action you can take to decrease the risks of cancer, heart disease, and other conditions associated with aging. The operative word here is modest. It is very important to bear in mind that the largest benefit of vitamin intake is smaller than the benefit that can be achieved by making important lifestyle adjustments such as stopping smoking, losing excess weight, and exercising. While there is disagreement over the value of antioxidant supplements, there is uniform agreement that a diet high in vegetables and fruits and fiber is protective. Your mother was right : Eat your vegetables.

Having improved your lifestyle, can you expect further benefit by taking high doses of antioxidant vitamins? We believe that the evidence says yes for vitamin E, yes for vitamin C in combination with vitamin E, and no for beta carotene; it's inconclusive for the other antioxidant supplements. Here are our recommendations for taking antioxidant vitamin supplements.

1. Take a multivitamin supplement with minerals every day. Make sure the supplement contains selenium and folic acid and 100 percent of the RDA for each of the eleven vitamins. This product will provide all of the vitamins you need for optimum antioxidant status, except vitamins E and C, and will provide adequate amounts of selenium. A generic product containing 100 percent of the RDA value of all vitamins and selenium can be purchased for $4 to $8 per 100 tables. This is inexpensive and safe insurance.
2. Take 200 to 400 IU of natural vitamin E everyday. Higher doses are not needed and lower doses have proven to be less effective in human studies. Natural vitamin E is absorbed and utilized better that the synthetic form, though most clinical studies have used the synthetic. The label should say d-alpha tocopherol. If it does not or says d1-alpha tocopherol, it is synthetic vitamin E.
3. Take 250 to 500 mg of vitamin C every day. Generic, synthetic vitamin C is fine. As discussed, the vitamin C works together with vitamin E in removing damaging oxygen radicals. Vitamin C without vitamin E does not appear to be especially helpful.
4. Eat a few carrots everyday and increase your intake of other vegetables. The carrot will provide a nice mixture of carotenoids, and the other vegetables will provide flavonoids shown to have protective antioxidant properties. Avoid taking a synthetic beta carotene supplement. Evidence from large human clinical trials says it does nothing for, or might be even harmful to, smokers or former smokers. Beta carotene, at least the synthetic variety, is not the magic ingredient in vegetables that provides protection.
5. Avoid specialty antioxidant products. They are expensive and often contain ingredients of unproven value.
6. Don't give up on this program. Studies show that vitamin E will benefit you only after you have taken it for many months

No other vitamin has attracted as much attention from both basic scientists and clinical scientists over the past decade as vitamin E. Interest grew as researchers learned that oxidative damage to vital tissues plays an important role in the development of many chronic diseases and in the aging process. The presence of vitamin E in cell membranes helps protect the cell because it serves as a fat-soluble free-radical scavenger and antioxidant. It works hand in hand with the other antioxidant vitamins and compounds in the body. And it explains the role of antioxidant vitamins and evidence for their usefulness in maintaining good health. This section summarizes the properties of vitamin E.

FUNCTION

Vitamin E sits in cell membranes, and its primary function is as a biological antioxidant and cell membrane protector. Oxygen is life-giving, but it can also be harmful. One of the most potentially damaging reaction involving oxygen is with unsaturated fatty acids. Free radicals generated during normal metabolic reactions in which oxygen is involved can react with unsaturated fatty acids in cell membranes to form substances called organic peroxides. Organic peroxides are toxic to cells because they can take part in a chain reaction with other neighboring fatty acids, eventually destroying the cell. Without vitamin E and other antioxidant vitamins, oxygen can, in effect, convert fluidlike unsaturated fatty acids to inactive solids, rendering them unable to function. The body has several other antioxidants and free- radical- scavenging compounds that back up and complement the action of vitamin E after it has been inactivated by picking up a free radical.

There is a ample research on this role for vitamin E. For instance, people who eat more polyunsaturated fat in their diet need more vitamin E to prevent cellular damage. Relatively little vitamin E in the diet may lead to the deposition of oxidized fats in tissues. That is not to say that vitamin E can stop the aging process; it cannot. But it is possible that vitamin E deficiency may speed the aging of essential tissues. Unless free radicals are quenched, they can react with blood fats, setting up an inflammatory process associated with atherosclerosis that leads to the formation of blood clots, and possibly heart attack. A free-radical attack on the cell nucleus can result in mutations that could lead to cancer. Low vitamin E intake has been associated with a higher risk of heart disease and cancer. Thus vitamin E's main function is unlike most other vitamins in that it does not participate in biochemical reactions. Rather, vitamin E simply acts as a sponge to soak up damaging free radicals.

DAILY REQUIREMENTS

The strength of vitamin E was originally based on measures of biological activity and expressed in international units (IU), and different forms of the vitamin have slightly different IU equivalents.

In human nutrition, the most important form of vitamin E is alpha tocopherol, and the natural form of this substance is d-alpha tocopherol. It has strength of 1.5 IU per mg. Synthetic alpha tocopherol, d1-alpha tocopherol, come in two types: d1-alpha tocopheryl acetate has a strength of IU per mg, and d1-alpha tocopherol has a strength of 1.1 IU per mg. In 1980 the RDA for vitamin E was changed from IUs to d-alpha tocopherol equivalents (TE). One TE is mg of d-alpha tocopherol and also to 1.5 IU. Vitamin products still use IU to express the amount of contained vitamin E. Nutrition tables have switched to TE values, however.

Based on early studies, an RDA of 30 IU of vitamin E per day was set in 1968. In 1974 the National Research Council reduced the RDA to 10 TE for adult males and 8 TE for adult females on the basis of dietary surveys that revealed that most diets contained between 10 and 15 IU per day. The RDA value has not been altered since 1974. Since there were no obvious sign of vitamin E deficiency in the United States, it was assumed that the previous recommendation was too high. This decision was extremely controversial. On one hand, there was no evidence that 15 IU per day would not satisfy human needs for the vitamin. On the other hand, emerging knowledge of the important role vitamin E plays in removing damaging free-radical compounds in the cells suggests to many that more, not less, vitamin E is needed for optimal health. Since vitamin E is nontoxic, it is not unreasonable to push for higher intakes. This controversy is still not settled. While it would be difficult to get more that 30 IU from food, it seems prudent to increase our consumption of whole grains and unprocessed foods to increase vitamin E intake. Vitamin E supplements may be warranted as discussed in "Antioxidant Vitamins".

DIETARY SOURCES

The tocopherols are made by plants, probably as protection against oxidation of other vital fatty acids. Animals pick up their tocopherols from plant sources and use them as protection from the adverse effects of oxygen. There are more than six tocopherols found in plants, but alpha-tocopherol is the most potent. Unlike vitamins A and D, which are stored only in body fat and the liver, vitamin E is found in all body tissues in the cell membranes, so it is present in meats, but in rather low amounts. Over 60 percent of the dietary vitamin E consumed in the United States comes from plants, especially from corn or cottonseed oil, green vegetables, and wheat germ. Other good sources are listed in the accompanying table.

Vitamin E is destroyed in the presence of oxygen and heat. Thus the vitamin E content of foods variety widely depending on how they were handled during processing and storage. Prolonged freezing of vitamin E - containing foods will destroy vitamin E content unless care is taken to prevent exposure to air. Eating uncooked fresh fruits and vegetables will help increase vitamin E intake.

Vitamin E Content of Selected Foods
(Average adult RDA is 10 TE, or 15 IU)

DEFICIENCIES

Most vitamin E deficiency signs and symptoms are related to oxidative damage to cell components. One perplexing point is that while a vitamin E - deficient diet is life-threatening to animals, humans are not affected as severely. Vitamin E - deficient animals develop sterility, liver damage, muscular dystrophy, heart degeneration, and anemia, but no such vitamin E deficiency symptoms exist for humans. Part of the reason for the difference may be that vitamin E is widespread in our diets and that we have some reserves stored in our body fat.

A true human vitamin E deficiency state was not discovered until the 1960s, when a group of premature infants was accidentally given formula with no vitamin E. The infants became anemic and developed edema that responded to vitamin E treatments. In Illinois, a group of volunteers was given a diet with low levels of vitamin E. These studies showed that red blood cells from normal individuals survived longer than cells from those who were vitamin E-deficient. There were no other obvious deficiency signs in the volunteers. The findings of this study, which originally set out to determine how much vitamin E would be needed to return the volunteer's red blood cells to normal, led to the 1968 recommendation by the Food and Nutrition Board to set the RDA at 30 IU of vitamin E.

Patients who have a problem absorbing and digesting dietary fats may with the time develop a vitamin E deficiency. People with bile problems have difficulty absorbing fats, as to premature infants and cystic fibrosis patients. After several years, signs of nerve damage being to appear, leading to loss of reflexes, loss of sensation, muscles weakness, problems with eye movement, and difficulty with balance and coordination. If the vitamin E deficiency is not corrected, the damage may be irreversible.

Because of the high susceptibility of the red blood cell membranes to oxygen damage, hemolysis may occur in people deficient in vitamin E. Patients with inherited conditions that predispose them to oxidative stress, such as glucose-6-phosphate dehydrogenase (G6PD) deficiency, are prone to vitamin E deficiency. Iron is a pro-oxidant that can place an increased demand on vitamin E stores. Patients taking an iron-containing product or those who have trouble eliminating iron from their body should take vitamin E supplements.

TOXICITY

There are no major side effects associated with vitamin E; it is remarkably nontoxic.

One of the best evaluations of vitamin E toxicity was conducted at the National Institutes of Health. Twenty-eight institute employees voluntarily took doses ranging between 100 and 800 IU a day for an average of three years. A battery to tests designed to uncover possible toxic effects was performed on each volunteer, and none was found. There are a few reports in the medical literature describing possible stomach upset, diarrhea, dizziness, and increased blood-clotting time with high doses of the vitamin, but most agree that vitamin E is nontoxic in doses below 800 IU per day.

INTERACTIONS

Vitamin E facilitates the absorption, tissue storage, and utilization of vitamin A. People who must take vitamin A to correct a deficiency should also take vitamin E. However, in huge doses, vitamin E can actually slow the absorption of vitamins A and K from the gastrointestinal tract.

Vitamin E can also inhibit formation of the active forms of vitamin K, thereby inhibiting the ability of blood to clot. It can also inhibit the ability of blood platelets to aggregate. This may be beneficial, for less-sticky platelets theoretically confer a reduction in the risk of stroke, blood clots in the lungs, and heart attacks.

Vitamin E supplements should probably not be used in doses larger than 50 IU per day by people taking anticoagulant drugs, aspirin or similar drugs with an effect on platelets, or those with blood-clotting disorders.

THERAPEUTIC USES

Vitamin E is perhaps the most important of the protective antioxidant and free-radical-scavenging compounds in the body. It has a clear role in protecting the body against the damaging effects of oxygen. Higher intakes lower the risk for heart disease and cancer. This aspect of vitamin E is covered in "Antioxidant Vitamins". Below are listed some other uses for vitamin E based on the ability of this vitamin to act as a fat soluble free-radical scavenger and antioxidant.

• Reduce environmental hazards such as ozone, nitrogen dioxide, and cigarette smoke. Increasing levels of pollutants in our atmosphere can lead to adverse health effects because these components are reactive and cause free-radical oxidative change. Some suggest that people who live in areas with air pollution problems should increase their intake of antioxidant vitamins, especially vitamin E.
• Reduce cardiac toxicity of the anticancer drugs daunorubicin and doxorubicin. These drugs are toxic to the heart muscle because they promote the formation of free-radical intermediates. Vitamin E supplements have been shown to reduce this damage.
• Treat hemolytic anemia associated with hereditary deficiencies of the enzymes known as G6PD and gluathione peroxidase. Both of these conditions can lead to excess oxidation and consequent damage to body tissues. Vitamin E supplements have been shown to reduce breakdown of red blood cells in people with these disorders.
• Relieve PMS symptoms. There are several small studies indicating that a supplement of 400 IU per day of vitamin E may reduce some symptoms of premenstural syndrome. Vitamin E can modulate prostaglandin synthesis through its antioxidant action, and this may be a possible mechanism of action here.
• Relieve intermittent serve leg muscle pains (intermittent claudication). Intermittent claudication is characterized by attacks of lameness and pain brought on by walking. The pain comes from arteriosclerosis in the blood vessels of the legs; the reduced blood flow means that the calf and buttock muscles receive insufficient oxygen. Several studies have evaluated the usefulness of vitamin E in this condition by measuring the exercise tolerance of patients receiving the vitamin compared with patients who received traditional treatment and others receiving no treatment at all. By all criteria, vitamin E in doses over 400 IU per day was shown to be of some benefit after six months of continuous use.
• Relieve nighttime leg cramps. There is limited evidence that vitamin E might offer some benefit to those who suffer from this annoying affliction, but controlled studies on the effectiveness of vitamin E for this problem are lacking. One study showed that a dose of 400 IU, taken before bed, was effective in reducing the frequency and severity of attacks.
• Speed healing of wounds and clearing of scars. Although this use of vitamin E has not been thoroughly tested, many people claim to have experienced great benefit from applying vitamin E creams or the oil from vitamin E capsules directly to wounds and scars. Vitamin E cream is a cosmetically elegant, more expensive way of applying the vitamin to your skin that simply using the oil from a vitamin E capsule, which can be removed by puncturing the capsule with a pin and squeezing the oil out. Either form of the vitamin should be applied to the wound to scar two or three times a day. Presumably vitamin E is working as an antioxidant and free-radical scavenger in preventing further damage to the tender new tissue being formed during the healing process, although this has not been proven. If so, the vitamin would presumably work best when applied to a wound that has closed and is starting to heal. There are few adverse effects to this remedy, as long as you don't rub the cream or oil directly into an open wound. If you have a stubborn wound that is not healing as fast as you would like, this controversial treatment may be worth a try. But you should remember that a sore that doesn't heal may be warning sing of cancer or another serious medical problem, so get medical attention if you have any doubts.
• Decrease platelet aggregation. Aggregation of blood platelets is part of the process of blood clot formation, but an increased tendency to platelet aggregation is dangerous because of the risk for the formation of unwanted clots, leading of strokes and heart attacks. Vitamin E can decrease the aggregation of platelets in doses of greater than 200 IU per day. While this is generally beneficial, you should not take vitamin E if you have blood-clotting problems or are taking "blood thinners" such as warfarin.
• Alleviate deficiencies in cystic fibrosis patients. Individuals with cystic fibrosis do not absorb fats, and they show deficiencies of the fat-soluble vitamins, especially vitamin E. Doses of 200 IU per day or more are needed.
• Reduce risk of cataracts. Studies have shown that people who take vitamin E supplements have a lower risk of cataract formation. Lipid peroxidation may be part of the process of the formation of cataracts. More studies are needed to define the optimal doses and the extent of their benefit, but vitamin E supplements may be beneficial for this and many other degenerative conditions in the elderly.
• Benefit people who engage in heavy exercise. Vitamin E has long been used by athletes in the hope of improved performance. Strenuous exercise has been shown to result in increased lipid peroxidation and free-radical damage in muscle tissue. Most studies on vitamin E and exercise have been done in animals; careful studies on student athletes in England and on members of a college swimming team in Louisiana have shown that vitamin E did not help, but studies with high-altitude mountain climbers indicated that vitamin E supplements have some benefits compared to placebo. More work is needed in this area.
• Reduce tardive dyskinesia. Tardive dyskinesia is a side effect of antipsychotic drugs. It is characterized by involuntary head movements and may be a consequence of free-radical damage to nerves. Small studies have shown that vitamin E in very high doses helps reduce these movements.
• § Protect premature infants. Premature infants have a low capacity for protection against oxidative damage. Vitamin E is sometime supplemented to prevent damage to their lungs and eyes. Earlier use of a vitamin E injection product resulted in some deaths associated with the product, and most supplementation now is given orally.
• Prevent cancer, heart disease, atherosclerosis, and decreased immune function. The application of vitamin E supplements in the prevention of these diseases is considered in " Antioxidant Vitamins"
• Slow the progression of Alzheimer's disease. A well designed study showed that high dose vitamin E slowed the progression of Alzheimer's as well as did a drug called selegiline, a standard treatment. While this study does not represent a major breakthrough, this benign vitamin may help people with Alzheimer's and their families. Further study may reveal other uses in mental degeneration.

UNSUBSTANTIATED CLAIMS

Treatment of cystic breast disease

Noncancerous breast lumps affect millions of American women. Early studies indicating benefit with vitamin E have not been substantiated.

Treatment of angina

While vitamin E has a role in the prevention of heart disease and the prevention of further heart attacks after the first, it does not seem to be of help in treating angina.

Improvement of sexual function

Sorry - despite its reputation, vitamin E will not do anything for your sexual prowess. A Canadian evaluation could not demonstrate any effect of vitamin E on the sexual activities of couples when compared with a group receiving a placebo.

Vitamin E has also been promoted for other uses for which its value has not been proven. We cannot recommend that you take this vitamin to treat acne, allergies, anemia, arthritis, athlete's foot, backache, baldness, bedsores, boils, bronchitis, bursitis, colitis, the common cold, constipation, cystitis, dandruff, diabetes, emphysema, eyestrain, fatigue, fluid retention, gallstones, gout, hay fever, headache, hemorrhoids, impetigo, impotence, infertility, kidney stones, loss of vision measles, Meniere's disease, menstrual cramps, mental illness, multiple sclerosis, muscular dystrophy, nephritis, night blindness, obesity, osteoporosis, Parkinson's disease, phlebitis, prostatitis, sciatica, sinusitis, sunburn, thyroid disease, ulcers, vaginitis, or warts.

AVAILABILITY

Another controversial point about vitamin E is the merit of using the natural form, d-alpha tocopherol, versus either of the synthetic forms, d1-alpha tocopherol or d1-alpha tocopherl acetate. Most common vitamin products contain synthetic vitamin E. However, the natural d-alpha tocopherol seems to bind better with one of the proteins that help move vitamin E into and within the cell. The implications of this observation are that with equal amounts of synthetic or natural vitamin E, the natural would be better-utilized. Since generic natural vitamin E is readily available and not much more expensive than the synthetic kind, we recommend purchase of the natural product. But be careful : Some brands have Nature or Natural as part of the brand name, thus giving the consumer the impression that vitamin E in the bottle is the natural kind. But unless the product label says it is d-alpha tocopherol, the vitamin E is synthetic. The "semisynthetic" d-alpha tocopheryl acetate is recommended also. The acetate group confers stability to the molecule and is readily removed by enzymes in the intestine, thereby releasing the d-alpha tocopherol.

Recently some vitamin E products have appeared on the shelves labeled as all natural vitamin E, but close examination of the label reveals that the capsules contain a mixture of natural d-alpha tocopherol and synthetic d1-alpha tocopherol. These products are basically mislabeled and should be avoided. If you want to take the all natural vitamin E, demand a product that is 100 percent d-alpha tocopherol. Some natural vitamin E products contain "mixed tocopherol". These products contain a mixture of tocopherols obtained from the plant source. As far as we know, 40 0IU of mixed natural tocopherols is a beneficial as 400 IU of d-alpha tocopherol. The knowledgeable consumer can make a good choice in purchasing dietary supplements, but it will require careful scrutiny of the label. When in doubt, ask you pharmacist for assistance.

Another product is micronized or emulsified vitamin E. These products are water-soluble because the vitamin has been dispersed into fine droplets in water. For those with fat-absorption problems, it may be worthwhile to use these water soluble products because they do not need to be absorbed like fats.

Capsules and tablets of vitamin E are available without a prescription in strengths ranging from 200 to 1,000 IU. The concentration in multivitamin products is usually 30 IU. Vitamin E ointments, lotions, and creams are also available without a prescription. The usual concentration of vitamin E in these products is 30 IU per gram.

Despite the long history of experience and research with vitamin C, dating back several centuries to the search for the cause of scurvy among sailors on long voyages, we still have much to learn about how it works in the human body. We know that humans are one of the few creatures on earth that don't make their own vitamin C, but we don't know why.

Professor Linus Pauling proposed that humans' inability to make ascorbic acid and the decrease in C content of our diet over the years, particularly as early humans shifted from an all vegetarian diet to a partly meat diet, has placed us at risk for getting less vitamin C than we need for optimum health. Some vitamin C advocates are quick to point out that animals that make their own vitamin C produce the human equivalent of 10 to 20 per day. The average human diet, on the other hand, contains only 30 mg per day. They also point to apes, which get an average of 5 g of vitamin C a day in the wild.

This theory is disputed by many nutritional experts, who claim the humans' diet was probably never strictly vegetarian and has always contained both meat and vegetables. Conventional wisdom tells us that if the ability to make vitamin C had been needed in our species' early history, it would have been carried down to today's human through own genes. Some evidence indicates that animals make their own vitamin C in large amounts because they use it up much faster than we do. Perhaps humans are more efficient than most members of the animal kingdom in that we efficiently absorb and can store small amounts of vitamin C. why carry the machinery to make vitamin C when you can let plants do it for you? Both sides of this debate are pure speculation, and no one can conclusively prove any of these points. Nevertheless, as knowledge of the importance of antioxidants in the diet grows, increasing vitamin C intake seems like a good idea.

FUNCTION

Vitamin C is a modified sugar molecule that is water soluble. One of the important functions of vitamin C is to serve as a water-soluble antioxidant and free-radical scavenger. It is one of the compounds in the body that protects us from oxidative free-radical damage.

It is also known that vitamin C is necessary in the synthesis of hydroxyproline and hydroxylysine. These hydorxylated amino acids are building blocks of collagen, the main supporting component in connective tissue, which is the tissue that holds us together. Some types of connective tissue are cartilage, tendons, and fibers. A lack of vitamin C causes defects in the formation of mucous membranes and interferes with the normal healing of wounds. Without sufficient vitamin C, the tissue that surrounds and supports capillaries breaks down, and the capillaries themselves then break from lack of support. This results in back - and- blue bruise marks as blood leaks into tissue and clots there. The hallmark of scurvy, the vitamin C deficiency disease, is a lack of collagen synthesis.

Vitamin C also stimulates the adrenal glands to manufacture cortisone and other body hormones involved in helping us cope with stresses of daily life. Vitamin C levels are high in the adrenal glands. Vitamin C is known to participate in the hydroxylation of a chemical called dopamine in the adrenal gland to form the neurotransmitter norepinephrine. Norepinephrine is essential to life because it affects many parts of the central nervous system and all of our major organs. Another important chemical in the body whose synthesis is dependent on vitamin C is carnitine. Carnitine is needed to move sugars into the mitochondria of the cells so that they can be metabolized to yield energy.

Vitamin C increased the amount of iron absorbed from non-meat sources through the intestines by chemically reducing and chelating the iron. To be effective, the vitamin C must be taken at the same time as the iron. If you have iron-deficiency anemia, taking the iron tablet simultaneously with 100 to 200 mg of vitamin C will increase absorption by 30 to 40 percent. The vitamin C is involved in the conversion of folic acid to its active form, dihydrofolic acid, in the body. In fact, one of the features of vitamin C deficiency is an anemia similar to the kind found in people deficient in folic acid. Small amounts of ascorbic acid are also needed to break down cholesterol in the blood.

White blood cells contain relatively large amounts of vitamin C, and it seems to be key to the ability to these cells to attack and engulf invading bacteria. Immune function is diminished in vitamin C deficiency. Deficient individuals are more susceptible to viral and bacterial infections. Interferon production by cells is stimulated by vitamin C, which may account for its importance in the defense against viruses. In addition, vitamin C is involved in the manufacture of a group of enzymes that are essential to the body's ability to break down drugs and other chemicals the body considers foreign.

DAILY REQUIREMENTS

Only about 10 mg a day of ascorbic acid is enough to protect against scurvy, which is the disease resulting from a deficiency of vitamin C. Nevertheless, the average adult RDA for ascorbic acid has been set at 60 mg to provide an extra margin of safety during times of illness and stress. In the United States it is estimated that 20 to 30 percent of adults consume less than the RDA value. A current controversy is whether levels of vitamin C over the RDA value are needed for optimal health. Given the importance of this vitamin as a water-soluble antioxidant we believe that a higher levels would be beneficial. In considering what intakes might be optimal, it is important to note that 200 mg will provide about 80 percent of complete saturation of blood. Because vitamin C is "pumped" into cells by an enzymatic process, blood cells and body tissues are completely saturated at this dose. Doses of 500 mg to 1,000 mg will saturate blood. Vitamin C intakes of RDA amounts will not saturate. Thus if you believe that for optimum health, you want to saturate your body with vitamin C, you will need to take in more than 200 mg per day. If five portions of fruits and vegetables were consumed each day, as recommended by nutrition authorities, vitamin C intake would be in the 100 to 300 mg per day range. Researchers at the National Institutes of Health note that 100mg to 200 mg of vitamin C daily will benefit most healthy Americans. Intakes higher than 300 mg will be difficult to achieve without taking supplements.

DIETARY SOURCES

Fruits, potatoes, and green vegetables are the best natural sources of this vitamin. There is little vitamin C in meats, cereals, grains, and the foods we normally think of as being loaded with B vitamins. Interestingly, the richest sources of vitamin C are not the citrus fruits, as we have been led to believe, but rose hips, broccoli, Brussels sprouts, and green peppers. Additional good sources are listed in the accompanying table.

Vitamin C is chemically unstable and therefore presents some problems in terms of storage and processing. Drying fruits and vegetables destroys much of their vitamin C content. In one experiment up to 54 percent of the vitamin was destroyed by drying. Vitamin C also breaks down after exposure to light and air. In addition, long storage of fruits and vegetables allow the vitamin to be broken down by natural enzymes. Another problem unique to ascorbic acid is that if fruits and vegetables are picked before they reach their fully ripened state, they will not have produced their full quota of vitamin C.

