Presenter: Jeffrey Bland, Ph.D., Institute for Functional Medicine

Moderator: Susan Lord, M.D., Center for Mind-Body Medicine

Dr. Bland is a nutritional biochemist with a 26-year career in clinical nutrition. He has been president of the Northwest Academy for Preventive Medicine and has worked with the Linus Pauling Institute for Science and Medicine. He is the founder and CEO of HealthComm International, Inc. and founder of the Institute for the Functional Medicine and the Director of Research at the Functional Medicine Research Center. As a pioneer in nutritional research, he has brought biochemistry to a level that is highly relevant to the health professions. In this workshop Dr. Bland reviewed the science underlying the connection between cancer and nutrition.

This session addressed the philosophical underpinnings of functional medicine. It included a presentation of clinical case histories, epidemiology, animal work, randomized clinical controlled trials, and basic science.

Even the advocates of conventional cancer treatments would agree that chemotherapy and radiotherapy are not "functional" treatments. Although cytotoxic drugs may sometimes lead to desired outcomes, they work against the basic nature and rhythm of the human body. Chemotherapy "is probably a transition methodology to the next biologically-based era of cancer treatment. We will probably look back at this era some 50 years from now thinking that we were very primitive," he said.

Providing some background to his presentation, Dr. Bland emphasized that in a lifetime the average human body goes through approximately 10¹⁶ cell divisions, a process which is remarkably efficient. Statistically, only 10-100 of these cell divisions turn out to be imperfect. This makes cancer an improbable event. Moreover, metabolically, cancer is inefficient. In order to compensate for its inefficient metabolism, the cancer cell has evolved personality characteristics that hide it from the rest of the body. "If we can throw it [the cancer cell] into the light of day, then we can make it much more easily observed as a foreigner and we can have the body do its job," asserted Dr. Bland. "The body has an extraordinary ability to kill cancer cells, once they have been exposed as a foreigners to it" Dr. Bland made the following four points:

• Cancer is improbable
• Cancer is weak
• The body has built-in mechanisms to defend against it
• What we need to do is obviate the cancer cell’s personality so that its mechanisms of defense can be fully recognized

Nutrition is the key to preventing and treating cancer, argued Dr. Bland. Yet it is still not adequately taught in medical schools. In a recent article by James S. Goodwin and Michael R. Tangum entitled "Battling Quackery: Attitudes About Micronutrient Supplements in American Academic Medicine" (Archives of Internal Medicine 1998 158 (20):2187-2191), the two authors discuss the resistance of academic medicine to potential benefits of nutritional supplementation. They propose that medicine eschews nutrition because many of the people who advocate nutrition are "outsiders" who directly to the general public. The medical establishment doesn’t like that. Instead it presents nutrition in a manner that is unscientific, non-analytical, emotional, and biased. Moreover, it does not invest itself in understanding the science behind it.

"I cannot believe in this day and age that nutritional therapeutics and nutritional pharmacology is not being practiced in every center of excellence in cancer today," said Dr. Bland. "To not do so, to me, is like throwing away one of the best possible tools the therapists have. And when people say, ‘Well, I some day should consider doing more nutrition,’ my answer is, ‘Yes. Like right now!’ If you’re not doing something with the molecules of life, only with the molecules of death, then you’re missing half of the equation at least. The cytotoxic drugs are molecules of death. The molecules that we’re talking about today that relate to substances that have historically been consumed by people in complex diets growing in good soils are molecules of life. When I set up an equation of living, I like to have both sides represented. I might want to kill some bad things, but I might want to nourish some good things. What we’re going to learn today, if there’s any single take-away, is that the molecules of life that we’ll be describing are molecules that can repair and support the regeneration of healthy tissues. The message for that healthy tissue resides within every gene of our body, every chromosome, every genome. In the case of the cancer patient often the wrong messages are turned on and the right messages are turned off. Nutrients play a role in turning on and off messages at the gene. I don’t know if you’ve ever thought about that, but your food is information that speaks to your genes. Your food is information. You can eat disinformation or you can eat coherent information."

