The following article was published in 2002. It is a long article, but interesting. These doctors are recommending Cholestyramine to detox your system of neurotoxins which they believe cause CFS. Has anyone here ever tried this drug? The treatment protocol Cholestyramine (CSM) is an FDA-approved medication which has been used to safely lower elevated levels of cholesterol for more than 20 years. It isn't absorbed; if it's not taken with food, it binds cholesterol, bile salts and biological toxins from bile in the small intestine, and then the CSM-toxin complex is excreted harmlessly. Science - or Shoemaker and Hudnell -doesn't have definitive answers yet as to exactly how or why CSM clears neurotoxins from the body, but a double-blind, placebo-controlled, cross-over clinical trial of eight Pfiesteria patients positive for biotoxins showed that those who took a placebo remained ill, but improved following CSM treatment. Data from 30 others he's gathered since matches the original study data. Below is the complete article: New Theory Links Neurotoxins with Chronic Fatigue Syndrome, lyme, MCS and Other Mystery Illnesses ImmuneSupport.com 11-29-2002 By Patti Schmidt PART 1 of 2 Two doctors believe they've discovered a new brand of illness and a new way for pathogens to make people sick. They also have an FDA-approved treatment that was effective in a small, preliminary clinical trial. neurotoxic /nõr'ò tok'sik/, anything having a poisonous effect on nerves and nerve cells, such as the effect of lead on the brain and nerves. -The Mosby Medical Encyclopedia There are many theories and much disagreement about what causes Chronic Fatigue Syndrome (CFS), Multiple Chemical Sensitivity (MCS), fibromyalgia (FM) and some other chronic multi-symptom illnesses. Some science points to abnormalities in the immune system's viral-fighting pathways; other research to a cascading combination of genealogical, environmental, and health-and personality-related events and factors that begin with a predisposition and a "bug" and ends with someone who's chronically ill. And despite a rash of recent scientific evidence to the contrary, some out-of-touch physicians still insist sufferers are just depressed. While some blame stress and societal ills for the widespread fatigue, depression, joint pain and cognitive problems common to these illnesses, recent research suggests these problems may instead be linked to toxins generated by cells gone awry-that many people are chronically ill due to biotoxins in their system they cannot eliminate naturally. Two scientists - family practice physician Ritchie C. Shoemaker and EPA neurotoxicologist H. Kenneth Hudnell, Ph.D., - have collected data to back up this "neurotoxin-mediated illness" theory, and they've developed both a simple way to test for neurotoxins and a treatment protocol featuring an effective, FDA-approved prescription medicine that flushes toxins safely from the body. Shoemaker's website features information and research as well as a way to measure toxin exposure potential. After answering a brief health questionnaire about symptoms and some questions designed to eliminate confounding factors, it takes just five minutes and $8.95 to take the online Visual Contrast Sensitivity (VCS) test, which measures the impact of neurotoxins on brain function. Data from the questionnaire and vision test are analyzed immediately to determine if users are likely "positive" or "negative" for neurotoxins. The website doesn't make an official diagnosis, but gives a push in the right direction. Users can then take the test results to a physician so they can be treated if necessary. The two say they have data to support the claim that 90 percent of the people who test positive for neurotoxins improve following their treatment protocol. "If you have the VCS deficit, the potential for biotoxin exposure, and don't have other exposures or medical conditions that could explain the deficit, our data indicate that the response to toxin-binding therapy is over 90 percent," says Ritchie C. Shoemaker, M.D., the physician who helped develop the theory and the treatment. The story of how a small-town family practice physician and a civil servant who works for the EPA came up with that theory- and how they found a treatment for the 10 million Americans they claim it can help- is at least as interesting as the theory itself. The scientist Ritchie Shoemaker always planned to have a rural primary care practice. He graduated from Duke University Medical School in North Carolina in 1977, courtesy of the National Health Service Corps, which paid for his medical education in return for a stint serving under-served areas of the U.S. In July of 1980, following a Family Practice residency in Williamsport, Pa., the NHSC sent him to its clinic in Pokomoke City, Md. "I could hardly believe that the government was going to pay my way through a few years at Duke Medical School, in order to do something I already wanted to do," he said. Pokomoke City was then a thinly populated small town situated along the Pokomoke River, a tributary of the 200-mile long Chesapeake Bay. The Pokomoke itself flows South from Delaware, 80-miles long and just 50 yards wide in some places. At the time they settled there, Shoemaker and his young wife JoAnn were newlyweds. Taking great pleasure in the idyllic setting, they became involved in civic activities; had a daughter, Sally; and began protecting the unique ecology of the Lower Eastern Shore, building and restoring wetland ponds, wetland gardens and a mile-long nature trail. "This was everything I had ever wanted," said the doctor. " I had the love of a spouse and family, the love of my practice and of my land. I was happy." In 1996, the first reports of "sick fish" in the river began appearing in local newspapers. It wasn't long afterward that some of his friends and patients began complaining of flu-like symptoms. "They had nasty headaches, diarrhea, rash, cough, persistent muscle aches and failures in short-term memory," says Shoemaker. His intuition, backed by a solid grounding in science (he was a biology major in his undergraduate days) told him the sick fish and the sudden illness among his patients were related. When someone brought him a dead fish, fresh from the Pokomoke, the curious young doctor put it under a microscope. "The link was the river," Shoemaker says in the book he wrote about these events, Pfiesteria: Crossing Dark Water. "Each one of them had spent time working or playing in the slow-moving Pokomoke during the summer of 1997." He had no idea that what was under that microscope would change his life and put him at the uneasy nexus where politics, ecology and medicine meet. The collaborator Meanwhile, Shoemaker's research collaborator Hilton Kenneth Hudnell, PhD, a calm, soft-spoken neurotoxicologist, was building a civil service career at the Environmental Protection Agency. Ken Hudnell grew up in North Carolina, where the Neuse and Trent rivers join at New Bern. In a twist of fate, the Neuse was where Pfiesteria-related fish kills were first found - the very same organism thought to produce the devastating effects Shoemaker observed under his microscope and in his clinic. "It's not the same river system that I played on while growing up," says Hudnell today. "Back then there were few fish kills, and people didn't associate human illness with them. My nemesis was seaweed growing on the bottom and clogging my outboard motor. Now in many places, the seaweed has been choked out by surface blooms of cyanobacteria-blue-green algae- due to pollutant runoff from massive hog farms upstream from New Bern." A one-celled