Freezing does not destroy the vitamin C content of foods. A typical cup of freshly squeezed orange juice contains 100 mg of ascorbic acid, while a cup of juice reconstituted from frozen concentrate contains about 120 mg of the vitamin, probably because of a special effort to concentrate ascorbic acid during the quick freezing process and the fact that vitamin C is most stable in an acid medium, such as fruit juice. However, the vitamin in frozen orange juice can be broken down by oxygen as soon as the juice is reconstituted and warmed to refrigeration temperatures.

Vitamin C (Ascorbic Acid) Content of Selected Foods
(Average adult RDA is 60 mg)

Estimates of actual cooking losses range between 30 and 60 percent, although some procedures, such as blanching vegetables and then cooking them in iron or copper pots, can result in the destruction of almost all of the vitamin C. In summary, the vitamin C content of foods is highly variable. For optimal C content, consume fresh, uncooked fruits and vegetables and drink reconstituted frozen juices.

DEFICIENCIES

The disease associated with vitamin C deficiency is scurvy, which was common in sailors in the days before vitamin C was known. Also hard hit were people in northern climates who did not have access to fresh fruits and vegetables during the long winter months. Now our ability to transport fresh food over great distances has dramatically decreased the amount of scurvy world wide. Nevertheless, marginal vitamin C deficiencies still exist in some people, even in Westernized countries. It takes several months of a vitamin C - deficient diet before scurvy develops. However, marginal deficiencies can develop sooner.

Deficiency Symptoms

Our basic descriptions of the symptoms of scurvy come from the logs Jacques Cartier kept during long sea voyages. Cartier's log, written in 1535, graphically tells how severe the disease can be : "unknown sickness began to spread itself amongst us at the strangest sort that was ever heard or seen; inasmuch that some did lose all their strength and could not stand upon their feet; the did their legs swell, their sinews shrunk and became black as coal. Others also their skins spotted with spots of blood, of a purple colour. It ascended up their ankles, knees, thighs, shoulders, arms and neck. The mouth became stinking; their gums so rotten that the flesh came away to the roots of their teeth, which at last did fall out." The latter symptom is a result of periodontal disease, which can be caused by vitamin C deficiency as well as other factors.

Some symptoms of marginal deficiency are fatigue, shortness of breath, digestive difficulties, bleeding gums, easy bruising, swollen or painful bone joints, nosebleeds, anemia, more frequent infections, and slow wound healing. Some nutrition experts claim that people deficient in C who are at risk for heart attacks or strokes are more likely to develop one of these serious problems because of blood vessel weakness.

Vitamin C can be measured directly in the blood. The symptoms of scurvy start to appear when the blood level falls below 1 mg for every 100 ml of blood. The vitamin can also be measured in white blood cells. These levels are often taken as a better representation of the amount of vitamin C in body tissues because they are not as subject to variation as the blood level.

PEOPLE WHO MAY BENEFIT FROM SUPPLEMENTATION

Senior Citizens

Marginal C deficiencies have been found in seniors, particularly those living in nursing homes or other health care facilities. The reasons for this deficiency seem to be inattention to diet. The loss of appetite, and in some cases difficulty digesting foods rich in vitamin C, many of which are also high in roughage. On the basis of this information, we suggest that all people over age sixty-five take a daily multivitamin containing at least 60 mg of ascorbic acid. Of course, this does not eliminate the need for a balanced diet, including vitamin C-rich foods, but it does provide a measure of protection against possible deficiencies.

Other Groups

Pregnant women should supplement their daily vitamin C intake because of the demands by the fetu's developing bones, teeth, and connective tissue. Breast-feeding women also bleed supplemental C because they must supply enough vitamin C in their milk to support their baby's rapid growth. Smokers women who take oral contraceptives, and people under any kind of stress should supplement their daily intake of vitamin C, but the amount does not have to exceed 500 mg per day.

TOXICITY

Vitamin C is considered nontoxic in doses less than 1 g per day. Over 1 g, less is known about long-term consumption. However, large-scale clinical trials involving thousands of volunteers who received between 1 and 30 g of vitamin C per day revealed very few problems. Since the 1970s large doses of vitamin C have been consumed by millions in the United States with very few reports of adverse effects. As discussed later, the body is saturated at about 500 mg per day, and higher doses are simply eliminated in the urine.

There are scattered reports of a variety of adverse reactions to vitamin C, including upset stomach and diarrhea, but these are rare. Because vitamin C is metabolized in the body to oxalic acid, which is relatively insoluble in urine, high doses of C have the potential to contribute to the formation of kidney stones. High doses can also block the body's ability to eliminate urate, which could be deposited in joints, causing gout. The significance of these risks is controversial, but if you have bladder problems, kidney stones, or gout, we suggest not using large amounts of vitamin C because of potential problems associated with crystal deposits.

Patients with iron overload conditions should avoid large amounts of vitamin C because it will increase iron absorption. Hemolysis has been reported in patients having glucose-6-phosphate dehydrogenase deficiency. This deficiency makes patients susceptible to hemolysis from taking many common drugs. These patients need to avoid high-dose vitamin C.

Sudden stoppages of large doses of vitamin C have been reported to result in deficiency symptoms. This is called rebound scurvy ; it is considered a very rare event and is not well documented megadoses of vitamin C. They have developed deficiency symptoms soon after birth, probably because their body tissues had become used to very large amounts of vitamin C in the blood circulating from their mother. High doses of any vitamin or mineral should be avoided during pregnancy because the risks are simply not known.

INTERACTIONS

Vitamin C can interfere with certain urine and blood tests for sugar and for the test for occult blood in the stool.

THERAPEUTIC USES

Vitamin C supplements may be given to counteract any of the standard symptoms of vitamin C deficiency reviewed earlier in this profile. However, such symptoms will not be alleviated by vitamin C unless they are, infact, caused by vitamin deficiency.

Antioxidant Uses

The important role of vitamin C as a water-soluble antioxidant and free-radical scavenger is discussed. Low dietary vitamin C intake has been associated with increased risk for cancer, especially cancer of the stomach, throat, intestines, and lungs. Low intake also increases the risk for heart disease, high blood pressure, and cataracts.

Wound Healing

Vitamin C is often given after surgery to speed the healing of surgical wounds. Vitamin C has an important role in the synthesis of new connective tissue, and controlled studies have shown that supplements speed up healing of bedsores and experimentally administered cuts in the mouth. Not all studies show benefit, however. We suggest that supplements be used following any significant injury or surgery in order to ensure ample vitamin C to help speed the healing process. Doses of 250 to 500 mg per day are sufficient for this effect.

UNSUBSTANTIATED CLAIMS

The claim that vitamin C will cure or prevent the common cold is of obvious interest to everyone. This is not a new idea, but it was popularized in 1970 with the publication of vitamin C and the common cold, by Dr. Linus Pauling. Incredibly, surveys have shown that as many as half the American people have, at sometime, taken extra vitamin C to prevent or treat the common cold, an illness responsible for billions of dollars' worth of lost time and productivity each year. Advocates of this treatment claim that between 1 and 5 g a day of ascorbic acid will prevent the common cold and that still higher doses are useful in treating cold symptoms, if you are unlucky enough to get sick in spite of the prevention regimen.

What is the evidence ? Vitamin C advocates usually cite the results of studies conducted in the 1940s and 1950s, but most of these early studies are technically incorrect and have been criticized for that reason. The publication of Linus Pauling's book and the increased popularity of vitamin C have sparked careful evaluation by a number of reputable investigators. At least ten careful, technically correct studies have appeared in the literature since 1970. What emerges from these investigations is a picture far less optimistic than that presented by advocates. In these large, controlled studies, vitamin C does not seem to have much of an effect in preventing the cold but has a small effect in decreasing its severity.

One study worth nothing was conducted using school-age twins as subjects. One twin from each pair was given vitamin C , while the other was given a placebo with the same appearance and taste of the vitamin C. As the twins lived in the same household, they were exposed to all the same factors, such as diet and contact with others, that could potentially influence a cold. Technically, this was a nearly ideal experiment. The results of this study were similar to those reported by other investigators: The children taking vitamin C had some what less severe colds, but the number of colds was essentially the same as experienced by those taking placebo.

Despite the evidence from the large clinical trials, many claim to benefit from taking vitamin C during the winter months. Probably everyone has friends and coworkers who swear by vitamin C and claim. " I never get a cold while I take vitamin C." It is difficult to evaluate these claims of success. The evidence shows otherwise. There may be a subset of the population that strongly benefits, but their response does not show up in the large trials. On the basis of the evidence, you might expect a mild reduction in cold symptoms, although the high doses usually suggested do not seem to be necessary. Studies have been conducted in which a dose of between 80 and 200 mg per day was sufficient to produce this effect. It is possible that a small number of people are deficient in vitamin C or need unusually large amounts. Taking extra vitamin C will help these few people. We believe that a saturation - level dose of vitamin C is enough to provide excellent antioxidant and free-radicals scavenging activities and will optimize the immune system to fight infection such as the common cold.

Cancer

In the 1970s there was some enthusiasm for using very high doses of vitamin C in the treatment of cancer. Interest has waned, however, as the results from several trials did not show benefit. Now most attention is focused on the antioxidant properties of vitamin C and the connection between supplementation with antioxidants and protection against cancer. As discussed in Vitamin C is an important link in the antioxidant sequence, but vitamin E may be the most important antioxidant vitamin with respect to cancer and heart disease prevention. Consumption of fruits and vegetables high in vitamin C is protective, and this is the best step you can take to decrease risks. Additionally, we recommended daily consumption of 200 to 500mg of vitamin C to optimize antioxidant and free radical protection.

Detoxifying Alcoholics and Drug Abusers

There are small number of unverified reports attesting to the usefulness of enormous doses of ascorbic acid, in some cases given by injection, in drying out alcoholics and detoxifying people addicted to narcotics and tranquilizers. People treated with vitamin C are given massive doses and are supposed to experience fewer of the adverse effects normally associated with drug withdrawal : cramps, nausea, generalized discomfort. This application of vitamin C should be considered unproven, although future research may shed some light on a possible role for this vitamin in this regard.

Cholesterol and Lipid Lowering

The story of vitamin C and blood lipids is riddled with conflicting information. While there is agreement that ascorbic acid will lower blood cholesterol in vitamin -deficient patients, it does not necessarily follow that cholesterol levels in other people will be affected. In fact, studies have shown that people with high blood cholesterol who are otherwise healthy are not affected by vitamin C. There are better drugs to lower cholesterol.

AVAILABILITY

A stroll down the vitamin aisle of your local pharmacy, health food, or vitamin store will soon make you aware that ascorbic acid is available in just about every possible dosage form and strengths. The combination of vitamin C with bioflavonoids improves vitamin C absorption somewhat, but these products are more expensive, and at doses of over 500 mg per day, the small extra amount absorbed is probably not important. Timed-released products are poorly absorbed. Synthetic vitamin C tablets are fine and are inexpensive.

Historically, vitamin A has been most well known as a cure for night blindness. In fact, night blindness is a symptom of vitamin A deficiency, which can be alleviated by taking sufficient amounts of that vitamin. Symptoms of night blindness were first recognized in ancient Egypt around 1500 B.C. Although at the time the problem was not linked to a dietary deficiency of any kind, the symptoms were treated by placing roasted or fried liver over the eyes. Later, Hippocrates suggested eating beef liver, a rich source of vitamin A, as a cure for night blindness. Today we known that vitamin A serves several other important functions in the body, and chemical derivatives of vitamin A have important medical benefits, particularly in the area of treatment of skin conditions and in cancer treatment. We also know that vitamin A deficiencies lead to a higher risk for some cancers. Including lung cancer in smokers.

Several compounds with similar chemical structures in nature have vitamin A activity. In animal - derived foods, most vitamin A exists as retinol or retinal. Vitamin A from plants is in the form of carotenoids. Carotenoids are considered "provitamins" because they must be metabolized in the body before they can act as a vitamin. Alone, however, they may serve as free-radical scavengers and quenchers of singlet oxygen. There are many carotenoids in plants, but not all have vitamin A activity. Beta carotene is the most common, and it has the most potent vitamin A activity.

All compounds with vitamin A activity are fat-soluble; like all fats, they are absorbed from the intestinal tract with the help of bile.

FUNCTIONS

Vitamin A in essential to a variety of biochemical and physiological processes, the vitamin must undergo a minor chemical change to allow it to participate in that function. Vitamin A, as retinal, is a part of the pigment called rhodopsin, found in the retina of the eye. Rhodospin in sensitive to small amounts of light and is essential for night vision because it allows us to discern objects in very low light. To function in this way, the retina of the eye must contain a large concentration of vitamin A.

Retinoic acid is present in very small amounts, yet it has an important function in promoting cell growth and cell differentiation. Skin cells and the cornea of the eye are especially affected by vitamin A deficiency. The skin turns rough and scaly, and hair follicles become obstructed. Vitamin A, as retinoic acid, probably plays an important role in preventing cancer because of its ability to regulate cell division and differentiation.

Vitamin A, as retinol, is needed for reproduction. Rats deprived of vitamin A cannot reproduce. Retinoic acid will not cure the infertility.

Vitamin A is also important in maintaining a normal immune system. Vitamin A deficiency results in an increased susceptibility to infections, and it has been called the "anti-infective vitamin". In recent years it has been recognized that measles occurring in vitamin A - deficient children is very severe, often resulting in death. A program started by the World Health Organization gives occasional high oral doses of vitamin A to children in certain developing countries that have a high death rate from measles and other infections. The association between very severe measles requiring hospitalization and low vitamin A status has been made even in United States, and a call has been made to pay more attention to vitamin A intake in children. Some have suggested that all hospitalized children with measles be given a high-dose vitamin A supplement.

Beta carotene, the most potent plant - derived precursor of retinol, retinal, and retinoic acid, ahs a biological activity of its own. It is an excellent free-radical scavenger, and it neutralizes reactive singlet oxygen. However, other plant carotenoids may be even more important in protecting us against the damaging effects of oxygen.

DAILY REQUIREMENTS

The strength of vitamin A can be expressed in terms of a measure of biological activity, international units, or as retinol equivalent, which indicates the amount of retinol to which the substance can be converted in the body. The use of IU is older and has been mostly replaced in nutrition tables by the use of RE values. Commercial vitamin products, however, still use the old IU system and the older U.S. RDA values, which are in IU. To convert between system, simply remember that 1 RE of vitamin A equals 3.3 IU.

The adult RDA for vitamin A is 1,000 RE for men and 800 RE for women. Pregnant or breast-feeding women need an additional 200 and 400 RE, respectively. The U.S. RDA value for adults is 5,000 IU. The RDA for infants and children is smaller than that for adults, but when compared on a pound-for-pound basis, it is considerably larger because of the need for vitamin A in normal processes of growth and development.

Small amounts of vitamin E will increase the capacity of all body tissues, including the retina and liver, to store vitamin A. For this reason, people who must take vitamin A to correct a deficiency state should also take vitamin A to correct a deficiency state should also take a modest amount of vitamin E. Most comprehensive multivitamin formulas have enough vitamin E in the m to satisfy this need for the vitamin.

DIETARY SOURCES

It is easy to recall which foods are rich in vitamin A if you remember that retinols dissolve in fat and carotenes are found in yellow plant pigments. Some rich animal sources of vitamin A are liver, whole milk, cream, and butter. Additional good sources are listed in the accompanying table. Four ounces of beef liver has more than a seven-day supply of vitamin A, and fish liver has even more. Cold liver oil was commonly used as a source of this vitamin and of vitamin D before purified vitamin A was available. A single teaspoon of cod liver oil will fulfill the adult RDA High concentration of carotene are found in dark green vegetables, where the green of chlorophyll usually covers the yellow to-orange carotenoid color, and yellow-orange vegetables such as carrots, pumpkin, and squash. Other sources are listed in the accompanying table.

Vitamin A content of Selected Food
(Average adult RDA is 900 RE, or 4,500 IU)

Carotene is converted to retinol in the wall of the small intestine as it is being absorbed into the blood. The process of conversion continues only as long as retinol is needed. Once the need for retinol has been satisfied, the conversion process stops, so high doses of beta carotene do not result in toxic levels of retinal.

Vitamin A is sensitive to oxygen. Thus, prolonged beating in the presence of air will destroy the vitamin A activity of any food. To minimize this loss while cooking you food, place a lid on the pot or pan used to boil such vegetables as squash or carrots, and use a small pot with just enough water to cover the vegetables. Acid also destroys A, but most food sources of this vitamin are nonacidic, so this is not a practical problem.

DEFICIENCIES

About 15 percent of Americans, mostly infants and children, get less than the RDA value for vitamin A. Fortunately, the average person has about a two-year supply of vitamin A in their liver, so you have to eat a vitamin A - deficient diet for many months before symptoms will develop.

Deficiency Symptoms

Mild vitamin A deficiency may be easily overlooked. Dry, rough skin is common. Sometimes the skin can crack and may even become infected. The infection develops because cracks and rough areas in the skin leave openings for microorganisms to enter and because vitamin A is needed for a strong immune response.

The most recognizable sign of vitamin A deficiency is night blindness. This is followed by further damage to the cornea in the form of a condition called xerophthalmia. If left untreated, severe vitamin A deficiency can lead to permanent blindness. Vitamin A deficiency is the leading worldwide cause of blindness in childhood and is an enormous problem is many developing countries.

People who are deficient in vitamin A have an increased susceptibility to respiratory infections because of changes in the cells that line the respiratory tract. Because of their depressed immune response, deficient children develop more severe forms of common childhood diseases. And a mentioned earlier, measles can be lethal in a vitamin A - deficient child.

Other possible effects of vitamin A deficiency include slow growth, thickening of bone, kidney stone that originate with changes in some of the cells that line the kidney tubules, diarrhea, and reduced production of steroid hormones in the body. Steroids are produced by the adrenal gland and are a part of your natural response to stress and your immune function. Failure to make these important hormones will leave your immune system in a less-than-ideal state. Damage to hearing, taste, and smell, nerve damage, and reduced sweat gland function may also occur.

It is possible to measure vitamin A in your blood, but the results of this test are difficult to interpret because of the large amounts that are stored in the liver. Repeatedly low blood values are a direct indication of a severe vitamin deficiency that demands immediate attention.

TOXICITY

Adults may develop symptoms of vitamin A toxicity after taking more than 50,000 IU a day for long periods of time or after taking a single dose of 300,000 IU or more. Infants given 7,500 to 15,000 RE of vitamin A for thirty days have developed toxicity symptoms. In children, vitamin A toxicity has usually been caused by an overzealous parent giving excessive quantities of supplemental vitamin A. Infants and children who are given 6,000 RE of vitamin A a day and who are not deficient are likely to develop overdose symptoms after several months.

Vitamin A overdose is characterized by vomiting, fatigue, swelling due to fluid accumulation, hydrocephalus, and headache. Vitamin A overdose has, in some cases, been misdiagnosed as a brain tumor. Other symptoms of overdose are liver and lymph gland enlargement, difficult sleeping, joint pains, constipation, and rough skin. The effects of an overdose of vitamin A will usually reverse themselves after you stop taking the vitamin.

Since the body will convert as much carotenoid to retinol as it needs, it is possible to have excess unconverted carotene in the blood. A very high concentration of unconverted carotenoids in the blood is known as hypercarotenosis and can cause a yellow discoloration of the skin. This condition has been confused with jaundice, but the two are not related. Hypercarotenosis is unsightly but usually not dangerous.

Toxicity and Pregnant Women

Pregnant women taking excess vitamin A risk bearing a child with birth defects because of the action of the vitamin on the developing fetus. Some of the possible defects are urinary tract malformations, hydrocephalus, and bone deformities. If you are pregnant, do not exceed your doctor's recommendation for any vitamin or drug, including vitamin A. Current recommendations are to take no more than 10,000 IU per day during pregnancy, and prenatal vitamins contain no more than this amount. But vitamin supplements containing up to 50,000 IU per capsule are readily available, so be careful when selecting a product.

INTERACTIONS

Vitamin A can interact with corticosteroid - type -drugs, oral contraceptives, calcium, zinc, and mineral oil. It can also interfere with certain blood tests.

THERAPEUTIC USES

Vitamin A supplements may be given to counteract any of the standard symptoms of vitamin A deficiency reviewed earlier in the profile. However, such symptoms will not be alleviated by vitamin A unless they are, in fact, caused by vitamin deficiency.

Antioxidant Uses

Plant carotenoids are excellent free-radical scavengers and quenchers of singlet oxygen. As such, they play a role in protecting our cells against oxidative damage and presumably help protect us from a number of chronic diseases linke4d to free-radical damage.

Measles

As discussed earlier, measles can be life-threatening if the child is deficient in vitamin A. It has been recommended that the vitamin A status of all seriously ill patients with measles be checked and a high dose supplement given if needed. A program of providing vitamin A supplements to children to some developing countries has lowered the infant death rate due to infections.

Cancer Prevention

Animals deficient in vitamin A get cancer more often and their tumors spread more quickly than animals without this deficiency. There is evidence that the same thing holds true for people: Those who are deficient in vitamin A may be at a an increased risk of developing cancer, and individuals who do get the disease may find that their cancer spreads more quickly. Low vitamin A intake from vegetable is directly related to tan increase in cancer of the lung, bladder, and larynx,. However, it is not known whether the protective effect of vitamin A can be attributed to beta carotene, other plant carotenoids, retinol , or some other component of green and yellow vegetables. Our best advice is to eat plenty of vegetables, as high vegetable intake is consistently associated with a lower risk of cancer.

Retinoic acid is the form of vitamin A required for normal cell differentiation and thus cancer prevention. Unfortunately, it is metabolized too quickly and is too toxic in high doses to be practical for therapeutic use in cancer treatment. Other synthetic derivatives of retinoic acid show some promise and are under investigation.

Treatment of Acne

One of the symptoms of vitamin A deficiency is an acnelike condition. The observation led to the use of vitamin A capsules as an acne treatment in the 1950s and 1960s and consequently to the discovery that high doses of vitamin A are toxic. After several decades of using vitamin A capsules to treat acne, the consensus is that the treatment is only marginally effective and carries a significant risk of toxicity.

In the 1970s retinoic acid applied to the skin became popular as an acne treatment, and it is still used today. Topical retinoic acid appears to reduce the plugging of sebaceous glands. Plugged sebaceous glands can become infected and turn into pimples. Retinoic acid also mildly irritates the skin and causes peeling, which also helps to free plugged sebaceous glands.

Retinoic acid cream or lotion is not the ideal treatment. It can take months for the treatment to begin working, and it is irritating to the skin. In the search for more potent and less toxic retinoic acid derivatives, researches have discovered several that can be taken by mouth without the usual adverse effects. Isotretinoin, or 13-cis-retinoic acid, has been of some benefit to people who suffer from the most severe from of acne and who have not responded to other forms of treatment. These retinoic acid derivatives are strong teratogens, and patients on the drug must take steps to make sure they do not get pregnant.

Treatment of Psoriasis

Several retinoic acid derivatives are used with some success to treat psoriasis. These drugs are available only by prescription and carry a significant risk for causing birth defects if taken during pregnancy.

UNSUBSTANTIATED CLAIMS

We cannot recommend that you take this vitamin to treat alcoholism, allergies, angina pectoris, arteriosclerosis, arthritis, asthma, bad breath, broken bones, bronchitis, canker sores, cataracts, colitis, the common cold, constipation, cystitis, diabetes, diarrhea, double vision, ear infections, emphysema, epilepsy, eye strain, fever, flu, gout, hair problems, hay fever, headache, heart attack, heart failure, hemorrhoids, hemophilia, hepatitis, infertility, jaundice, kidney stones, learning disabilities, liver cirrhosis, meningitis, mononucleosis, muscular dystrophy, nail problems, osteomalacia, prostate trouble, psychosis, sinusitis, stroke, swollen glands, thyroid disease, tuberculosis, vaginitis, varicose veins, or worms.

AVAILABILITY

Despite its toxicity, vitamin A can be obtained in any strength without a prescription. Attempts by the FDA to attempt to limit the doses that can be purchased without a prescription have been met with fierce opposition by nutritionally oriented consumer groups.

We do not recommended taking more than 10,000 IU a day unless you are under the guidance of a licensed health care professional who is expert in therapy with vitamin A. This is especially true if you are or might become pregnant. Do not take vitamin A doses over 10,000 IU per day if you are pregnant or if there is any chance you may become pregnant.

Selenium may be very important in human nutrition because this mineral may aid in preventing some cancers.

FUNCTIONS

Selenium is a component of one form of an important enzyme called glutathione peroxidase. This enzyme exists in fluid in and around all body cells and it inactivates substances called peroxides, which contain high level of oxygen. Since excess oxygen can be toxic to body cells and cause tissue destruction, peroxide pose a treat to vital tissues and membranes, causing cancer or even death.

Glutathione peroxidase is thought to be our first line of defense against peroxidase damage. Vitamin E, located inside cell membranes, is a second line of defense against peroxide. Thus, selenium and vitamin E go hand in hand in their protective role for body tissue.

DAILY REQUIREMENTS

Human selenium requirements are not known with certainty. An estimated safe and adequate daily selenium intake is between 50 and 200 mcg. Since our daily requirement is not known and many vitamin/mineral supplements do not contain selenium, we are faced with a difficult challenge when it comes to choosing a selenium supplement. Because of possible toxicity concerns, you should keep your daily intake below 100 mcg. This, together with the selenium in your food, should be ample.

DIETARY SOURCES

The selenium content of food is highly variable because of the wide variability in selenium concentrations in the soil in which foods are grown. Seafoods, organ meats, and whole grains are considered to be good sources of selenium. Fruits and vegetables are considered to be selenium-poor. Food - refining processes, cooking, and discarding the water in which foods are cooked all contribute to our difficulty in getting enough selenium in our diet.