Seventh Day Adventists in Los Angeles County tend to eat more natural foods than the average citizen. Moreover, many are vegetarian and abstain from alcohol and other stimulants. Despite the fact that they live in a polluted environment, they have 54% lower incidence in overall cancer mortality. On the other hand, Japanese women who immigrate to Hawaii and take up the American diet experience a fourteen-fold increase in breast cancer rates within one generation. If we believe that cancer is caused only by genetics, then we have missed the salient message of the human genome project. To prevent poor metabolic performance we need to match our diet and lifestyle with our genes. "The most powerful determinants of our health after the age of 40 is not what drugs we took or what surgery we were given, but is what we did to our genes over the course of our first four decades of living," he argued. "Fortunately, your genes are plastic. They are polymorphic. You can change the messages that they express as phenotype if you give them a different set of inputs."

Dr. Bland went on to debunk the following two theories:

• Determinism: Less than 10% of breast and colon cancers occur because people were born with cancer genes. Most cancers are not a consequence of inheriting mutant oncogenes. Cancer is a consequence of highly improbable developmental mutations of multiple oncogenes during the course of living. Although familial cancer genes do exist, they are not the main cause of cancer. Moreover, people who inherit them can take action to prevent their full expression.
• The one renegade cell: It is not the case that a single cell which has transformed into a cancer cell will go on to become an expressed cancer. Every day we create potential cancer cells. But these cells are quickly recognized and excised by our immune system. When a cell transforms into a cancer cell it becomes immortalized, embryonic, dedifferentiated, and clonal. The greater the dedifferentiation of a cancer cell, the greater its invasiveness and malignancy. One can, therefore, grade the seriousness of a cancer based on the degree to which it has lost the personality of the progenitor cell from which it came.

• Dedifferentiated and metabolically primitive
• Invasive: it has the ability to invade the adjacent tissue
• Selfishly replicative: it replicates without cooperating with other cells
• Angiogenic: at a certain size, it starts to develop its own blood supply
• Metastatic: it breaks off and travels to other parts of the body

In 1931, the German biochemist Otto Warburg talked about aerobic and anaerobic glycolysis. Twenty four years later, at his second Nobel Prize induction, Warburg claimed that the origins and treatment of cancer had finally been discovered. He explained that cancer is caused by cells that are deprived of oxygen and are forced to shift their metabolism to anaerobic glycolysis. In so doing, they develop a new personality of dedifferentiation, invasiveness, selfish replication, and metastasis. The treatment of cancer, argued Warburg, consists of delivering oxygen to tissues or enhancing oxidative metabolism by giving patients the precursor molecules that stimulate it. Warburg’s theory was very influential. It inspired many alternative cancer therapists to focus their efforts on increasing oxygen delivery to tissues. Warburg’s theory about anaerobic metabolism and cancer cells was factually correct. What Warburg missed, however, was that the anaerobic metabolism of cancer cells is not the cause of cancer—it is its effect. Therefore, cancer treatment must not be limited to the delivery of oxygen. It must achieve an alteration of the metabolic profile of the cancer cell in such a way that the cell becomes less capable of living in its environment.

"In 1953," said Dr. Bland, "the biggest single breakthrough in our thinking that will color everything I say subsequently about nutrition and cancer occurred." That was the time when James Dewey Watson and Francis Crick published their paper about the structure of the double helix. Nutrition plays a role in manipulating the expression of our genes. The theory evolving to describe the appearance of most cancers is "molecular injury." Molecular injury leads to a change in metabolic homeostasis. Viruses, stress, and chemicals can all produce molecular injuries. Such injuries turn on and off certain messages that lead to dedifferentiated, clonal, invasive, selfishly replicative, metastatic cancers. Some people think that medicine’s future lies in the excision of bad genes and their replacement with better genes. "This scares the heck out of me," said Dr. Bland. "I don’t know how you feel about this. But my feeling is, this is not where medicine is going nor should go. What medicine should do is to celebrate the extraordinary diversity of the human genome, which is the power of the human to be creative and to do and manifest unusual things that are miracles. When we take the Monte Carlo effect of genes we get these extraordinary outcomes—rather than all homogenized genes—and we should then learn how to turn on and turn off those gene messages to give rise to the best phenotypic outcome. That’s the future of medicine." We carry different genetic susceptibility factors. If we learn how to modify gene expression we can avoid many diseases and have high level living. In fact, through macro- and micronutrients we already have the capability to modulate the expression of inducible genes. Constitutive genes, on the other hand, which amount to approximately 2/3 of our genes, are not as easy to regulate.

