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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 2:39 am
Ivanhoe.com article Reported February 1, 2005 Calcium and Vitamin D Effective for Treating Crohn's (Ivanhoe Newswire) -- A new study shows patients with Crohn's disease do not have improved bone mineral density by adding bone-building drugs to calcium and vitamin D therapy. However, the study also shows treating patients with calcium and Vitamin D alone can improve BMD by 3 percent to 4 percent per year. Crohn's is an inflammatory bowel disease that causes chronic inflammation of the intestinal wall. It usually begins in the teenage years and is characterized by abdomen pain, diarrhea, and weight loss. Patients with Crohn's disease suffer bone mass loss and bone fractures due to treatment with corticosteroids, poor nutrition, active inflammation, and calcium and vitamin D deficiencies. Researchers from the University of Alberta studied the effectiveness of the bone-building drug etidronate (Didronel) in patients with Crohn's. They found it adds no additional benefit to calcium and vitamin D therapy. They found, "Calcium and vitamin D therapy alone provide benefit to Crohn's patients who suffer from osteoporosis and osteopenia." They add, "We encourage physicians to look for loss of bone density in high-risk patients with Crohn's disease and to start calcium and vitamin D therapy immediately if there is either osteoporosis or osteopenia." They conclude, "These results imply that physicians should only consider BMD testing and drug therapy for patients who are at higher risk for osteoporosis and fractures, not those who merely have Crohn's disease as a diagnosis." Clinical trials are underway to determine if newer, bone-building drugs will, in fact, benefit patients. Until then, researchers suggest patients should be primarily treated with vitamin D and calcium supplementation. SOURCE: Clinical Gastroenterology and Hepatology, Feb. 1, 2005
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 3:05 am
Ivanhoe.com article Reported March 7, 2005 New Approach to Crohn's In-Depth Doctor's Interview Alan Buchman, M.D., explains work with a new drug to treat patients with Crohn's disease. Ivanhoe Broadcast News Transcript with Alan Buchman, M.D., Gastroenterologist, Northwestern University Feinberg School of Medicine, Chicago, Illinois TOPIC: New Approach to Crohn's How far along are you in this study for the new drug called CNI-1493 to treat Crohn's disease?} Dr. Buchman: We're currently doing a phase II or phase III study, which means that we're past the step in which we want to prove that there's a likelihood or possibility that the drug could work. A phase II is a larger study in which we look for safety data, some efficacy data. We compare the effects of the drug vs. a fake drug because almost no matter what the disease is, there are always going to be patients that respond to fake medication. So, the only way that we can truly tell that the drug works is to compare the response to it vs. the fake medication when neither the doctor nor the patient know which drug that they're receiving. Do you have some efficacy results from earlier studies? Dr. Buchman: We've done two studies with this drug so far. The first was a small 10-patient study. The second was a larger study of 45 patients, which actually was placebo controlled. This means that some patients received the fake medicine and others received the medication. These are patients who are really quite ill, and we did see that there was a trend towards an effect. We're now studying it in a much larger population of patients across the United States as well as in Europe and Israel. How is the drug given to the patients? Dr. Buchman: The drug is given as an intravenous infusion into the vein three times a week for two weeks in a row. That's how we're currently studying the drug. If we find that this drug does help patients with Crohn's disease, it's likely that the molecule will be tweaked so that it's not required to provide it so frequently to the individuals. If the study results continue to go as you've seen in the earlier studies, what would that mean for patients with Crohn's? Dr. Buchman: This would be another alternative therapy for patients with Crohn's disease. They are still searching for the Holy Grail. None of these therapies are going to be a magical cure, but we're also finding, as we develop new therapies, that there are certain patients who respond to these therapies and others that don't. This may actually lead us to find that there's a different pathogenesis for the disease in some patients vs. the disease in other patients. With Crohn's disease, it is so hard for some patients to find relief and now you're thinking that there might be something new to control the disease. What does that do for you as a doctor? Dr. Buchman: Crohn's disease is a very difficult disease to deal with. The most common reason that patients come to see a gastroenterologist is because of abdominal pain or diarrhea. But when these patients have abdominal pain or diarrhea, it's often much worse than would be ordinary. They're fatigued. They've lost their ability to work and their ability to study. The disease is not necessarily a disease of young people, but it often starts in young individuals. Even as young as a few months of age. For these individuals to be able to lead a normal lifestyle takes a lot of perseverance on their part. As a healthcare provider and as a physician, we try to provide the framework to help these individuals live as normal a life as they can, whether it's work, study or what have you. It's a very complicated disorder that affects various aspects of the patient's life. What are your hopes with this drug for the future? Dr. Buchman: I don't think that this drug is going to be a magic bullet, but it may be an alternative therapy for some patients who have not responded to other therapies or have developed side effects from other therapies. I hope it will be a further advancement in the therapy of Crohn's disease. The type of molecule that's used is a prototype, and it's likely that if we show that the drug has some value for these patients that further drugs of this type will be developed in the future. Are you looking at other medicines for Crohn's disease? Dr. Buchman: In the research that we do we're always searching for medications that not only work better for patients and enable them to live more normal lives but that are also safer than other medications that are currently available for these patients. Our primary goal with the medical therapy in these patients is to avoid surgery if at all possible. Unfortunately, there are those that will require surgery despite our best attempts. But we try to do whatever we can to preserve their intestine so that they can avoid surgery. END OF INTERVIEW
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 6:57 am
Crohn's disease causes inflammation in the small intestine. Crohn's disease usually occurs in the lower part of the small intestine, called the ileum, but it can affect any part of the digestive tract, from the mouth to the anus. The inflammation extends deep into the lining of the affected organ. The inflammation can cause pain and can make the intestines empty frequently, resulting in diarrhea. Crohn's disease is an inflammatory bowel disease (IBD), the general name for diseases that cause inflammation in the intestines. Crohn's disease can be difficult to diagnose because its symptoms are similar to other intestinal disorders such as irritable bowel syndrome and to another type of IBD called ulcerative colitis. Ulcerative colitis causes inflammation and ulcers in the top layer of the lining of the large intestine. Crohn's disease affects men and women equally and seems to run in some families. About 20 percent of people with Crohn's disease have a blood relative with some form of IBD, most often a brother or sister and sometimes a parent or child. Crohn's disease may also be called ileitis or enteritis.

