Generic available: no

Tablet size: 25, 50 mg

Intravenous administration possible

Dose: variable

Effective within: two weeks to three months

Cyclophosphamide is by far the most potent and dangerous of the immunosuppressive drugs used in the treatment of RA. Like azathioprine, it was first used as a form of cancer chemotherapy. Its effectiveness in the treatment of RA is undisputed, but its potentially severe side effects preclude its use in the treatment of mild or moderate RA. Cyclophosphamide is generally reserved for the treatment of unusually severe or life-threatening complications of RA such as vasculitis, Felty’s syndrome, and other complications with organ involvement. In these very serious situations the benefits of cyclophosphamide outweigh the risks.

Side effects of cyclophosphamide

Cyclophosphamide has essentially the same potential side effects as azathioprine. Because cyclophosphamide has the most potent effect on the bone marrow and immune system, the occurrence and severity of these side effects are higher than in people taking azathioprine, although the precise risk is difficult to ascertain. We do know that a low white blood cell count occurs so frequently during cyclophosphamide therapy that it is often considered an expected effect rather than a side effect. The risk of severe blood abnormalities and infection increases in proportion to the dose and length of time which cyclophosphamide is prescribed.

Unlike azathioprine, cyclophosphamide can cause cystitis or bladder inflammation. Uncomfortable urination and the appearance of blood in the urine are symptoms of cystitis.

Hair loss can occur, particularly at very high doses. The amount of hair loss is highly variable, but in almost all patients it re-grows after the treatment is discontinued.

An important concern in cyclophosphamide therapy is the long-term increased risk of bladder or blood cancers (leukemias and lymphomas). It is estimated that with long-term daily cyclophosphamide use the risk of developing these cancers nearly doubles. Because cyclophosphamide is prescribed almost exclusively for severe, unremitting RA or for life-threatening complications, this potential risk of cancer in the future is usually at a tolerable level.

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David was feeling desperate. A 32-year-old disc jockey, he was at the point of quitting his job. He couldn’t focus on his work because of his hair obsessions, and was often late because he couldn’t tear himself away from the mirror in the morning. Even the expensive new hairpiece he’d bought to hide his slightly receding hairline didn’t help him feel any better. “I don’t like going out in public, and I’ve given up on dating,” he said. “I don’t want to date because someone will run their fingers through my hair and know it’s a hairpiece. I can’t focus on conversations because I think people are looking at my hair. At times I stay in completely; I don’t even food shop.”

In the week before he first saw me, David missed work three times and had considered going to an emergency room because he was so panicked about his hair. “I hate myself and how I look. I’m really down on myself. I’ve even had thoughts of ending my life. I can’t live the rest of my life like this. How can you live in your own body if you can’t stand it?”

David started taking fluoxetine (Prozac) right away. He continued supportive psychotherapy (see description below) which had helped him cope a little better but didn’t diminish his BDD symptoms. As expected, the medication didn’t work immediately, and the first month of treatment was rocky. David and I considered hospitalization several times. But with the support of friends, family, and his therapist, he maintained his will to live. About a month after beginning treatment, David started to feel somewhat better. His hair preoccupation began to wane, and the thoughts were less painful. He was more willing to see his friends. He didn’t check mirrors all the time, and he sought reassurance less often. He was no longer considering suicide.

He then started CBT while continuing the medication. His CBT therapist helped him stop mirror checking and reassurance seeking. He started going out more and seeing friends. Finally, he even gave up his hairpiece. He received many compliments on his new hair style, and his self-confidence greatly improved.

*229\204\8*

What is penicillamine?

Penicillamine (Cuprimine, Depen) is a chelating agent, which means that it binds metals in the blood and aids in their removal. It is very effective in treating RA, but it also has some toxicity, including muscle weakness, a lupus-like syndrome of the kidney (protein in the urine), and other effects on the blood counts. It is not related to the antibiotic penicillin.

This drug is modestly useful in patients with RA. It used to be the standard of care but has been replaced by newer agents.