In 1993 the article "A Short-Term Trial of Butyrate to Stimulate Fetal-Globin-Gene Expression in The Beta-Globin Disorders" [NEJM 328 (2):81-86] stated that when butyrate was administered to people who have sickle cell anemia characteristics, it upregulated the expression in the latent fetal hemoglobin gene—25% of the subject’s hemoglobin became fetal hemoglobin as opposed to sickle hemoglobin—and prevented the crystalization of the other 75% of the adult sickle hemoglobin. The authors concluded that, "In patients with beta-hemoglobinopathies butyrate, a natural fatty acid, can significantly and rapidly increase fetal-globin production to levels that can ameliorate beta-globin disorders." Dr. Bland said that the mechanism by which nutrients affect gene expression in cancer cells is now starting to be unraveled. Physicians who are not taking heed of these developments are obsolete.

Citing a recent study on the relationship between cigarette smoking, the enzyme NAT2, and breast cancer risk, ("Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk" JAMA 276(18):1494-1501), Dr. Bland explained that if you smoke and don’t have activity of NAT2, you are more vulnerable to the carcinogenic insult of tobacco. An editorial in the same issue of JAMA states that 30% of our enzymes are polymorphic and 7% of people have two forms of an enzyme: one form is expressed under one set of environmental conditions and the other is expressed under a different set of environmental conditions. "Clinically," stated Dr. Bland, "this means that it’s possible for a person to be eating one kind of diet and be a good detoxifier and eating another kind of a diet and be a poor detoxifier. One person may be tenfold more able to detoxify the same carcinogen as another individual." This phenomenon has important consequences not only for our exposure to environmental chemicals, but also for the way in which we use chemotherapy and understand pharmacology.

Dr. Bland noted that from 1948 to 1968 Dr. Ernst Wynder, now president of the American Health Foundation, had been claiming that something about smoking altered gene expression. Yet the association he made between tobacco and lung cancer was ridiculed. In fact, in 1964, the biggest advertisers in JAMA were the tobacco companies. But four years later the work of several epidemiologists confirmed Dr. Wynder’s theory, and the health hazard of smoking began to be taken seriously. One reason for the medical establishment’s 2-decade long resistance to Dr. Wynder’s claims was that no one could understand the mechanism by which molecules could create cancer. This event "shows you how much inertia has to be overcome in a mindset to create change in science and medicine. And so when people say, ‘Why aren’t we doing more nutrition?,’ it’s because there’s a huge inertia that has to be overcome. Nutrition is still viewed by many to be Betty Crocker." And it is still not taught in many medical schools.

Summary:

• Cancer is not deterministic. The view that malignancy is the inevitable result of one’s genes is wrong.
• Cancer is not caused by a single renegade cell.
• There are many levels of escape from cancer. Nutrition, lifestyle, and environment can influence the formation of malignancies in each one of the following steps: initiation; transformation; propagation; angiogenesis; and metastasis. It’s never too late to intervene.

B. Mechanisms of Action

This step is believed to occur when one is exposed to a carcinogen. A normal cell sustains a molecular injury and begins to turn into a clonal and invasive cell. In the late 19^th century, cancer was seen as an infectious disease. And although today some cancers are associated with infectious organisms, the mechanisms suggested for the formation of these cancers show covariable interrelationships between other factors (e.g., chemicals). For example, Helicobacter pylori infection leads to a significantly increased risk of stomach cancer. The suggested explanation for this phenomenon is that the body’s immune reaction to the organism produces agents like peroxy nitrite, which create their own genetic injuries. Therefore, that certain viral or bacterial infections may be linking themselves to cancer via chemical, carcenogenic in situ mechanisms. The dominant origin of cancer is probably not viruses, but chronic viruses do stress the immune system and potentially play a role in turning on oncogenic messages.

Historically, proto-oncogenes go as far back as yeast. They are highly conserved genes. The question that many scientists ask is why characteristics related to malignancy are built into our genes. One theory suggests that proto-oncogenes do not always code for malignancies. They are not death genes. They also code for cell signaling functions that are beneficial for the cycle of the cell. Proto-oncogenes can lead to malignancies when they sustain an injury and mutate along with other mutated genes. Factors that weigh upon the genes in such a way as to turn on and off different messages include viruses, ionizing radiation, non-ionizing radiation, EMF, physical agents such as asbestos, endogenous chemicals such as hormones, and exogenous chemicals that are absorbed endogenously such as colonic bacteria. Yet all these factors are modifiable.