dinoflagellate, Pfiesteria piscicida is colloquially known as the "fish killer" in areas where it has wreaked its havoc on the local ecosystem. Pfiesteria wasn't the first dinoflagellate that caught Ken Hudnell's attention. After majoring in chemistry and psychology at the University of North Carolina at Chapel Hill, he moved to the Virgin Islands for three years to start a diving business. "I soon learned that you don't eat certain types of fish that feed around the reefs," he remembered. "Those fish ate a dinoflagellate called Ciguatera and accumulated their toxins. When people ate the fish, they got violently ill. Many recovered completely after a few days, but others remained chronically ill. Now I know why - they had biotoxin circulating in their bodies that they couldn't eliminate." His experience with ciguatoxins and other biotoxins in the Caribbean compelled Hudnell to return to the U.S. to enter graduate school. "I wanted to understand the relationships between neurobiology, toxic exposures and human illness," he said. Hudnell received a graduate degree from his alma mater and is an adjunct professor there now. His work at the EPA's National Health and Environmental Effects Research Laboratory, which involves using a battery of neurobehavioral and electrophysiological tests to measure sensory, motor and cognitive functions in people affected by toxic exposures, has been recognized with two of the agency's Science and Technology Achievement Rewards. At the EPA, Dr. Hudnell developed a theory explaining the worldwide increase in biotoxin-related events: human activities and natural events impact the earth's water, land and air, altering the habitat and promoting the development and spread of toxic organisms. Those toxic organisms, in turn, impact man as well as the ecosystem we all have to share. It's an interdependent circle, which features mankind using up land, air and sea resources, all the while ignoring the symptoms of burgeoning environmental problems that place us in peril. Two hundred and fifty miles north, Ritchie Shoemaker was independently coming to the same conclusions. Chronic illness, he was beginning to believe, was partly a result of the damage we've done to the ecosystem. Take lyme disease, for example: As millions of people in the city moved to the suburbs- and then further out into the countryside when the suburbs became crowded- they altered the habitat to one favored by mice and deer. Houses and new landscaping provided food and cover, and eliminated the predators of a growing deer population. Deer and mice are tolerant hosts, allowing ticks to complete their life cycle by providing a reservoir of blood-borne pathogens for the ticks to deposit into a human who happens to be in the "wrong" place (like his back yard), at the wrong time, leaving behind a tell tale trail of acute or chronic illness. If we hadn't destroyed their original habitat, in other words, we may never have gotten close enough to become a temporary feeding trough for the tick. The doctor and the scientist met when Shoemaker, hungry for more data on Pfiesteria, called Hudnell at the EPA one July morning in 1998. "At 10:15 a.m., I read that Ken had found Pfiesteria patients showed a visual contrast deficit that lasted a year or more," remembers Shoemaker. "By 10:17 a.m., we were on the phone and working together." Hudnell's early work as a UNC undergraduate led him to the VCS literature. He developed a VCS test on an oscilloscope screen early in his graduate studies there, soon after it was first reported in the scientific literature that the visual system was more sensitive to mid-size bar patterns than to smaller- or larger-size bar patterns. "I realized that this meant there were different processes in the eye and brain for detecting different aspects of a visual pattern, and I wanted to understand how they worked," he said. "Later I found that those processes were differentially susceptible to disruption by various toxins and disease processes." While VCS testing had been used in neurotoxic exposure, Hudnell was the first to use it to measure the effects of biotoxin exposure and heavy metal toxicity, or as a marker for neurotoxic exposures like Pfiesteria. The mystery Back at microscope in the summer of 1997, Shoemaker found a slimy fish that was the first example he saw of just how much damage a toxin-producing organism could do in the right set of circumstances. In his search for answers, over the next few years he became intimately familiar with the habits and neurotoxic illnesses of fresh water and sea animals including fish, birds, alligators, turtles and pelicans. He studied basic and esoteric subjects, including predator-prey relationships of aquatic invertebrates; plants; phytoplankton; the pathology of invertebrate organisms in marine and estuarine environments; pesticide physiology; and the study of the rhizosphere, the interface between a root and its immediate environment. He consulted experts in fields such as pathology; toxicology; biochemistry; geochemistry; physiology; estuarine limnology; and even membrane ionophore chemistry, the study of the passage of organisms and molecules in aqueous solutions across membranes. He learned how pesticides degrade in air, water and subsoils. Given the intense political controversy that an environmentally acquired illness like Pfiesteria created, he needed this knowledge to piece together a mystery: Was there a link between the fish kills and the illnesses his patients were suffering? Why didn't the body rid itself of these toxins naturally? Do bacteria, fungi, algae and other tiny organisms manufacture toxins that linger on in the human body, long after the organisms themselves are dead? Eventually, Shoemaker figured out that his patients had a new illness, originally named Pfiesteria human illness syndrome in his 1997 article in the Maryland Medical Journal. The CDC renamed the illness "Estuarine-Associated Syndrome" in 1998, and "Possible Estuarine-Associated Syndrome" (PEAS) in 2000. It took Shoemaker a few more years to put together his "chronic neurotoxin-mediated illness" theory and some time after that to gather the data to tell him his theory was sound. In the end, he believes he and Hudnell have discovered a new brand of illness and a new way for pathogens to make people sick. The two have continued to gather data fleshing out the theory with more clinical and molecular information. In the meantime, Shoemaker built up his medical practice, winning the 2000 Maryland Family Doctor of the Year Award and being named one of five finalists for the National Family Practice Doctor of the Year Award in 2002. At the same time, he battled state and local bureaucrats who continued to tell people, "the river is safe," despite evidence to the contrary. When Shoemaker went to the press with his theory and his data during the outbreak in Maryland in 1997, the bureaucrats did everything they could to ruin his reputation. One state official quoted in the local newspapers accused him of "scientific malpractice," and claimed he was "out of his field" when it came to the sciences. Their refusal to see -and say -the truth simply drove him to work harder. When residents near the St. Lucie River near Stuart on Florida's East Coast suffered a rash of dinoflagellate illnesses in 1998, they listened to Shoemaker's theories of copper toxicity. Copper binds to pesticides, giving them easier entrance into organisms. If predators of dinoflagellates are more susceptible to the copper-pesticide toxicity than dinoflagellates, a decrease in the predator population could result in an increase in the dinoflagellate population. Also, if