Dietary surveys indicate that daily average intake various from 50 to 150 mg a day.

DEFICIENCIES

Selenium deficiency has been well documented and studied livestock and lab animals. Animal deficiencies cause a variety of serious and life-threatening conditions, including infertility, muscular dystrophy, exudative diathesis in fowl, pancreatic fibrosis in chicks, hepatosis in pigs, and unthrifitness or sickliness in cattle and sheep. These deficient states are much the same as those associated with vitamin E deficiency, and large doses of selenium will cure most, but not all, vitamin E deficiency symptoms. Since both selenium and vitamin E play a role in protecting against oxidative damage, it is not surprising that one cn sometimes be substituted for the other.

Human selenium deficiency is almost unknown, even in areas of the country where livestock suffer selenium deficiency. Selenium deficiency has, however, been seen in a few people with alcoholic cirrhosis and a few people receiving long-term intravenous feeding without added selenium. They suffered from heart problems that responded to selenium supplements. There is also speculation that Keshan's disease, a fatal heart disease seen in children living in certain sections of China, may be related to selenium deficiency.

TOXICITY

Selenium toxicity in animals can lead to blindness, excess salivation, paralysis, and difficulty breathing. Interestingly, human selenium poisoning has not been reported to come from foods grown in the same areas where livestock are being poisoned by selenium. Selenium poisoning has, however, been reported in several Chinese villages where drought forced villagers to eat vegetables high in selenium. In these villages, daily intakes were found to be 3,000 to 7,000 mcg a day. Villagers suffered hair and mail loss and nervous system problems.

Epidemiological studies have also demonstrated a relation ship between high selenium concentrations in water and dental cavities.

THERAPEUTIC USES

Animal studies have conclusively demonstrated that selenium deficiencies increase the number and growth rate of tumors when cancer-causing chemicals are administered. High selenium intake seems to exert a protective effect in these studies. Since the selenium-dependent enzyme gluathione peroxidase protects against cellular peroxidase damage, as discussed under "Function," it seems reasonable to assume peroxidase damage is somehow related to cancer.

The only evidence that selenium may protect against tumors in man is obtained from broad-based epidemiological studies. If one compares the selenium content of drinking water with cancer death rates in various parts of the country, or even between countries, one finds the following relationship : Higher selenium levels are associated with a lower cancer rate. Other factors obviously enter into this and cancer is still a problem in high selenium areas. It has been estimated that the risk for some cancers is twice as high in low-selenium areas than in high-selenium areas. High selenium concentrations can be found in parts of Wyoming, Alaska, Arkansas, Mississippi, South Dakota, and Colorado. Low selenium concentrations can be found in California, Ohio, Washington, Oregon, Pennsylvania, Indiana, and New York, Breast, colon, and lung cancers, our biggest killers, seem to be affected by selenium intake.

Zinc, cadmium, and copper counteract the effects of selenium in the body, and high intakes of these minerals may even counter the cancer-protective effects of selenium, though there are no human studies to support this claim. We believe it is better to take a mineral mixture balanced by Mother Nature - that is, the kind found in whole grains and seafood - than to fool with potent mineral supplements, at least until more is known.

The associated of selenium deficiency with heart problems in humans has created interest in the therapeutic benefit of selenium supplements in heart disease. The answer to this proposition is not yet in.

UNSUBSTANTIATED CLAIMS

Selenium, like manganese, has been erroneously promoted for an antiaging effect because of its role in controlling oxygen levels. Other unsubstantiated claims include detoxifying heavy metals, drugs, alcohol, and cigarette smoke; improving skin problems; increasing male potency and sex drive; and arthritis treatment.

AVAILABILITY

Some vitamin/mineral supplement formulas contain selenium, and it is also available in tablet form.

BONE SCAN

BACK

Test Overview

Nuclear scanning tests use a special camera to take pictures of certain tissues in the body after a radioactive tracer accumulates in the tissues to make them visible. Each type of tissue that may be scanned uses a different radioactive compound as a tracer. The tracer remains in the body temporarily before it is eliminated as waste, usually in the urine or stool.

For a bone scan, the tracer (radioactive technetium disphosphonate) is injected into a vein in the arm. The tracer then travels through the blood stream and into the bones. Areas of rapid bone growth of repair absorb increased amounts of the tracer show up as bright or "hot" sports in the pictures. Hot spots may indicate the presence of a tumor, a fracture, or an infection. Areas where little or no tracer is absorbed appear as dark or "cold" spots, which may indicate a lack of blood supply to the bone or the presence of a certain types of cancer.

Bone scans are used to evaluate damage to the bones, to detect cancer that has spread to the bones, and to monitor conditions that can affect the bones. A bone scan can often detect a problem months earlier than a regular X-ray test.

This test may be done on the entire body or just a part of it.

Why it is Done

A bone scan is done to :

• Determine whether a cancer from another area (such as the breast, lung, kidney, thyroid gland or prostate gland) has spread (metastasized) to the bone.
• Help diagnose the cause of unexplained bone pain.
• Help diagnose broken bones not clearly evident on X-ray
• Detect damage to the bones caused by infection or other conditions.

How to Prepare

Before the bone scan, tell your doctor if :

• You might be pregnant.
• You are breast-feeding.
• Within the past 4 days, you have had an X-ray test using barium contrast material or have taken a medication that contains bismuth. Barium and bismuth can interfere with test results.

You usually have to wait 1 to 3 hours after the radioactive tracer is injected before your bone scan is done. Therefore, you may want to bring some reading materials or items for another project to pass the time during this waiting period. For some types of bone scans, pictures are taken during the tracer injection, immediately afterward, and then 3 to 5 hours after the injection.

No other special preparations are needed before having a bone scan.
You should empty your bladder just before the test begins.

How it is Done

A bone scan is usually done by a radiology or nuclear medicine technologist. The resulting pictures are usually interpreted by a doctor who specializes in evaluation nuclear scanning tests (radiologist or nuclear medicine physician).

You will need to remove any jewelry that might interfere with the scan. You may need to take off all or most of your clothes, depending on which area is being examined. You will be given a cloth or paper covering to use during the test.

The technologist cleans the site on you arm where the radioactive tracer will be injected. An elastic band is then wrapped around your upper arm to temporarily stop the flow of the blood through the veins in your arm. This makes it easier put the needle into a vein properly because the veins below the band get larger and do not collapse easily. A small amount of the radioactive tracer is then injected, usually into a vein on the inside of your elbow.

It takes 1 to 3 hours for the tracer to distribute throughout your body. During this time you may be asked to drink 4 to 6 glasses of water to help eliminate any of the radioactive substance that does not collect in your bones. Just before the scan begins, you will usually be asked to empty your bladder to prevent any radioactive urine from blocking the view of your pelvic bones during the scan.

During the scan, you will lie on your back on a table and the scanning camera will be positioned closely above you. It may move slowly above and around your body, scanning for radiation released by the tracer and producing pictures of the tracer's distribution in your bones. The camera does not produce any radiation, so you are not exposed to any additional radiation while the scan is being done. You may be asked to move into different positions so the area of interest can be viewed from other angles. You need to lie very still during each scan to avoid blurring the pictures.

The scan takes about an hour.

How it feels

You may feel nothing at all from the needle puncture when the tracer is injected, or you may feel a brief sting or pinch as the needle goes through the skin. Otherwise, a bone scan is painless. You may find it uncomfortable to remain still in different positions during the scan. Ask for a pillow or blanket to make yourself as comfortable as possible before the scan begins.

Risks

There is always a slight risk of damage to cells or tissue from being exposed to any radiation, including the low level of radiation released by the radioactive tracer used for this test. However, if this test is really needed, the risk of damage from the tracer is usually very low compared with the potential benefits of the test. Most of the tracer will be eliminated from your body within a day. Allergic reactions to the tracer are very rare.

Occasionally, some soreness or swelling may develop at the site where the radioactive tracer was injected. These symptoms can usually be relieved by applying moist, warm compresses to your arm.

Results

The results of a bone scan are usually available within 2 days.

Bone Scan
Normal : The radioactive tracer is evenly distributed among the bones. No areas of abnormally high or low accumulation are seen.

Abnormal : The tracer may accumulate in certain areas of the bone, indicating one or more hot sports. Hot spots may be caused by a fracture that is healing, bone cancer, a bone infection (osteomyelitis), arthritis, or a disease of abnormal bone metabolism (such as Paget's disease).

Certain areas of the bone may lack the presence of radioactive tracer, indicating one or more cold spots. Cold spots may be caused by a certain type of cancer (such as multiple myeloma) or lack of blood supply to the bone (bone infarction).

What affects the test

• A bone scan is not usually done for a pregnant woman because the radiation could damage the developing fetus.
• Barium and bismuth can interfere with test results. If a bone scan is needed, it should be done before any tests that use barium (such as a barium enema).
• The results of a bone scan may not be accurate if the person cannot remain still during the test.
• A full bladder can block the view of the pelvic blocks.

What to think about

• A bone scan does not distinguish between normal and abnormal bone growth. Therefore, bone scan results must be interpreted along with the results of X-ray tests. In addition, other tests (such as magnetic resonance imaging, MRI) may also be needed to further evaluate abnormal bone scan results. For more information, see the following medical tests :

  - Chest X-ray
  - Extremity X-ray
  - Spinal X-ray
  - Magnetic Resonance imaging (MRI) of the Body
  - Magnetic Resonance imaging (MRI) of the spine

• A woman who is breast -feeding and has a bone scan should ask her doctor whether she needs to wait for a period of time before she resumes breast-feeding her child.

DIABETES

BACK

What is Diabetes?

When you or someone you love has diabetes, you discover that you must think about a part of life that others take for granted. Your never-changing goal becomes reaching a subtle balance between glucose and insulin. The more learn about diabetes, the better you can be at your balancing act, and the richer your life shared with this chronic disease can be.

TYPES OF DIABETES

Diabetes refers to a set of several different diseases. The most common types of diabetes are type 1, or immune-mediated diabetes mellitus, and type 2, or insulin - resistant diabetes mellitus. A third type of diabetes, gestational diabetes mellitus, occurs during some pregnancies.

All types of diabetes have similar symptoms, because all forms of the disease result in too much sugar, or glucose, in the blood. This is because your body is unable to remove glucose from your blood and deliver in to the cells in your body. Your cells use glucose as a source of energy in order to say alive. But the reasons why your body cannot use glucose from the blood are different for type 1 and type 2 diabetes.

People with type 1 diabetes do not make enough insulin. Insulin is a small protein made by the pancreas that helps the body use or store glucose from food. People with type 1 diabetes can be treated with injections of insulin. In contrast, people with type 2 diabetes, like women with gestational diabetes, do make insulin, but for some reason, the cells in their bodies are resistant to insulin's action or they don't make enough insulin. In all types of diabetes, if glucose does not get into the cells and tissues that need it, it accumulates in the blood.

About half of all cases of type 1 diabetes appear in childhood or in the early teenage years. For this reason, it used to be called juvenile-onset diabetes. If your symptoms first appeared during the early teenage years, your doctor probably suspected diabetes right away. If you were a young child when the disease developed, it might have occurred so fast that you went into a coma, before anyone suspected diabetes. Type 2 diabetes most often develops in adulthood and used to be called adult-onset diabetes. Usually, it does not appear suddenly. Instead, you may have no noticeable symptoms or only mild symptoms for years before diabetes is detected, perhaps during a routine exam or blood test. Gestational diabetes only appears during pregnancy in women with no previous history of type 1 or type 2 diabetes and goes away after pregnancy. Pregnant women are tested for gestational diabetes.

All people with diabetes have one thing in common. They have too much sugar, or glucose, in their blood. People with very high or poorly controlled blood glucose level share many similar symptoms.

• An unusual thirst
• A frequent desire to urinate
• Blurred vision
• A feeling of being tried most of the time for no apparent reason.

People with type 2 diabetes may also experience leg pain that may indicate nerve damage or poor circulation. Many people with type 1 diabetes and some people with type 2 diabetes also find that they lose weight even though are hungrier than usual and are eating more.

Even if they have lost weight, people with type 2 diabetes still tend to be overweight. Three-fourths of all people with type 2 diabetes are or have been obese - that is, they are at least 20 percent over their desirable body weight. Type 2 diabetes tends to develop in people who have extra body fat. Where you carry your excess fat may determine whether you get type 2 diabetes: Extra fat above the hips is riskier than fat in the hips and thighs for developing for 2 diabetes. And leading an inactive "couch potato" lifestyle can also leads to diabetes. It also contributes to obesity.

If you have recently been diagnosed with diabetes, you are not alone. Nearly 16 million Americans - about one of every 17 people - have the disease. About 1,800 new cases each year. Ninety to ninety-five percent of all cases of diabetes in people over age 20 are type 2 diabetes. And half of all people with type 2 diabetes are unaware they even have the disease. Because of the nature of type 2 diabetes, it is possible to have mild symptoms or signs of type 2 diabetes for years before diabetes worsens. In contrast, few cases of type 1 diabetes go undetected to long. The symptoms of type 1 diabetes are severe enough that the person goes to the doctor for help.

WHO HAS DIABETES?

Almost 16 million Americans have diabetes. This is about 6 percent of the people in the country. In 1999, it was estimated that 500,000 to 1 million people had type 1 diabetes. It is hard to get an exact count of the number of people with diabetes because we have no nationwide diabetes registry. Slightly under half of the people with type 1 diabetes are children and teenagers age 20 and younger. Type 1 diabetes is more common in whites than in African Americans, Hispanic Americans, Asian Americans, and Native Americans.

In 1999, it was estimated that about 9.5 million people had diagnosed type 2 diabetes. Another 5 to 6 million people are undiagnosed. It is common in older people. Nearly 11 percent of Americans age 65 to 74 have type 2 diabetes. It is more common in some ethnic groups than others. In American age 45 to 74, over 14 percent of Mexican Americans and Puerto Rican Americans have type 2 diabetes, over 10 percent of African Americans have type 2 diabetes, and about 6 percent of Cuban Americans and whites have type 2 diabetes. Type 2 diabetes is even more common in Nature Americans: In some groups, almost half of adults age 30 to 64 have type 2 diabetes.

About 135,000 women develop gestational diabetes each year. Of these, about 40 percent get type 2 diabetes within 15 years.

TESTS FOR DIABETES

Although your physician may suspect that you have diabetes because of your symptoms, the only sure way to tell is with blood tests. Blood tests are used to diagnose both type 1 and type 2 diabetes, as well as gestational diabetes. Your doctor may repeat your blood tests to be sure of the diagnosis.

The blood tests are based on the fact that diabetes keeps your blood glucose, or sugar, levels above normal some or all of the time. Your blood glucose levels may be high even though you haven't eaten recently. In addition, your body cannot get rid of the extra glucose that appears in the blood after eating.

Random plasma glucose tests are the simplest way to detect diabetes. This test measures the amount of glucose in the blood at any given time and is done without fasting. If you have obviously symptoms of diabetes and the amount of glucose in your blood is 200 mg/dl or higher, your doctor will diagnose diabetes. Symptoms of diabetes include frequent urination, intense thirst, blurred vision, unexplained weight loss, and extreme tiredness.

The preferred method for diagnosing diabetes is the fasting plasma glucose test. For this test, your doctor will ask you not to eat for at least 8 to 10 hours. Then, a sample of your blood is taken, and the amount of glucose present in the blood is measured. Normally after fasting, the amount of glucose is less than 126 mg/dl, the doctor will suspect diabetes. In diabetes, extra glucose remains in the blood, even after fasting, because it cannot enter the body's cells. This is due to a lack of insulin or resistance to the action of insulin. Doctors usually make a firm diagnosis of diabetes when two fasting plasma glucose tests, done on different days, are over 126 mg/dl.

If your test results are greater than 110 mg/dl but less than 126
mg/dl, you may be diagnosed with impaired fasting glucose. This is not diabetes, but sometimes occurs before diabetes, usually type 2 diabetes, develops. Some people with impaired glucose tolerance nerve get diabetes. However, some of the same problems that result from having diabetes also occur in people with impaired glucose tolerance. If you have been diagnosed with impaired glucose tolerance, your physician will want to watch carefully for diabetes. Also, you need to talk with your doctor about reducing your risk of heart disease, keeping your weight in the healthy range, and exercising regularly to lower your chances of developing diabetes.

Not Sure Which Type of Diabetes You Have?

Certain pregnant women with no history of diabetes are at high risk for developing gestational diabetes. These are women who are 25 years of age or older, are overweight, have a patient or sibling with diabetes, or are Hispanic, Native American, Asian, or African-American.

If you have nay of these characteristics, your obstetrician will screen you for gestational diabetes with a glucose challenge. This is done between the 24th and 28th weeks of pregnancy. At this time, the hormones of pregnancy naturally begin to cause temporary insulin resistance that lasts until the baby is born. The glucose challenge helps your doctor determine whether your body is able to overcome the insulin resistance on its own. You are given a glucose drink to finish at a certain time, without regard to eating. If the glucose in your blood 1 hour later is 140 mg/dl or above, you may have gestational diabetes. Your doctor will need to give you another test, for which you may need to fast, for a firm diagnosis.

TYPE 1 OR TYPE 2?

If tests reveal that you have diabetes, your doctor must then decide whether you have type 1 or type 2 diabetes. Although the symptoms and blood test results are similar for both type 1 and type 2 diabetes, the cause are very different.

DIABETES : FACT OR MYTH?

"I used to have type 2 diabetes, but now I have type 1 diabetes. My doctor put me on insulin last year".

Lot of people, over 40 percent of adults with diabetes, use insulin. But because there are about 90 adults with type 2 diabetes to every 5 adults with type 1 diabetes, this means there are a lot of people with type 2 diabetes must use insulin to make up for their pancreas no longer making it. You don't necessarily have type 1 diabetes just because you have to take insulin. Many people with type 2 diabetes need extra insulin to overcome their body's resistance to the insulin already being made by the pancreas.

Type 1 diabetes and type 2 diabetes, while having a lot in common, are two different disease. They have different causes. The type of diabetes you have does not change as you age or if you lose or gain weight or change treatment.

It will help your doctor to know whether there has been type 1 or type 2 diabetes in your family. Your age is not the only clue about what type of diabetes you have. It's true that most people younger than age 20 who show signs of diabetes have type 1 diabetes and that most people diagnosed with diabetes when they're over age 30 have type 2 diabetes. But there are exceptions. In some cases, families carry a genetic trait for developing type 2 diabetes as young people. And in some Native American families, obesity is so prevalent that children as young as 10 years old have type 2 diabetes.

If you are overweight or obese, it is more likely that you have type 2 diabetes.

• If you suddenly developed signs of diabetes, such as frequent urination, unusual thirst and hunger, and weight loss, perhaps after an illness, and are a young adult or child, it is more likely that you have type 1 diabetes.
• If you are not overweight and there are ketones in your urine, it is more likely that you have type 1 diabetes.
• If you are African American or Hispanic American, are older than 50, are overweight, and haven't been feeling quite "right" for along time, it is more likely that you have type 2 diabetes.
• If your doctor treats you with insulin injections, you could have either type 1 or type 2 diabetes.

WHO GETS DIABETES?

The risk factors associated with type 1 or type 2 diabetes are different. For both type 1 and type 2 diabetes, having a family hisotry of diabetes puts you at a higher risk for developing the disease than for a person with no family hisotry of diabetes. However, many people with type 1 diabetes have no known family history of the disease. Type 1 diabetes is more common among whites than among members of other racial groups. In contrast, members of Native American, African American, and Hispanic ethnic groups are at higher risk for developing type 2 diabetes. Perhaps the genetic make up of nonwhites predisposes them to the obesity and diabetes that tend to result from a 20th century sedentary American lifestyle.

A major difference in the characteristics of individuals with type 1 and type 2 diabetes is the age of onset. Typically, type 1 diabetes develops in individuals under the age of 40. Half of all people diagnosed with type 1 diabetes are under the age of 20. In contrast, most of the

people diagnosed with type 2 diabetes are over the age of 30, although type 2 diabetes is on the rise in teenagers. The risk for type 2 increases with age. Half of all new cases of type 2 diabetes ae in people age 55 and older.

Type 2 diabetes is more common in overweight and obese individuals, whereas body weight does not seem to be a risk factor for type 1 diabetes. Type 2 diabetes is often found in women with a history of giving birth to babies weighing more than 9 pounds an din women who were previously diagnosed with gestational diabetes. In both men and women, high blood pressure and very high concentrations of fats in the blood are more common in people with type 2 diabetes.

You can't get diabetes - either type 1 or type 2 - from stress, exposure to someone who already has diabetes, or from something you ate. And although diabetes may reveal itself after an illness or a stressful experience, these may have only speeded up the appearance of the disease.

CAUSES OF TYPE 1 DIABETES

In people with type 1 diabetes, the immune system mistakenly destroys the insulin - producing beta cells in the pancreas, treating them as if they were a foreign invander. This is called an autoimmune response. Autoimmune responses also occur in other disease such as multiple sclerosis, lupus, and thyroid diseases like hypothyroidism and hyperthyroidism. Researchers do not know exactly why this happens. But for diabetes, researchers have found many factors that appear to be linked to type 1 diabetes. These include genetics, autoantibodies, viruses, cow's milk and oxygen free radicals.

GENETICS

Scientists have long suspected that heredity plays a role in diabetes, especially in type 1 diabetes. This is because type 1 diabetes seems to run in families - if your mother or father had diabetes for example, you are more likely to develop the disease that someone without a family history. Also, type 1 diabetes seems to be more common in certain racial groups. Whites, for example, are more likely to develop the disease than are people from other racial backgrounds. Type 1 diabetes occurs in less than 1 in 100,000 people in Shanghai, China, but occurs in greater than 35 in 100,000 people in Finland.

Everyone is born with a set of instructions that tells the cells in your body how to grow live, and function. These instructions lie in the particular chemical sequence of units known as bases that make up the DNA in every cell in your body. Each cell in your body contains 46 chromosomes, which are made up of DNA of protein. Each DNA strand is like a long string that contain millions of bases. Along the strand lie the genes, unique segments of DNA that tell you cells what kind of protein to make.

But just as books sometimes contain typographical errors, so too does the sequence of DNA. If there is a mistake, or mutation, in the DNA within a gene, then a faulty protein may be made that can't do its job. Scientists are trying to determine how to mistakes in specific genes cause diabetes. If mutated genes occur in germ cells - the eggs and sperm - then the DNA mutations can be passed on from generation to generation.

Researchers have identified several different genes that might make a person more likely to develop type 1 diabetes, However, they have not found one single gene that makes all people who inherit it develop the disease. Instead, it sems that there are several genes known as "diabetes susceptibility" genes.

One particular set of genes that may predispose a person to diabetes is responsible for the human leukocyte antigens, or HLAs. These genes code for certain proteins called antigens, which identify a person's own cells as "self". They tell the immune cells not to destroy the cells that are part of person's body. Scientists believe that some HLA antigens incorrectly identify the beta cells as non-self. Then the immune cells, which normally destroy froeign invading cells, destroy these cells. This called autoimmunity - an immune attack on a person's own cells. In type 1 diabetes, the insulin - producing cells of the pancreas are destroyed in an autoimmune attack, and the body can no longer make insulin. This destructive process occurs over many months.

Each person has many kinds of HLA genes, and thus there are many typesof HLAs. Each person inherits one of each kind of HLA gene from each parent. One type of HLA gene, known as HLA-DR, is most strongly linked to type 1 diabetes. There are many variations of HLA-DR, but 95 percent of people with type 1 diabetes have the DR3 form, the DR4 form, or both. This makes researchers suspect that having the DR3 and DR4 variants may make a person more likely to get type 1 diabetes. However, this is not the whole answer, because 45 percent of people without type 1 diabetes have the DR3 or DR4 variants. Also, variants of another HLA gene, known as HLA-DQ, may also play a role in type 1 diabetes.

Just because a person inherits a susceptible HLA variant doesn't mean that person witll develop diabetes. Most people with DR3 or DR4 variants remain helathy. But if there is a family hisotry of type 1 diabetes, then screening may help predict the risk of developing the disease. For example, borthers and sisters of a person with diabetes who have two of the same HLA-DR variants have a 15 percent chance of getting type 1 diabetes. But if they share only one variant, the risk is only 5 percent. If no variants are the same, the risk of developing type 1 diabetes is 1 percent or less.

The more we study how people get type 1 diabetes, the more we understand that the answers are not simple. No one event or characteristic seems to bring on diabetes. Researchers have identified several other gene clusters on different chromosomes in addition ot these HLA variants that may also play a role in type 1 diabetes.

AUTOANTIBODIES

The immune system protects you from disease by killing germs and other foreign invaders. It does this largely through the action of white blood cells, or lymphocytes. T lymphocytes, or T cells, can attack foreign cells directly. B lymphocytes, or B cells, produce special proteins called antibodies that recognize this shapes of molecuels on the surface of specific invaders.

B cells sometimes manufacture antibodies that recognize a person's own cells. These self recognizing antibodies are called autoantibodies. Autoantibodies are found in many people with autoimmune disorders, but three autoantibodies are especially common in people with type 1 diabetes. These antibodies recognize :

• Islet cells (beta cells are just one type of islet cell in the pancreas)
• Insulin
• Glutamic acid decarboxylase, a protein made by the beta cells in the pancreas. This protein is also called GAD, or the 64K protein.

These three types of autoantibodies all seem to act as markers. Researchers believe that these antibodies contribute to the demise of the beta cells of the pancreas by identifying which cells are to be attached. It is really the T cells that ultimately destroy the insulin - producing cells of the pancreas. Of people newly diagnosed with type 1 diabetes, 70 to 80 percent have antibodies to islet cells, 30 to 50 percent have anitbodies to insulin, and 80 to 95 percent have antibodies to GAD.