Transformation occurs when the character of cells changes from normal to unregulated and embryonic. Messages become immortal. Mutated ras oncogene, for example, remains on all the time. It then triggers a variety of other effects to linked genes that alter the metabolic state of the cell. The cell then becomes anaerobic. Membrane transport of ions increase, which leads to a depletion of ATP. Starving for energy, the cell goes to a second level of energy production called anaerobic glycolysis. Cancer patients, as well as patients of other degenerative diseases, crave sugar.

Almost all of the effects of altered signal transduction (i.e., the transduction of a signal across a membrane) result from phosphorylation reactions, which are epigenetic influences on various enzymes. The enzymes responsible for these reactions are protein tyrosine kinases. Protein tyrosine kinases are the enzymes responsible for phosphorylating specific enzymes that get their message from genes which regulate cell cycling. When the expression of the cell regulation mechanism is upregulated, protein tyrosine kinases can become overly active and may increase one’s risk of cancer. Things that can downregulate protein tyrosine kinases may be considered anticancerous. There are many nutritional substances that are protein tyrosine kinase inhibitors. In most cases, however, when ras is mutated and it starts triggering abnormal replicative cell growth, the cell kills itself without other interventions. Because within cells there are many mechanisms that allow for the control of cancer formation.

Constitutive mutant oncogenes and constitutive mutant tumor suppressor genes constitute approximately 10% or less of all cancers. 90% of cancers result from an induced mutation caused by chemicals, viruses, radiation, or physical agents. This mutation alters the cell’s replicative cycle if it comes in conjunction with altered cellular surveillance through the immune system. Diet plays a big role in the cause of, prevention against, and treatment of malignancy. Nutrition influences a) the oncogene expression and tumor suppressor gene expression, b) cell signaling, c) cell cycling, d) immune function, e) epigenetic modification of proteins with regard to hyper-phosphorylation, f) methylation and DNA repair. As humans we will never live in a world without some carcinogens. But we must aim for enough anti-carcinogenic support; and, if the molecular injury has occurred, enough repair mechanisms to repair the injury. No point in this models suggests hopelessness.

After 1977, when Dr. E. P. Benditt published "The Origin of Atherosclerosis" in Scientific American, investigators began to see that the origins of degenerative diseases in mid-life have something in common. They consist of altered signals which affect gene expression and create altered cell regulatory growth, development, and cycling. Proper intercellular communication takes a good communicator and a good listener. In fact, activities such as guided imagery, stress-management, relaxation therapy, and exercise might have an impact upon the course of degenerative disease. Dr. Bland argued against the metaphor of the body as a machine. "The body is a holographic interacting group of connected web-like parts working in space," he said. "In the liver is the brain, and in the brain is the liver, and in the liver is the gastrointestinal tract, and so forth and so on." In support of his observation, animal studies have shown that animals exposed to a carcinogen and a stress-inducing environment simultaneously sustain a significantly greater molecular injury than animals exposed to a carcinogen alone. In terms of diet, one can eat molecules that create hostility and molecules that create peace. "If we eat under the principle of survival of the fittest," said Dr. Bland, "and we eat under the principle of the hunter—not the gatherer, but the hunter—and we live in a society in which we want to be pastoral, is there something about the molecules we get from eating animals that are being hunted, and being put in feedlocks, and given chemicals, and so forth that creates then an altered sense of message to us? Because we eat information." Over the course of a lifetime mutations can increase by an increase in one’s exposure to carcinogens or a decrease in one’s repair rates. 75% of cancers appear in people over the age of 60. Cancer is a disorder of entropy. It is a condition in which the organizing energy of the body is replaced with a disorganized and selfish replicator: the cancer cell.