prey of dinoflagellates are killed at lower exposure levels than dinoflagellates, this might put pressure on the dinoflagellates to produce and release toxins in order to kill fish for a food source. Then Florida officials earmarked $30 million to build lagoons that filter runoff from copper-laden citrus groves, bought wetland farms to restore them and dredged contaminated sections of the St. Lucie. They levied a three-year, one percent sales tax to pay for these improvements. The CSM treatment proved just as effective in Florida as it did in Maryland. About 15 residents and investigators working on the St. Lucie became ill with multiple systems symptoms and suffered a VCS deficit. They responded well to CSM therapy given by four local Florida physicians. But like the guy who discovered that a bug causes ulcers, Shoemaker found the medical community in Maryland reluctant to applaud his new theory. In fact, it was met with active resistance, he said. For example, the head of ophthalmology at the University of Maryland School of Medicine dismissed the value of visual contrast testing in helping to diagnose lyme disease by simply saying, "I don't think so." In his spare time, Shoemaker also wrote four books: Gateway Press, in Baltimore, Md., published Pfiesteria: Crossing Dark Water, a 360-page tally of the outbreak in the waters of the Pokomoke, in 1997; Weight Loss and Maintenance: My Way Works, a 325-page explanation of a weight loss mechanism with maintenance rates that exceed 70 percent, in 1998; and Desperation Medicine, the 519-page saga of his findings that neurotoxins are responsible for many chronic illnesses, in 2001. His latest book, Lose the Weight You Hate, is a 454-page update of his earlier diet primer which adds recipes, an explanation of how neurotoxic illnesses contribute to obesity and diabetes, and a discussion of the importance of genes and how they effect weight loss. The test Despite the disbelief, Shoemaker and Hudnell can point to data, accumulated since the mid-60s, that visual contrast sensitivity deficits exist in diseases like Type 1 diabetes, multiple sclerosis, and in Alzheimer's and Parkinson's disease. In fact, experts suspect that many diseases involve deficits in visual perception, but there's little research relating toxic exposures to differences in visual function before diagnosing disease. Visual contrast sensitivity testing assesses the quality of vision. It differs from typical visual acuity testing in that it simulates "real-world" circumstances, while routine visual acuity testing measures eyesight under the best possible conditions. "That's why measuring visual contrast sensitivity in patients who report difficulty with their vision, yet see well on the conventional visual acuity eye chart, is particularly useful," says Hudnell. The test is performed by showing the patient a series of stripes or bars that slant in different directions. The patient must identify which way each series of stripes is tilted. As the test progresses, the bars become thinner and lighter. People with excellent contrast sensitivity can discern the orientation of even very light, thin bars; patients with neurotoxic damage cannot. After chronic exposure to many organic solvents, VCS is the most sensitive indicator of effects from many toxins, either because the visual system is highly susceptible to neurotoxins or because even small deficits can be measured, according to Hudnell. "The visual system is the ideal place to look for evidence of neurotoxicity," he says. "The retina is a microcosm of the brain; it contains most of the cell types and biochemicals that are in the brain. So the retina is as susceptible as the rest of the brain to neurotoxic effects." According to Hudnell, this "piece of brain," being near the front of the face, is in close contact with the environment. Chemicals may be directly absorbed from the air into the retina, so the potential for exposure to neurotoxins is greater in the retina than in the brain. But unlike the brain, he points out, the visual system has few functional outputs (pattern and motion detection, or color discrimination, for example) and we can easily measure them. The VCS test measures the least amount of stimulation needed to detect a stationary pattern. "As neurologic function decreases due to toxicity, more and more stimulation is needed to see the patterns," he explains. The effect can be huge; the Pfiesteria cohort in one of Shoemaker and Hudnell's studies showed a 60 percent loss of VCS on average relative to controls. "When we see VCS drops like this following exposure, and see it recover following treatment to eliminate the toxins, we're seeing an indication of how strongly the toxins may be affecting the entire nervous system," says Hudnell. "Of course, biotoxins don't just affect the nervous system. They trigger release of inflammatory agents in the body that can inflame almost any organ and cause multiple-system symptoms." The theory And that's where Shoemaker and Hudnell's theory begins, with biotoxins in the body that some people - as many as 10 million Americans - cannot naturally eliminate, resulting in many chronic illnesses. The two men believe these poisonous chemical compounds continually circuit the human body, shuttling from nerve to muscle to brain to sinus to G.I. tract and other organs, triggering the familiar symptoms. These symptoms are similar to those caused by infectious agents, and so is the effect they have on nerve, muscle, lung, intestines, brain and sinus, say the researchers. Shoemaker and Hudnell say the compounds are manufactured by a growing number of microorganisms that thrive in our ecosystem due to changes in the human habitat. "New biotoxins or toxin-forming organisms are being identified all the time," notes Hudnell. Some, like the deer tick that passes along lyme disease, do so directly. Toxin-forming bugs such as the fungi (Stachybotrys and others) that cause "sick-building syndrome" and the blue-green algae (Cylindrospermopsis and Microcystis) that poison people and animals in most of the lakes in Central Florida, do their work by releasing their toxins into air or water. And although the pathogens differ, Shoemaker and Hudnell say the biotoxins they produce all do their damage by setting off a similar "exaggerated inflammatory response" in humans. While hiding out in fatty tissues where blood-borne disease-fighters can't get at them, they trick the body's immune system into launching attacks against joints, muscles, nerves and brain. There is increasing evidence to show these attacks are carried out by a newly discovered group of molecules, the "pro-inflammatory cytokines," and that the destruction they cause is linked to recent surges in the rates of heart disease, obesity and diabetes. Illnesses once blamed solely on diet and life-style choices are now being shown to have an inflammatory basis. And while infections cause a cytokine response from white blood cells, especially macrophages, the cytokine response to neurotoxins comes from fat cells. "The body can turn off the macrophage cytokine response, so that the achiness, fever, headache and fatigue of a cold will go away, but there's no negative feedback that stops the cytokine response from fat cells," says Shoemaker. "So the illness doesn't self-heal." The team's research found that through typing of immune response genes, the HLA DR, they can show that individual susceptibility to particular neurotoxins is associated with particular genetic factors not found in others with a different neurotoxic illness or in controls. In other words, they're beginning to crack the code to show that some