The antibodies may be present several years before diabetes is dagnosed. The islet cell antibodies disappear later on. Because these antibodies are so common in people with type 1 diabetes and because they so often appear before the symptoms of diabetes appear, researchers are finding that theya re useful in screening people for type 1 diabetes who are at high risk for the disease. Although the risk for developing diabetes may only be 1 to 10 percent for people with a parent or sibling with the disease, a much higher percentage of people who also have antibodies to islet cells develop type 1 diabetes within 5 years. And for many, having combinations of these antibodies and certain HLA genes results in an even higher risk.

By testing relatives of people with type 1 diabetes for autoantibodies, doctors and researcheres can often predict who is likely to develop the disease. This could be especially useful as new therapies emerge, because they can be strated before damage to the pancreas is too extensive. For example, by identifying people who are likely to develop type 1 diabetes at are early stage, researchers may be able to treat with insulin or drugs that suppress the immune system and thus prevent the T cells from destroying the beta cells in the pancreas.

Some people with a high risk of getting type 1 diabetes have participated in studies to see whether immunosuppressants such as azathioprine or cyclosporine delay or prevent the onset of the disease. Researchers are also testing to see whether long-acting insulin, oral insulin, or nicotinamide can delay or prevent diabetes. These studies suggest that axathioprine or cyclosporine can reduce the dose of insulin needed in people who have already developed type 1 diabetes, if the drug is started at the time the disease is diagnosed.

Other therapies may also be tested as researchers learn more about how autoantibodies contribute to diabetes. For example, if autoimmunity to GAD turns out to be a primayr trigger of type 1 diabetes, it might be possible to develop a vaccine that would protect people from developing the disease.

VIRUSES

Perhaps surprisingly, many scientists also suspect that viruses may cause type 1 diabetes. This is because people who develop type 1 diabetes have often recently had a viral infection, and "epidemics" of type 1 diabetes often occur after viral epidemics. Viruses, like those that cause mumps and German measles and Coxsackie family of viruses, which is related to the virus that causes polio, may play some role in cauisng type 1 diabetes.

A small region of the GAD molecule is almost identical to a region of a protein found in the virus known as Coxsackie B4. The two similar protein regions probably have similar shapes and may be recognized by the same T cells. Thus, to a T cell hunting for foreign invaders, the GAD protein, which is part of the body, might look the same as the Coxsackie virus protein, which is part of an invading cell. After a viral infection by the Coxsackie virus, the T cell, bent on destroying the invading virus, might actually destroy the body's own beta cells that bear the GAD protein. This would destroy the cells that produce insulin and result in type 1 diabetes.

Other theories may also explain how a viral infection might lead to diabetes. Some researchers believe that when a virus in fects a body, it might somehow change the structure of the antigens on the surface of the islet cells. If this occurs, then the altered antigen might appear to be foreign to the immune system, and a person's own insulin-producing islet cells might be destroyed.

Gian Franco Bottazzo, a well-known diabetes researcher, has another theory. He believes that diabetes is a relatively new disease caused by a slow acting virus. Although such a virus has not been found, Bottazzo holds that the virus causes the immune system to attack proteins in the pancreas. A drastic increase in the number of cases of type 1 diabetes occurred on the island of Sardinia, Italy, in the 1960s and in Finland in the 1970s, and he believes that such a slow-acting virus could be the culprit.

COW'S MILK

It seems unlikely, but different kinds of food may pay a role in the development of type 1 diabetes. For example, one group of researchers found a connection between being fed cow's milk early in life and type 1 diabetes. They showed that children newly diagnosed with type 1 diabetes have higher amounts of antibodies that recognize a specific protein in cow's milk. These autoantibodies appear to bind to a protein that sometimes appears on the surface of the insulin-producing beta cells int eh pancreas after an illness. The researchers speculate that, after an illness, the transient protein may appear on the surface of beta cells. The immune response to the milk protein might be to then recognize the beta cell surface proteins and attack the beta cells, leading to a destruction of the insulin - producing cells of the pancreas, and thus, to type 1 diabetes.

However, other researchers have looked for but not found an increased risk of type 1 diabetes if cow's milk is given early in life and if breast feeding is done for a short period. Cow's milk is only one kind of food that may play a role in the development of type 1 diabetes. Studies in diabetes - prone rats show that withholding wheat and soy helps delay or prevent diabetes.

OXYGEN FREE RADICALS

No, these are not part of some terrorist organization, but they may as well be. Oxygen free radicals, formed a s a by product of many chemical reactions in the body, wreak havoc wherever they go. Normally, the body has ways of quenching free radicals. But smoke, air pollution, diet, and even genetics can be contribute to the formation of excessive amounts of free radicals, which the body cannot always handle. Uncontrolled, the reactive molecules can destroy the body's own cells as well as bacteria. Oxygen free radicals contribute significantly to the aging process and to the development of several other diseases. Researchers have implicated free radicals in the development of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, a degenerative neuromuscular disease.

Some researchers believe that oxygen free radicals may also contribute to type 1 diabetes. Islet cells have very low levels of the enzymes that break down free radicals. Thus, agents that increase free radical production could result in destruction of pancreatic cells. If this is true, then researchers may be able to develop drugs that block the formation of free radicals in the islet cells.

CHEMICALS AND DRUGS

Several chemicals have been shown to trigger diabetes. Pyriminil, a poison used to kill rats, can trigger type 1 diabetes. Two prescription drugs, pentamidine, used to treat pneumonia, and L-asparaginase, an anticancer drug, can also cause type 1 diabetes. Other chemicals have been shown to make animals diabetic, but scientists don't know for sure whether they have the same effect in humans.

It is unlikely that either genetics or environmental factors alone cause diabetes. But it does appear that a person could start with a genetic susceptibility - the inheritance of a particular set of genes. If this person is then exposed to some environmental "triggering" factor, such as a virus or a chemical, then diabetes may develop. Although no one is destined to develop diabetes with certainty, a person's heredity increases the odds.

CAUSES OF TYPE 2 DIABETES

The reasons that type 2 diabetes occur are different from those that trigger type 1 diabetes. Unlike people with type 1 diabetes, who become unable to produce insulin, people with type 2 diabetes produce insulin. But, either the body does not respond to insulin's action - it's resistant - or there is just not enough insulin to go around - there's too much body for the amount of insulin that's made. Either problem leads to the same outcome: insulin can't deliver glucose to the cells that need it, and there's too much glucose in the blood.

Virtually all cells in the body contain special proteins called receptors that bind to insulin. They work like a lock and key. In order for glucose to enter the cell, insulin must first fit into the insulin receptor. But for some reason, in some people with type 2 diabetes, there is a faulty lock, or insulin receptor. The key doesn't open the lock, and glucose is shut out of the cell. And in some people with type 2 diabetes, there are not enough locks, or insulin receptors, on the cells to allow enough glucose to enter. But for most people with diabetes it's not so much that the key doesn't fit the lock, but that insulin doesn't work properly. In rare cases, the insulin is mutated, or built incorrectly, and does not fit the insulin receptor.

In addition to problems with insulin and the insulin receptor, in many people with type 2 diabetes, the beta cells in the pancreas do not produce enough insulin. Without enough insulin to meet the body's needs glucose level rise and diabetes results. Scientists do not know why the pancreas does not function well in these people. Some believe that the system that controls glucose levels in the blood and tells the pancreas to make more insulin does not function properly. Other think that the pancreas, after many years of working overtime, overproducing insulin to overcome insulin resistance, simply begins to "burn out."

Although researchers do not fully understand why type 2 diabetes develops, they have uncovered many factors that may contribute to the disease.

GENETICS

Genetics also appear to play a role in how type 2 diabetes develops. Like type 1 diabetes, type 2 diabetes also appears to run in families, and it is most likely due to the inheritance of certain genes. The link to genetics seems even stronger in type 2 diabetes than in type 1 diabetes. If a person with type 1 diabetes had an identical twin, there is a 25 to 50 percent chance that the twin, will develop diabetes. But if a person with type 2 diabetes has an identical twin, there is 60 to 75 percent chance that the person will develop diabetes.

More evidence for the role of genes in type 2 diabetes comes from studying minorities. Compared with whites, African Americans, Asian Americans, Hispanic Americans, and Native Americans all get type 2 diabetes more often. Native Americans have the highest rate of type 2 diabetes in the World. Hispanic groups, such as Mexican Americans, that share genes with Native American groups have a higher rate of type 2 diabetes than Hispanic groups, such as Cuban Americans, where less intercultural contact has occurred.

Researchers have not yet isolated a single "type 2 diabetes" gene, but they are finding errors in several that may contribute to type 2 diabetes. For example, researchers have identified a protein called PC-1 that shuts down the insulin receptor, which creates insulin resistance. This protein is prevalent in most people with type 2 diabetes, compared with people without diabetes. For some reason, too much of the inhibitor protein is made in some people, and the insulin receptor cannot do its job properly, which can lead to insulin resistance.

Researchers believe that the genes that lead to obesity may also play a role in diabetes. In mice, scientists have identified a gene they called the obese gene. The obese gene appears to regulated body weight by making proteins that affect the center in the brain that tells you whether you're full or hungry. When the obese gene is mutated, the mice become obese and develop type 2 diabetes.

AGE, OBESITY, AND LIFESTYLE

The most important environmental trigger of type 2 diabetes appears to be obesity. Obesity is defined as weighing more than 20 percent over your desirable body weight. Genetics may play a role in obesity and, thus, in triggering type 2 diabetes.

In some way, having too much body fat promotes resistance to insulin. This is why, for so many years, type 2 diabetes has been treated with diet and exercise. Losing weight and increasing the amount of muscle while decreasing the amount of fat helps the body use insulin better. There is also a link between type 2 diabetes and where your body is too fat. People with central body obesity, which means carrying excess fat above the lips, have a higher risk of developing type 2 diabetes than those with excess fat on the hips and thighs.

Central body obesity, as well as overall obesity, is more common in African Americans than in whites. This may be one reason why type 2 diabetes is also more common in African Americans than in whites.

Age also appears to play a role. Half of all new cases of type 2 diabetes occur in people over age 55. Because people tend to gain weight as they age, many researchers think that the reason more older people develop diabetes is because more older people are overweight.

Leading an inactive, sedentary lifestyle and consuming a high-calorie diet can also lead to type 2 diabetes, presumably by contributing to obesity. Obesity, as well as type 2 diabetes, are common in Asian Americans and Hispanic Americans who have "westernized" their eating and activity habits.

CAUSES OF GESTATIONAL DIABETES

Like the other types of diabetes, the exact cause of gestational diabetes is unknown. However, experts do have some clues.

HORMONES

During pregnancy, the placenta, which is the organ that nourishes the growing baby, produces large amounts of various hormones. Hormones are important for the baby's growth. However, these hormones may also block insulin's action in the mother's body, causing insulin resistance. All pregnant women have some degree of insulin resistance.

Gestational diabetes usually appears around the 24th week of pregnancy. This is when the placenta begins producing large quantities of the hormones that cause insulin resistance. For this reason, the period between the 24th and 28th weeks of pregnancy is a good time to screen for gestational diabetes.

GENETICS

Because insulin resistance, rather than underproduction of insulin, seems to cause gestational diabetes it is more like type 2 diabetes than type 1 diabetes. And having gestational diabetes increases your chances of someday developing type 2 diabetes. Researchers suspect that the genes responsible for type 2 diabetes and for gestational diabetes may be similar.

Some women show signs of high blood glucose even before the 28th week of pregnancy. Doctors believe that these women probably had diabetes that was unrecognized before the pregnancy began. The weight gain and hormonal changes of pregnancy stressed the body and revealed the diabetes. This can happen with either type 1 or type 2 diabetes. Doctors would carefully watch what happens after the pregnancy in order to diagnose type 1 or type 2 diabetes.

OBESITY

Gestation diabetes is more common in groups that have more obesity. For instance, it is found more often in areas with a large number of Hispanic Americans, in whom obesity is more common. Obesity can trigger gestational diabetes as well as type 2 diabetes.

Traveler's Diarrhea

BACK

Whenever a person travels from one country to another - particularly if the change involves a marked difference in climate, social conditions, or sanitation standards and facilities - diarrhea is likely to develop within 2 - 10 days. There may be up to ten or even more loose stools per day, often accompanied by abdominal cramps, nausea, occasionally vomiting, and rarely fever. The stools do not usually contain mucus or blood, and aside from weakness dehydration there are no systemic manifestations of infection. The illness usually subsides spontaneously within 1 - 5 days. Although 10% remain symptomatic for a week or longer, an din 2% symptoms persist for longer than a month.

Bacteria cause 80% of cases of traveler's diarrhea, with enterotoxigenic E coli, shigella species, and campylobacter jejuni being the most common pathogens. Less common causative agents include aeromonas, salmonella, noncholera vibrious. Entamoeba histolytica, and Giardia lamblia. Contributory causes may at times include unusual food and drink, change in living habits, occasional viral infections, and change in bowel flora. In patients with fever and bloody diarrhea, stool culture may be indicated, but in most cases cultures are reserved for those who do not respond to antibiotics. Chronic watery diarrhea may be due to amebiasis or giardiasis or, rarely, tropical sprue.

For most individuals, the affliction is short-lived, and symptomatic therapy with opioids or loperamide is all that is required provided the patient is not systemically ill and does not have dysentery, in which case antimotility agents should be avoided. Packages of oral rehydration salts to treat dehydration are available over the counter in the USA and in many foreign countries. Avoidance of fresh foods and water sources that are likely to be contaminated is recommended for travelers to developing countries, where infectious diarrheal illnesses are endemic. Prophylaxis is remended for those with significant underlying disease and for those whose full activity status during the trip is so essential that even short periods of diarrhea would be unacceptable. Prophylaxis is started upon entry into the destination country and is continued for 1 or 2 days after leaving. For stays of more than 3 weeks, prophylaxis is not recommended because of the cost and increased toxicity. For prophylaxis, bismuth subsalicylate is effective but turns the tongue and the stools black and can interfere with doxycyline absorption, which may be needed for malaria prophylaxis. Numerous antimicrobial regimens for once-daily prophylaxis also are effective, such as n orfloxacin 400 mg, ciprofloxacin 500 mg, lfloxacin 300 mg, or trimethoprim - sulfamethoxazole 160/80 mg. Because not all travelers will have diarrhea and because most episodes are brief and self-limited, an alternative approach that is currently recommended is to provide the traveler with a supply of antimicrobials to be taken if significant diarrhea occurs during the trip. Loperamide with a single dose of ciprofloxacin, or olfloxacin cures most cases of traveler's diarrhea. If diarrhea is severe, associated with fever or bloody stools, or persists despite single-dose ciprofloxacin treatment, then 3 - 5 days of ciprofloxacin 500 mg twice daily, levofloxacin 500 mg once daily, norfloxacin 400 mg twice daily, or ofloxacin 300 mg twice daily can be given. Trimethoprim-sulfamethoxazole 160/800 mg twice daily can be used as an alternative, but resistance is common in many areas.

BACK

Disorders due to Heat

BACK

Four medical disorders comprise a spectrum of illness that can result from excessive exposure to hot environments: heat syncope, hear cramps, heat exhaustion, and heat stroke. A stable internal temperature requires a balance between heat production and heat loss, which the hypothalamus regulates in initiating changes in muscle tone, vascular tone, and sweat gland function.

Etiology

Sweat production and evaporation is a major mechanism of heat removal. Conduction - the direct transfer of heat from the skin to the surrounding air - also occurs, but with diminished efficiency as the ambient temperature rises. The passive transfer of heat from a warmer to a cooler object by radiation accounts for 65% of body heat loss decreases as the temperature of the surrounding environment increases up to 37.2, the point at which heat transfer reverses direction. At normal temperatures, evaporation accounts for approximately 20% of the body's heat loss, but at high temperature is becomes the major mechanism for dissipation of heat; with vigorous exertion, sweat loss can be as much as 2.5 L/h. This mechanism is also limited as humidity increases.

Health conditions that inhibit sweat production or evaporation and increase susceptibility to heat disorders include obesity, generalized skin diseases, diminished cutaneous blood flow, dehydration, malnutrition, hypotension, and reduced cardiac output. Medications that impair the sweating mechanism are the anticholinergics, antihistamines, phenothiazines, tricyclic antidepressants, monoamine oxidase inhibitors, and diuretics; reduced cutaneous blood flow results from use of vasoconstrictors and - adrenergic blocking agents; and dehydration results from use of alcohol. Illicit drugs eg, phencyclidine, LSD, amphetamines, and cocaine - can cause increased muscle activity and thus generate increased body heat. Drug withdrawal syndromes may have the same effect, as may prolonged seizures.

The risk of heat disorder also increased with age, impaired cognition, concurrent illness, reduced physical fitness, and insufficient acclimatization.

Prevention

Medical evaluation and monitoring should be used to identify individuals at increased risk of heat disorders. The exposed public should be made aware of the early symptoms and signs of heat disorders. It is not recommended to make salt tablets available for use without medical supervision; close monitoring of fluid and electrolyte intake may be necessary in situations necessitating activity in hot environments. Athletic events should be organized and managed with attention to thermoregulation: the WBGT Index should be encouraged, and medical support should be immediately accessible. Competition is not recommended when the WBGT exceeds 28 C. Workers should not begin work in hot temperatures without proper acclimatization and should be encouraged to drink water or balanced electrolyte fluids frequently.

Protective cooled suits have been used successfully in industry for prolonged work in environment up to 60 C.

Acclimatization is achieved by scheduled regulated exposure to hot environments and by gradually increasing the duration of exposure and the work load until the body adjusts by starting to produce sweat of lower salt content in greater amounts at later ambient temperatures. Acclimatization is accompained by increased plasma volume, cardiac output, and cardiac stroke volume and a slower heart rate.

SPECIFIC SYNDROMES DUE TO HEAT EXPOSURE

1. Heat Syncope

Sudden unconsciousness can result from cutaneous vasodilation with consequent systemic and cerebral hypotension. Systolic blood pressure is usually less than 100 mm Hg, and there is typically a history of vigorous physical activity for 2 hours or more just preceding the episode. The skin is typically cool and moist and the pulse is weak.

Treatment consist of rest and recumbency in a cool place, with fluids by mouth

2. Heat Cramps

Fluid and electrolyte depletion can result in slow, painful skeletal muscle contractions and even severe muscle spasms lasting 1 - 3 minutes, usually of the muscles most heavily used. Cramping results from salt depletion as sweat losses are replaced with water alone. The skin is moist and cool, and the muscles are tender. There may be muscle twitching. The victim is alert, with stable vital signs, but may be agitated and complaining of pain. The body temperature may be normal or slightly increased. Involved muscle groups are hard and lumpy. There is almost always a history of vigorous activity just preceding the onset of symptoms. Laboratory evaluation may show low serum sodium, hemoconcentration, and elevated urea and creatinine.

The patient should be moved to a cool environment and given oral saline solution to replace both salt and water. Because of their slower absorption, salt tablets are not recommended. The victim may have to rest for 1 - 3 days with continued dietary salt supplementation before returning to work or resuming strenuous activity in the heat.

3. Heat Exhaustion

Heat exhaustion results from prolonged heavy activity with inadequate salt intake in a hot environment and is characterized by dehydration, sodium depletion, or isotonic fluid loss with accompanying cardiovascular changes.

The diagnosis is based on prolonged symptoms and a rectal temperature over 37.8 C, increased pulse rare - usually more than half again the patient's normal rate - and moist skin. Symptoms associated with heat syncope and heat cramps may also be present. The patient may be quite thirsty and weak, with central nervous system symptoms such as headache, fatigue, and, in cases due chiefly to water depletion, anxiety, paresthesias, impaired judgment, hysteria, and occasionally psychosis. Hyperventilation secondary to heat exhaustion can lead to respiratory alkalosis. Heat exhaustion may progress to heat stroke if sweating ceases.

Treatment consist of patient location in a shaded, cool environment, providing adequate hydration, salt replenishment - orally, if possible - and active cooling if necessary. Physiologic saline or isotonic glucose solution can be administered intravenously in severe cases or when oral administration is not appropriate. Intravenous 3% saline may be necessary if sodium depletion is severe. At least 24 hours of rest is recommended.

4. Heat Stroke

Heat stroke is a life - threatening medical emergency resulting from failure of the thermoregulatory mechanism. Heat stroke is imminent when the core temperature approaches 41 C. It presents in one of two forms: Classic heat stroke occurs in patients with compromised hoemostatic mechanism: exertional heat stroke occurs in previously healthy persons undergoing strenuous exertion in a thermally stressful environment. Morbidity or even death can result from cerebral , cardiovascular, hepatic, or renal damage.

The hallmarks of heat stroke are cerebral dysfunction with impaired consciousness, high fever, and absence of sweating. Persons at greatest risk are the very young, the elderly or chronically infirm, and patients receiving medications that interfere with heat-dissipating mechanisms.

Exertional heat stroke and exertion - related illnesses, including rhabdomyolysis, are appearing more frequently as including rhabdomyolysis, are appearing more frequently as complications of participation by unconditioned amateurs in strenuous athletic activities such as marathon running and triathlon competition.

Clinical Findings

A. Symptoms and Signs
Failure of the heat dissipation mechanism for any reason result in dizziness, weakness, emotional liability, nausea and vomiting, diarrhea, confusion, delirium, blurred vision, convulsions, collapse, and unconsciousness. The skin is hot and initially covered with perspiration. Later it dries. The pulse is strong initially. Blood pressure may be slightly elevated at first, but hypotension develops later. The core temperature is usually over 41 C. As with heat exhaustion, hyperventilation can occur, leading to respiratory alkalosis.

Exertional heat stroke may present with sudden collapse and loss of consciousness followed by irrational behavior. Anhidrosis may not be present. Twenty-five percent of heat stroke victims have prodromal symptoms for minutes to hours that may include dizziness, weakness, nausea, confusion, disorientation, drowsiness, and irrational behavior.

B. Laboratory Findings :
Laboratory evaluation may reveal dehydration leukocytosis, elevated BUN, hyperuricemia, hemoconcentration, acid-base abnormalities, and decreased serum potassium, sodium, calcium, and phosphorus; urine is concentrated, with elevated protein, tubular casts, and myoglobinuria. Thrombocytopenia, increased bleeding and clotting times, fibrinolysis, and consumption coagulopathy may also be present. Rhabdomyolysis and myocardial, hepatic, or renal damage may be identified by elevated serum creatine kinase and aminotransferase levels and BUN and by the presence of anuria, proteinuria, and hematuria. Electrocardiographic findings may include ST - T changes consistent with myocardial ischemia.

Treatment
Treatment is aimed at reducing the core temperature rapidly and controlling the secondary effects. Evaporative cooling is rapid and effective and is easily performed in most emergency settings. The patient's clothing should be removed and the entire body sprayed with water while cooled or ambient air is passed across the patient's body with large fans or other means at high velocity. The patient should be in the lateral recumbent position or supported in a hands - and - knees position to expose as much skin surface as possible to the air. Other alternatives include use of cold wet sheets accompained by fanning or immersion in chilled water. Cardiopulmonary bypass provides rapid cooling but is often not practical.

Immersion is an ice-water bath as initial treatment is no longer preferred because of its greater potential for complications of hypotension and shivering. However, it should be considered if core temperature is not decreased rapidly in response to other treatment. Alternatives include hand forearm immersion in cold water, ice packs, and iced gastric lavage, though these are much less effective than evaporative cooling.

Treatment should be continued until the rectal temperature drops to 30 C. The temperature remains stable in most cases, but it should continue to be monitored for 24 hours. Chlorpromazine or diazepam can be give initially and then every 4 hours to control shivering and other muscular activity associated with increased heat load. Antipyretics have no effect on environmentally induced hyperthermia and are contraindicated.

Hypovolemic and cardiogenic shock must be carefully distinguished, as either or both may occur. Central venous or pulmonary artery wedge pressure should be monitored. Five percent destrose in half-normal or normal saline should be administered for fluid replacement.

The patient should also be observed for renal failure due to rhabdomyolysis, hypokalemia, cardiac arrhythmias, disseminated intravascular coagulation, and hepatic failure. Hypokalemia frequently accompanies heat stroke but may not appear until rehydration. Maintenance of extracellular hydration and electrolyte balance should reduce the risk of renal failure due to rahbdomyolysis. Fluid administration to ensure a high urine output, mannitol administration , and alkalinizing the urine are recommended. Corticosteroids have not been shown to be of value.

Fluid output should be monitored through the use of an indwelling urinary catheter.

Because sensitivity to high environmental temperature continues in some patients for prolonged periods following an episodes of heat stroke, immediate reexposure should be avoided.

BACK

DROWNING

BACK

Drowning is the fifth leading cause of accidental death in the USA. The number of deaths due to drowning could undoubtedly be significantly reduced if adequate preventive and first aid instruction programs were instituted.

The asphyxia of drowning is usually due to aspiration of fluid, but it may result from airway obstruction caused by laryngeal spasm while the victim is gasping under water. About 10% of victims develop laryngospasm after the first gulp and never aspirate water. The rapid sequence of events after submersion - hypoxemia, laryngospasm, fluid aspiration, ineffective circulation, brain injury, and brain death - may take place within 5 - 10 minutes. This sequence may be delayed for longer periods if the victim, especially a child, has been submerged in very cold water or if the victim has ingested significant amounts of barbiturates. Immersion in cold water can also cause a rapid full in the victim's core temperature, so that systemic hypothermia and death may occur before actual drowning.

The primary effect is hypoxia due to perfusion of poorly ventilated alveoli, intrapulmonary shunting, and decreased compliance. The first requirement of rescue is immediate cardiopulmonary resuscitation.