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Metoo
Member
02-22-2005
| Friday, August 12, 2005 - 7:20 am
Thanks HP. You always find good articles. Hope you are doing well these days.
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 8:08 am
What causes Crohn's disease? Theories about what causes Crohn's disease abound, but none has been proven. The most popular theory is that the body's immune system reacts to a virus or a bacterium by causing ongoing inflammation in the intestine. People with Crohn's disease tend to have abnormalities of the immune system, but doctors do not know whether these abnormalities are a cause or result of the disease. Crohn's disease is not caused by emotional distress. What are the symptoms? The most common symptoms of Crohn's disease are abdominal pain, often in the lower right area, and diarrhea. Rectal bleeding, weight loss, and fever may also occur. Bleeding may be serious and persistent, leading to anemia. Children with Crohn's disease may suffer delayed development and stunted growth. How is Crohn's disease diagnosed? A thorough physical exam and a series of tests may be required to diagnose Crohn's disease. Blood tests may be done to check for anemia, which could indicate bleeding in the intestines. Blood tests may also uncover a high white blood cell count, which is a sign of inflammation somewhere in the body. By testing a stool sample, the doctor can tell if there is bleeding or infection in the intestines. The doctor may do an upper gastrointestinal (GI) series to look at the small intestine. For this test, the patient drinks barium, a chalky solution that coats the lining of the small intestine, before x rays are taken. The barium shows up white on x-ray film, revealing inflammation or other abnormalities in the intestine. The doctor may also do a colonoscopy. For this test, the doctor inserts an endoscope—a long, flexible, lighted tube linked to a computer and TV monitor—into the anus to see the inside of the large intestine. The doctor will be able to see any inflammation or bleeding. During the exam, the doctor may do a biopsy, which involves taking a sample of tissue from the lining of the intestine to view with a microscope. If these tests show Crohn's disease, more x rays of both the upper and lower digestive tract may be necessary to see how much is affected by the disease. What are the complications of Crohn's disease? The most common complication is blockage of the intestine. Blockage occurs because the disease tends to thicken the intestinal wall with swelling and scar tissue, narrowing the passage. Crohn's disease may also cause sores, or ulcers, that tunnel through the affected area into surrounding tissues such as the bladder, vagina, or skin. The areas around the anus and rectum are often involved. The tunnels, called fistulas, are a common complication and often become infected. Sometimes fistulas can be treated with medicine, but in some cases they may require surgery. Nutritional complications are common in Crohn's disease. Deficiencies of proteins, calories, and vitamins are well documented in Crohn's disease. These deficiencies may be caused by inadequate dietary intake, intestinal loss of protein, or poor absorption (malabsorption). Other complications associated with Crohn's disease include arthritis, skin problems, inflammation in the eyes or mouth, kidney stones, gallstones, or other diseases of the liver and biliary system. Some of these problems resolve during treatment for disease in the digestive system, but some must be treated separately. What is the treatment for Crohn's disease? Treatment for Crohn's disease depends on the location and severity of disease, complications, and response to previous treatment. The goals of treatment are to control inflammation, correct nutritional deficiencies, and relieve symptoms like abdominal pain, diarrhea, and rectal bleeding. Treatment may include drugs, nutrition supplements, surgery, or a combination of these options. At this time, treatment can help control the disease, but there is no cure. Some people have long periods of remission, sometimes years, when they are free of symptoms. However, the disease usually recurs at various times over a person's lifetime. This changing pattern of the disease means one cannot always tell when a treatment has helped. Predicting when a remission may occur or when symptoms will return is not possible. Someone with Crohn's disease may need medical care for a long time, with regular doctor visits to monitor the condition. Drug Therapy Most people are first treated with drugs containing mesalamine, a substance that helps control inflammation. Sulfasalazine is the most commonly used of these drugs. Patients who do not benefit from it or who cannot tolerate it may be put on other mesalamine-containing drugs, generally known as 5-ASA agents, such as Asacol, Dipentum, or Pentasa. Possible side effects of mesalamine preparations include nausea, vomiting, heartburn, diarrhea, and headache. Some patients take corticosteroids to control inflammation. These drugs are the most effective for active Crohn's disease, but they can cause serious side effects, including greater susceptibility to infection. Drugs that suppress the immune system are also used to treat Crohn's disease. Most commonly prescribed are 6-mercaptopurine and a related drug, azathioprine. Immunosuppressive agents work by blocking the immune reaction that contributes to inflammation. These drugs may cause side effects like nausea, vomiting, and diarrhea and may lower a person's resistance to infection. When patients are treated with a combination of corticosteroids and immunosuppressive drugs, the dose of corticosteriods can eventually be lowered. Some studies suggest that immunosuppressive drugs may enhance the effectiveness of corticosteroids. The U.S. Food and Drug Administration has approved the drug infliximab (brand name, Remicade) for the treatment of moderate to severe Crohn's disease that does not respond to standard therapies (mesalamine substances, corticosteroids, immunosuppressive agents) and for the treatment of open, draining fistulas. Infliximab, the first treatment approved specifically for Crohn's disease, is an anti-tumor necrosis factor (TNF) substance. TNF is a protein produced by the immune system that may cause the inflammation associated with Crohn's disease. Anti-TNF removes TNF from the bloodstream before it reaches the intestines, thereby preventing inflammation. Investigators will continue to study patients taking infliximab to determine its long-term safety and efficacy. Antibiotics are used to treat bacterial overgrowth in the small intestine caused by stricture, fistulas, or prior surgery. For this common problem, the doctor may prescribe one or more of the following antibiotics: ampicillin, sulfonamide, cephalosporin, tetracycline, or metronidazole. Diarrhea and crampy abdominal pain are often relieved when the inflammation subsides, but additional medication may also be necessary. Several antidiarrheal agents could be used, including diphenoxylate, loperamide, and codeine. Patients who are dehydrated because of diarrhea will be treated with fluids and electrolytes. Nutrition Supplementation The doctor may recommend nutritional supplements, especially for children whose growth has been slowed. Special high-calorie liquid formulas are sometimes used for this purpose. A small number of patients