The drug decreases the formation of antibodies, stops the white cells in their tracks, decreases the function of the T cells, and removes damaging molecules called free radicals.

Gold used to treat RA

Gold therapy is an old remedy that still has a place in the treatment of RA. In fact, many doctors feel that gold therapy can induce a complete remission of the disease.

There are injectable forms of gold and an oral form to treat RA. The oral form is less effective than the injectable form.

As with all drugs, gold therapy has its problems. It may cause mouth ulcers, rashes, protein in the urine, and, rarely, low platelets (blood-clotting particles) and a low white cell count.

The usual dose of injectable gold is a test dose of 10 milligrams, followed one week later by 25 milligrams once a week for two weeks, and then 50 milligrams weekly for up to 20 weeks. It can be given longer if the patient has a dramatic remission.

Your doctor will keep a record of your injections and test you before each new dose. The doctor will take urine and a blood count to make sure that all is well.

*36/141/5*

Neonatal Seizures

Seizures in the newborn are virtually always a consequence of metabolic causes, damage to the brain, or lack of oxygen, thus virtually always “symptomatic.” Since they may or may not be associated with later epilepsy, they do not require long-term treatment unless other seizures recur.

Neurofibromatosis

Neurofibromatosis is also an inherited condition involving many organ systems and with skin abnormalities consisting of multiple brown birth marks (“cafe-au-lait spots”). As with tuberous sclerosis, abnormalities of cell development within the brain may cause mild mental retardation and seizures. Tumors may occur on nerves, creating pressure on the surrounding nervous system tissue, leading to paralysis and other disabling conditions. Your doctor can discuss with you the many forms of this condition, their varying outcomes, as well as the genetic implications.

Special Conditions that Cause Epilepsy

Most children who have epilepsy do not have mental retardation, cerebral palsy, or other problems. Most children who do have mental retardation or cerebral palsy do not have epilepsy. However, sometimes brain damage due to lack of oxygen, head trauma, or problems of brain development may lead to both epilepsy and mental retardation or cerebral palsy.

Let us talk briefly about some of these special conditions.

*99\208\8*

Let’s suppose you are sitting down to a meal. Take a brief time to clear your mind and concentrate on the meal ahead. Relax, and take a deep breath. Slowly exhale. You are not in any hurry. Remind yourself that eating is an important activity in your day and it should not be rushed. Remind yourself that awareness and focus are the keys to your success in overcoming your binge eating.

Look at the food you are about to eat. Take a close look. Silently ask yourself the following questions and think deeply about your answers to each:

What does each item of food look like?

What colors are these foods?

What are the shapes of the foods?

How are the foods arranged on the plate?

How much of each food do I have in front of me?

How big a portion of each food do I have?

As you begin to contemplate these questions, begin eating. I want your eating to be normal so you don’t have to take an extraordinarily long time for these mindfulness questions. After you do this a few times, mindful eating will become more automatic and natural. You’ll begin to think about the details of the food throughout the meal. Don’t think about this as a chore. You are practicing mindful-eating awareness to enhance your enjoyment of the experience and to increase your powers of self-control.

*70\358\8*

Vocalizing – for example singing or chanting – exercises muscles throughout the body and is thus a very good way of building up strength and stamina. It also develops lung capacity. In fact, any form of vocalization, if performed with good use in mind, can help to improve your use and bring you back into a more balanced state. Making sounds can be used as a way to connect into your inner self, which should help you to tune into the natural rhythms of birth.

For a great many women making sounds makes it much easier to cope with the intensity of contractions when they are in labour. It is a way of tuning in to the pain, and of expressing it, instead of the pain becoming internalized as tension in the body. Vocalizing involves focusing on the sound you make and using it as a way of keeping control. It is important that you do not let it turn into screaming, as screaming is extremely exhausting and can make you feel even more distressed. You are also likely to have a sore throat after the birth, as letting the breath out in an uncontrolled rush damages the vocal chords.