people are genetically predisposed to get certain chronic fatiguing illnesses. But the research that links these things - the exaggerated inflammatory response, which may also involve an autoimmune response by a process called "molecular mimicry" -and its link to heart disease, for example, is in its infancy, so the medical community remains skeptical. Nonetheless, Shoemaker thinks these provocative discoveries will eventually require researchers to confront the grim possibility that these organisms have learned how to skew immune responses by using powerful toxins to decimate the body's disease protection system. The diagnosis According to Shoemaker, a diagnosis of chronic, biotoxin-induced illness is based on biotoxin exposure potential, multiple system symptoms, the VCS deficit discovered by Dr. Hudnell, and no other reasonable explanation for the illness. "As opposed to illnesses which have no supporting tests or biomarkers like fibromyalgia, CFS, depression, irritable bowel disease, or just getting older, our approach gives the physician readily obtained hard data to use as a marker and, more importantly, as a monitor that changes dynamically with response to treatment," says Shoemaker. Hudnell points out that new tests for cytokine levels, hormone levels and blood flow in the microvasculature of the retina help characterize how biotoxins induce chronic illness. The new HLA genotype tests (the DNA PCR assays -not the serology or transplant tests) also help identify people who are at risk for developing chronic illness from particular biotoxins because they're unable to eliminate those toxins. "Patients must have a compatible history, the deficit in VCS, the HLA genotype, an abnormal cytokine response, and the abnormal effects of cytokines on hypothalamic hormones, especially melanocyte stimulating hormone (MSH)," said Shoemaker. "All CFS patients should have the MSH test done." Shoemaker and Hudnell's data show that there's a group of CSM treatment-resistant CFS patients who are coagulase negative Staph (CNS) positive and who have high leptin levels. Leptin is a hormone made by fat cells that signals the satiety center in the hypothalamus that a person is no longer hungry. Leptin stimulates the production of alpha melanocyte stimulating hormone (MSH), which in turn controls production of endorphins (the body's natural "opiates") and melatonin (which regulates sleep) in the hypothalamus. CFS patients rarely have much MSH. Eradicating CNS does nothing to the high leptin and low MSH levels in patients with "end-stage CFS," says Shoemaker, but it certainly does in patients who are diagnosed acutely and treated aggressively, preventing irreversible damage to the MSH-manufacturing pathway. "We must recognize that the process by which CFS develops may include an acute neurotoxic event which includes upper respiratory symptoms," says Shoemaker. Shoemaker believes that the secondary cytokine damage from neurotoxic exposure changes the mucus membranes in the nose, allowing biofilm-forming, slow-growing CNS to release hemolysins (once called delta toxins) that in turn activate a powerful cytokine response. The boost in cytokines disrupts the leptin-MSH production link. This classic, positive feedback system increases cytokines and CNS and reduces MSH. "While the data is certainly compatible with this model, I haven't asked for volunteers to put CNS in their noses to watch for subsequent development of CFS," says Shoemaker jokingly. But the team has found particular genotypes of the immune response genes in HLA-DR that show marked consistency within a diagnosis group and marked disparity in other diagnostic groups. Shoemaker won't yet say that the HLA DR genes or the abnormalities in the leptin/MSH pathway are the "Holy Grail" of CFS research, but will admit that there are unique HLA genes in his CFS patients; that his Sick Building Syndrome patients have at least three unique triplets of gene biomarkers; his Post-lyme patients have two; and that these gene-types are quite different from each other. Is CFS an illness that includes a genetic susceptibility to particular neurotoxins, which trigger cytokines associated with carrying CNS, that produce nerve, hormone and immune system dysfunction in the ventromedial nucleus of the hypothalamus? Maybe, says Shoemaker. "If our study shows that replacement of MSH improves many (or most!) of the abnormalities of CFS, I'll believe that," says Shoemaker. That study will be done after the animal studies required by the FDA are completed. They hope it will establish an effective MSH dose and the most effective method of MSH delivery, as well as confirm that symptoms reoccur when MSH is stopped, and then again show benefit when an effective does is reinstituted. They'll do baseline VCS tests and MSH levels first, and will attempt to show that high levels of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha and leptin improve after treatment. A longer trial is planned, pending initial results. That study, which will be done when funds are obtained, will also attempt to show that high levels of PAI-1 and leptin improve after treatment. Shoemaker believes PAI-1 is likely to be responsible for the extra clotting and vascular disease frequently found in CFS patients, and that once leptin levels fall, CFS patients who have gained weight will be able to lose it. The website Before you can take the CS exam at Dr. Shoemaker's web site (http://www.chronicneurotoxins.com), you have to register and get a log-in identity and password, as well as answer symptom and medical history questionnaires. Then you can buy a VCS test for $8.95, or a package with several tests and treatment protocols for $49.95. The preliminary test (a free questionnaire) assesses the symptoms commonly associated with biotoxin-induced illness, as well as your potential for exposure. "Many symptoms of and potential exposures to biotoxins are not yet well known by physicians," says Shoemaker, "So they're easily overlooked." After you take the test, your results are available immediately. They can also be sent to your physician. If your physician isn't familiar with the theory or protocol, the website mentions a list of referral physicians across the nation, or you can request to see Dr. Shoemaker in his Pokomoke City office. (A second part to this article will detail the author's diagnostic and treatment experiences at Dr. Shoemaker's clinic.) The treatment protocol Cholestyramine (CSM) is an FDA-approved medication which has been used to safely lower elevated levels of cholesterol for more than 20 years. It isn't absorbed; if it's not taken with food, it binds cholesterol, bile salts and biological toxins from bile in the small intestine, and then the CSM-toxin complex is excreted harmlessly. Science - or Shoemaker and Hudnell -doesn't have definitive answers yet as to exactly how or why CSM clears neurotoxins from the body, but a double-blind, placebo-controlled, cross-over clinical trial of eight Pfiesteria patients positive for biotoxins showed that those who took a placebo remained ill, but improved following CSM treatment. Data from 30 others he's gathered since matches the original study data. Shoemaker says while some patients notice immediate improvements, lyme disease patients who've been sick for more than five years usually require toxin-binding therapy for 4-8 weeks, he says. "Most patients improve in two weeks, some with complete abatement of symptoms, but depending on the amount of toxin in your body, it may take longer," says Shoemaker. He believes the response of these patients to CSM therapy shows the underlying common theme of neurotoxin-mediated