may need periods of feeding by vein. This can help patients who need extra nutrition temporarily, those whose intestines need to rest, or those whose intestines cannot absorb enough nutrition from food. Surgery Surgery to remove part of the intestine can help Crohn's disease but cannot cure it. The inflammation tends to return next to the area of intestine that has been removed. Many Crohn's disease patients require surgery, either to relieve symptoms that do not respond to medical therapy or to correct complications such as blockage, perforation, abscess, or bleeding in the intestine. Some people who have Crohn's disease in the large intestine need to have their entire colon removed in an operation called colectomy. A small opening is made in the front of the abdominal wall, and the tip of the ileum is brought to the skin's surface. This opening, called a stoma, is where waste exits the body. The stoma is about the size of a quarter and is usually located in the right lower part of the abdomen near the beltline. A pouch is worn over the opening to collect waste, and the patient empties the pouch as needed. The majority of colectomy patients go on to live normal, active lives. Sometimes only the diseased section of intestine is removed and no stoma is needed. In this operation, the intestine is cut above and below the diseased area and reconnected. Because Crohn's disease often recurs after surgery, people considering it should carefully weigh its benefits and risks compared with other treatments. Surgery may not be appropriate for everyone. People faced with this decision should get as much information as possible from doctors, nurses who work with colon surgery patients (enterostomal therapists), and other patients. Patient advocacy organizations can suggest support groups and other information resources. (See For More Information for the names of such organizations.) People with Crohn's disease may feel well and be free of symptoms for substantial spans of time when their disease is not active. Despite the need to take medication for long periods of time and occasional hospitalizations, most people with Crohn's disease are able to hold jobs, raise families, and function successfully at home and in society. Can diet control Crohn's disease? No special diet has been proven effective for preventing or treating this disease. Some people find their symptoms are made worse by milk, alcohol, hot spices, or fiber. People are encouraged to follow a nutritious diet and avoid any foods that seem to worsen symptoms. But there are no consistent rules. People should take vitamin supplements only on their doctor's advice. Is pregnancy safe for women with Crohn's disease? Research has shown that the course of pregnancy and delivery is usually not impaired in women with Crohn's disease. Even so, women with Crohn's disease should discuss the matter with their doctors before pregnancy. Most children born to women with Crohn's disease are unaffected. Children who do get the disease are sometimes more severely affected than adults, with slowed growth and delayed sexual development in some cases. Hope Through Research Researchers continue to look for more effective treatments. Examples of investigational treatments include * Anti-TNF. Research has shown that cells affected by Crohn's disease contain a cytokine, a protein produced by the immune system, called tumor necrosis factor (TNF). TNF may be responsible for the inflammation of Crohn's disease. Anti-TNF is a substance that finds TNF in the bloodstream, binds to it, and removes it before it can reach the intestines and cause inflammation. In studies, anti-TNF seems particularly helpful in closing fistulas. * Interleukin 10. Interleukin 10 (IL-10) is a cytokine that suppresses inflammation. Researchers are now studying the effectiveness of synthetic IL-10 in treating Crohn's disease. * Antibiotics. Antibiotics are now used to treat the bacterial infections that often accompany Crohn's disease, but some research suggests that they might also be useful as a primary treatment for active Crohn's disease. * Budesonide. Researchers recently identified a new corticosteroid called budesonide that appears to be as effective as other corticosteroids but causes fewer side effects. * Methotrexate and cyclosporine. These are immunosuppressive drugs that may be useful in treating Crohn's disease. One potential benefit of methotrexate and cyclosporine is that they appear to work faster than traditional immunosuppressive drugs. * Natalizumab. Natalizumab is an experimental drug that reduces symptoms and improves the quality of life when tested in people with Crohn's disease. The drug decreases inflammation by binding to immune cells and preventing them from leaving the bloodstream and reaching the areas of inflammation. * Zinc. Free radicals—molecules produced during fat metabolism, stress, and infection, among other things—may contribute to inflammation in Crohn's disease. Free radicals sometimes cause cell damage when they interact with other molecules in the body. The mineral zinc removes free radicals from the bloodstream. Studies are under way to determine whether zinc supplementation might reduce inflammation. For More Information Crohn's & Colitis Foundation of America, Inc. 386 Park Avenue South, 17th Floor New York, NY 10016–8804 Phone: 1–800–932–2423 or 212–685–3440 Email: info@ccfa.org Internet: www.ccfa.org Pediatric Crohn's & Colitis Association, Inc. P.O. Box 188 Newton, MA 02468 Phone: 617–489–5854 Email: questions@pcca.hypermart.net Internet: http://pcca.hypermart.net Reach Out for Youth with Ileitis and Colitis, Inc. 15 Chemung Place Jericho, NY 11753 Phone: 516–822–8010 United Ostomy Association, Inc. 19772 MacArthur Blvd. #200 Irvine, CA 92612–2405 Phone: 1–800–826–0826 or 949–660–8624 Fax: 949–660–9262 Email: uoa@deltanet.com Internet: www.uoa.org SOURCE: National Digestive Diseases Information Clearinghouse 2 Information Way Bethesda, MD 20892–3570 Email: nddic@info.niddk.nih.gov The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases. Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. This e-text is not copyrighted. The Clearinghouse encourages users of this e-pub to duplicate and distribute as many copies as desired. NIH Publication No. 03–3410 January 2003
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 8:12 am
Hey, Metoo. I am actually doing well. Glad you find these helpful. I am searching for an article I read a while back and didn't post cuz I thought it was so weird (had to do with swalling a worm--a technique used in France---you have to read the article before you dismiss the idea. I think. Kona will probably give us the lowdown on it, once I find it.). It supposedly cleans out the bad bacteria, but you never digest the worm cuz it is indigestible (dunno why) and then you 'naturally' rid yourself of the worm, and wallah! the Crohn's is gone. Well, I am off looking for it. Dunno if I could ever get the nerve to do that, though. Ick!
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Vee
Member
02-23-2004
| Friday, August 12, 2005 - 8:18 am
Wow! That would be incredible and sounds a lot like the maggot treatment that is used on serious wounds...the maggots eat the "rotten" meat and leave the healthy tissue. It does sound gruesome, but if it works, it works, and I would definitely be nutty enough to try it. HP, you provide a valuable service with all this information.