A number of circumstances or primary events may precede near drowning and must be taken into consideration in management: (1) use of alcohol or other drugs, (2) extreme fatigue, (3) intentional hyperventilation, (4) sudden acute illness, (5) head or spinal cord injury sustained in diving, (6) venomous stings by aquatic animals, and (7) decompression sickness in deep water diving.

When first seen, the near-drowning victim may present with a wide range of clinical manifestations. Spontaneous return of consciousness often occurs in otherwise healthy individuals when submersion is very brief. Many other patients respond promptly to immediate ventilation. Other patients, with more severe degrees of near drowning, may have frank respiratory failure, pulmonary edema, shock, anoxic encephalopathy, cerebral edema, and cardiac arrest. A few patients may be deceptively asymptomatic during the recovery period - only to deteriorate or die as a result of acute respiratory failure within the following 12 - 24 hours.

Clinical Findings

A. Symptoms and Signs

The patient may be unconscious, semiconscious, or awake but apprehensive, restless, and complaining of headaches or chest pain. Vomiting is common, Examination may reseal cynaosis, trismus, apnea, tachypnea, and wheezing. A pink froth from the mouth and nose indicates pulmonary edema. Cardiovascular manifestations may include tachycardia, arrhythmias, hypotension, cardiac arrest, and circulatory shock. Hypothermia may be present.

B. Laboratory Findings :

Urinalysis shows proteinuria, hemoglobinuria, and acetonuria. Leukocytosis is usually present. The Pao2 is usually decreased and the Paco2 is increased or decreased. The blood pH is decreased as a result of metabolic acidosis. Chest X-rays may show pneumonitis or pulmonary edema.

Prevention
Prevention consists of avoidance of alcohol during recreational swimming or boating, close supervision of toddlers, swimming lessons early in life, and use of personal flotation devices when boating. All swimming pools should be fenced.

Treatment

A. First Aid :

Immediate measures to combar hypoxemia at the scene of the incident - with sustained effective ventilation, oxygenation, and circulatory support - are critical to survival with complete recovery. Hypothermia and cervical spine injury should always be suspected.

1. Standard CPPR is initiated if pulse and respiration are absent.
2. Do not waste time attempting to drain water from the victim's lungs, since this measure is most often in no value. The Heimlich maneuver should be used only if airway obstruction by a foreign body is suspected. The cervical spine should be immobilized if neck injury is possible.
3. Do not discontinue basic life support for seemingly "hopeless" patients until core temperature reaches 32 C. Complete recovery has been reported after prolonged resuscitation of hypothermic patients.

B. Hospital Care :

Careful observation of the patient; continuous monitoring of cardiorespiratory function; serial determination of arterial blood gases, pH, renal function, and electrolytes; and measurement of urinary output are required. Pulmonary edema may not appear for 24 hours.

1. Ensure optimal ventilation and oxygenation
The danger of hypoxemia exists even in the alert, conscious patient who appears to be breathing normally. Oxygen should be administered immediately at the highest available concentration. Endotracheal intubation and mechanical ventilation are necessary for patients unable to maintain an open airway or normal blood gases and pH. Nasogastric intubation will allow removal of swallowed water and prevention of aspiration. If the victim does not have spontaneous respirations, intubation is required. Oxygen saturation should be maintained at 90% or higher. Continuous positive airway pressure is the most effective means of reversing hypoxia in patients with spontaneous respirations and patients airways. Positive end expiratory pressure is also effective for treating respiratory insufficiency. Assisted ventilation may be necessary with pulmonary edema, respiratory failure, aspiration, pneumonia, or severe central nervous system injury. Serial physical examinations and chest X-rays should be carried out to detect possible pneumonitis, atelectasis, and pulmonary edema. Bronchospasm due to aspirated material may require use of bronchodilators. Antibiotics should be given only when there is clinical evidence of infection - not prophylactically.

2. Cardiovascular support - Central venous pressure may be monitored as a guide to determining whether vascular fluid replacement and pressors or diuretics are needed. If low cardiac output persists after adequate intravascular volume is achieved, pressors should be given. Otherwise, standard therapy for pulmonary edema, cardiogenic or not, is administered.

3. Correction of blood pH and electrolyte abnormalities - Metabolic acidosis is present in 70% of near-drowning victims, but it is usually of monitor importance and corrected through adequate ventilation and oxygenation. While controversial, bicarbonate administration has been recommended for comatose patients.

4. Cerebral injury - Some near-drowning patients may progress to irreversible central nervous system damage despite apparently adequate treatment of hypoxia and shock. Mild hyperventilation to achieve a PaCo2 of approximately 30 mm Hg is recommended to lower intracranial pressure.

5. Hypothermia - Core temperature should be measured and managed as appropriate.

Course & Prognosis
Victims of near drowning who have had prolonged hypoxemia should remain under close hospital observation for 2 - 3 days after all supportive measures have been withdrawn and clinical and laboratory findings have been stable. Residual complications of near drowning may include intellectual impairments, convulsive disorders, and pulmonary or cardiac disease.

BACK

ELECTRIC SHOCK

BACK

The possibility of life-threatening electrical injury exists wherever there is electric power or lightning. The amount and type of current, the duration and area of exposure, and the pathway of the current through the body determine the degree of damage. If the current passes through the heart or brain stem, death may occur immediately owing to ventricular fibrillation or apnea. Current passing through skeletal muscle can cause muscle necrosis and contractions severe enough to result in bone fracture. Current traversing peripheral nerves can cause acute or delayed neuropathy. Delayed effects can include damage to the spinal cord, peripheral nerves, bone, kidneys, and gastrointestinal tract as well as cataracts.

Direct current is less dangerous than alternating current. With alternating currents of 25 - 300 Hz, low voltages tend to produce ventricular fibrillation; high voltages, respiratory failure; intermediate voltages, both. More than 100 mA of domestic house current of 110 volts at 60 Hz is, accordingly, dangerous to the heart, since it can cause ventricular fibrillation. DC current contact is more likely to cause asystole.

Lightning injuries differ from high-voltage electric shock injuries in that lightning usually involves higher voltage, briefer duration of contact, asystole rather than ventricular fibrillation, nervous system injury, and multisystem pathologic involvement.

Electrical burns are of three distinct types: flash burns, flame burns, and the direct heating effect of tissues by the electric current. The latter lesions are usually sharply demarcated, round or oval, painless yellow-brown areas with inflammatory reaction. Significant subcutaneous damage can be accompanied by little skin injury, particularly with larger skin surface area electrical contact.

Electric shock may produce loss of consciousness. With recovery there may be muscular pain, fatigue, headache, and nervous irritability. The physical signs vary according to the action of the current. Ventricular fibrillation or respiratory failure can occur; the patient may be unconscious, pulseless, hypotensive, cold and cyanotic, and without respirations.

Electric shock may be a hazard in equipment that is usually considered to be harmless. Proper installation, utilization, and maintenance of equipment by qualified personnel should minimize this hazard.

Treatment

A. Emergency Measures :

The victim must be freed from the electric current prior to initiation of CPR or other treatment; the rescuer must be protected. Turn off the power, sever the wire with a dry wooden - handled axe, make a proper ground to divert the current, or drag the victim carefully away by means of dry clothing or a leather belt.

Lightning injury. Victims of lightning injury, in whom coma may last for a few minutes to several days, should receive prompt and sustained artificial resuscitation. This should be continued as long as there is no clinical evidence of brain death.

B. Hospital Measures :

Lightning or unstable electric shock victims should hospitalized when revived and observed for shock, arrhythmia, thrombosis, infarction, sudden cardiac dilation, hemorrhage, and myoglobinuria. A urinalysis, serum Ck and CK-MB, and an electrocardiogram should be obtained immediately. Victims should also be evaluated for blunt trauma, dehydration, skin burns, hypertension, posttraumatic stress, acid-base disturbances, and neurologic damage. Indications for hospitalization include significant arrhythmia or electrocardiographic changes, large burn, loss of consciousness, pulmonary or cardiac symptoms, or evidence of significant deep tissue or organ damage. Extra caution is indicated when the electroshock current has followed a transthoracic route (hand to hand or hand to foot) and in patients with a cardiac history.

To counteract fluid losses and myoglobinuria due to electric shock (not lighting ) burns, aggressive hydration with Ringer's lactate should seek to achieve a urine output of 50-100 mL/h.

Prognosis

Complication may occur in almost any part of the body but most commonly include sepsis, gangrene requiring limb amputation, or neurologic, cardiac, cognitive, or psychiatric dysfunction.

TREATMENT OF COMMON SPECIFIC POISONINGS
(ALPHABETICAL ORDER)

BACK

ACETAMINOPHEN

Acetaminophen is a common analgesic found in many nonprescription and prescription products. After absorption, it is metrabolized mainly by glucuronidation and sulfation, with a small fraction metabolized via the P450 mixed-function oxidase system to a highly toxic reactive intermediate. This toxic intermediate is normally detoxified by cellular glutahione. With acute acetaminophen overdose, hepatocellular glutathione is rapidly depleted and the reactive intermediate attacks other cell proteins, causing necrosis. Patients with enhanced P450 activity, such as chronic alcoholics and patients taking anticonvulsants, are at increased risk of developing hepatotoxicity. Hepatic toxicity may also occur after chronic accidental overuse of acetaminophen - eg, as little as 1 g of acetaminophen every 4 - 6 hours for 1 - 2 days in a patient with chronic accidental overuse of acetaminophen - eg, as little as 1g of acetaminophen every 4 - 6 hours for 1 - 2 days in a patient with chronic excessive alcohol use.

Clinical Findings

Shortly after ingestion, patients may have nausea or vomiting, but there are usually no other signs of toxicity until 24 - 48 hours after ingestion, when hepatic aminotransferase levels begin to increase. With severe poisoning, massive hepatic necrosis may occur, resulting in jaundice, hepatic encephalopathy, renal failure, and death.

The diagnosis of severe poisoning after acute over-dose is based on measurement of the serum acetaminophen level. Plot the serum level versus the time since ingestion on the acetaminophen nomogram. Ingestion of sustained-release produces or coingestion of an anticholinergic agent, salicylate, or opioid drug may cause delayed elevation of serum levels.

Treatment

A. Emergency and Supportive Measures :

Empty the stomach by emesis or gastric lavage. Administer activated Charcoal. Although charcoal may bind the oral antidote aceylecysteine, this is not considered clinically significant.

B. Specific Treatment

If the serum acetaminophen level is higher than the upper toxic line on the nomogram, begin treatment with a loading dose of acetylcysteine, 140 mg/kg orally, followed by 70 mg/kg every 4 hours. Dilute the solution to 5% with water, juice, or soda. If vomiting interferes with oral acetylcysteine administration, give the dose by gastric tube and use metoclopramide, 1 - 2 mg/kg intravenously. The most widely used protocol in the USA continues treatment for 72 hours. However, other regimens have demonstrated equivalent success with 20 - 48 hours of treatment. Treatment with acetylcysteine is most effective if started within 8 --10 hours after ingestion. If the precise time of ingestion is unknown or if the patient is at higher risk of hepatotoxicity, then use a lower threshold for initiation of acetylcysteine.

Acetylcysteine may also be given intravenously; this is the preferred method in Europe and Canada, but there is no approved parenteral formulation or dosing schedule in the United States. If the patient cannot tolerate acetylcysteine despite antiemetics and administration via a gastric tube, the United States formulation may be give intravenously. Call a regional poison control centre or medical toxicologist for assistance.

ACIDS, CORROSIVE

The strong mineral acids exert primarily a local corrosive effect on the skin and mucous membranes. Symptoms include severe pain in the throat and upper gastrointestinal tract; bloody vomitus; difficulty in swallowing, breathing, and speaking; discoloration and destruction of skin and mucous membranes in and around the mouth; and shock. Severe systemic metabolic acidosis may occur both as a result of cellular injury and from systemic absorption of the acid.

Severe deep destructive tissue damage may occur after exposure to hydrofluoric acid because of the penetrating and highly toxic fluoride ion. Systemic hypocalcemia and hyperkalemia also may occur after fluoride absorption, even following skin exposure.

Inhalation of volatile acids, fumes, or gases such as chlorine, fluorine, bromine, or iodine causes severe irritation of the throat and larynx and may cause upper airway obstruction and noncardiogenic pulmonary edema.

Treatment

A. Ingestion

Do not induce emesis. Dilute immediately by giving a glass of milk or water to drink. Do not give bicarbonate or other neutralizing agents. Some experts recommend immediate gastric lavage.

Perform flexible endoscopic esophagoscopy promptly to determine the presence and extent of injury. X-rays of the chest and abdomen may reveal the presence of free air in patients with esophageal or gastric perforation. Perforation, peritonitis, and major bleeding are indications for surgery.

B. Skin Contact :

Flood with water for 15 minutes. Use no chemical antidotes; the heat of the reduction may cause additional injury.

For hydrofluoric acid burns, soak the affected area in magnesium sulfate solution or apply 2.5% calcium gluconate gel; then arrange immediate consultation with a plastic surgeon or other specialist. Binding of the fluoride ion may be achieved by injecting 0.5 mL of 5% calcium gluconate per square centimeter under the burned area. (Caution : Do not use calcium chloride).

C. Eye Contact

Anesthetize the onjunctiva and corneal surfaces with topical local anesthetic drops. Flood with water for 15 minutes, holding the eyelids open. Check pH with pH 6.0 - 8.0 test paper, and repeat irrigation, using 0.9% saline, pH is near 7.0. Check for corneal damage with fluorescein and slitlamp examination; consult an ophthalmologist about further treatment.

D. Inhalation

Remove from further exposure to fumes or gas. Check skin and clothing. Treat pulmonary edema.

ALKALIES

The strong alkalies are common ingredients of some household cleaning compounds and may be suspected by their "soapy" texture. Those with alkalinity above pH 12.0 are particularly corrosive. Clinitest tables and disk batteries are also a source. Alkalies cause liquefactive necrosis, which is deeply penetrating. Symptoms include burning pain in the upper gastrointestinal tract, nausea, vomiting, and difficulty in swallowing and breathing. Examination reveals destruction and edema of the affected skin and mucous membranes and bloody vomitus and stools. X-ray may reveal the presence of disk batteries in the esophagus or lower gastrointestinal tract.

Treatment

A. Ingestion

Do not induce emesis. Dilute immediately with a glass of water. Some gastroenterologists recommend immediate gastric lavage after ingestion of liquid caustic substances to remove residual material.

Immediate endoscopy is recommended to evaluate the extent of damage. If X-ray reveals the location of ingested disk batteries in the esophagus, immediate endoscopic removal is mandatroy.

The use of corticosteroids to prevent stricture formation is of no proved benefit and is definitely contraindicated if there is evidence of esophageal perforation.

B. Skin Contact :

Wash with running water until the skin no longer feels soapy. Relieve pain and treat shock.

C. Eye Contact :

Anesthetize the conjunctival and corneal surfaces with topical anesthetic. Irrigate with water or saline continuously for 20 - 30 minutes, holding the lids open. Check pH with pH test paper, and repeat irrigation, using 0.9% saline, for additional 30 minute periods until the pH is near 7.0. Check for corneal damage with fluorescein and slitlamp examination; consult an ophthalmologist for further treatment.

AMPHETAMINES & COCAINE

Amphetamines and cocaine are widely abused for their euphorigenic and stimulant properties. Both drugs may be smoked, snorted, ingested, or injected. Amphetamines and cocaine produce central nervous system stimulation and a generalized increase in central and peripheral sympathetic activity. The toxic does of each drug is highly variable and depends on the route of administration and individual tolerance. The onset of effects is most rapid after intravenous injection or smoking. Amphetazine derivatives and related drugs include methamphetamine, and methcarthinone. Nonprescription medications and nutritional supplements may contain stimulant or sympathomimetic drugs such as ephedrine or caffeine. Phenylpropanolamine was recently withdrawn from the market because of an increased incidence of hypertensive intracerebral hemorrhage in young women.

Clinical Findings

Patients may present with anxiety, tremulousness, tachycardia, hypertension, diaphoresis, dilated pupils, agitation, muscular hyperactivity , and psychosis. Metabolic acidosis may occur. In severe intoxication, seizures and hyperthermia may occur. Sustained or severe hypertension may result in intracranial hemorrhage, aortic dissection, or myocardial infarction. Hyponatremia has been reported after MDMA use; the mechanism is not known but may involve excessive water intake, SIADH, or both.

The diagnosis is supported by finding amphetamines, cocaine, or the cocainemetabolite benzoylecgonine in the urine. Blood screening is not sensitive enough to detect these drugs.

Treatment

A. Emergency and Supportive Measures

Maintain a patent airway and assist ventilation, if necessary. Treat coma or seizures. Rapidly lower the body temperature in patients who are hyperthermic. Treat agitation or psychosis with a benzodiazeine such as diazepam, 5 - 10 mg intravenously, o rmidazolam, 0.1 - 0.2 mg/kg intramuscularly.

For poisoning by ingestion, perform gastric lavage and administer activated charcoal, or administer activated charcoal alone without prior gut emptying. Do not induce emesis, because of the risk of seizures.

B. Specific Treatment

Treat agitation with a sedative as lorazepam, 2 - 3 mg intravenously. Treat hypertension with a vasodilator drug such as phentolamine or nifedipine or a combined - and - adrenergic blocker such as labetalol. Do not administer a pure beta - blocker such as propranolol alone, as this may result in paradoxic worsening of the hypertension as a result of unopposed - adrenergic effects. Treat tachycardia or tachyarrhythmias with a short-acting beta-blocker such as esmolol.

ANTICOAGULANTS

Warfarin and related compounds inhibit the clotting mechanism by blocking hepatic synthesis of vitamin K-dependent clotting factors.

Anticoagulants may cause hemoptysis, gross hematuria, bloody stools, hemorrhages into organs. Wide spread bruising, and bleeding into joint spaces. The prothrombin time is increased within 12 - 24 hours after a single overdose. After ingestion of brodifacoum and indanedione rodenticides, inhibition of clotting factor synthesis may persist for several weeks or even months after a single dose.

Treatment

A. Emergency and Supportive Measures:

Discontinue the drug at the first sign of gross bleeding, and determine the prothrombin time. If the patient has ingested an acute overdose, empty the stomach by emesis or lavage and administer activated charcoal.

B. Specific Treatment

Do not treat prophylactically - wait for the evidence of anticoagulation. If the prothrombin time is elevated, give phytonadione, 5 - 10 mg subcutaneously or 10 - 25 mg orally, and additional doses as needed to restore the prothrombin time to normal. Give fresh-frozen plasma as needed to rapidly correct the coagulation factor deficit if there is serious bleeding. If the patient is chronically anticoagulated and has strong medical indications for being maintained in that status, give much smaller doses if vitamin k and flesh - frozen plasma as titrate to the desired prothrombin time.

If the patient has ingested brodifacoum or a related superwarfarin, prolonged observation and repeated administration of large doses of vitamin k may be required.

ANTICONVULSANTS
(Carbamazepine, Phenytoin, Valporic Acid)

There drugs are widely used in the management of seizure disorders. In addition, carbamazepine and valproxic acid are increasingly used for treatment of mood disorders.

Phenytoin can be given orally or intravenously. Rapid intravenous injections of phenytoin can cause acute myocardial depression and cardiac arrest owing to the solvent propylene glycol; a never form of phenytoin is available that does not contain this diluent. Phenytoin intoxication can occur with only slightly increased doses because of the small toxic- therapeutic window. Phenytoin intoxication can also occur following acute intentional of accidental overdose. The overdose syndrome is usually mild even with high serum levels. The most common manifestations are ataxia, nystagmus, and drowsiness. Choreoathetoid movements have been described.

Carbamazepine was first used for the treatment of trigeminal neuralgia. It has since become a first-line agent for temporal lobe epilepsy and other seizure disorders. Intoxication causes drowsiness, stupor, and, with high levels, coma and seizures. Dilated pupils and tachycardia are common. Toxicity may be seen with serum levels greater than 20 mg/L, though severe poisoning is usually associated with concentrations greater than 30 - 40 mg/L. Because of erratic and slow absorption, intoxication may progress over several hours to days.

Valporic acid intoxication produces a unique syndrome consisting of hypernatremia, metabolic acidosis, hypocalcemia, elevated serum ammonia, and mild liver aminotransferase elevation. Hypoglycemia may occur as a result of hepatic metabolic dysfunction, Coma with small pupils may be seen and can mimic opioid poisoning. Encephalopathy and cerebral edema can occur.

Treatment

A. Emergency and Supportive Measures :

For recent ingestion, give activated charcoal orally or by gastric tube. For large ingestions of carbamazepine or valporic acid - especially of sustained-release for mulations - consider whole bowel irrigation. Multiple-dose activated charcoal may be beneficial in ensuring gut decontamination for large ingestions and may enhance elimination of absorbed drugs.

B. Specific Treatment

There are no antidotes. Naloxone was reported to have reversed valptoic acid overdose in one anecdotal case. Consider hemodialysis or hemoperfusion for massive intoxication.

ARSENIC

Arsenic is found in pesticides and industrial chemicals. Symptoms of poisoning usually appear within 1 hour after ingestion but may be delayed as long as 12 hours. They include abdominal pain, vomiting, watery diarrhea, and skeletal muscle cramps. Profound dehydration and shock may occur. In chronic poisoning, symptoms can be vague but often include those of peripheral sensory neuropathy. Urinary arsenic levels may be misleading and are falsely elevated after certain meals that contain large quantities of relatively nontoxic organic arsenic.

Treatment

A. Emergency Meausres

Induce vomiting or perform gastric lavage, and administer 60 - 100 g of activated charcoal.

B. Antibote :

For symptomatic patients or those with massive overdose, give dimercaprol injection, 10% solution in oil, 3 - 5 mg/kg dimercaprol intramuscularly every 4 - 6 hours for 2 days. The side effects include nausea, vomiting, headache, and hypertension. Follow dimercaprol with oral penicillamine, 100 mg/kg/d in four divided doses, 10 mg/kg every 8 hours, for 1 week. Consult a medical toxicologist or regional poison control centre for advice regarding chelation.

ATROPINE & ANTICHOLINERGICS

Atropine, scopolamine, belladonna, diphenoxylate with atropine. Datura stramonium, Hyoscyamus niger, some mushrooms, tricyclic antidepressants, and antihistamines are antimuscarinic agents with variable central nervous system effects. The patient complains of dryness of the mouth, thirst, difficulty in swallowing, and blurring of vision. The physical signs include dilated pupils, flushed skin, tachycardia, fever, delirium, myocolonus, ileus, and flushed appearance. Antidepressants and antihistamines may induce convulsions.

Antihistamines are commonly available with or without prescription. Diphenhydramine commonly causes delirium, tachycardia, and seizures. Massive overdose may mimic tricyclic antidepressant poisoning. The nonsedating agents terfenadine and astemizole have caused QT interval prolongation and torsade de pointes. Loratidine has not caused this problem.

Treatment

A. Emergency and Supportive Measures

Perform gastric lavage, and administer activated charcoal. Do not induce emesis in patients who have ingested antihistamines or antidepressants, because seizures may occur abruptly. Tepid sponge baths and sedation are indicated to control high temperatures.

B. Specific Treatment

For pure atropine or related anticholinergic syndrome, if symptoms are severe, give p hysostigmine salicylate, o.5 - 1 mg slowly intravenously over 5 minutes, with electrocardiographic monitoring, until symptoms are controlled. Bradyarrhythmias and convulsions are a hazard with physostigmine administration, and it should not be used in patients with tricyclic antidepressed overdose.

BETA-ADRENERGIC BLOCKERS

There are wide variety of beta-adrenergic blocking drugs, with varying pharmacologic and pharmacokinetic properties. The most commonly used and most toxic beta-blocker is propranolol. Propranolol competitively blocks beta1 and beta2 adrenoceptors and also has direct membrane depressant and central nervous system effects.

Clinical Findings

The most common findings with mild or moderate intoxication are hypotension and bradycardia. Cardiac depression from more severe poisoning is often unresponsive no conventional therapy with beta-adrenergic stimulants such as dopamine and norepinephrine. In addition, with propranolol and other lipid - soluble drugs, seizures and coma may occur.

The diagnosis is based on typical clinical findings. Routine toxicology screening does not usually include beta-blockers.

Treatment

A. Emergency and Supportive Measures :

Initially, treat bradycardia or heart b lock with atropine, isoproterrenol by intravenous infusion, titrated to the desited, or an external transcutaneous cardiac pacemaker. Specific antidotal treatment may be necessary.

For ingested drugs, empty the stomach by gastric lavage and administer activated charcoal. Do not induce emesis because of the risk of seizures.

B. Specific Treatment :

If the above measures are not successful in reversing bradycardia and hypotension, give glucagon, 5 - 10 mg intravenously, followed by an infusion of 1 - 5 mg/h. Glucagon in an inotropic agent that acts as a different receptor site and is therefore not affected by beta-blockade.

CALCIUM CHANNEL BLOCKERS

Calcium channel blockers used in the United States include verapamil, diltiazem, nifedipine, nicardipine, amlodipine, felodipine, isradipine, nisoldipine, and nimodipine. These drugs share the ability to cause arteriolar vasodilation and depression of cardiac contractility, especially after acute overdose. Patients may present with bradycardia. AV nodal block, hypotension, or a combination of these effects. With severe poisoning, cardiac arrest may occur.

Treatment

A. Emergency and Supportive Measures

Maintain a patient airway and assist ventilation, if necessary. Treat coma, hypotension, and seizures as described at the beginning of this chapter. Treat bradycardia with atropine, isoproterenol, or a transcutaneous or internal cardiac pacemaker.