illness, and that the proof that toxins were responsible for the illness is found when patients recover, i.e., have no symptoms following treatment with his protocol. "The proof of neurotoxin effect comes from watching the biomarkers change with treatment and relapse with re-exposure," says Shoemaker. "There's very strong evidence, especially in the Sick Building Syndrome patients." Hudnell agrees. "The best evidence that biotoxins are causing the illnesses comes from cases with repeated illness," says the toxicologist. "When you see patients with chronic illness recover vision as symptoms resolve while being treated with a drug that can do nothing but remove compounds from circulation, then see vision plummet and symptoms return following re-exposure to sources of toxins, and finally see re-recovery with re-treatment, sometimes for three or four cycles, you become convinced that it's the toxins causing the illness." In another study of 51 post lyme disease patients treated with CSM after a tick bite, both those who tested positive and those who tested negative to lyme had the same number of symptoms after treatment as matched controls. Shoemaker says that data from more than 500 other patients he's seen since matches the study data. Prior to treatment, the chronic lyme disease patients had a statistically significant VCS deficit. Following treatment, all patients' clinical syndrome was gone; and their VCS scores and the number of symptoms were the same as that of the controls. Some of these lyme disease patients, especially those who'd been sick longer then three years, suffered what Shoemaker calls "a symptom intensification reaction" early in CSM therapy, similar to, but more intense than, the Herxheimer reactions experienced previously during antibiotic treatment. The reaction was reduced with pioglitazone (Actos) therapy or prevented by pretreatment with Actos, which downregulates proinflammatory cytokine production by fat cells. Patients who weren't reexposed to another tick bite didn't relapse, though follow-up was stopped at 18 months. There are other diagnoses- chronic Ciguatera seafood poisoning, Possible Estuary Associated Syndrome, brown recluse spider bites and mycotoxicosis-that were thought to involve biotoxins, but for which there was no known, effective treatment. Shoemaker has treated patients with these illnesses successfully with cholestyramine, too. Over the years Hudnell has done studies that linked environmental exposure to neurotoxicants like airborne solvents and metals to adverse neurologic effects in humans, including VCS deficits. But there was no treatment for it. "There was nothing I could do to help them, and the impairments were permanent," he said. "So I was ecstatic when we found that a simple treatment, taken for a short period of time, could benefit so many people who had suffered severe chronic illness due to biotoxins." News spreading Others have gotten excited about this research: Paul Cheney has used the VCS test and a modified version of the protocol to treat patients at his Bald Head Island Clinic in North Carolina. Chuck Lapp, director of the Hunter Hopkins Center in Charlotte, NC, also plans to put one of the machines in his office. "A number of my patients have complained that I wear loud, patterned clothing, and that it bothers their vision when I wear a patterned tie, so I think there may be something to this," he said. There are also almost 50 physicians in a nationwide referral network who are familiar with the VCS test and the treatment protocol; for more information, contact the website for the name and number of the doctor nearest you. Recent advances In June, Hudnell and Shoemaker presented data from their latest studies on Sick Building Syndrome and Post lyme Syndrome at the 8th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health in Brescia, Italy, where Dr. Hudnell chaired a session on biotoxins. Shoemaker co-chaired. Next, they plan to conduct human studies that will more definitively characterize the proinflammatory cytokine basis of chronic, biotoxin-induced illness, and describe the permanent damage that they think has occurred in the hypothalamic-pituitary-adrenal (HPA) axis of those who had the highest exposure levels for the longest periods of time. They also want to do the animal studies and human trials needed for FDA approval of hormone replacement therapy that they think will help those with permanent damage. To that end, Dr. Shoemaker has established a not-for-profit corporation, the Center for Research on Biotoxin Associated Illness (CRBAI). "If the research is to get done, CRBAI needs to raise funds through grants and donations from private organizations and individuals because there is virtually no Federal funding of research in this area," said Shoemaker. In the meantime, he still sees patients every day in his Market Street office, many suffering from chronic, neurotoxic illnesses. Both Shoemaker and Hudnell routinely get calls from all over the world asking for advice on toxic outbreaks and how to treat them. New patients are still taking the tests on the website and beginning CSM treatment. So as physician William Osler advocated long before the advent of the biotoxin-mediated illness theory, to find the proper diagnosis, Ritchie Shoemaker listens to the patient. "Recognizing the pattern of a neurotoxic illness is as subtle as being run over by a steamroller, once you learn how to ask the right questions," he says. Physicians need to learn to ask the patient a few more questions in a new order-in essence, take an organized neurotoxin history, he says. "All our biomarkers and all our data and all our nice molecular models simply provide an academic foundation for what the bedside physician already knows to be true," insists Shoemaker. "The toxins did it." PART 2 Patti Schmidt is an award-winning writer and PWC (Person with CFIDS), a former CFIDS support group leader, co-founder of the Greater Philadelphia CFIDS Alliance, and is an officer of the Board of Directors of the CFIDS Association of America. Ms. Schmidt has written about a wide variety of topics relating to coping with the disease and seeking out effective treatment. The first part of this two-part series explained how two scientists, Maryland family practice physician Ritchie C. Shoemaker and EPA neurotoxicologist H. Kenneth Hudnell, developed their "neurotoxin-mediated illness" theory explaining why many multisystem illnesses like Chronic Fatigue Syndrome (CFS), Multiple Chemical Sensitivity (MCS), fibromyalgia (FM), Sick Building Syndrome (SBS) and Lyme Disease are making people sick these days. Hudnell and Shoemaker believe they have both a biomarker for neurotoxic illness and an effective treatment. (The first part of the article can be read online at http://www.ImmuneSupport.com/library/showarticle.cfm/id/3990/.) The first article also detailed the clinical trials in which they tested the theory; the new, simple, inexpensive way they test for neurotoxins; and described their treatment protocol, which features an effective, FDA-approved prescription medicine that flushes toxins safely away. The two became convinced that many of these illnesses are neurotoxic when clinical trials found their treatment for Pfiesteria - cholestyramine (CSM) - also helped many of those patients improve. Pfiesteria, the toxic dinoflagellate Pfiesteria piscicida, is the cause of many major fish kills and fish disease events all over the Eastern seaboard, especially North Carolina and Florida. As part of my research for this series, I agreed to go through Dr. Shoemaker's diagnostic and treatment protocols. I've been ill with