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 8:37 am
Hi, Vee! Yes, I recalled that, too, and it was the ONLY reason why I continued to read that article. Otherwise, I would have been highly skeptical. Thanks, Sweetie. Helping myself, too, you understand! Every time I read an article, I remember a little more-- of the basic stuff, anyway. So, although some of this information is repetitive, hearing it in a different articles is good, I think.
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 8:49 am
The Specific Carbohydrate Diet: Does It Work? Vegetables This is from our upcoming issue of CCFA's national magazine, Take Charge. If you're a CCFA member, you'll be seeing this in your mailbox soon. Not a member? Join now to get a full year of research information, news on medical treatments, diet tips, coping support, and other great content coming to your mailbox four times per year. It's been featured in The Wall Street Journal, evokes passionate testimonials from its adherents, and spawned a best-selling book, now in its 11th printing. Yet the Specific Carbohydrate Diet, or SCD, has few published studies behind it, can be very difficult to follow, and has been dismissed by some doctors as scientifically unproven and even potentially risky. All of which leaves the person with Crohn's or colitis caught in the middle, wondering whether the SCD is truly an effective treatment for inflammatory bowel disease (IBD) or a dead end. This article will review the available facts and offer a variety of perspectives on the diet to help readers navigate its complexities and form their own opinions as to its value for treating IBD. The Theory Behind the Diet The Specific Carbohydrate Diet was developed and popularized by biochemist Elaine Gottschall in her 1994 book, Breaking the Vicious Cycle: Intestinal Health Through Diet. Gottschall, who spent time exploring the changes that occur in the intestinal wall in IBD while at the University of Western Ontario, wrote her book after observing the effects of a low-carbohydrate, gluten-free diet on her eight-year-old daughter, who had been diagnosed with colitis at age five. She and her husband took their daughter to see Drs. Sidney V. and Merrill P. Haas, physicians who had written a book called Management of Celiac Disease, which espoused a low-carbohydrate nutritional approach to celiac and other gastrointestinal diseases. Within two years of starting a radical version of the diet – the precursor of the SCD – Gottschall writes, her daughter was free of symptoms. The girl returned to a normal diet a few years later and has remained in good health for more than 20 years. The SCD is a grain-free, lactose-free, and sucrose-free meal plan that is several degrees more restrictive than the gluten-free diet. It is built on the premise that carbohydrates are the primary energy source for the intestinal microbes that contribute to the development of IBD. Gottschall believes that undigested carbohydrates in particular spur the formation of acids and toxins that can injure the small intestine, destroying the very enzymes that allow for carbohydrate digestion and absorption in a kind of vicious cycle. Nuts and Bolts You can almost think of the SCD as the ultimate in low-carb diets. Specifically, it prohibits: * Sugar, molasses, sucrose, fructose, high-fructose corn syrup, or any processed sugar * Canned vegetables * All grains, including corn, wheat, wheat germ, barley, oats, rye, rice, buckwheat, soy, spelt, amaranth, and others * Some legumes, including chick peas, bean sprouts, soybeans, mung beans, faba beans, and garbanzo beans * Starchy tubers, such as potatoes, yams, and parsnips * Seaweed and seaweed byproducts, such as agar and carrageenan * Canned and most processed meats, particularly those that contain additives such as corn products, starch, and sugars * All milk, high-lactose cheeses (generally soft cheeses like ricotta, mozzarella, cottage cheese, cream cheese, feta, and processed cheeses and cheese spreads), as well as commercial yogurt, heavy cream, buttermilk, and sour cream * Bread, pasta, and other starchy foods * Canola oil, commercial mayonnaise (because of additives), ice cream, candy, chocolate, carob, whey powder, margarine, commercial ketchup, stevia, baking powder, commercial nut mixes, balsamic vinegar, and products containing FOS (fructooligosaccharides). So what does that leave? Well, unprocessed meats, poultry, fish, shellfish, eggs, honey for sweetening (if tolerated), most fresh, frozen, raw or cooked vegetables, a variety of legumes, including dried navy beans, lentils, peas, split peas, unroasted cashews, and peanuts in a shell, all-natural peanut butter, lima beans, and string beans, cheeses such as cheddar, Colby, Swiss, havarti, and dry curd cottage cheese, and homemade yogurt fermented for at least 24 hours. Additionally, most fruits and nuts are allowed, as are most oils, tea, coffee, mustard, vinegar, and juices with no additives. Arthur D. Heller, M.D., a New York City gastroenterologist who is certified by the American Board of Nutrition, points out several inconsistencies in the diet. "Foods are excluded," he says, "because of their purported inability to be digested well. But of the foods allowed, legumes are known to contain certain carbohydrates that are not well digested by humans. And while the diet prohibits regular sugar, it allows most fruits and fruit juices, which are high in fructose, or fruit sugar. Not only is fructose dense in carbohydrates, but fructose malabsorption can cause cramps and diarrhea, intensifying the very symptoms the diet is designed to alleviate." Stepping Back A Bit The SCD has its fans and its critics. It's fair to say that, overall, it's getting mixed reviews from both patients and physicians. The reasons why are twofold: the diet is hard to follow, and there's little scientific evidence to show whether it is truly effective or which patient population it helps. Edward V. Loftus, Jr., M.D., Associate Professor of Medicine and member of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN, hears a lot about the SCD from his patients. Some manage to remain on it successfully, while others try and fail. "I have one guy on this diet and he swears by it," says Dr. Loftus. "He was diagnosed with Crohn's when he was a kid and had a lot of trouble with colonic problems and fistulas. He went on the diet and did very well; no medications for years. He has intermittent trouble every now and then with fistulas, but overall he's done well." And that's fine. Dr. Loftus isn't going to dissuade his patients from going on the diet, he says. "We're not ruling out the possibility that it works, but you need more than a few successes to establish proof. In the absence of that, it's hard to recommend this or any diet." There may be thousands of people whom the diet helped, he adds, but how many other thousands are not being heard from who have had no relief from the diet? "In my experience," says Dr. Loftus, "for every patient I see who tried the diet and it worked, there are three to four others who tried it and it didn't work." Additionally, doctors are asking whether there is something biologically different about the patients who have responded favorably to the SCD, or to any treatment. After all, some people do well on biologic therapy, while others respond better to immunomodulators such as methotrexate, azathioprine, or 6-MP, and still others experience spontaneous remission without drugs. In other words, is the success of any treatment, pharmacological or non-pharmacological, dependent on an individual's genetically determined disease sub-type? The Need for Research One of the few published reports on the diet appeared in Tennessee Medicine in September 2004. It wasn't actually a study, but a case report on two patients who followed