It may sound artificial to suggest that you practise making sounds before the actual labour, but in fact it is important that you do. You need to learn to connect your voice into your body, and you need to train up the correct muscles for producing the voice. If you are using your voice well, the abdominal muscles and the action of your lower ribs will be providing the breath for the sound. If you are using your voice badly, you will be pushing the sound from your upper chest and throat.

An ideal exercise for preparing the voice for labour is the whispered ah. Chanting and singing are also excellent. If you are practising the Alexander Technique with a group of pregnant women you will find that chanting together, or singing rounds, is an enlivening and uplifting experience. The antenatal classes run by the French obstetrician Michel Odent at the clinic in Pithiviers, France, used to be group singing sessions. It is thought that singing and chanting release endorphins , the body’s natural way of suppressing pain and anxiety.

*55\346\2*

According to the American Heart Association, hypertension is a contributing factor in the 1.1 million heart attacks and more than 300,000 heart attack deaths in the United States each year. Hypertension hurts the heart by pushing it to the limits. Years of overexertion cause the heart to become weak and damaged – the pump just wears out.

Hypertension is the leading risk factor for heart attack, or myocardial infarction (MI). A heart attack occurs when part of the heart’s blood supply is suddenly reduced or cut off, usually due to a blockage in one of the coronary arteries supplying blood to the heart. The portions of the heart muscle that cannot get adequate oxygen and nutrients die. The more extensive the damage, the more serious the heart attack.

Hypertension is also the chief cause of left ventricular hypertrophy, one of the hallmarks of hypertension, especially untreated hypertension. Like any muscle, the heart bulks up with overuse. In particular, the muscular walls of the left ventricle – the discharge chamber that actually pumps blood into the arterial system – thicken and swell. As the walls thicken, the volume of the chamber shrinks, and the amount of blood it can hold and pump throughout the body is reduced. Because the heart is now pumping less blood with each beat, it works even harder to maintain circulation. This may lead to further weakening of the heart – it simply tires out and swells up like a weak balloon. This end-stage disease is called congestive heart failure (CHF). The pumping efficiency of the heart is now so poor that it cannot maintain adequate circulation of the blood. Blood pools in the vessels and the patient becomes weak and has difficulty breathing. The swollen, hypertrophied heart muscle becomes so overburdened that it eventually just stops working.

*19/313/5*

The question the reader will ask at this point is ‘Given all this epidemiological study, do we know the causes of cancer?’ Broadly the answer is ‘yes’ in many circumstances and for many cancers, and the opportunities for prevention that this understanding generates are there to be taken. We do not always know how the factors that have been identified by the epidemiological studies discussed in this chapter link up to what is being learned in the laboratories of the molecular biologists. This connection is being made rapidly and will be increasingly clear by the end of the century. Epidemiology has been very successful in discovering or confirming which features of our lives in the Western world can be now identified as causes of cancer.

Simple infections do not cause cancer. Pneumonias and urinary infections, for instance, are usually caused by bacteria and there is no evidence that such infections predispose to cancer in any way. Animal cancers can be caused by viruses but human cancers are not usually caused by viruses. There are, however, some notable exceptions to this general statement. The virus described by Epstein and Barr (Epstein-Barr virus, EBV) probably causes a rare cancer of the lymph glands, particularly in Africa, and may cause cancer of the nasal passages among the Chinese. Hepatitis B virus infection, when chronic, probably contributes to the high incidence of liver cancers in the Far East, the evidence for this being a most convincing cohort study in Taiwan. Rare types of leukaemia, particularly in Japan and the Caribbean, have been linked to infection with a particular kind of virus (human T lymphotrophic virus type 1), which seems to be spread early in life but which may alio, like AIDS, be spread by sexual activity and drug abuse. AIDS infection predisposes patients to a number of cancers of a rare kind which may be very difficult indeed to treat. As indicated above, viruses are being investigated as a possible explanation for a link between cancer of the neck of the womb and multiple sexual partners. It should be emphasized that human cancer is not in any simple way an infectious disease, that patients with cancer do not require isolation and that people need not be concerned about sharing homes or workplaces with cancer patients.