CFIDS, FM, Irritable Bowel Syndrome (IBS) and a few others for more than 20 years, so I had little hope that his treatments would "cure" me. But CSM, often prescribed to lower cholesterol levels, has a long safety record, so it probably wouldn't hurt me, either. But then Dr. Shoemaker's diagnostic process found something unexpected, putting a whole new spin on things; And suddenly, the world was a very different place for me. The Diagnosis Dr. Shoemaker's office is located in Pocomoke City, Maryland. First I sat in a medium-sized, cheerful front office and filled out medical information and insurance forms. Within minutes, I was led to a small, clean exam room. I took out my notebook and a tape recorder. Dr. Ritchie Shoemaker entered the room suddenly. He read my medical history and health questionnaire and it was immediately clear from his comments that the challenge of figuring out and treating these diseases is what drives him. We spent the next two hours going over my history, symptoms and his theories. (See part one for theory details.) To help me visualize how his theory works, he begins drawing on a roll of white paper stretched taut on the patient's examining table between us. Some of Dr. Shoemaker's questions are a bit odd, including, "Have you ever felt a sudden, sharp pain like a lightning bolt or a feeling like an ice pick stabbing you?" But odd or not, once while driving to work years ago, I got an intense pain in my heart and thought I was having a heart attack. I detoured to my physician's office just minutes away and was diagnosed with costochondritis, an inflammation of the ribcage's costochondral joints. I know FM patients often experience that. Do I have light sensitivity or a metallic taste in my mouth, he asked? Yes, I'm sensitive to light, I told him, and the weird tastes I get sometimes in my mouth seem more like either mayonnaise or pennies to me. He checked ‘yes’ for that one, too. Shoemaker hears complaints of strange tastes often from his neurotoxic patients. He asked me a group of hypothalamic-related questions: Do I ever have mood or appetite swings, profuse sweats, night sweats or an inability to control my body temperature? All of them, I say. Divide 7 into 91, he said, looking for how I handle numbers. I'm surprised and a little humbled when I can't do it, even after he gave me extra time. Most neurotoxic patients have these symptoms, too. Do I suffer from excessive thirst, frequent urination or a susceptibility to static electrical shocks? Yes to all three, I answered, especially the shocks. But I'm curious: what do those things have in common? Is a tendency to give people electrical shocks tied to illness somehow? What do all of these things signify? Shoemaker answered the shock question first: Hormonal deficiencies cause neurotoxic patients to lose water, and as salt becomes more concentrated in their blood, sweat glands respond to protect the blood from excessive salt by excreting it in sweat. In fact, cystic fibrosis patients are diagnosed by the amount of chloride in their sweat, and often neurotoxic patients have even more chloride in their sweat than cystic fibrosis patients. The salty sweat dries on the skin, making it a very large, efficient conductor of electricity. I'm happy to know why this happens, but I had no idea it had anything to do with my health problems. As he examined me, then has an assistant take 12 vials of blood, he answered my other questions. He ordered several tests, including levels of ACTH (adrenocorticotrophic hormone), cortisol and ADH (antidiuretic hormone). He also wanted to know my osmolality (the amount of salt in my blood). He also tested for MSH (melanocyte-stimulating hormone) and leptin levels (see part one of this series for a detailed description of how MSH and leptin effect patients with neurotoxic illness); ordered an HLA-DR by PCR (human immune response gene testing, done by polymerase chain reaction); and tested for androgen levels, including total testosterone, androestenedione, dehydroepiandrosterone sulfate (DHEA-S),* and MMP-9, the enzyme that delivers inflammatory elements from the blood into the brain, lung, heart and joints. He also ordered a Tumor Necrosis Factor (TNF) level test; a plasminogen activator inhibitor-1 (PAI-1) test; and a test to see if I have a Coag Negative Staph infection. MMP-9 levels are increased by the immune system's response to biotoxins, and it delivers inflammatory elements into joints, lungs, heart and brain. Shoemaker's research shows that patients with high MMP-9 are often the ones who also have Unidentified Bright Objects (UBOs) on their MRIs. He believes it may be that UBOs come from ischemia (lack of oxygen), inflammation or from the same kind of demyelination that Multiple Sclerosis (MS) patients suffer from. But after treatment with Actos and CSM, MMP9 levels fall and UBOs disappear. Shoemaker believes every neurotoxic patient should know their MSH and leptin levels. Leptin initiates MSH production. The damage to the MSH production pathway (also known as leptin resistance) that's seen in neurotoxic patients is a marker for biotoxic illness. He says he answers the question, "How long will I be sick, doctor? with this: "As long as your MSH is low, you'll continue to have symptoms." MSH controls peripheral cytokine production, thought to cause inflammation throughout the body. An MSH deficiency allows cytokine production to go wild. MSH also controls defenses in mucus membranes in the nose and GI tract, which is why Shoemaker tests for Coag Neg Staph, an opportunistic colonizer found in the deep recesses of the nose. In the gut, research has yet to define the mechanism that allows people to lose nutrients into stool, often referred to as "leaky gut," and which creates the IBS symptoms like bloating, gas and cramps, diarrhea and constipation that neurotoxic patients often suffer from. MSH also controls pituitary function, which controls hormones. If you're deficient in MSH, you'll likely be deficient in ADH and prolactin, growth hormone, ACTH, LH (luteinizing hormone) and FSH (follicle-stimulating hormone), says Shoemaker. "Not all patients have all of these deficiencies, but it's unlikely that an MSH-deficient patient won't have at least one." Luteinizing hormone plays an important role in controlling ovulation and in controlling the secretion of hormones by the ovaries and testes. Without androgens (male hormones like testosterone), the adverse effects of peripheral cytokines are multiplied. That dysfunction causes the rest of the hormones in your body to dysfunction, resulting in symptoms like low libido in both sexes; impotence in men and menstrual irregularities, endometriosis, sexual dysfunction and premature production of uterine fibroids in women. "Hormones may be why more women tend to get these illnesses," says Shoemaker. "It's a never-ending cycle that will continue until the source of MSH deficiency is corrected." When each of these feedback loops is damaged, each causes specific dysfunction. Lyme patients take Actos to correct the cytokine excess. Working backwards to correct the MSH deficiency, we need to remove the damage to the MSH production pathway. That means that we need to block excessive cytokine production, which comes from fat cells. Enbrel, a drug for Rheumatoid Arthritis, suppresses cytokine production, but not cytokines produced by fat cells. Only Actos does that. Actos also blocks MMP-9, excessive leptin production and turns on uncoupling proteins which burn fat directly. That process, which causes weight loss, also mobilizes fatty acids, reducing insulin resistance that in turn lowers the adverse effects