The only source that powers our organizational energy is the food we eat. Under normal circumstances of living there is a balance between proto-oncogenes and tumor-suppressor genes. When the genome sustains an injury, however, the cell starts releasing DNA fragments, it alters mitochondrial function. It shifts its physiology from a normal balance of redox chemistry toward oxidative chemistry. Under oxidative stress, it upregulates the expression of nuclear regulatory factors like Nf-kappa b, which results in cell death. This process of cell-suicide is called apoptosis. Apoptosis—a process that does not require immune system involvement—is a very desirable process if a cell sustains an injury. Moreover, nutrition has the capacity to alter apoptotic cell rates in damaged tissues. The reduction of caloric intake, for example, enables normal cells to recognize and excise damaged cells quickly. On the other hand, high caloric intake overstimulates the oxidoreductive machinery and can facilitate cell damage.

This raises the question: are antioxidant supplements, which help block oxidant reactions, bad for cancer patients? Dr. Bland’s response, "Not necessarily." Vitamin E, for instance, is good for prostate cancer, plus it can ameliorate some of the side-effects of chemotherapy. But there has to be a balance. Excessive amounts of micronutrients can indeed be harmful. And yet in the cancer cell, antioxidants are probably not as important as in the normal cell, because the cancer cell has a low level of expression of internal enzymatic antioxidants, which makes it less sensitive to exogenous antioxidants. In cancer the shift from the reduction-oxidation balance toward oxidation is caused, in part, by the messages transmitted through cell membranes by things like pro-inflammatory mediators. Moreover, cancer’s pro-inflammatory characteristic increases the risk for metastasis. "Metastatic events are in part stimulated by chronic inflammatory mediators," said Dr. Bland. This is why studies are underway to evaluate the role of anti-inflammatory agents in the prevention of metastatic tumors.

What helps guard the human genome against alterations in function are the tumor suppressor gene loci which help regulate cell cycling. In human cancer, p53 is the most frequently altered gene. Free-radicals (i.e., organic compounds with an unpaired electron) can induce damage to the genome and can increase the risk of p53 mutations. But if one can increase free-radical pathology in a cell that has undergone damage to its genome, one can increase the chances of this cell’s apoptotic death. The DNA molecule has the highest electron density in the human cell. High production of free-radicals near DNA starts mutational injury. The mutagenic injury to DNA, which is in part related to cancer risk, can be measured in the laboratory by measuring in lymphocytes the amount of 8-hydroxy-deoxyguanosine that is present in the cells. Increased levels of 8-hydroxy-deoxyguanosine are clinically associated with increased risk to cancer, heart disease, diabetes, and arthritis. Research suggests that if on the surface of the cell there is an external message that influences the formation of ras protein, that ras protein will communicate with the nucleus of the cell in such a way as to increase the upregulation of expression of nuclear factor kappa B (NFkappaB). NFkappaB then goes out into the cell and, if it is released from its inhibitor (I-kappaB), it acts on the mitochodria. The mitochondria, in turn, upregulate oxidative chemistry and increase the apoptitic activity of the cell. Therefore, in some ways, increase in the expression of a mutant form of ras can lead to the expression of oxidant stress that kills the cell.

"Most of your cytotoxic drugs work in part by poisoning the electron transport chain," said Dr. Bland. One can preserve energy function by knowing how to use lipoic acid, coenzyme Q-10, vitamin E, manganese-copper-zinc, selenium, and vitamin B2. Dr. Bland urges the use of nutritional supplementation in cancer patients between radiotherapy and chemotherapy treatments. The combination of nutritional supplementation and conventional treatments can give patients the advantageous damage to the cancerous cell as well as the protection of the non-tumor cell. The goal is to increase oxidative chemistry in the cancer cell while enabling the host cell to maintain proper aerobic efficiency. Some animal studies suggest that the administration of antioxidants in conjunction with certain kinds of chemotherapy improves the efficacy of chemotherapy. He asserted that this is a controversial topic.

Contrary to what many people believe you don’t want to activate the immune system in the cancer patient. You want to balance the immune system. For an overactive immune system can be harmful. The way that the immune system kills foreign cells is through chemical warfare, which can itself lead to mutational injury. A mutational injury to DNA within the mitochondriua can be as risky as a mutational injury to DNA in the nucleus. Moreover, mitochondrial DNA is more susceptible to injury than nuclear DNA, which is bound up by a protective coat of non-histone and histone proteins. A whole series of disorders are associated with mitochondrial dysfunction. Although mitochondrial dysfunction is not the cause of cancer, it is certainly one of its components.