the diet: a 51-year-old woman with colitis and a 24-year-old woman with Crohn's disease. Both found significant relief within one month of starting the diet, the authors wrote, and each was able to taper off her medications, remaining in remission on the diet alone. Most doctors, however, want to see well-designed, randomized controlled trials involving large numbers of people, in which one group follows the diet, one group follows a different diet or no diet, and the results are compared, before recommending a particular treatment. Those studies just don't exist yet. "Studies are expensive and someone has to pay," Dr. Loftus says. Most clinical studies in this country are funded by pharmaceutical companies, he notes, and since there's no potential drug at stake with this diet, it would be difficult to find the funding. Another challenge is designing such a study. For instance, he asks, how would you determine the comparator diet so that the results of the trial weren't tainted by investigator or patient bias? The first step, speculates William J. Sandborn, M.D., Professor of Medicine at the Mayo Clinic, would be to conduct a pilot study of a small group of patients on the SCD for a finite period. Patients would be examined via endoscopy at the beginning and end of the study to measure disease-related damage in the GI tract. "There would need to be some compelling pilot data indicating benefit – i.e., a measurable demonstration of healing – before a controlled trial was undertaken," Dr. Sandborn says. Carefully controlled studies of diet are technically difficult to conduct, he adds. The good news is that there's a growing interest at the national level (among groups such as the National Center for Complementary and Alternative Medicine at the NIH) in looking at the effects of diet on chronic illness. As the ability to conduct such studies improves, the CCFA will, in all likelihood, play an important role in fostering research on nutrition and IBD. Drs. Loftus and Sandborn note that some aspects of the theory behind the SCD make sense. For instance, current thinking holds that IBD is caused by an abnormality that prevents the immune system in the gut from shutting itself off when it encounters bacterial or viral threats, real or "imagined." So if you starve the bacteria in the gut via this elemental diet, says Dr. Loftus, there may be fewer stimuli, resulting in less inflammation. Potential Harm? Even if the SCD only works for a percentage of the people who try it, doesn't that at least make it worth trying? Maybe, says Dr. Heller. But he's also concerned about the potential for nutritional deficiencies on the diet. Excluding starchy vegetables and grains eliminates dietary sources of short-chain fatty acids, the preferred fuel source for colon cells, he says. "This is important because without that fuel source, those cells don't function as well." In fact, he notes, in a condition called diversion colitis, which sometimes occurs in any remaining colon after a colectomy, colon cells are depleted of short-chain fatty acids. Restoring those nutrients through an enema cures the diversion colitis. "Thus," he says, "this diet could make the colitis worse. To exclude the dietary source of short-chain fatty acids without a compelling reason just doesn't make sense to me." The SCD does change the intestinal flora, Dr. Heller adds, but there may be less extreme ways of doing the same thing. Many of his own patients do well on probiotics, antibiotics, and moderate changes in diet – treatments he feels are at least as effective as the SCD and far less intrusive into a person's lifestyle. Dr. Loftus' concern is that the low-calorie diet might create additional problems for a patient who is already underweight, something he's seen in the past. However, he notes, like most Americans today, IBD patients are increasingly overweight, so that's probably not going to be a major problem – at least not in adults. But when it comes to kids, a different picture emerges. Athos Bousvaros, M.D., Associate Director of the IBD Center at Children's Hospital in Boston, thinks the diet, while difficult to follow, is probably safe. However, there is a risk that the SCD may not provide the calories children need to grow and thrive. Calorie issues are more important than vitamin issues, he believes. You can give a child a multivitamin supplement to prevent deficiencies, but it can be challenging for a child to get enough calories on such a restrictive diet. "If you do decide to put your child on the diet," he says, "do it under the guidance of an experienced nutritionist. Decide on a reasonable time frame – say, three to four months – and don't do anything else new for the duration of that period." That way, if your child's condition improves, you can be reasonably sure that the diet is associated with that improvement. Dr. Bousvaros warns, however, that imposing such a restrictive diet on a child could be psychologically stressful. "Kids with IBD are already probably taking 15-20 pills a day," he says. "Now you're telling them they can't eat what they like? That takes a toll on a child, and it could also fuel family tensions. To avoid needless stress all around, it's important that parents and child agree before taking on the diet as a family project. And remember to do so only under medical supervision." "Most doctors will condone the diet as long as the patient continues to be monitored," adds Dr. Heller. In other words, don't start the diet and stop other medical treatment. Unfortunately, he says, that often happens: "Patients start the diet and then stop their medicine without the doctor knowing." Still, he says, the diet "may be worth a try." After all, he notes, there are much worse diets being touted in cyberspace and elsewhere. "But don't abandon your conventional treatment," he warns, "and keep in touch with your doctor." Dr. Loftus concurs. "From what I've read, it sounds like it would be awfully difficult to follow. For instance, you couldn't eat any processed foods because they all have carbs in them. But there may be something to it. It's not unreasonable for motivated patients to give it a try." Where Do We Go From Here? The SCD has gained popularity among some within the IBD community who seek a complementary approach to the treatment of their Crohn's disease or ulcerative colitis. Unfortunately, though, research studies that prove or disprove the diet's effectiveness are lacking at present. The bottom line: The decision to go on the SCD should be a topic of discussion between the patient, the physician, and the nutritionist on the team. And in the meantime, be sure to keep taking your medicine. -- Written by Debra Gordon Source: 
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 9:00 am