*34\194\4*

Despite the dietary advice given in the last chapter, many of my patients protest that because some alcohol beverages are low in yeast content they should be allowed to drink a little.

They should not. For many reasons, alcohol almost invariably makes the problems worse and much more difficult to treat. Strangely enough, it may be alcohol, or rather one of its metabolites, which is responsible for some of the mental and emotional problems experienced by people who suffer with yeast infections, even if they don’t touch a drop of alcohol. This is because some people who harbour excessive Candida in their digestive systems make their own alcohol from ingested carbohydrates.

The Acetaldehyde Connection

Yeast organisms have the ability to convert sugars, especially fruit sugars (fructose), to a chemical called pyruvate. This can lead to a number of seemingly unrelated problems. An increase in pyruvate will often lead to an increase in lactate at the expense of blood sugar (glucose). As a result, some individuals will experience the symptoms of hypoglycaemia and, at the same time, may suffer varying degrees of anxiety. This is a well-known effect of excessive lactate because this natural chemical is ‘panicogenic’, meaning that it can cause panic feelings, and even anxiety or panic attacks, in susceptible individuals. Some of the pyruvate is converted to acetaldehyde and carbon dioxide. The carbon dioxide is probably the main culprit in the bloating and gas which many Candida sufferers note. Alcohol (ethanol) quickly becomes acetaldehyde, once ingested, and current scientific opinion holds that most, if not all, the deleterious effects of alcohol are in fact due to the potential toxicity of acetaldehyde.

The scientific literature shows that there have been cases where Candida albicans has produced enough ethanol to induce an increase in blood alcohol levels sufficient to make a person drunk, even though not a drop of alcohol has been ingested. Try to explain that to the police next time you are stopped by a booze bus!

The first reported case (Time, 20 July 1969) occurred in Japan. A 46-year-old man, Kozo Ohishi, kept getting ‘drunk’ over a 25-year period, in spite of the fact that he was a teetotaller. When placed on a low carbohydrate diet because he wanted to lose some weight, his episodes of drunkenness decreased. After an investigation at Hokkaido University Hospital, he was found to have an enormous colony of Candida albicans yeast fungi in his digestive system. These produced enough alcohol to make him drunk. Once treated with anti Candida medication, he stayed sober! Since then at least thirty more cases have been reported in Japan, in patients ranging in age from 3 to 74 years. The condition is called Meitei sho in Japanese, which literally means ‘drunk disease’. On Sunday 25 September 1983, the Los Angeles Times reported the case of Duffy Mayo, a five year old who had been diagnosed as autistic. He would stagger around and giggle and laugh, very much like a drunk, and his breath smelled of alcohol! After treatment with anti-yeast medications and special diets, little Duffy improved.

According to Dr Bernard Rimland, an authority on children’s behavioural problems and autism:

There is a very strong likelihood that there are many of them out there somewhere. The trick is to find them.

He was referring, of course, to autistic children who may be suffering from systemic yeast infections. Dr Rimland is the author of the first and most influential textbook on infantile autism, published in 1964, the director of the Institute for Child Behaviour Research in San Diego and the winner of a Century Psychology Series Award. In a personal communication, he speculated that many cases of abnormal behaviour, learning disabilities and mental retardation may be caused or aggravated by yeast infection. But let us get back to acetaldehyde.

Once blood levels of acetaldehyde begin to rise the liver starts to suffer. The number of microtubules decreases, protein retention occurs and lipids may start to accumulate. It also depresses liver d glutathione levels, allowing the number of free radicals to increase.