of cholesterol, triglycerides and blood sugar, thus helping us avoid heart disease and diabetes. "All of this cytokine chemistry goes for naught if the person is still exposed to toxins," warns Shoemaker. "Then, regardless of which treatment you try, cytokines will increase." In other words, you must get rid of all confounding variables that might also be making you sick. That means that Lyme patients have to be treated for Lyme before they can be treated for the neurotoxic effects of Lyme; that the SBS patient must be removed from further exposure; and that Coag Neg Staph must be removed from the nose. But back to the office visit: the Coag Negative Staph test isn't pleasant. To get a sample from deep inside your nose where the Staph organisms hide, he sticks a long Q-tip two inches up your nose. No one likes that test, but it's necessary because if it's a complicating factor, he must treat it first. Dr. Shoemaker also noted the results of a recent Complete Blood Chemistry, thyroid testing, and a few hormone tests like estrogen and estradiol that were ordered by my primary care physician, my gynecologist or a specialist. I asked what the significance is of sudden sharp pains, which he called neuropathic pains. "They reflect damage to nerves," Shoemaker replied. Many neurotoxic patients suffer from them, including CFIDS, FM and Lyme Disease sufferers. Light sensitivity, mood swings, sweats, and the other symptoms symptomatic of autonomic system dysfunction signify "hypothalamic neurotoxicity," otherwise known as CFIDS. At the end of two hours, Shoemaker believes he has a complete picture of my medical history and previous diagnoses. He also notes my health questionnaire answers and the data from the physical exam. He asks about previous Lyme tests. All negative, I say. He frowns: do I know which tests were done? Find the reports, he says, because based on everything he's seen, he believes I have Lyme Disease. I'm shocked; I'm not sure what to think. Then I remember that the University of Pennsylvania had tested my spinal fluid while looking for reasons for cluster headaches a few years back. Isn't that a sure sign of being Lyme-free, I ask? "You cannot rely on test results alone to make a Lyme Disease diagnosis," explains Shoemaker. "Not the Western Blot, not the Elisa, not the PCR test of cerebral spinal fluid. Lyme Disease is now considered a clinical diagnosis, which means a physician has to look at a patient's symptoms in order to make a diagnosis." I didn't know that. My head is spinning. I doubted that I'd been misdiagnosed because I'd seen some of the best doctors in the field. How could they each have missed something so obvious? I can hardly wait to get home to do some research. Lyme Disease Soon, genetic testing results confirm that Dr. Shoemaker was right about my genotype; additional results were also compatible with Shoemaker's preliminary diagnosis of Lyme Disease. I had no confounding exposures, i.e., nothing else that would explain these symptoms. (The Lyme was probably what caused the CFIDS, FM, IBS and other illnesses.) In the meantime, my research confirmed that Lyme Disease was a clinical diagnosis, and that there were two scientific camps: one that believes that as little as a three week-long course of antibiotics would eradicate Borrelia burgdorferi (the bacterium responsible for causing Lyme Disease) and another that believes chronic Lyme Disease patients needed much longer antibiotic treatment. Naturally, insurance companies are in the short-term camp. According to the LymeTruth organization's website (http://www.lymetruth.org/), serological tests may not detect up to 60 percent of cases of Lyme disease. In some areas, 100 percent of deer ticks harbor Lyme disease spirochetes. More than 50 percent of infected humans never notice a rash or a bite; I did have a rash in the 1980s that no doctor was able to diagnose, but it wasn't the typical "bullseye" rash Lyme patients get. I contacted several Lyme experts. One went over my medical history in detail with me, and we found 13 indications of Lyme Disease, including an incident of Bell's Palsy in 1977 and meningitis in 1986. A recent significant improvement while taking Amoxicillin was also an indicator - it's one of the best Lyme killers. I had chronic Lyme Disease. It was probably why I first got CFS, and was also probably the reason for the last - and worst - of my many relapses, the one that finally knocked me out of the working world. Shoemaker was confident I had chronic Lyme Disease before he got the test confirmation because his research has shown that people with my specific group of symptoms, diagnoses and exposure (i.e., where I'd lived) all shared the same genotype, a "15-6-51," and a "1-5." (Differential association of HLA-DR genotypes with chronic neurotoxin-mediated illness: Possible genetic basis for susceptibility, R Shoemaker, presented Nov. 11, 2002 at the American Society of Tropical Medicine and Hygiene's 51st annual meeting. Abstract available at http://www.chronicneurotoxins.com/learnmore/latestAbstracts.cfm) That research hadn't been available to my other physicians previously, so they never knew to run that test. The research is still preliminary as well. But Shoemaker notes that it's not surprising that individual susceptibility to illness caused by toxins made by invertebrates is controlled genetically. (An invertebrate is any animal lacking a backbone.) The immune response genes, including HLA-DR, along with immunoglobulins and white blood cells called T cells, are only found in vertebrates. It's also not surprising that deficiencies of the immune response to those toxins result in illnesses in some patients with exposure, but not in other patients with the same exposure who don't have the same immune response gene defect. "Basically, if you get bit by a tick and develop Lyme Disease, you will develop chronic Lyme Disease if you have those genes," says Shoemaker. The "1-5" genes also predict I would develop low MSH, which is why I have chronic pain and chronic fatigue, pituitary abnormalities and alterations in gut and nose function. "The '1-5' genotype will give you MSH deficiency regardless of which toxin you're exposed to, if you also have one of the genes for susceptibility to the toxin you're exposed to," says Shoemaker. Shoemaker's current research is finding ways to replace MSH in MSH-deficient neurotoxic patients. (See his website at http://www.chronicneurotoxins.com for details.) He also says the Lyme tests that were done on me didn't meet CDC criteria. "No one would have diagnosed you with Lyme Disease [before]," he said. That's because in 1994 a group of experts decided that you must have 5 of 10 bands present on the Western Blot Lyme test to be positive for Lyme. I didn't have all 10, but most "Lyme-literate" physicians would also consider some of the other symptoms I've had, like the meningitis, and diagnose me with Lyme anyway because research shows many Lyme patients don't have all 10 bands. "The difficulty is, the bands they chose were based on a European Borrelia, which guaranteed Lyme was rarely diagnosed," Shoemaker points out. My local Lyme support group leader agreed with that assessment and told me that many patients still remain undiagnosed, just as I was. He also said he gets calls every week from patients previously diagnosed with CFIDS or fibromyalgia who find out they've had Lyme for some time. (See my sidebar for more information about how to determine if you've been adequately tested for Lyme Disease. If you have any doubts, make sure a "Lyme-literate" physician examines you and your health history in detail.) New Possibilities