Throughout most of the 20th century, Crohn's disease and ulcerative colitis were seen as two diseases with some overlap, and doctors tended to lump patients into one category or the other. Now, as scientists continue to uncover the genetics and immunology behind IBD, they're discovering that what they thought were just two diseases are turning out to be more numerous. In other words, there are several types of Crohn's and several types of colitis. Immunologic Biomarkers As researchers have grown more aware of the complexity of IBD, they've stepped up the search for immunologic biomarkers -- measurable patterns or substances in the blood, stool, or elsewhere in the body that help identify the disease subtype. Each subtype, in turn, is associated with a particular set of symptoms and potential complications. One type of Crohn's disease, for example, is restricted to the small intestine and results in fistulas, and one subtype of ulcerative colitis begins in childhood. By predicting the course of the disease in different groups of people, these markers will help doctors tailor treatments to the exact type of disease a patient has. Many markers are actually antibodies, which are proteins produced by specialized immune cells after they come into contact with an antigen -- a substance that stimulates an immune response. The presence of antibodies is a sign that the immune system is reacting to a real or imagined invader. In IBD, that immune reaction becomes abnormal and excessive. New studies have linked specific biomarkers to particular subtypes of IBD, including the following: * Anti-flagellin antibody (CBir1) is found in a higher proportion of people with disease in the small intestine complicated by fistulas, perforations, and other serious problems. * Anti-saccharomyces cerevisiae antibody (ASCA) may be indicative of small-bowel Crohn's disease in children. * A blood test showing an immune response to various bacterial species may predict more rapid disease progress in children. * Calprotectin, a calcium-binding protein measured in the stool, may predict IBD relapse. * High levels of C-reactive protein (CRP) are predictive of patients' response to biologic therapies (e.g., infliximab (Remicade®). Some of these markers are clinically available. Some doctors are already using them as an adjunct for diagnosis and to measure disease activity and response to treatment. With this growing arsenal of biomarkers, physicians will be able to diagnose IBD subtypes with far greater accuracy and predict their patients' response to specific kinds of treatments. That means they may be able to bring a person's disease under control more quickly and move away from the trial-and-error approach when it comes to prescribing the best medication. Anti-OmpC -- the antibody to a specific protein on the outer membrane of a bacterium called Escherichia coli (E. coli) -- has recently been identified as another significant biomarker. New data show that anti-OmpC levels are high among members of families that have a history of both Crohn's and colitis. Researchers speculate, then, that ulcerative colitis in these "mixed" families may be a different disease from that found in colitis-only families. Genetic Markers New studies continue to illuminate the relationship between genotype and phenotype: in other words, between genetic makeup and particular disease characteristics. Most of the newer data are non-confirmatory, either ruling out the role of a genetic abnormality in IBD or calling for additional studies to confirm tentative findings. Several links between mutated genes and disease complications have been established. One, the NOD2 (also known as CARD15) gene mutation, was identified in 1998 as linked to the presence of Crohn's disease. Now, NOD2 turns out to be relevant for patients with ulcerative colitis in that it may predict chronic pouchitis -- inflammation of the internal pouch created after surgical removal of the colon. Several other genes may also be markers for disease subtypes, although scientists have not yet confirmed their overall role in increasing a person's susceptibility to IBD: * The CARD8 gene, when found together with high levels of OmpC, may predict more aggressive Crohn's disease including intestinal perforation as a possible complication. * Mutations of OCTN1 and OCTN2 are associated with Crohn's disease complicated by perianal fistulas. Mutations in the OCTN1, OCTN2, and Dlg5 genes may turn out to be linked to a patient's overall susceptibility to IBD, but none of these genes has yet been confirmed as such. Mind-Body Connection Another recent study has named three major predictors of relapse: * high levels of C-reactive protein; * fistulizing disease; and * a high biopsychosocial index number. This last factor measures a patient's perceived level of stress and the way that person deals with it. The study's authors found that people with low stress who face things directly tend to do well. For those living under high stress, however, it may pay to stick one's head in the sand. In other words, a little avoidance can be a good thing when the going gets tough. Behavior modification, therefore, may be an effective treatment strategy that can teach patients to cope better with high levels of stress. Probing Probiotics Probiotics are "good" bacteria that improve intestinal microbial balance. Found in dairy products such as yogurt and available in supplement form, probiotics are sometimes taken to alleviate antibiotic-induced diarrhea. Recently, they have become the focus of formal research, widely recognized for their potential as treatments for Crohn's and colitis. A group of researchers recently engineered a probiotic bacterium that produces IL-10, a protein that calms inflammation. Just as there are new treatments for blocking TNF-alpha, a protein that aggravates inflammation, scientists are developing other drugs capable of increasing a person's levels of IL-10 in order to calm out-of-control inflammation. Experts say the study lays the groundwork for larger-scale clinical trials of probiotic bacteria, which are being planned for the near future. Bone Marrow Transplantation Yet another novel study has recently found that when mice engineered to develop Crohn's disease underwent bone marrow transplantation from healthy mice, their disease improved markedly. The study has breathed new life into this line of investigation and earned recognition for excellence at Digestive Disease Week 2005, the largest international meeting of physicians, researchers, and academics in gastroenterology, hepatology, endoscopy, and gastrointestinal surgery, held in Chicago this past May. Up in Smoke? It is a well-known fact that smoking reduces a person's risk of developing ulcerative colitis. A recent study has isolated the carbon monoxide (CO) in cigarette smoke as a likely component in a unique anti-inflammatory pathway, or series of biochemical reactions that reduce inflammation. Researchers found that CO was indeed effective in warding off colitis in experimental mice. Although the substance is toxic in large quantities, researchers believe that understanding this pathway could help us learn why smoking, a health threat in most contexts, is a "good guy" when it comes to preventing colitis. In time, CO itself may prove to be an actual treatment for IBD, although it must be noted that nobody is advocating smoking as a treatment for IBD. Also, it has been known for years that smoking worsens Crohn's disease. Conclusion For most of us, the science behind IBD can seem like a sandstorm of possibilities. Will the real IBD culprits be found? Is it all about a few needles hiding in a huge haystack? The answers to these questions are yes and no respectively, today's researchers say. The culprits will be found, and not in some impossibly huge haystack. Scientists are homing in on the genes, microbes, proteins, and pathways governing the development of IBD. CCFA will continue to report on these many-sided efforts to solve the IBD puzzle. SOURCE 
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 9:10 am
Crohn's Disease Crohn's disease is a chronic, recurrent inflammatory disease of the intestinal tract. The intestinal tract has four major parts: (1) the esophagus, or food tube; (2) the stomach, where food is churned and digested; (3) the long, small bowel, where nutrients, calories, and vitamins are absorbed; (4) and the colon and rectum, where water is absorbed and stool is stored. The two primary sites for Crohn's disease are the ileum, which is the last portion of the small bowel (ileitis, regional enteritis), and the colon (Crohn's colitis). The condition begins as small, microscopic nests of inflammation which persist and smolder. The lining of the bowel can then become ulcerated and the bowel wall thickened. Eventually, the bowel may become narrowed or obstructed and surgery would be needed.