According to Dr Orion Truss, author of The Missing Diagnosis, the first book about Candida, acetaldehyde also increases the ratio of a compound known as NADH (Nicotine Amide Dinucleocide Hydrogenase) to another called NAD (Nicotine Amide Dinucleocide). The doctors claim this can lead to several biochemical abnormalities and disturbances. The levels of lactate rise and tolerance to galactose decreases. Some food intolerances are more likely to develop because of this. One of the most controversial and spectacular hypotheses advanced by Dr Truss and Charles Lieber is that an increased NADH to NAD ratio can alter the metabolism of several brain amines which act as neurotransmitters, thus slowing down the degradation of serotonin (5HT) to its metabolite Hydroxy indole aceto acid (5HIAA). Excessive amounts of serotonin in the brain may be one of the results and this can cause severe behavioural disturbances in some people.

An interesting example is our observation, at the Institute for Orthomolecular Research in Sydney, that alcoholics, heavy drinkers and some patients with a previous history of psychosis can react paradoxically to heavy supplementation with tryptophan, an amino acid frequently prescribed to improve sleep and ameliorate some types of depression. Tryptophan is the precursor of serotonin and, if administered correctly, can cause a sudden elevation in brain levels of serotonin. As too much serotonin can be just as bad as too little, alcoholics given this supplement often remain totally unable to sleep for days. A truly paradoxical effect.

Even some ‘normal’ patients who are obviously highly susceptible to brain levels of that neurotransmitter have reported feeling ‘spaced out’ after taking oral tryptophan.

Acetaldehyde may have other powerful effects on the brain. It has been suggested that it is primarily responsible for the development of alcohol addiction. Some of the amines which act as brain neurotransmitters are inactivated by monoamino oxidase (enzymes) and eventually converted to other chemicals by a mechanism which shares an enzyme used in the metabolism of acetaldehyde. Leiber suggests that acetaldehyde in the brain may compete for that enzyme so that unmetabolised products can combine with neurotransmitters and form compounds similar to opiates, which are notorious for their ability to create dependence and addiction. Some of these combinations may produce pseudo neurotransmitters which could have profound effects on human moods, behaviour and mental function.

In July 1982 at Dallas, Texas, and in Birmingham, Alabama in 1983, two international symposia were held — the Candida albicans conference and the symposium on the yeast-human interaction. Much of the information presented here is taken from those meetings, as well as from several articles presented in the Journal of Orthomolecular Psychiatry, interwoven with my own clinical experience over a decade of treating these conditions. Dr Truss and other scientists have advanced the hypothesis that yeast infections may play a role in several autoimmune diseases, including lupus (a degenerative disease of connective tissue throughout the body) and Crohn’s disease (a severe inflammatory disease of the digestive system), by interfering with those cells which normally prevent ‘killer’ cells from attacking organs and tissues. Dr Truss also found marked abnormalities in the urine of Candida sufferers, suggesting that the infection may produce dangerously low levels of an important neurotransmitter called ‘GABA’ (Gamma amino butyric acid).

*52\145\2*

- Acute infectious diarrhea is a common complaint in the outpatient practice.

- Most cases of diarrhea are mild and self-limited, but severe and life-threatening illness can occur with certain pathogens and in certain demographic groups, most notably the immunosuppressed, the very old, and the very young.

- A detailed history may elicit clues to identify potential causative agents, and the decision to pursue laboratory testing, prescribe empiric antibiotics, or manage conservatively depends on both the suspected enteropathogen and the host.

- Because most death from diarrhea is secondary to dehydration, physicians must counsel patients to be diligent with oral replacement therapy and recognize individuals who are not maintaining adequate hydration so that intravenous therapy can be initiated.

- Physicians should encourage frequent hand washing to prevent the spread of disease, especially among day care workers, employees of nursing homes, and food handlers, who may need to abstain from their activities.

- When diarrhea persists and diagnostic testing fails to identify a pathogen, noninfectious or extra-intestinal causes of diarrhea should be considered, which may prompt further laboratory work, imaging, endoscopy, and referral to a gastroenterologist.

- Further research is needed to develop more concrete algorithms for the diagnosis and treatment of acute diarrhea. Primary care physicians must employ a sound knowledge of epidemiologic risk factors, potential etiologic agents, pathophysiology, and at-risk patients to provide cost-effective care to the many patients seen each year with acute infectious diarrhea.

*76/348/5*