A cocktail of antioxidants that helps to defend redox potential within healthy cells could be considered desirable when you are trying to increase oxidative chemistry in tumor-bearing tissues. In cancer patients daily doses of mitochondrial-protection nutrients can be:

• the natural mixture of vitamin E (which includes alpha, beta, and gamma forms along with 200-400 mg tocotrienols) as opposed to the synthetic mixture (up to 1,000 IUs)
• lipoic acid (500-2,000 mg)
• coenzyme Q10 (50-200 mg)
• N-acetylcysteine (500-2,000 mg)
• elemental zinc (50 mg)
• selenium (400 micrograms)
• in manganese-deprived patients with lower superoxide dismutase (SOD) activity, elemental manganese (under 10 mg and more in the range of 5 mg)
• when patients are copper-insufficient, elemental copper (up to 5 mg). Evidence argues for the combination of antioxidants and "not the single-vitamin-of-the-month club."

In a detailed discussion about the gastrointestinal tract, Dr. Bland stated that "there is this incredible symphony that is occurring among our food, our gut bacteria, our gut mucosal lymphoid tissue—which is the principal place where 60% of our antibodies are produced. Our food, our agricultural system, speaks in language to our gut bacteria which, if friend or foe, speak then to our gut receptor sites, which then speak to the rest of the body. And it translates a message of function or dysfunction." Butyrate, for example, a very small molecule, can speak to the genes through the histone deacetylation process to "modify regions of the gene that can be expressed in terms of their translation and transcription." Elevated insulin-like growth factor-1 (IGF-1), elevated prostate specific antigen (PSA) in males, elevated levels of beta-glucuronidase in the stool, and reduced levels of butyrate in the stool are covariables indicating increased risk of cancer. Functional Medicine offers a treatment called the 4-R Program (Remove, Replace, Re-innoculate, Repair), which has been characterized as the most influential contribution of Functional Medicine. "If you don’t know about the 4-R Program, you need to know about it," Dr. Bland said. "It really works clinically for a variety of problems related to gut dysfunction."

Given that we will never rid our environment of every carcinogen, we rely upon our defense mechanism to protect us from proto-carcinogens. There are a variety of ways to improve detoxification in people exposed to carcinogens. Diets adequate in protein (especially vegetable protein) and Vitamins B3, B2, B1 tend to support proper upregulation of cytochrome P-450. Moreover, diets that are rich in phase II amplifying nutrients (e.g., certain nutrients from green tea, cruciferous vegetables, and citrus) help to bring balance. For more information, consult the Institute of Functional Medicine’s monograph on detoxification.

Angiogenesis is the process by which malignant cells, once they reach a certain mass, form a blood supply to receive nutrients. Angiogenesis is activated during periods of ovulation, menstruation, implantation, and pregnancy and during the process of malignancy formation. Along the cells of a normal blood vessel an initiating factor creates a clonal growth which then starts to form a bifurcation and leads to a new vessel. In angiogenesis alpha and beta growth factors are released by the tumor and contribute to the alteration in blood vessel morphology. Yet opportunities to remediate angiogenesis are emerging. For example, soy isoflavones have been found to be anti-angiogenic. Right now 33 molecules are being tested in clinical trials for their potential to work as anti-angiogenic factors. Arthritis, cancer, psoriasis, and retinopathy are all conditions associated with increased angiogenesis. There is a functional similarity between tumor invasion and angiogenesis. In fact, the two tend to go together. A fundamental block that increases stimulation of angiogenesis is tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a pro-inflammatory cytokine. When one has chronic inflammation, it induces angiogenesis and increases metastatic risk. This phenomenon underlies the theory that anti-inflammatory agents may help prevent increasing angiogenesis of pre-existing tumors. There are many natural anti-inflammatory agents (e.g., curcumin, fish oils, and the ancient Ayurvedic herb boswellia serrata).

"I guess I can leave you with a very optimistic view," concluded Dr. Bland, "the edge of this paradigm shift in which we merge the experience of vitalism with that of the scientific reductionistic method is really upon us. The best of tradition will be that integration, and it’ll be really a treat and a privilege to be part of that process of transformation and with you through it."

For more information on Functional Medicine contact the Institute for Functional Medicine, P.O. Box 1729, Gig Harbor, WA 98335; tel: 800-228-0622; web site: http://www.fxmed.com