For ingested drugs, perform gastric lavage and administer activated charcoal. In addition, whole bowel irrigation should be initiated as soon as possible if the patient has ingested a sustained - release product. Because of the risk of hypotension and seizures, do not induce emesis.

B. Specific Treatment :

If bradycardia and hypotension are not reversed with these measures, administer calcium chloride intravenously. Start with calcium chloride 10%, 10 mL, or calcium gluconate, 20 mL. Repeat the dose every 3 - 5 minutes. The optimum dose has not been established, but there are reports of success after as much as 10 - 12 g of calcium chloride. Calcium is most useful in reversing negative inotropic effects and is less effective for AV nodal blockade and bradycardia. Epinephrine infusion and glucagon, 5 - 10 mg intravenously, have also been recommended.

CARBON MONOXIDE

Carbon monoxide is a colorless, odorless gas produced by the combustion of carbon-containing materials. Poisoning may occur as a result of suicidal or accidental exposure to automobile exhaust, smoke inhalation in a fire, or accidental exposure to an improperly vented gas heater or other appliance. Carbon monoxide avidly binds to hemoglobin, with an affinity approximately 250 times that of oxygen. This results in reduced oxygen-carrying capacity and altered delivery of oxygen to cells.

Clinical Findings
At low carbon monoxide levels, victims may have headache, dizziness, abdominal pain, and nausea. With higher levels, confusion, dyspnea, and syncope may occur. Hypotension, coma, and seizures are common with levels greater than 50 - 60%. Survivors of acute severe poisoning may develop permanent neurologic deficits. The fetus and newborn may be more susceptible because of high carbon monoxide affinity for fetal hemoglobin.

Carbon monoxide poisoning should be suspected in any person with severe headache or acutely altered mental status, especially in cold weather, when improper heating systems may have been used. Diagnosis depends on specific measurement of the arterial or venous carboxyhemoglobin saturation, although the level may have declined if high-flow oxygen therapy, has already been administered. Routine arterial blood gas testing and pulse oximetry are not useful because they may give fulsely normal oxyhemoglobin saturation determination.

Treatment

A. Emergency and Supportive Measures :

Maintain a patent airway and assist ventilation, if necessary. Remove the victim from exposure. Treat patients with coma. Hypotension, or seizures, as described at the beginning of this chapter.

B. Specific Treatment :

The half-life of the carboxyhemoglobin complex is about 4 - 5 hours in room air but is reduced dramatically by high concentration of oxygen. Administer 100% oxygen by tight-fitting high flow reservoir face mask or endotracheal tube. Hyperbaric oxygen can provide 100% oxygen under higher than atmosphere pressures, further shortening the half-life; it may be useful if immediately available for patients with coma or seizures and in pregnant women, though controlled studies have failed to prove that HBO is superior to high - flow oxygen at normal pressure.

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Candidiasis
(Oral Thrush; Vaginal Yeast infection; Esophageal Candidiasis)

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What is it?

Thrush, also called candidiasis, is a disease caused by a fungus. Everyone has this fungus both on and inside their bodies. It can be found on the skin, in the stomach, the colon and rectum, the vagina, and in the mouth and throat. Most of the time. Candidia albicans is harmless and actually helps keeps bacteria levels in check. Sometimes. However, there is an overgrowth of this fungus, which can lead to a variety of problems.

Both HIV-positive and HIV-negative people can develop candidiasis. Many women experience vaginal yeast infections, a type of candidiasis. Similarly, a person can experience an overgrowth of fungus in their mouth or the back of their throat. Stress, poor diet, or not getting enough rest can contribute to these problems. Also, a person who takes antibiotics for bacterial infections, especially for long periods of time, can develop thrush in their mouth or vagina. Candidiasis in the mouth can also occur in people who use inhaled steroids, such as those used to treat asthma and other lung problems.

Poor oral hygiene and smoking can also play a role in fungal overgrowth in the mouth. Excessive alcohol and sugar consumption have also been linked to the development of candidiasis.

In HIV-positive people, oral thrush and vaginal yeast infections can occur at any time, regardless of their T-cell counts. The more the immune system becomes damaged, oral thrush and vaginal yeast infections are more likely to occur and recur more frequently. HIV-positive people with damaged immune systems, usually with a T-cell count less than 200, are also more likely to develop candidiasis deeper in their bodies, such as in their esophagus or their lungs.

What are the symptoms of candidiasis?

Symptoms of candidiasis depend on the part of the body affected. If you have any of the symptoms, you should contact your doctor:

The symptoms of candidiasis

• Oral candidiasis : Some of the general symptoms of oral thrush include burning pain in the mouth or throat, altered taste, and difficulty swallowing. Oral candidiasis appears as white or pinkish-red blotches on the tongue, gums, the sides or roof of the mouth, and the back of the throat. Sometimes, oral candidiasis can cause the corners of the mouth to become chapped, cracked, and sore.
• Vaginal candidiasis: The most obvious symptom of vaginal yeast infections is a thick white discharge resembling cottage cheese. It can also cause itching and burning in or around the vagina, as well as a rash and tenderness of the outer lips of the vagina. HIV-positive women are more likely to experience recurrent vaginal yeast infections than HIV-negative women.
• Esophageal candidiasis: This is a type of candidiasis that occurs deep down in the throat and can't always be seen by looking into the mouth. It can cause chest pain, as well as pain and difficulty when swallowing. Esophageal candidiasis is much common in HIV-positive people with suppressed immune systems.

How is candidiasis diagnosed?

Most of the time, a doctor can diagnose candidiasis simply by looking in the mouth, at the back of the throat, or in the vagina. Sometimes it is necessary to scrape the overgrowth so that a sample can be sent to a lab. X-rays and a special scope - called an endoscope - are used to look for candidiasis down the throat.

How is candidiasis treated?

Just as there are three different types of candidiasis, there are three somewhat different ways to treat the disease.
Oral Candidiasis

The most common method of treating oral thrush is to use a medicated liquid that is swished around the mouth and swallowed, or a lozenge that is sucked, dissolved in the mouth, and swallowed. The three most common treatments are:

• Clotrimazole: These trouches, or lozenges, are used either four or five times a day for one or two weeks. Lozenges should be dissolved in the mouth slowly and should not be chewed or swallowed whole. Clotrimazole can cause stomach upset.
• Nystain : Nystatin is available in liquid and pastille form. The liquid dose is 5 milliliters four times a day for one or two weeks; it should be swished around the mouth slowly, for as long as possible, and then swallowed. One or two pastilles are taken four or five times a day for 7 to 14 days; they should be dissolved in the mouth slowly and should not be chewed or swallowed whole.
• Amphotericin B: Amphotericin B is available in a liquid for the treatment of oral candidiasis. The usual dose is 100 mg a day, four times a day. A medicine dropper is used to place the liquid directly onto the tongue. The liquid should be swished around the mouth slowly, for as long as possible, and then swallowed.

If oral candidiasis does not go away with the use of these drugs or recurs soon after treatment is stopped, more potent drugs such as ketoconazole, itraconazole, or fluconazole can be taken. Unlike swish-and-swallow liquids and lozenges, these drugs are swallowed immediately and are more likely to cause side effects, including stomach upset, diarrhea, nausea, and elevated liver enzymes.

Another possible treatment for oral cnadidiasis is gentian violet. This is a dye made from coal tar and can be purchased from some pharmacies, health food stores, and other places where complementary / alternative therapies are sold. Gentian violet is very messy and can stain clothing. It should be handled with care. For oral thrush, one of the best ways to apply the dye is by using a cotton swab. Dip the swab in the dye and coat the Candida blotches in the mouth. It is best to avoid swallowing the drug, as it can cause stomach upset. Gentian violet can also stain the inside of the mouth, but this fades over time.

Vaginal Candidiasis
The most common method of treating vaginal yeast infections is to use a medicated cream or an insert placed into the vagina. The most common treatments for vaginal candidiasis are available over-the-counter and can be purchased in many pharmacies. Many vaginal creams and suppositories can weakencondoms and diaphragms, which can increase the risk of pregnancy and HIV transmission.

• Clotrimazole (Gyne-Lotrimin cream): Five grams of this cream and applied everyday, using a special applicator, for 7 to 14 days.
• Clotrimazole (Mycele vaginal suppositories): Available in 100 mg and 500 mg strength suppositories and are available by prescription. The 100 mg suppositories are used every day for seven days. Alternatively, two 100 mg suppositories can be used every day for total three days. The 500 mg suppository is much more powerful than that 100 mg inserts and only needs to be inserted once.
• Miconazole (Monistal vaginal cream) : five grams of this cream are applied every day, using a special applicator, for seven days.
• Miconazole (Monistat vaginal suppositories) : Available in 100 mg, 200 mg, and 500 mg strengths. The 100 mg and 200 mg suppositories are available over-the-counter and the 500 mg suppositories are available by prescription. The 100 mg suppositories are used once a day for seven days and the 200 mg suppositories are used once a day for three days. The 500 mg suppository only needs to be inserted once.
• Terconazole (Terazol 3 and Terazol 7 creams) : Terazol 3 contains a higher dose of terconazole than Terazol 7. Terazol 7 is applied every day, using a special applicator, for seven days. Terazol 3 is applied every day for three days.
• Terconazole (Terazol 3 suppositories ) : These suppositories contain 80 mg terconazole and are inserted every day for three days.
• Tioconazole (Vagistat ointment) : The ointment contains 300 mg tioconazole and is inserted, using a special applicator, only once.
• Butoconazole (Fernstat cream) : Five grams of this cream are applied every day, using a special applicator, for three days.

As with oral candidiasis, if vaginal yeast infections do not go away while using these creams of suppositories, or if the infection returns soon after treatment is stopped, more potent drugs such as ketoconazole, of fluconazole can be prescribed by a doctor. Women who are pregnant should not use these oral drugs. They may harm the developing fetus.

Another possible treatment for vaginal yeast infections is gentian violet. This is a dye made from coal tar and can be purchased from some pharmacies, health food stores, and other places where complementary/alternative therapies are sold. Genapax can be purchased in a tampon formulation; each tampon contains 5 mg of gentian violet. Gentian violet tampons can be messy and can stain clothing and undergarments. They should be handled and inserted with care. To treat vaginal yeast infections, gentian violet tampons are inserted once or twice a day for one to two weeks.

Esophageal Candidiasis
Because esophageal candidiasis is considered to be more severe, deeper in the body, and harder to treat than either oral thrush or vaginal yeast infections, more powerful drugs - using higher doses than those used to treat oral of vaginal candidiasis - are usually needed to treat it. These drugs can cause liver enzymes to increase. They can also interact with other medications, including protease inhibitors, non-nucleoside reverse transcriptase inhibitors, as well as certain antihistamines and sedatives. Be sure to check with your doctors about other drugs you are taking before taking these antifungal treatments.

• Itraconazole : This drug is frequently used to treat esophageal candidiasis. Many doctors are now recommending that the liquid formula be used. If the itraconazole tablets are used, they are often taken with another drug, flucytosine, to increase effectiveness. For oral candidiasis, the dose of itraconazole used is usually 100 mg a day for one or two weeks. For esophageal candidiasis, the dose is usually 200 mg a day for two or three weeks. Itraconazole tablets should be taken with food; itracanazole liquid should be taken on an empty stomach.
• Fluconazole: To treat esophageal candidiasis, a 200 mg tablet of fluconazole is taken once a day or two or three weeks.
• Ketoconazole: 400 mg of Nizoral is taken every day for three or four weeks. This drug interacts with many antiretroviral drugs. It can increases indinavir, saquinavir, and amprenavir levels in the blood. Ritonavir can increase the amount of ketoconazole in the blood and, as a result, the daily ketoconazole dose should not exceed 200 m.

Severe or Drug-Resistant Candidiasis
Sometimes, candidiasis can become resistant to the "azole" drugs or is so severe that it cannot be adequately treated using any of these treatments. As a result, a drug called amphotericin B is often used. It is usually administered in a hospital through an IV line. The two types of amphotericin B are standard amphotericin B and liposomal amphotericin B.

Amphotericin B can cause serious side effects, include kidney damage, allergic reactions, bone marrow damage, nausea vomiting, and headache. The risk of kidney damage is increased if amphotericin B is combined with cidofovir or ganciclovir, two drugs used to treat CMV, and pentamidine, a drug used to treat PCP. The risk of bone marrow damage is increased if amphotericin B is taken at the same time as AZT, flucytosine, or ganciclovir.

Generally speaking, the liposomal amphotericin B brands are less toxic than standard amphotericin B. However, standard amphotericin B is faster acting than any of the liposomal drugs and is usually the drug of choice when candidiasis or other fungal infections and severe and an immediate threat to life.

Can candidiasis be prevented?

There is no guaranteed way to prevent oral thrush, vaginal yeast infections, or the more serious forms of candidiasis from occurring. These infections are more likely to occur in HIV-positive people with compromised immune systems. Thus, one way to help prevent candidiasis from occurring is the keep the immune system healthy, such as by using antiretroviral drugs, reducing stress, eating right, and getting plenty of rest.

There is still some debate regarding the use of antifungal drugs to prevent candidiasis. There have been a few studies showing that fluconazole can reduce the number of oral or vaginal fungal infections experienced by HIV-positive people with compromised immune systems. However, it may be possible that prolonged use of fluconazole - or any of the "azole" drugs - may lead to the development of drug-resistant. Candida albicans. The can prevent the drugs from working correctly when they are most needed. Because of this, many doctors do not recommended that these drugs be used continuously to prevent candidiasis. However, the prolonged to continual use of antifungal may be the best option for people with a history of frequent outbreaks of oral thrush or vaginal yeast infections.

There are a number of health tips all HIV- positive people should consider to help prevent candidiasis :

Healthy topics to prevent Candidiasis

• Watch your diet: it may be helpful to avoid foods high in sugar, dairy, yeast, wheat and caffeine. These types of ingredients are believed to promote fungal overgrowth.
• Eat yogurt : Many experts also recommend eating lots of yogurt that contains lactobacillus acidophilus, a "good" bacteria believed to keep Candidia albicans in check. Not all yogurt brands contain the bacteria, so be sure the packaging says "contains Lactobacillus acidophilus."
• Practice good oral hygiene: This includes brushing regularly, flossing, using an antiseptic mouthwash, and reducing/eliminating the use of tobacco products such as chewing tobacco and cigarettes.
• For vaginal yeast infections: To help reduce the risk of vaginal infections, wear loose, natural-fiber clothing and undergarments with a cotton crotch. Also, stay away from deodorant tampons and feminine deodorant sprays.

Are there any experimental treatments in development for candidiasis?

Candidiasis is a problem for many people, regardless of whether or not they are infected with HIV. This is especially true for people who have strains of Candida that are resistant to currently available drugs. Thus, new drugs are always being developed for candidiasis and other fungal infections.

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Progressive Multifocal Leukoencephalopathy (PML)

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What is it?

Progressive multifocal leukocencephalopathy (PML) is a life-threatening infection of the brain that can occur in people living with HIV. It is caused by a virus - the JC virus. The "JC" are the initials of the first patient to be diagnosed with PML. The virus is a polyomavirus, a family of viruses that also includes human papillomavirus (HPV).

The "progressive" in PML means that it continues to get worse and often leads to serious brain damage. The "multifocal" means that the JC virus causes disease in several different parts of the brain. The "leukoencephalopathy" means that the disease affects the white matter of the brain. More specifically, the JC virus infects cells in the brain called oligodentrocytes. These cells are responsible for producing myelin, a fatty substance that helps protect nerves in the brain. If too much myelin is lost and not replaced by oligodentrocytes, the nerves become damaged and eventually stop working correctly.

More than 70% of all adults in the United States are infected with the JC virus, usually during early childhood. However, the virus only becomes active in people who have compromised immune systems. The includes people undergoing immune-suppressive chemotherapy for cancer and people with damaged immune systems due to HIV. Prior to the use of combination anti-HIV drug therapy. It was estimated that between 3% and 10% of all people with AIDS developed PML. It usually occurs in people with vary low T-cell counts, but has been seen in some HIV-positive people with as many as 500 T-cells.

PML is almost always progressive and fatal. Death usually occurs between one and four months after the first symptoms appear. However, there have been a number of reported cases with survival ranging from several months to years. What's more, up to 10% of people with PML spontaneously recover, either with or without treatment.

What are the symptoms of PML?

Symptoms of PML include mental deterioration, vision loss, speech disturbances, ataxia, paralysis, and coma. In rare cases, seizures may occur.

How is PML diagnosed?

Many of the symptoms of PML are similar to those seen with other HIV-related diseases. Thus, it is important to determine the exact cause of these symptoms so that the correct treatment can be started.

The most accurate way to diagnose PML is by conducting a brain biopsy. To do this, a surgeon will need to remove a small piece of brain tissue and send it to a lab for analysis. However, a brain biopsy can be risky, especially for those with compromised immune systems. It is also possible to diagnose PML by analyzing magnetic resonance imaging scans of the brain and/or by looking for the JC virus in the fluid surrounding the spinal column. This requires a spinal tap - a needle inserted into the lower back to drain spinal fluid so that it can be analyzed.

How is PML treated?

Unfortunately, there are no treatments that have been proven to be effective for PML. A handful of drug treatments have been studied in clinical trials, including:

• Cytarabine, also known as cytosine arabinoside for Ara-C, is approved for the treatment of certain cancers. Early studies of this drug suggested that it was a possible treatment for PML. However, a larger study conducted by the U.S. government did not find cytarabine to be particularly effective, whether the drug was injected into a vein or directly into the brain.
• Even though clinical trial results do not support its use, cytarabine is still prescribed for some patients with PML. To receive cytarabine, a patient will need to have a shunt surgically implanted into his or her skull. This allows doctors to inject cytarabine, through the tube, directly into the brain. When treatment is started, cytarabine is administered every day for three days. After that, it is given twice a week for two weeks, followed by once-weekly intrathecal injections for life.
• Topotecan is also used to treat certain cancers. Like cytarabine, early studies suggested that it was effective as a treatment for PML, but a larger study reported in early 2001 did not find it to be effective.
• Cidofovir is approved for the treatment of cytomegalovirus. Early test tube studies found that it was effective against viruses similar to the JC virus. Two small studies involving humans suggested that it might be useful in treating PML. Larger studies are still needed to determine how effective cidofovir really is. Cidofovir can damage the kidneys, thus it should be combined with probenecid to help protect kidney function.
• High - dose , delivered through an intravenous line, was one of the first treatments studied for PML. While it did help slow progression in some patients, few patients experienced a reversal of symptoms or were able to prevent death.

The treatment of PML is not without hope, however. Combination anti-HIV drug therapy has been shown to be extremely beneficial for HIV-positive patients with PML. Because PML is most likely to occur in patients with suppressed immune systems - and anti-HIV therapy has been shown to significantly increased T-cell counts and the general health of the immune system - HIV-positive patients with PML are more likely to live longer and to see their symptoms improve, sometimes dramatically.

Many researchers agree that HIV-positive patients with PML should use anti-HIV drugs that are known to cross the "blood-brain barrier" - a protective coat that lines blood vessels in the brain to prevent toxins from passing through. Many of the nucleoside analogues, especially, and the non-nucleoside analogues, particularly, easily pass through the blood-brain barrier, and are often used to treat patients with other HIV-related brain diseases . If AZT is used to help treat PML, researches suggest that a daily dose of 1,000 to 1,200 mg be used.

Can PML be prevented?

No, not at the present time. But because immune suppression plays a major role in the development of PML, the best possible way to prevent this diseases is to keep the immune system healthy. This includes starting anti-HIV therapy before the immune system becomes impaired.

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Risks To Your Liver (hepatotoxicity)

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Introduction

The liver is one of the largest and most important organs in the human body. It is located behind the lower right section of your ribs and carries out numerous functions that your body requires to remain healthy. These are just a few of the liver's many functions:

• Storing important nutrients from the food that you eat
• Building necessary chemicals that your body needs to stay healthy
• Breaking down harmful substances, like alcohol and other toxic chemicals
• Removing waste products from your blood

For HIV-positive people, the liver is of major importance, as it is responsible for making new proteins needed by the immune system, helps the body to resist infection, and processes many of the drugs used to treat HIV and AIDS-related infections. Unfortunately, these same medications can also damage the liver, which can prevent the liver from performing all of its necessary tasks and can eventually cause damage to the liver.

"Hepatotoxicity" is the official term for liver damage caused by medications and other chemicals. This lesson has been prepared by the staff to help readers better understand hepatotoxcity, including the ways in which medications can cause liver damage, the factors that can increase the risk of hepatotoxcity, and some of the ways in which you can monitor and protect the health of your liver. If you have questions or concerns about hepatotoxicity, particularly as it relates to the anti-HIV drugs you are taking, do not be afraid to discuss them with your doctor.

How do anti-HIV drugs causes hepatotoxicity?

Even though anti-HIV drugs are intended to do your health good, the liver recognizes these medications as toxic compounds. After all, they are not naturally produced by the body and do contain some chemicals that could potentially cause damage to your body. Working with the kidneys and other organs, the liver processes these drugs to render them safer. In the process, the liver can become "overworked," which can lead to liver damage.

There are actually two ways that anti-HIV meds can lead to liver damage:

Direct damage to liver cells:
Liver cells, called hepatocytes, play a vital role in the functioning of the liver. If these cells begin working too hard to remove chemicals from the blood, or if they are harmed by other infections, abnormal chemical reactions can occur that can damage these cells. There are actually three ways in which this can happen:

• Taking a very high dose of a drug. If you were to swallow a high dose of an anti-HIV drug or another medication, this can cause immediate and sometimes severe damage to liver cells. Almost any drug, if an overdose is taken, can cause this type of liver damage.
• Taking standard doses of medication for a long period of time. If you take medications on a regular basis for a long period of time, there is also a risk of damage to these liver cells. This usually occurs after several months or years of taking certain medications. Protease inhibitors have the ability to cause damage to liver cells if they are used for long periods of time.
• An allergic reaction. When we hear the term "allergic reaction," we often think of itchy skin or runny eyes. However, allergic reactions can also take place in the liver. If you are allergic to a particular drug, your immune system can cause your liver to become inflamed as a result or interactions between very liver proteins and the drug. If the drug is not stopped, the inflammation can worsen and can cause serious damage to the liver. Two anti-HIV drugs known to cause such allergic reactions in HIV-positive people are Ziagen and Viramune. Allergic reactions such as these usually occur within a few weeks or months after the drug is started and either may or may not be accompanied by other allergy-repeated symptoms.

How do I find out if my anti-HIV drugs are causing liver damage?

The best indicator o fhepatotoxicity is an increase in certain liver enzymes that circulate in the bloodstream. The most important enzymes are AST (aspartate aminotransferase), ALT (alanine aminotransferase), alkaline phosphotase, and bilirubin. These four enzymes are normally checked as a part of a "chem screen," a panel of tests that your doctor probably orders every time you have blood drawn to check your T-cells and viral load.

If you or your doctor has any reason to suspect that a drug you are taking has been causing liver injury, then a blood test should be performed, it is always best to detect hepatotoxicity in its early stages so that steps can be taken to prevent it from getting worse and to allow the liver to heat.

Most of the time, hepatotoxicity takes several months or years to develop and usually begins with mild increases in either AST or ALT that progresses to more serious increases. Generally speaking, if your AST or ALT levels are elevated but are no higher than five times the normal range, you have mild to moderate hepatotoxicity. If your AST is higher than 215 IU/L or your ALT is above 300 IU/L, you have severe hepatotoxicity, which can learn to permanent liver damage and serious problems.

Fortunately, as stated above, the vast majority of doctors order chem screens on a regular basis and are usually able to catch mild-to-moderate hepatotoxicity before it progresses to severe hepatotoxicity. However, some drugs, such as Ziagen and Viramune, can result in an allergic reaction in the liver that can cause liver enzymes to increase sharply soon after the medication is started. In turn, it is very important that your doctor check your liver enzymes every two weeks for the first three months if your begin taking either of these medications.

Increased liver enzymes can rarely be felt. In other words, you may not have any physical symptoms, even if your liver enzymes are elevated. Thus, it is very important that you and your doctor monitor your liver enzymes on a regular basis using blood tests. However, symptoms can occur in people with severe hepatotoxicity and these symptoms are very similar to those associated with viral hepatitis. Symptoms of hepatitis include :

• Anorexia
• Malaise
• Nausea
• Vomiting
• Light-colored stools
• Unusual tiredness/weakness
• Stomach or abdominal pain
• Jaundice
• Loss of taste for cigarettes

If you are experiencing any of these symptoms, it is very important that you speak with your doctor or another health-care provider.

Does hepatotoxicity occur in everyone taking anti-HIV drugs?

No, it does not. There have been a number of studies looking at the percentage of patients who develop hepatotoxicity, according to the different anti-HIV medications they are taking. One particular study, conducted by researches at the National Institute of Health, looked at rates a hepatotoxicity among 10,611 HIV-positive people participating in 21 government-funded clinical trials conducted between 1991 and 2000. Overall, 6.2% of the clinical trial participants experienced severe hepatotoxicity. Among the participants who took a non -nucleoside reverse transcriptase inhibitor in combination with two nucleoside analogues, severe hepatotoxicity occurred in 8.2%. Among the participants who took a protease inhibitor in combination with two nucleoside analogues, severe hepatotoxicity occurred in 5%.

Unfortunately, clinical trials do not always reflect what is going to happen in the real world. Many clinical trials only follow participants for a year - and we know that HIV positive people will need to take these medications for many years, which can increase the risk of hepatotoxicity. What's more, most clinical trials enroll patients who don't have other conditions that can further increase the risk of hepatotoxicity. For example, it is believed that women and people over the age of 50 are at a higher risk of developing hepatotoxicity. Obesity and heavy alcohol use can also increase the chances of hepatotoxicity occurring. There is also a very real concern that HIV-positive people who are coinfected with hepatitis B or hepatitis C are more likely to experience hepatotoxicity than those who are city infected with HIV.