What Causes Crohn's Disease? There is now evidence of a genetic link as Crohn's frequently shows up in a family group. In addition, there is evidence that the normal bacteria that grow in the lower gut may, in some manner, act to promote inflammation. The body's immune system, which protects it against many different infections, is known to be a factor. There are still a number of unknowns about the cause of the disease. Fortunately, a great deal is known about the disease and especially its treatment. Who Develops Crohn's Disease? The condition occurs in both sexes and among all age groups, although it most frequently begins in young people. Jewish people are at increased risk of developing Crohn's, while African Americans are at decreased risk, which indicates the genetic link in this disease. Symptoms The symptoms of Crohn's disease depend on where in the intestinal tract the disorder appears. When the ileum (ileitis) is involved, recurrent pain may be experienced in the right lower abdomen. At times, the pain mimics acute appendicitis. When the colon is the site, diarrhea (sometimes bloody) may occur, along with fever and weight loss. Crohn's disease often affects the anal area where there may be a draining sinus tract called a fistula. When the disease is active, fatigue and lethargy appear. In children and adolescents there may be difficulty gaining or maintaining weight.
Diagnosis There is no one conclusive diagnostic test for Crohn's disease. The patient's medical history and physical exam are always helpful. Certain blood and stool tests are performed to arrive at a diagnosis. X-rays of the small intestine and colon (obtained through an upper GI series and barium enema) are usually required. In addition, a visual examination (sigmoidoscopy) of the lining of the rectum and lower bowel is usually necessary. A more thorough exam of the entire colon (colonoscopy) is often the best way of diagnosing the problem when the disease is in the colon. Course and Complications The disorder often remains quiet and easily controlled for long periods of time. Most people with Crohn's disease continue to pursue their goals in life, go to school, marry, have a family, and work with few limitations or inconveniences. Some problems, outside the bowel, can occur. Arthritis, eye and skin problems, and -- in rare instances -- chronic liver conditions may develop. As noted, the disease can occur around the anal canal. Open sores called fissures can develop, which are often painful. A fistula can also form. This is a tiny channel that burrows from the rectum to the skin around the anus. In addition, when inflammation persists in the ileum or colon, narrowing and partial obstruction may occur. Surgery is usually required to treat this problem. When Crohn's disease has been present for many years there is an increased risk of cancer. Treatment Effective medical and surgical treatment is available for Crohn's disease. It is particularly important to maintain good nutrition and health with a balanced diet, adequate exercise, and a positive, upbeat attitude. Five types of medications are available to treat this disease: Cortisone or Steroids -- These powerful drugs provide highly effective results. A large dose is often used initially to bring the disorder under quick control when the disease is severe. The drug is then tapered to a low maintenance dose, perhaps taken just every other day. Hopefully the drug may eventually be stopped altogether. This medicine is administered by pill or enema. Prednisone is a common generic name. Anti-inflammation drugs -- sulfasalazine (Azulfidine), Dipentum, Asacol, Rowasa, and Pentasa belong to a group of drugs called the 5-aminosalicylates. These drugs are most useful in maintaining a remission, once the disease is brought under control. They are most effective when the disease is present in the colon. These are available in oral and enema preparations. Immune System Suppressors -- These medications suppress the body's immune system, which appears to be overly active and somehow aggravates the disease. The names of two of these commonly used medications are azathioprine (trade name: Imuran) and 6 MP (trade name: Purinethol). These drugs are particularly useful for long-term care. There are other potent immune-suppressing drugs that may be used in difficult cases. Infliximab (trade name: Remicade) -- This drug is the first of a group of medications that blocks the body's inflammation response. It is given by intravenous infusion over several hours. These blocking antibody drugs are proving to be very effective in many patients with severe disease. Antibiotics -- Since there is frequently a bacterial infection along with Crohn's disease, antibiotics are often used to treat this problem. Two that are commonly used are ciprofloxacin (trade name: Cipro) and metronidazole (trade name: Flagyl). Diet and Emotions There are no foods known to actually injure the bowel. However, during an acute phase of the disease, bulky foods, milk, and milk products may increase diarrhea and cramping. Generally, the patient is advised to eat a well-balanced diet, with adequate protein and calories. A multivitamin and iron supplement may be recommended by the physician. Stress, anxiety, and extreme emotions may aggravate symptoms of the disorder, but are not believed to cause it or make it worse. Any chronic disease can produce a serious emotional reaction, which can usually be handled through discussion with the physician. Surgery Surgery is commonly needed at some time during the course of Crohn's disease. It may involve removing a portion of diseased bowel, or simply the draining of an abscess or fistula. In all cases, the guiding principle is to perform the least amount of surgery necessary to correct the problem. Surgery does not cure Crohn's disease. Summary Most people with Crohn's disease lead active lives with few restrictions. Although there is no known cure for the disorder, it can be managed with present treatments. For a few patients, the course of the disease can be more difficult and complicated, requiring extensive testing and therapy. Surgery sometimes is required. In all cases, follow-up care is essential to treat the disease and prevent or deal with complications that may arise. Source: 
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 9:16 am
DDW Update: Clinical Research Highlights Research presented at Digestive Disease Week® 2005 spotlighted the promise of several biologic therapies for IBD, along with new ways to maximize the effectiveness of currently available drugs. Held every year in May, DDW is the largest international gathering of physicians, researchers, and academics in gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. It's a vast forum where the most up-to-date IBD research results are disseminated and discussed among leaders in the field. The New Biologics Biologic drugs target particular parts of the immune response in order to control inflammation. In this respect, they differ from traditional immunosuppressive drugs, which suppress the immune system generally. Biologics were prominently featured in dozens of sessions at DDW. In recent clinical trials, three biologic agents have proven effective in easing symptoms and increasing rates of remission and response in IBD patients: infliximab (Remicade®), adalimumab (Humira®), and Alequel™ (a mixture of proteins extracted from the colon of the individual patient). Infliximab (Remicade®) Results from the ACT I and ACT II Trials show that infliximab may be a promising treatment for