Driving home from Shoemaker's office, there was a moment when I realized a new diagnosis opened up new treatment possibilities. Suddenly, the world was a very different place. At various points during the antibiotic treatment, if I experience a severe Jarisch-Herxheimer reaction (an immediate worsening of all symptoms while taking antibiotics, essentially a "die-off" reaction caused by a cytokine storm of TNF and MMP-9), Shoemaker will prescribe Actos to stem the tide. I'm instructed to call immediately if I start to feel much worse. Since Actos blocks cytokines, it's a pretreatment before taking CSM, which can also cause increased cytokines if the patient isn't adequately pretreated. Actos is a drug usually given to diabetics. The difference between Shoemaker's approach to treating Lyme is that he'll give oral antibiotics, like the oral Amoxicillin I took, a chance to do the job, but if the patient is still having symptoms, then he uses the Actos/CSM protocol to give the antibiotics an even better chance. "The response of a patient to Actos/CSM is predictable - if the Lyme organism is dead you'll improve," he says. "If there are still Lyme organisms actively circulating, however, then the patient must be treated with additional antibiotics, justifying the extra cost and risk." If still symptomatic after round two of antibiotics, then Shoemaker tries another CSM/Actos regimen. He's perfectly convinced that Lyme is both an infectious and a neurotoxic disease, so it makes sense to pulse these drugs alternatively, giving the drugs a chance to work on both. The first time we tried the CSM/Actos regimen, it didn't work - it made me feel worse slowly. Since I had been improving on Amoxicillin prior to that, a return to low energy, napping in the afternoon and all of the other symptoms I'd suffered didn't make me confident. But Shoemaker assured me that the return of those symptoms meant I still had Lyme organisms circulating, so we switched to another antibiotic, Doxycycline. Within a few days, I felt better. Within a week, I was back to feeling great. I've been on the Doxycycline for almost a month now, and soon we'll try another CSM/Actos treatment. If the oral antibiotics don't continue do the job, we'll try intravenous ones. If the antibiotics have done their job well, the Actos/CSM treatment will draw the neurotoxins out of my body, allowing it to heal on its own. The other day for the first time in many years, I woke up feeling refreshed and energetic, ready to tackle the world at 7 a.m. What a difference from before, when I'd have to start the day slowly, hoard my energy and hope that I'd have enough to read or write a bit by noon or 2 p.m. Maybe I'd get a second wind later in the evening and be able to write, read or think a bit, but many days, I didn't have any energy at all and was unable to accomplish much of anything. I'm not sure how 20 years of CFIDS has damaged my body, or what effect that damage will have on my Lyme Disease treatment. But I'm feeling better now than I have since-well, I can't even remember feeling this good, it's been so long. I've had so much energy, I moved into a new apartment recently and had everything put away and organized within three weeks. I'm actively writing every day, socializing and living an almost-normal life. I'm carefully pacing myself, following a strict drug regimen and otherwise taking good care of myself. I can't be sure what the future holds, of course. But I have more hope of recovery than I've had for a long time. SIDEBAR: Research teams find neurotoxins in CFS patients Two corollaries to Shoemaker and Hudnell's work made news recently; now Shoemaker and his team are not the only ones finding neurotoxins in CFS patients. Recent research by Dr. Yoshitsugi Hokama from the University of Hawaii at Manoa discovered high levels of ciguatoxin, a potent neurotoxin, in CFS patients' blood. The finding was announced at an international symposium on toxins held in Japan in November 2002; the preliminary research was sponsored by an association for CFS. Hokama's study found that many CFS patients had higher levels of ciguatoxin than cancer or hepatitis patients or people with acute ciguatera poisoning. "Chronic ciguatera poisoning has already been suggested as a scientific model for CFS," said Dr. Hokama. But when the research was published, Shoemaker said Dr. Hokama's development "opened up the thinking of the CFS community to the importance of biotoxins and chronic symptoms." In 1999, ciguatera was the second illness that Ken Hudnell and he had tried the VCS testing and CSM protocol successfully on. They also presented a paper in 2000 which detailed their protocol for diagnosing and treating ciguatera poisoning. "I have two patients who were tested by Dr. Hokama who had positive titers to ciguatoxin; he put them on six weeks of CSM therapy and retested them. I'm told that none had ciguatera afterward," said Dr. Shoemaker. Ciguatoxins are potent biological toxins, probably of dinoflagellate origin (like Pfiesteria), found in the flesh of marine animals. They're capable of producing powerful neurological symptoms like pain, tingling or numbness, and central nervous system symptoms like headache and autonomic dysfunction. They can also produce immune system, bowel, liver, heart and muscle problems. Dr. Hokama is a pathology professor at the University of Hawaii at Manoa's John A. Burns School of Medicine. He's written hundreds of peer-reviewed publications about various fish toxins. Hokama's assay, the Membrane Immunobead Assay test, tests a patient's blood serum using a monoclonal antibody for ciguatera toxin. His assay is the first to test for one of the eight known ciguatoxins. "Trying to find ciguatoxins in blood had been impossible previously," notes Dr. Shoemaker. While this assay has been available for a while, some in the molecular toxicology field have criticized it because it picks up a part of the chemical structure in ciguatoxin that's found in many other compounds. The ciguatoxin assay, therefore, is sensitive for ciguatoxin, but not specific for it. "Ciguatera remains far more common than I had thought, with the distinctive HLA genotype 4-7,8-53 present in 20 percent of the normal population and in more than 90 percent of patients with chronic ciguatera illness," said Dr. Shoemaker. Shoemaker sees Dr. Hokama's finding as evidence that as technology progresses, we'll likely find proof of more toxins that can damage humans. "Until we can definitively identify individual biotoxins in human tissue, we'll just have to use the tools of neurotoxin detection, including Visual Contrast Sensitivity (VCS) tests, watching symptoms and cytokine responses, and looking at HLA susceptibility and hypothalamic markers," he said. Dr. John Ramsdell, head of the NOAA Marine Biotoxin program in Charleston, SC, has been looking at mice and brevetoxin, another neurotoxin. Brevetoxin is associated with "red tide," the fish-killing organism that has been a problem in many tropical locations such as Jacksonville, Fla. He treated some of his mice with regular mouse chow and gave them brevetoxin. The mice died quickly. Then he gave the mice cholestyramine (CSM at 60 mg/kg three times per day by gavage) for one week and then gave them brevetoxin again. They all lived. "He's now looking at cytokine levels and brevetoxin levels in [blood] serum and he will look at taurine levels in CSM-treated mice versus control mice," said Dr. Shoemaker. "As we've seen with leptin, mice aren't men, so it's possible that there are different mechanisms of toxin behavior in mice. But finding protection from a toxin's effects is pretty exciting."