I have HIV and hepatitis C. Does this mean that I can't use anti-HIV medications?

No. Just because you have chronic hepatitis C or hepatitis B - two viral infections that can cause the liver to become inflamed and damaged - does not mean that you cannot take anti-HIV medications. However, it is important to understand that there may be a higher risk of liver damage occurring if you have either of these infections and are taking and HIV medications.

While there have been a number of studies looking at rates of hepatotoxicity among people coinfected with both HIV and hepatitis C or hepatitis B who are taking anti-HIV medications, the results often conflict with one another. For example, one study conducted by the San Francisco Community Health Network demonstrated that Viramune was the only anti-HIV medication to significantly increase the risk of hepatotoxicity in people connected with HIV and either hep C or hep B. But have also been study results suggesting that Viramune is no more or less likely to cause hepatotoxicity in coinfected patients than other anti-HIV medications, although it's still important to watch out for liver enzyme increases during the first three months of Viramune treatment.

As for the protease inhibitors, there have been a few studies demonstrating that Norvir is the most likely to cause hepatotoxicity in HIV positive people coinfected with hep C or hep B. However, Norvir is rarely used at the approved dose - much lower doses of Novir are usually used, as it is now most frequently prescribe to boost other protease inhibitor levels in the bloodstream. This, in turn, likely decreases the risk of hepatotoxicity in people who are only infected with HIV or coinfected with HIV and either hep C or hep B.
If one thing is clear, it is that people who are coinfected with HIV and either hep C or hep B should work closely with their doctors to come up with safe and effective treatment plans. For example, many experts now believe that, if you have HIV and hep C. you should consider starting hep C treatment while your T-cell counts are high, before treatment is needed for HIV. Successfully treating or controlling HCV is perhaps, the best way to reduce the risk of hepatotoxicity once anti-HIV medications are started.

It is also important to monitor your liver carefully while taking anti-HIV medications. You'll want to find out the levels of your liver enzymes before you begin taking anti-HIV medications. Even if they are higher than normal because of either hep C or hep B, you can then monitor your levels closely while on treatment.

Are there any ways to effectively reverse or prevent hepatotoxicity?

If you have been told you that your anti-HIV medications are causing liver toxicity, you and your doctor will likely want to figure out which drug - or which combination of drugs - are causing your liver enzymes to increase. Working together, you and your doctor can then determine if it's necessary to stop the offending drugs, with a possible switch to new medications that ar eless likely to cause liver toxicity.

Fortunately, taking proper care of your liver is not limited to avoiding or switching certain anti-HIV medications. The next few sections of this lesson review some of the most important things that you can do protect your liver while you are taking anti-HIV medications.

What's the deal with alcohol?

There's no shortage of information concluding that heavy alcohol use - generally defined as more than five drinks a day - can cause liver damage. It's also known that heavy alcohol use can worsen liver diseases in people with hep C and hep B. Although it's still not known if light or moderate drinking - no more than one to two drinks a day - is harmful to the liver, especially in people taking medications on a regular basis. If you drink alcohol, it is very important that you discuss this with your doctor. It's also important to note that the American Liver Association recommends no more than one drink a day. Some medicators, such as Flagy, should not be combined with alcohol, and most experts advise staying away from alcohol completely if you have hepatitis.

What about my diet? Can I eat better to improve the health of my liver?

Yes, absolutely. The liver is not only responsible for processing medications-it must also process and detoxify the liquids and foods we drink and eat on a daily basis. In fact, between 85%and 90% of the blood that leaves the stomach and intestines contains nutrients from the liquids and foods we consume for further processing by the liver. As a result, a well-balanced diet is a terrific way to help take some of the stress off the liver and to help it remain healthy. Here are some tips to consider:

• Eat plentiful amounts of fruits and vegetables, especially dark green leafy vegetables and orange and red colored fruits and vegetables.
• Cut down on fats that may put a lot of stress on the liver, such as dairy products, processed vegetables oils, deep fried foods that are not fresh and contain and contain rancid fats, preserved meats and fatty meats.
• Concentrate on eating "good fats" which contain essential fatty acids. These are found in cold pressed vegetable and seed oils, avocados, fish, flaxseed, raw nuts and seeds and legumes. Not only are good fats believed to be easier for the liver to process, they can help build healthy cell membranes around the liver cells.
• Do your best to avoid artificial chemicals and toxins such as insecticides, pesticides, artificial sweeteners, and preservatives. You should also be careful regarding the coffee you drink. Many nutritionists recommend no more than two cups a day and should be brewed from ground natural coffee, not instant coffee powders.
• Consume a diverse range of proteins from grains, raw nuts, seeds, legumes, eggs, seafood, and if desired, free range chicken and lean fresh red meats. If you are a vegetarian, you may want to consider supplements such as vitamin B 12, taurine, and carnitine to avoid poor metabolism and fatigue.
• Drink large amounts of fluids, especially water. Drinking at least eight glasses of water a day is a must, especially if you're taking anti-HIV medications.
• Be wary of raw fish or shellfish. Sushi can harbor bacteria that may harm the liver and shellfish can contain the hepatitis A virus, which can cause serious liver problems in people who have not received the hepatitis A vaccine. Also take care to avoid wild mushrooms. Many types of wid mushrooms contain toxins that can cause serious damage to the liver.
• Be cautious of iron. Iron, a mineral found in mean and fortified cereals, can be toxic to the liver, especially in people who have hepatotoxicity or infection that can cause hepatitis. Foods and cooking equipment - such as iron skillets - high in iron should be used sparingly.

There are a number of vitamins and minerals that have been shown to be healthful to the liver and many nutrition experts recommend that people at risk for liver toxicity seek out these foods at the grocery market. These include:

• Vitamin K. Green leafy vegetables and alfalfa sprouts are a great source of this vitamin.
• Arginine. The liver can sometimes have a difficult time processing protein. This can cause ammonia levels to increase in the bloodstream. Arginine, which is found in beans, peas, lentils, and seeds, can help detoxify ammonia.
• Antioxidants. Antioxidants work by neutralizing highly reactive, destructive compounds called free radicals, which are produced in abundance by highly active organs. Foods high in antioxidants include vegetables and fruits like carrots, celery, beets, dandelion, apples, pears, and citrus. Selenium, a powerful antioxidant, can be found in brazil nuts, brewers yeast, kelp, brown rice, liver, molasses, seafood, wheatgerm, whole-grains, gralic and onions.
• Methionine. A detoxifying agent found in beans, peas, lentils, eggs, fish, garlic onions, seeds, and meat.

What about nutritional supplements and herbs? My health-food store stocks many products that claim to be good for the liver.

Some complementary therapies that have been suggested to help prevent or control liver damage include thioctic acid, SSKT, coenzyme Q-10, glycerrhizin, milk thistle, NAC. Astragalus, chickory, dandelion, centaury. American mandrake, and celandine.

Unfortunately, there is not much research data to conclude that these complementary therapies are both safe and effective for either the prevention or treatment of hepatotoxicity or liver damage caused by infections. Some studies have suggested that milk thistle, a popular liver-health supplement, is safe for people to use. We also know that NAC is used throughout Europe and the United States to help reduce liver damage caused by acetanminophen.

It is important to remember that simply because these complementary therapies can be purchased without a prescription, this does not mean that they are always safe to take. Some complementary therapies have their own side effects. It's also clear that many complementary therapies can interact with certain anti-HIV medications. This can further increase the risk of side effects or, quite possibly, reduce the effectiveness of the anti-HIV medications begin used. Be sure to check with your health care provider before starting nay complementary therapy.

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The importance of Adhering to Your Treatment Regimen

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An introduction

One of the most important things to think about before beginning treatment for HIV disease is your ability to take the treatments properly. This is called "treatment adherence," and it may sound easy, but sometimes it's not. Studies show that even doctors have enormous difficulty taking even short-term drug regimens strictly according to the rules.

As far as we know, anti-HIV medicine has to be taken for life. Not taking the medicine properly can lead to "drug resistance," where HIV mutates and becomes resistant to a drugs effect. This in turn leads to treatment failure. Therefore, it's important to plan adherence strategies in advance.

You should raise questions about treatment adherence with your doctor when you're deciding what treatments to take. Different drugs have different rules - some drugs may be taken only once a day, while others must be taken with a high-fat meal. Because you will probably be taking several different medications, each drug may have different rules. It's importance to know which drug goes with which rules.

What do I need to know to ensure good adherence?

• How many pills of each different medicine are you supposed to take at a time?
• How many times a day are you supposed to take each medicine, when do you take them?
• What are the food requirements for each different medicine?
• What should you do if you forget a dose?

Planning a drug regimen that works with you schedule will help to improve your adherence. For instance, if you're often travelling from place to place in the middle of the day, then a drug that involves a dose in the middle of the day may give you problems. If you tend to eat at different times each day, then drugs with strict requirements about eating may give you a problem.

As you are considering different treatment regimens, plan out schedules that include the things you regularly do - such as taking your kids to school, going to work, or eating a late dinner - and then think about how different drug regimens might affect that schedule. For instance, let's compare two different treatment regimens.

You can see from these schedules how different drug regimens have different effects on your day.

Is there a way to prepare for a complicated drug regimen?

Sometimes, if you're not sure you can handle a drug regimen with a complicated schedule, it might be wise to practice a little first before starting the actual drugs.

This might sound silly, but you might try to use jellybeans first! Think of it as an experiment to see if you can adhere to a treatment regimen. For instance, a bag of red jellybeans might represent Videx and would be taken once a day on an empty stomach. A bag of blue jellybeans might represent Zerit, and would be taken twice a day with or without food. A bag of green jellybeans might represent viracept, and you'd take give green jellybeans twice a day, with a meal or a light snack.

By following the jellybeans regimen for a week or two, you can find out whether or not the schedule works for you. You can also spot potential problems times, and try to find solutions. That way, when you actually start the medicines, you've already taken important steps to change your schedule.

Once you think you're ready to start taking a new drug regimen, make sure to ask your doctor any questions you still have before she or he writes the prescriptions. One of the biggest problems with adherence is doctors who don't communicate enough information. Make your doctor write down the instructions for taking your medication, and read them back to her or him. It can be easy to confuse "two pills three time a day" with "three pills two times a day", so it's important to be sure that you understand how many pills you're supposed to take, and how many times a day you take them.

An important thing to know is that the times that you take the drugs are important. In other words, if your doctor says to take a drug every twelve hours or every eight hours, then it's important to stick pretty close to that schedule. Taking medicine properly prevents drugs resistance - the longer you wait to take a dose, the less there is of the previous dose in your system to fight HIV and drug resistance.

This all sounds to difficult, Is there an easier way?

It's just common sense, but it's important to know that there are studies showing that simpler treatment regimens are easier to adhere to than more complicated regimens. In other words, a drug regimen that involves fewer pills taken fewer times during the day may be easier to take properly than a drug regimen that involves lots of different pills taken may times a day.

If you don't think you can stick to a proposed drug regimen, then don't start it. Ask your doctor about the possibility of taking an easier regimen instead. Either way, you shouldn't start therapy until you are ready. Starting a treatment regiment that you are very ill, it might be better to wait until you're ready and able, or until easier treatment regimens become available.

Once I've started treatment, are there tools to help me stay compliant?

Yes! There are a number of tools you can use to help you remember your doses. For some people, a schedule on their refrigerator reminds them to take their medicine. Others rely on electronic pillboxes this beep at the appropriate time. Or how about a digital watch with multiple alarms.

Think about creative ways to remind yourself to take your medicine when you're supposed to take it. It also helps to recruit family and friends to help you remember. Encourage the people around you to ask, "Did you take your medicine today?" Lets face it - moral support is important!

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Tuberculosis (TB)

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What is it?

Tuberculosis (TB) is a serious respiratory disease that can be life-threatening if not treated correctly. TB is, in fact, the world's most common disease caused by an infectious organisms. Nearly 2 billion people in the world are diagnosed with TB every year, a disease that is also responsible for the deaths of nearly 3 million people annually.

In industrialized nations such as the United States, TB was well on its way to becoming extinct 15 years ago. With the HIV epidemic, however, TB rates started increasing again between 1985 and 1992. Since 1992, the total number of TB cases has once again decreased. However, in certain groups of people in the U.S. - such as people immigrating to the United States from countries where TB rates are very high - the TB rate is increasing. In 2000, there were 17,531 cases of TB. Although the number of TB cases continues to decrease, it remains one of the most common causes of sickness and death in U.S. residents infected with HIV. In fact, TB is the number - one cause of death of HIV-infected people across the globe.

Mycobacterium tuberculosis, the bacteria that causes TB, is spread from one person to another. Using microscopic drops of fluid produced by the lungs, the bacteria can travel from the lungs of an infected person and be deposited in the lungs of someone nearby. Once inside the lungs, the bacteria established infection. Even though 150,000 people in the United States have been infected with the bacteria, most people have immune systems that are healthy enough to prevent the bacteria from ever causing TB. In people with HIV, the immune system may eventually lose control to the bacteria, causing the infection to spread and cause active disease. This process can take many months or years. In other words, Mycobacterium tuberculosis can remain alive in someone's body for many years, but may only become active - i.e., cause tuberculosis - once the immune system becomes damaged.

Tuberculosis almost always causes disease of the respiratory system. In HV-positive people, particularly those with T-cell counts below 200, the bacteria the bacteria can also infect the lymphatic system

Compared to HIV-negative patients with TB, HIV-positive people with the disease may see their symptoms develop faster and with greater intensity. Treating TB in HIV-infected patients may also need to be more aggressive in order to clear the bacteria from the body.
What are the symptoms of TB?

Cough is a main symptom of tuberculosis, along with night sweats, chills, weight loss, fever, and fatigue.

How is TB diagnosed?

To test for Mycobacterium tuberculosis infection, a skin test called PPD can be performed in a clinic or doctor's office. PPD stands for purified protein derivative. It contains pieces of the bacteria and is injected directly under the skin. If someone has been exposed to the bacteria in the past, the immune system will immediately recognize the PPD, resulting in a firm, relatively large bump at the site of the injection. If this reaction occurs, a person is said to have a positive PPD.

A positive PPD generally calls for additional testing. An X-ray of the chest is performed to look for signs of active disease. Blood tests, along with sputum samples, may also be sent to a lab for analysis. If the bacteria is found in these samples, it may be tested further to see if it is resistant to nay of the drugs commonly used to treat tuberculosis.

If someone has a positive PPD but does not have nay signs or symptoms of active disease, he or she is said to have latent TB infection. It is generally recommended that people with latent TB infection begin taking drug therapy to prevent the infection from developing further. If someone has a positive PPD and has signs and symptoms of tuberculosis, her or she is said to have active TB, usually involves a combination of antibiotics to treat the infection.

PPD testing in people with HIV can be problematic. As discussed above, PPD testing doesn't test for the presence of Mycobacterium tuberculosis, but instead looks for signs that the immune system is currently fighting the bacteria. In HIV-infected patients with compromised immune systems, there might not be enough immune activity to either fight the infection or respond to the PPD test. In other words, the bacteria might be present but is not being recognized by the immune system and, as a result, may not show up using PPD testing.

Because PPD testing may not be reliable in HIV-positive people with compromised immune systems, a diagnosis of TB might not be made until symptoms are reported and X-rays or blood tests are performed. For some HIV-positive people with compromised immune systems, it is better to be safe than sorry. For example, if an HIV-positive person lives in the same house or works with someone who has active TB and may be spreading Mycobacterium tuberculosis, it is generally recommended that the HIV-positive person be isolated from the person with active TB and to begin treatment.

How is TB treated?

Treating TB depends on the situation. As discussed in the previous section, there are treatments for latent TB infection and treatments for active TB.

If your have latent TB infection - that is, a positive PPD test without any signs or symptoms of active TB- your doctor will probably prescribe one of these two possible treatments:

Treatments for latent TB infection (LTBI)
Ÿ Isoniazid: One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet. It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy. You will probably take this drug, every day, for nine months. Alternatively, isoniazid can be given twice a week for a total of nine months. However, if the twice-weekly dosing schedule is used. You will need to report to a clinic to receive your medication to make sure that you are not missing any of your doses. Some people take isoniazid for only six months. However, this is not recommended for people infected with HIV.

It is very important that you take your isoniazid and pyridoxine exactly as your doctor tells you to and that you continue taking these medications until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to isoniazid. If the bacteria becomes resistant to isoniazid, you can develop active TB that is harder to treat.

• Rifampin + Pyrazinamide : Combining these two powerful antibiotics has been shown to prevent LTBI from progressing to active TB, especially in HIV-positive people. If these two drugs are taken every day, treatment for latent TB infection can be completed in as little as two months, as oppossed to the longer isoniazid. However, this combination of drugs was studied in HIV-positive people before the protease inhibitors and non-nucleoside reverse transcriptase inhibitors were approved. We now know that rifampin can interact with many PIs and NNRTIs. Thus, if you are taking either a PI or an NNRTI, it is recommended that you take rifabutin instead of rifampin. But even rifabutin can interact with some anti-HIV medications. Thus, there are rules that doctors and HIV positive people need to be aware of :
• To be on the safe side, it is generally recommended that HIV-positive people who are taking either a PI or NNRTI follow the nine-month isoniazid treatment option. The rifabutin/pyrazinamide option is best for people who will have a hard time sticking to the strict nine-month isoniazid course.
• Rifampin or rifabutin should not be used by HIV-positive people who are taking either the original version of saquinavir or the NNRTI delavirdine. In this case, the nine-month course of isoniazid is the best option.
• The rifabutin dose will depend on the PI or NNRTI you are taking. If you are taking either ritonavir or lopinavir, the rifabutin dose in 150 mg twice a day. If you are taking any of the other protease inhibitors, the correct rifabutin dose is 150 mg once a day. If you are taking the NNRTI efavirenz, the rifabtuin dose is 450 mg to 600 mg once a day. It is very important that you take your rifampin and pyrazinamide exactly as your doctor tells you to and that you continue taking these medications until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to these two drugs. If the bacteria becomes resistant to the drugs. You can develop active TB that is harder to treat.

Active TB is treated using a combination of drugs. As with HIV, in which a combination of three antiretroviral drugs issued to help prevent resistance and keep viral load undetectable, tuberculosis is usually treated with a combination of four drugs to maintain control over the infection.

Some people are infected with strains of Mycobacterium tuberculosis that are resistant to one or more of the drugs commonly used to treat tuberculosis. This problem a becoming more and more common in some areas of the United States, including heavily populated cities like New York. As a result, testing the bacteria for drug resistance as a part of diagnosing TB is sometimes recommended.

Unfortunately, both a confirmed diagnosis and drug-resistance testing take a long time. Growing out Mycobacterium tuberculosis in test tubes can take more than a week, and drug resistance testing can take as long as a month. Thus, treatment is often started if key signs and symptoms are present.

For the first two months of therapy, a combination of four drugs are usually prescribed, all of which are taken by mouth:

• Isoniazid: One of the most effective antibiotics used to control TB. It can cause liver problems and tingling/numbness of the hands and/or feet. It is usually taken with a second drug, pyridoxine, to help prevent peripheral neuropathy.
• Rifampin : Another powerful antibiotic needed to manage TB. It can cause nausea, vomiting, diarrhea, rash, liver problems, red-orange discoloration of body fluids, along with a decrease in white blood cells and platelets. Rifampin can be a problem for some HIV-positive people. This is because it interacts with many of the medications used to treat HIV. It is not recommended that people stop their anti-HIV medications in order to treat their TB. Instead, your doctor will probably need to change the dose of either the rifampin or the anti-HIV medications to make sure that you are being treated correctly without the risk of additional side effects. If rifampin cannot be used, an alternative drug - rifabutin - will be prescribed.
• Pyrazinamide: The dose of this drug depends on the body weight of the person being treated. Its side effects are similar to those of rifampin.
• Ethambutol or streptomycin: Like pyrazinamide, the dose of these two drugs depends on the body weight of the person being treated. Ethambutol can cause vision problems and can cause hearing problems.

To help make these drugs easier to take, some of them have been combined into single pills. For example, if you take isoniazid and rifampin, your doctor can write a prescription for Rifamate, a capsule that contains both drugs. Two Rifamate capsules are taken twice a day, almost always in combination with other antibiotics. If your doctor has recommended a combination of isoniazid, rifampin, and pyrazinamide, you may be able to take Rifater, a tablet that contains all three drugs. Depending on how much you weigh, you will need to take four, five, or six Rifater tablets once a day, always on an empty stomach.

If a drug-resistant strain of Mycobacterium tuberculosis is present - either suspected by a doctor or confirmed by testing - additional drugs are often added to this combination. Additional drugs include: capreomycin, kanamycin, amikacin, ethionamide, ciprofloxacin, ofloxacin, lomefloxacin, clofazimine, cycloserine, and/or aminosalicylic acid. These drugs can also be used as a substitute for other anti-TB drugs that cause side effects.

Here are three ways tuberculosis can be treated using these drugs.

Standard course of therapy:

• This is the most common method used to treat TB, especially for HIV-positive people. For the first eight weeks of treatment, the four drugs listed above are used every day. After two months of therapy have been completed, isoniazid and rifabutin are continued for an additional 16 weeks. These drugs can be taken either every day or two or three times a week. If you have less that 100 T-cells, experts recommend taking rifabutin every day or three times a week. You will probably have to go to a clinic - or have a trained medical professional watch you take your medication every time you take your isonaizid and rifabutin during this period, especially if you are only taking them two or three times a week.
  First alternative course of therapy:
• For the first two weeks of treatment, the four drugs listed above are used every day. After two weeks of daily treatment have been completed, the same four drugs are taken two times a week for an additional eight weeks. After a total of eight weeks of four -drug treatment have been completed, isoniazid and rifabutin are continued for an additional 16 weeks.

These drugs can be taken either two or three times a week. Like the standard course of therapy, you will probably have to go to a clinic - or have a trained medical professional watch you take your medication - every time you take your medication.

Second alternative course of therapy:

For six months, the four drugs listed above are used three times a week. The dose of each drug will remain the same for the entire six months and you will need to take all four drugs until therapy is officially completed. Like the standard course of therapy, you will probably have to go to a clinic - or have a trained medical professional watch you take your medication - every time you take your medication.

It is very important that you take your medications exactly as your doctor tells you to and that you continue taking them until your doctor tells you that it is time to stop. This is necessary to prevent the bacteria from becoming resistant to the drugs. If the bacteria becomes resistant to these drugs, the TB may return and may be more difficult to treat.

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Peripheral Neuropathy

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What is it?

Peripheral neuropathy results from injury to the peripheral nerves in the body. These nerves carry signals between the central nervous system and the muscles, skin, and internal organs. When peripheral neuropathy first develops, people often report a tingling or prickling in the toes, although it can also start in the fingers. Over time, the tingling gradually spreads up the feet or hands and worsens into a burning, shooting, and/or throbbing pain. People who have severe peripheral neuropathy may experience extreme pain and may have difficulty walking, sometimes requiring the assistance of a cane or wheelchair to move around.

People who have peripheral neuropathy usually experience symptoms on both sides of their bodies. In other words, peripheral neuropathy almost always occurs in both feet and/or both hands. The sensations can be either constant or periodic. Sometimes they may not be noticeable, while at other times they may be extremely bothersome.

Not only can peripheral neuropathy be physically painful, it can also have a profound effect on qualify of life. The natural instinct to avoid or reduce pain can prevent people from going about their regular day-to-day activities, whether it be going up and down stairs, visiting with family or friends, or going to work. This can cause a great deal of anxiety and can lead to serious depression - serious emotional problems that can make life seem altogether frustrating.

What causes peripheral neuropathy?

There are several possible causes of peripheral neuropathy. Direct injury, such as a broken bone or a severe burn, can cause damage to peripheral nerves. Certain diseases, such as diabetes, arthritis, or lupus, can also result in nerve damage. A lack of essential vitamins and minerals, particular vitamin B12 and E, can contribute to nerve damage. Conversely, taking too much vitamin B6 can actually cause this condition.

HIV itself has also been shown to cause nerve damage, usually in people with seriously suppressed immune systems. In most HIV-positive people, however, peripheral neuropathy is a side effect of the medicines they use - certain drugs, including those used to treat HIV and certain AIDS - related infections, can damage peripheral nerves and eventually lead to symptoms of neuropathy.

Some of the HIV/AIDS drugs that can cause peripheral neuropathy include:

• ddc (Hivid)
• ddl (Videx; Videx EC)
• d4T (Zerit)
• isoniazid - for the prevention and treatment of tuberculosis (TB)
• vincristine - for the treatment of Kaposi's sarcoma (KS)
• ehtambutol - for the treatment of MAC and other bacterial infections
• metronidazole - for the treatment of amoebas and parasitic infections
• dapsone - for the treatment of Pneumocystis carinii pneumonia (PCP) and other infections.

While peripheral neuropathy is a common side effect of these drugs, this does not mean that all people who take them will experience nerve damage or develop symptoms of neuropathy. It's possible that people who combine these drugs - such as d4T and ddl, two popular nucleoside analogues that are often used together - are at a greater risk of experiencing neuropathy or developing more severe and painful symptoms. However, this has not been the case in some clinical trials. Many patients who combined d4T and ddl in clinical trials were no more likely to experience peripheral neuropathy than patients taking only one of these drugs.

What are the symptoms of peripheral neuropathy?

Because peripheral neuropathy is not the only nerve-related problem that can occur in HIV-positive people, it's important that you report any noticeable symptoms to your healthcare provider. Once you and your doctor have determined the source of these symptoms, you can work together to figure out what to do about it.

The symptoms of peripheral neuropathy usually occur in the feed and/or hands:

• Numbness/insensitivity to pain or temperature
• Extreme sensitivity to touch
• Tingling, prickling, or burning sensation
• Sharp pain/cramping
• Loss of balance/coordination
• Loss of reflexes
• Muscle weakness
• Noticeable changes in the way you walk

Other symptoms of nerve damage that you'll want to report to your doctor include:

• Noticeable increase in the number of times you need to urinate during the day and at night
• Difficulty walking up and down stairs
• Frequent stumbling or fails
• Erectile dysfunction

Should I stop my medicines that are causing the neuropathy?

Generally speaking, the best way to manage peripheral neuropathy is to stop any medications that may be causing the problem. For example, if you are taking an anti-HIV drug regimen consisting of indinavir, 3TC, and d4T and have symptoms of peripheral neuropathy, the most likely culprit is the d4T. In turn, the best approach would be to switch the d4T for another nucleoside analogue that is not known to cause peripheral neuropathy. Of course, you should discuss this option with your healthcare provider - do not attempt to stop any of your medications or to switch them without first checking in with your doctor.

It can sometimes take a few weeks or months for symptoms of peripheral neuropathy to improve after stopping on offending drug. In some cases, symptoms can worsen before they get better.

Unfortunately, stopping or switching medications is not always possible. This is particularly true for HIV-positive people whose virus is already resistant to other currently available medications. For example, if your HIV is already resistant to AZT, 3TC, and abacavir, using d4T or did in your regimen may be necessary to keep your viral load low and your T-cells high. As a result, it may be necessary to look into other options to deal with the peripheral neuropathy directly.

I can't switch my anti-HIV meds! What are the other options available to me?

Managing peripheral neuropathy can be a challenge. While there are a number of techniques available to help soothe the symptoms of this condition, we do not yet have any treatments that can repair underlying nerve damage. What's more, only a few of the treatments currently used to manage the symptoms of peripheral neuropathy have been studied in clinical trials. Thus, we don't really know which treatments are the most effective or most likely to work for HIV-positive people suffering from peripheral neuropathy. Figuring out which treatments will work best for you may require a process of "trial and error." It might be possible that you and your doctor will come upon a treatment that immediately helps to control your symptoms. it's also possible that you'll need to try several different treatment approaches, including combinations of different treatments, before you find one that is truly effective. By working closely with your doctor - letting him or her know when something is or is not being helpful - can definitely speed up the road to pain relief and recovery.

How do I determine which treatments are right for me?

There are a number of medications available to help manage the pain, tingling, and burring sensations of peripheral neuropathy. Deciding which medication to use depends on the frequency and severity of pain. It's also important to recognize that some medications used to treat peripheral neuropathy have side effects of their own. Thus, there are three major factors to consider when deciding which medications you might want to use.

1. Frequency of pain. Is the pain constant? Does the pain come and go? Does it follow certain activities, such as walking, running, or climbing stairs? If you're not sure when the pain kicks in, you might want to keep a seven-day pain diary - a week before seeing your doctor, you should make a list of all the times you feel pain, including the activities you were doing when the pain starts, along with activities you were doing immediately before the pain started. Knowing this will help you and your doctor figure out which medications to use and to determine when and how you should be using them.
2. Severity of pain. Trying to explain feelings of pain is a bit like trying to explain what chicken tastes like- we all know what it is, but words escape us when trying to define it. Even terms like "mild pain," "moderate pain," and "severe pain" - phrases that many doctors are keen on using - can seem terribly vague. Try rating your pain on a scale between 0 and 5, with 0 being no pain and 5 being severe pain. The following visual guide, developed by a team of pain specialists in 1998, has helped a number of children and adults best explain their pain to their doctors.
3. Understand the side effects of certain medications used to treat peripheral neuropathy. While there are certainly a number of drugs that can help reduce pain, many of these medicines can cause side effects of their own. Some of the more heavy-duty painkillers - narcotic medications - can help knock out even the most severe forms of pain, but they can also cause someone to feel extremely "drugged" or "out of it," to the point that they can't function normally. Narcotic drugs can also be a problem for HIV-infected people with a history of drug addiction who are currently in recovery. Thus, it's always best to begin treatment with the midest drugs and, if necessary, add stronger medications to maintain a healthy balance - less pain with the least number of additional side effects.

Okay, so which treatments are available?

• Non-narcotic pain relievers. These include aspirin, acetaminophen, ibuprofen, an dnaproxen. All of these are available over-the-counter at pharmacies and grocery stores. These medicines are often quite effective in handling mild pain associated with peripheral neuropathy. While they can irritate the stomach, they are not addictive and can be taken regularly to maintain comfort. Prescription versions of these drugs - which are reimbursed by most private and public health-insurance policies - are available for pain that is slightly more severe.
• Tropical medications. 5% Lidocaine gel, an anesthetic gel applied directly to the skin, has been shown in clinical trials to be safe and effective for HIV-positive patients dealing with painful neuropathy. Lidoderm is now available, with a doctor's prescription, in the United States.
• Tricyclic antidepressants. These drugs work by reducing certain chemicals in the brain, called "neurotransmitters," that are associated with pain and emotional distress. They are often combined with non-narcotic pain relievers and are usually recommended for the treatment of mild-to-moderate pain. They are also prescribed, in combination with narcotic painkillers, to help manage severe pain.
  
  The two most common tricyclic antidepressants are amitripytyline and nortriptyline. It is important that low doses of these drugs be used at first, with a slow buildup to the recommended daily doses. Amitriptyline should be started using a dose of 25 mg or less, usually at bedtime. Over time, the dose may be increased to 75 mg a day. With nortriptyline, the recommended starting dose is 10 mg these times a day, building up gradually to 30 mg three times a day. Increasing the dose gradually is necessary to prevent certain side effects, such as dry mouth, problems urinating, and sleepiness, that can occur with both of these drugs. Note: some anti-HIV protease inhibitors and non-nucleoside analogues can either increase or decrease blood levels of tricyclic antidepressants. As a result, your doctor may want to regularly check the amount of these drugs in your bloodstream. Be sure to discuss the possibility of drug interactions with your doctor.
  
  
• Anticonvulsants. Anticonvulsants are normally used to treat epilepsy, another neurologic disorder. These drugs help calm the central nervous system, including the part of the nervous system responsible for processing pain. While anecdotal reports from HIV-positive patients and doctors suggest that anticonvulsants are sometimes helpful in managing symptoms of peripheral neuropathy, data from clinical trials are either limited or have not shown that these drugs are, in fact, effective.
  
  Carbamazepine and phenytoin are two of the most common anticonvulsants used for pain associated with peripheral neuropathy. Two new anticonvulsants, gabapentin an dlamotrigine, have also been said to be effective treatments for HIV-positive people suffering from neuropathy symptoms. As with the tricyclic antidepressants, it might be necessary to increase the doses of these drugs over the first few weeks of treatments, and to alter your dose of these drugs if side effects occur. Some of the side effects of anticonvulsants include loss of muscle control, rash, and decreased blood pressure. Note: Some anti-HIV protease inhibitors and non-nucleoside analogues can either increase or decrease blood levels of anticonvulsants. As a result, your doctor may want to regularly check the amount of these drugs in your bloodstream. Be sure to discuss the possibility of drug interactions with your doctor.
  
  
• Narcotic pain relievers. When the symptoms of peripheral neuropathy get to be too much and don't subside with the use of the medication discussed above, it might be necessary to use some of the more powerful narcotic drugs to manage the pain. These drugs are usually used in combination with non-narcotic pain relievers, along with tricyclic antidepressants or anticonvulsants. While it's certainly safe to use narcotic pain relievers to manage pain over the short term - even for HIV-positive people with a history of drug addiction - they can become addictive if used on a long-term basis. Narcotic medications can also cause nausea, vomiting, and sleepiness. Thus, it's important to work closely with your doctor to find a dose that helps control the pain without the addition of unwanted side effects.

For moderate pain, the recommended narcotic pain relievers include morphine, oxycodone, codeine, and meperidine. For severe pain requiring heavy-duty relief, the options are usually sustained-release morphine, methadone, and fentanyl patches. Low doses of these drugs should be started at first and then gradually increased until the pain is more manageable without additional side effects. Note. Some anti-HIV protease inhibitors and non-nucleoside analogues can either increase or decrease blood levels of narcotic pain relievers. As a result, your doctor may want to regularly check the amount of these drugs in your blood stream. Be sure to discuss it with your healthcare provider.

What about things I can do for myself to control the pain?

Whether or not you decide to switch your anti-HIV therapies or start taking medications to manage the symptoms of peripheral neuropathy, there are a number of things you can do for yourself to control the pain and discomfort associated with the side effect. Consider some of the following :

• Avoid ill-fitting shoes. Just as shoes that are too tight can cause throbbing, rubbing and cramping, shoes that are too loose can actually worsen pain and may not provide enough support for already wobbly feet. The best bet is to wear comfortable, well-fitting sneakers. Sneakers are sturdy enough to provide support, yet flexible enough to provide the feet with the space they needed to remain comfortable. If something a bit more dressy is needed, whether it be for work of going out at right. It's best to invest in a good pair of leather of shoes, and to work closely with a knowledgeable salesperson who can work around the specific types of pain you're dealing with.
• Keep your feet and hand cool. Most HIV-positive people with peripheral neuropathy say that the pain is worse during the warm summer months or at right, when the feet are tucked away under sheets and blankets. Let your feet breathe! If at all possible, don't wear suffocating shoes around the house - opt for a comfortable pair of shocks or some soft slippers. Also, don't cover your feet at right. Cool air in your bedroom can have a numbing effect on your feet. This also helps keep the feet free of sheets and blankets, which can sometimes be extremely painful for people with severe peripheral neuropathy.
• Treat your feet and hands well. Massaging your hands or feet - or having someone message them for you - can be extremely relaxing and can increase circulation of the blood to these extremities. Massage can also help spark endorphins. Also try soaking painful hands and felt in cold water.

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Pregnancy & HIV

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Is it safe to be HIV+ and Pregnant?

Yes. Of course, as is the case with the rest of HIV and its treatment, they are no absolute certainties or across the board truths. Every woman is different.

However, there's no data suggesting that pregnancy accelerates the rate of HIV disease progression. HIV by itself won't stop you from having a safe pregnancy. If you're generally healthy, get good prenatal care, and are careful to avoid risk factors, your chances of avoiding things like premature delivery and birth defects are not significantly different from those of your HIV-negative counterparts.

It can be hard to deal with the judgemental attitudes of people, including doctors, who think that it is morally wrong for HIV-positive women to get pregnant. The good news is that there are many strategies for dramatically reducing the risk of passing the virus to your infant - often referred to as perinatal or vertical transmission - which you and your doctor should be ready to discuss. If your health-care provider isn't supportive or is being judgmental, it's your right to find someone who will be supportive.

What are the risks of Transmitting HIV?

An HIV-positive pregnant woman - provided that she does not take nay anti-HIV medications - has a 25% chance of passing HIV to her baby. However, if she takes anti-HIV drug therapy while she is pregnant, the risk of her passing the virus to her baby is much lower - in some cases as low as 2%.

How Does Transmission Work?

Researchers are not exactly sure when babies are infected with HIV during pregnancy. It has been said that a small percentage of all babies are infected with HIV with developing inside their mothers uteruses. However, this has not really been proven. It is known that the vast majority of infections occur during labor or after the body is born and is breast-fed by his or her HIV-infected mother.

Throughout pregnancy, a developing fetus has his or her own blood supply. In other words, the developing fetus does not come into contact with the blood of his or her mother. This helps protect the fetus from infections in the mother's blood, such as HIV. However, developing fetuses do receive nutrients and various proteins, such as immune system antibodies, from their mothers. While a mother's HIV may not enter the fetus, her antibodies to the virus will. These antibodies cannot harm the fetus, but will cause the baby to test "positive" to an HIV antibodies test when he or she is born.

At the time of birth, a baby often comes into contact with his or her mother's blood. If the mother's blood enters the baby's body, this is when HIV can be transmitted.

Don't all babies born to HIV-infected Mothers Test Positive for the Virus?

Yes, they do. It is important to keep in mind what the HIV test is. These tests look for antibodies to HIV, they do not look for the virus itself. Because a fetus is exposed to his or her mother's HIV antibodies, he or she will automatically test "positive" after birth. These antibodies can remain in the baby's body for more than 18 months after he or she is born.

Most hospitals now test babies born to HIV-infected women using "PCR". This test can be performed within a few days after delivery and looks for HIV itself in a blood sample collected from the baby. If the test is negative, it should be repeated within a few months after the birth to look for HIV.

Why is Prenatal Care So Important?

Every pregnant woman, regardless of her HIV status, should see a doctor regularly to receive prenatal care. Simply put, prenatal care is a specialized type of health care designed to protect the health of both the woman and her developing baby. Prenatal care can help all pregnant women figure out what they should do to improve their diets and vitamin/mineral intake and to reduce unhealthy habits such as smoking, drinking alcohol, and doing drugs.

If a pregnant woman does not know whether or not she's HIV positive, most prenatal care programs now recommend HIV testing. While some states are hoping to make HIV testing a requirement for all pregnant women, no prenatal care program has the right to test a pregnant woman for HIV without her consent. In New York State, the law allows for any newborn baby to be tested for HIV, regardless of whether or not the baby's mother permits the test to be performed.

If a pregnant woman finds out that she is positive while she is pregnant, or knew that she was positive before getting pregnant, prenatal care programs can help protect her health and the health of her developing baby. Usually, a prenatal care program calls for monthly visits to a clinic or doctor's office for the first eight months of pregnancy. During the eighth and ninth months of pregnancy, visits are more frequent, typically every two weeks.

Prenatal care for women who are HIV infected may include T-cell counts and viral loads tests, treatments to prevent AIDS-related infections, anti-HIV drug therapy, management of drug side effects, and importance nutritional care.

HIV-positive women might want to avoid some aspects of typical prenatal care. For example, amniocentesis, used to test for genetic defects in the baby, is done with a needle that passes through the mother's abdomen and into the womb. While this test may be necessary to look for any genetic problems that a developing baby may have, it can also increase the risk of transmitting HIV.

How can you Reduce the Risk of Transmission?

In the following sections, we'll discuss three topics that a pregnant woman should discuss with her doctor that can reduce the risk of transmission to her baby anti-HIV drug therapy. Cesarean sections, and the risk of breast-feeding.

For pregnant women who are infected with HIV, the topic of anti-HIV drugs will most definitely come up as a part of a prenatal care program. These drugs, if taken correctly, can drastically reduce the amount of HIV in a mother's blood at the time of birth. This can help reduce the chances of passing the virus along.

Cesarean sections - an operation in which the baby is removed through an incision in the belly - reduces the amount of time the baby comes into contact with his or her mother's blood and has been shown to reduce the risk of transmitting HIV.

Since breast milk can also transmit HIV, formula feeding, whenever clean water and formula are available, is strongly recommended.

What about Anti-HIV drug therapy?

Only one anti-HIV drug - Retrovir - has been approved by the U.S. Food and Drug Administration for the prevention of mother-to-infant HIV transmission. According to a major study conducted several years ago about the National Institute of Health, Retrovir therapy can reduce the risk of perinatal transmission from 25% to approximately 8%. While there are no guarantees that Retrovir therapy will prevent HIV from being transmitted from a mother to her baby, if greatly reduces this chance that transmission will occur.

Retrovir therapy during pregnancy is a three-part program :

1. A standard dose of the drug is started after the first trimester of pregnancy. In other words, and HIV-infected pregnant would should take Retrovir for Six months prior to giving birth to the baby. The dose is one 300 mg tablet taken twice a day.
2. At the time of delivery, whether it is by vaginal birth or C-section, higher doses of Retrovir are administered through an intravenous line.
3. A liquid form of Retrovir is given to the baby immediately after birth and continued for six weeks.

Is this the Only Regimen Available?

Researchers are still looking at other ways to use Retrovir to prevent mother-to-child transmission. For example, one study has already demonstrated that one does of Retrovir given either to the mother during labor or to the newborn within 48 hours after birth, reduced the risk of transmission by more than half.

Results from another study suggest that giving a single dose of Virmune to both mother and newborn infant reduces transmission rates by nearly 50%. This study was actually conducted in African women, many of whom do not receive adequate prenatal care. Nevirapine is current being studied in the United States and, if used in the setting of prenatal care or in combination with other anti-HIV drugs, the drug may prove to be very effective in reducing the risk of mother-to-child HIV transmission.

What about Combination Anti-HIV Therapy?

More and more women are taking combinations of anti-HIV therapies to keep themselves healthier and alive longer. Effective combination therapy can lower viral load to below the limits of detection and ease the pressure on the immune system. Not only are the effects of combination therapy good for the mother, they have also been said to further reduce the risk of transmitting HIV.

Given what is known about Retrovir, it is recommended that any combination of drugs used during pregnancy include this drug.

Figuring out whether or not to start combination therapy - or remain on combination therapy - is a difficult decision for all HIV-infected pregnant women. If you are HIV-positive and pregnant, here are some questions you should consider discussion with your doctor before starting combination therapy.

How have you been feeling?

What was your most recent T-cell count?

What was your most recent viral load?

Does your doctor think that you/re at risk for developing HIV-related illnesses?

Of course, HIV-infected pregnant women will want to consider how the drugs they're thinking of taking might affect the baby. There's new research being produce all the time about the safety and tolerability of different medications for pregnant women and their developing babies.

What about the Potential side effects of Combination Therapy?

Anybody who is HIV-positive and taking an anti-HIV drug combination faces the risk of side effects. HIV-infected pregnant women are no different. Side effects include metabolic changes and lipodystrophy, which can cause an increase in blood levels of flats and sugars. By itself, pregnancy is a risk factor for elevated glucose levels. It's not yet known if anti-HIV medications increase the risk of these metabolic problems occurring in pregnant women.

Some anti-HIV drugs can cause liver damage, such as increases in the liver enzyme bilirubin. Too much of this enzyme can harm a fetus. While most HIV-infected people taking a protease inhibitor only experience mild increases in this enzyme, pregnant women taking these drugs - especially the protease inhibitor Crixivan - should be extra careful and have their bilirubin levels checked regularly.

Another possible side effect of combination therapy is pre-term delivery. In early clinical trials, some women who used a combination of anti-HIV drugs that included protease inhibitors gave birth to their babies earlier than they should have. This can cause health problems for the baby. However, a number of studies conducted in recent years have not found that HIV-positive women receiving combination therapy are any more likely than other women to give birth to pre-term babies. But there is a risk.

There has also been concern about the drug efavirenz Sustiva. Pregnant monkeys who received this drug gave birth to babies with deformities, some of them quite severe. However, a number of HIV-infected pregnant women have used this drug and, to date, none have given birth to babies with the same deformities seen in the monkey experiments. Again, there is a risk of damage and many experts do not recommend this drug for HIV-infected pregnant women.

Some drugs, especially the nucleoside analogues, can damage the mitochondria- the tiny "powerhouses" inside cells that provide cells with energy. Cells that contain too many severely damaged mitochondria must resort to an abnormal type of energy production that doesn't rely on the mitochondria. Lactic acid is the chemical byproduct of this sort of abnormal energy production. If too much lactic acid builds up in the body, serious illness can occur, including fatigue, nausea/vomiting, painful inflammation of the pancrease, and liver damage.

Severe cases of lactic acidosis can be deadly. The U.S. food and drug administration ahs issued an important warning that HIV-positive women should not take Zerit and Videx or Videx EC at the same time if they are pregnant. Some pregnant women who took these drugs together developed lactic acidosis, some of whom died. It is not clear if any of the other nucleoside analogues cause lactic acidosis in women or mitochondiral damage in babies born to mothers taking these drugs. Fortunately, Retrovir has been studied for many years in pregnant women and babies and has not been shown to cause any of these problems.

What if I Become Pregnant While I'm on Therapy?

If you become pregnant while you're receiving anti-HIV drug therapy, you have several options. The first is to stay with your combination. If it's working - that is, it's keeping your viral load at or near undetectable levels and doesn't cause you lots of side effects - staying on therapy might be a good option. A recent review of roughly 3,500 pregnancies in HIV-positive women found that the rates of "adverse events" - complications during or after pregnancy- weren't increased in women who took combination therapy.

You may also consider stopping therapy for the first three months of your pregnancy to minimize fetal exposure to drugs during the earliest stages of development. After the first three months, you can restart your old regimen. Or, you may choose to stay off therapy altogether for the remainder of your pregnancy. No matter what, you should strongly consider taking AZT to reduce the risk of transmission.

If you've been having a hard time taking all your pills, or if the side effects are really bothering you, it may be a good idea to stop, at least for the beginning of your pregnancy. There's no way of knowing how you'll feel while you're pregnant - morning sickness on top of daily drug-related nausea could be the last straw. Stopping a complicated drug regimen also minimizes the risk of developing drug -resistant virus, which can limit your subsequent treatment options, and could even get passed on to your baby.

A word of caution: Accidents happen. Some oral contraceptives - birth-control pills - do not mix well with some anti-HIV drugs. For example, efavirenz can increase blood levels of oral contraceptives and, in turn, may increases the side effects of the hormones found in these pills. The protease inhibitors ritonavir and nelfinavir can decrease the amount of oral contraceptives in the blood. This can increase the chance of becoming pregnant. If you're trying to avoid pregnancy, it might be best to use a barrier method - e.g., condoms, diaphragm, etc - while using anti-HIV drugs.

Should HIV+Pregnant Women have drug - resistance Tests?

Seeing that the goal of anti-HIV drug therapy is to reduce viral load to undetectable levels - preferably to less than 50 copies/mL - all HIV-positive pregnant women should consider having a drug resistance test if their viral load becomes detectable while receiving therapy. These tests can determine which drugs are no longer working and help figure out which drugs to switch to. In this way, drug-resistance tests are valuable for anyone who is receiving anti-HIV drug therapy, not just pregnant women.

What About Cesarean Sections?

Cesarean Section - often called a "C-section" - is a type of surgery that has been said to greatly reduce an HIV-positive woman's risk of passing along the virus to her baby at the time of birth. However, it is still not known if C-sections are nay more effective than taking a powerful andit-HIV drug combination in reducing this risk. It is also not known if a woman who takes a powerful anti-HIV drug combination and has a C-section has a lower chance of passing along the virus to her baby than a woman who takes anti-HIV drugs and has a vaginal delivery.

To perform a C-section, a needle is inserted into the woman's spine and injected with morphine. This causes numbness from the waist down, allowing the doctor to make a long incision under the bellybutton to remove the baby.

There is also a surgical procedure called a "bloodless C-section". This type of surgery goes a sleep further than regular C-sections. In a bloodless C-section, the blood vessels near the womb are weided, or "cauterized", using a laser to prevent them from bleeding. This procedure lowers the risk that the baby will come into contact with his or her mother's blood.

Some experts do not like the idea of C-sections. Because C-sections are a type of surgery, there are risks of infection and other complications. It is also important to remember that a combination of anti-HIV-drugs - which may include AZT plus two other drugs - might do a better job of stopping transmission, without even needing a C-section. According to some studies, in HIV-positive pregnant women who have an undetectable viral load at the time of birth, the risk of delivering a baby infected with the virus is less than 2%. Again, it is not known if C-sections reduce this risk any further.

Many doctors - particularly obstetricians and gynecologists - recommend to their HIV-infected pregnant patients that they have a C-section to deliver their babies. However, it is important that HIV-infected pregnant women.
Ÿ C-sectors are an option, not a requirement. No patient should ever be forced to have a surgical procedure. An HIV-infected pregnant woman has the right to refuse a C-section.
Ÿ If a doctor has recommended a C-section, he or she should explain the procedure and discuss the possible benefits and the potential risks.

What about breast - feeding?

Breast milk carries HIV too, and breast-feeding adds considerable risk of transmission. As with transmission via blood, there's some indication that risk increases along with viral load. So far, research shows that the risk of breast milk transmission is highest in the first six months of life. However, there's no threshold or time point beyond which it becomes absolutely safe to breast - feed.

Wherever clean water and formula are available. It's recommended that HIV-positive women exclusively formula feed their infants.

In the past year, a handful of studies have also looked at breast milk pasteurization, a procedure that allows women to express their breast milk and treat it themselves so that it becomes safe for their infants to drink. Right now, these studies have been done in resource-poor settings; your doctor may have more information about this strategy.

What Else Can I Do?

What's good advice for people with HIV is great advice for pregnant women: take good care of yourself and gets lots of support. Support can mean a lot of different things, but it definitely means having someone to talk to someone who can listen, who won't judge you and your decisions, and will help you figure out what to do when things get murky. This could be a counselor, family member, partner or friend. Ideally, it will be a collection of these folks.

Look for a team of people to work with you: a good OB/GYN and an HIV specialist, and possibly a case manger who will help you navigate whatever benefits and services you need during and after your pregnancy. Find a nutritionist who can help you satisfy your cravings - and will also help you to eat right. And talk, talk, talk to other positive mothers about their experiences. Be sure you have a plan for yourself and the baby so you're prepared after the birth.

Taking great care of yourself while you're pregnant is important - but it's just as important that you pay attention to yourself after your baby is born. Lots of women have trouble keeping to their pill schedules once the whirlwind of nursing and feeding and cleaning begins. It's fine to stop all your drugs. Just discuss it with your doctor first. Or, you may want to switch to a simpler regimen. Just remember, your health matters too. Look for ways to make things more manageable - for instance, some clinics are set up so that you and your baby can have doctor's visits on the same day.

Most of all, do whatever you need to feel good about yourself. Trust your instincts. Take time to pamper yourself. You, and your baby, are worth it.

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