ulcerative colitis. Approved for Crohn's disease in1998, infliximab now appears to be effective in easing the symptoms of colitis, achieving and maintaining remission, promoting healing, and reducing the need for corticosteroid therapy. The drug was generally found to be safe and well tolerated. Infliximab blocks the action of tumor necrosis factor-alpha (TNF), a specialized protein that promotes inflammation in the intestines. "Given that anti-TNF agents like infliximab appear to be effective in treating Crohn's disease, it made sense to explore its use in ulcerative colitis as well," said Dr. William Sandborn of the Mayo Clinic and lead investigator of the ACT II trial. "I am pleased to say that the ACT I and ACT II results suggest that infliximab is an effective and well-tolerated treatment for ulcerative colitis." Centocor, the company that manufactures infliximab, has filed for FDA approval of the drug for ulcerative colitis, receiving "fast-track" designation from the agency. In this way, the FDA gives priority to promising drugs designed to treat serious diseases and address an unmet medical need. To stay abreast of these and other relevant issues, please visit http://www.livingwithuc.com/, an online educational resource built by patients for patients and sponsored by Centocor. Adalimumab (Humira®) Researchers from the Mayo Clinic have found that patients with moderate to severely active Crohn's disease responded well to treatment with adalimumab. Nearly four out of five Crohn's patients showed improvement, and one in three experienced clinical remission after 24 weeks of therapy. Adalimumab is currently approved as a treatment for rheumatoid arthritis, another member of the immune-mediated group of diseases. The Mayo study, called CLASSIC II (Clinical assessment of Adalimumab Safety and efficacy Studied as an Induction therapy in Crohn's), was designed to evaluate the long-term efficacy and safety of adalimumab, an anti-TNF biologic therapy, in patients with moderate-to-severe disease. Side effects in the study were mild to moderate in severity. Dr. Sandborn, a leader in the field of IBD, sees the study's results as especially promising, because "patients not only showed clinically meaningful improvement during the six-month study, but their response continued to improve over time." Alequel™ Alequel, a mixture of colon-extracted proteins derived from the same person who receives the drug as a treatment, is an experimental therapy for Crohn's disease. Like gene therapy, autologous (self-derived) proteins represent a patient-tailored approach to treating disease. Personalized treatments are widely seen as the wave of the future, but, according to researchers at Hadassah Hebrew University Medical Center and Enzo Therapeutics, that future is fast approaching. Thirty-one patients with moderate-to-severe Crohn's disease were enrolled in a 27-week trial. Clinical remission rates observed during the trial were 58% for patients receiving Alequel, compared to 29% for those on placebo. A clinical response – a measurable improvement in disease signs and symptoms – was seen in 67% of the participants receiving the drug as against 29% of those on placebo. Based on these results, larger confirmatory trials are being pursued, according to one of the study investigators. Other Findings Mesalamine (Asacol®) Two University of Chicago-sponsored studies have found that for patients with moderately active ulcerative colitis, starting treatment with twice the standard dose of mesalamine – 4.8 grams a day rather than 2.4 grams – was more effective with no increase in side effects. These findings could change the way patients with moderately active ulcerative colitis are treated, said lead investigator Stephen Hanauer, M.D., Professor of Medicine and Clinical Pharmacology at the University of Chicago Pritzker School of Medicine. "Moderately active ulcerative colitis is a distinct disease classification that warrants aggressive treatment," Hanauer said. "Most patients suffer from moderately active disease, but very few receive 4.8 grams per day. Some are switched from standard dose mesalamine to other therapies before they are offered a higher dose." If approved, the higher dose will address an important need for patients with moderately active ulcerative colitis, researchers say. Postscript Sargramostim Shortly after DDW, the New England Journal of Medicine (NEJM) published data from a Phase II multi-center clinical trial focusing on sargramostim (Leukine®, Berlex, Inc.) for the treatment of moderately to severely active Crohn's disease. The study showed that patients receiving the drug had significantly greater response and remission rates than those given placebo. Additionally, those on sargramostim had improved quality-of-life scores. The study data are especially encouraging, researchers believe, as they show the drug's potential as an alternative treatment option that does not involve suppressing the immune system. It is widely believed that well before chronic inflammation sets in, Crohn's disease begins with a breakdown in the intestinal barrier, composed of several layers of cells that protect the gastrointestinal tract. Sargramostim might be capable of "fixing" the problem by helping to improve how cells function within the intestinal barrier. Source: 
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 10:10 am
This is not the original article I read, but it is an excellent one, published in 2001: Worms! (My title) PatientCommunity.com: Perhaps we should provide some background and discuss the "hygiene hypothesis." Dr. Weinstock: The hygiene hypothesis argues that increased hygiene and a lack of exposure to microorganisms of various types have affected our immune systems, resulting in the development of certain diseases. This idea has been embraced in Europe and in England, but has been neglected in the United States. There are certainly many opinions on it, but very little scientific data yet to lend validity. When you look at inflammatory bowel disease, multiple sclerosis, perhaps several other diseases…in this interview we'll just focus on Crohn's disease…one of the striking observations is that people are pretty sure these diseases have emerged over the last seventy years. Our ability to accurately diagnose Crohn's disease has improved steadily over the years and doctors are much more aware of the disease today than ever before, so some of this increase in disease frequency could be related to improved healthcare. On the other hand, there are clear data suggesting that Crohn's disease was, at one time, truly rare and is now becoming common… In the 1930's, Crohn's disease was first recognized in New York City, in Jewish populations, and was then assumed to be a Jewish disease - something genetically related to European Jewish origins. A few years later, cases of Crohn's disease were recognized in whites that were non-Jewish. People soon said, "Well, it can occur in whites - Jews much more commonly than non-Jews." Next it was recognized that there was a north-south gradient. That is, we see it in the north, but not in the south, of the United States. In Europe, the disease also showed a north-south gradient - common in the north, rare in the south. It was common in Scandinavia and England, but rare in Spain and Italy. These gradients seem to be disappearing. It was also said that African Americans did not get IBD, but by the 1960's/late 1970's inflammatory bowel disease in African Americans became more common. In Israel, IBD is common in Jewish children, but rare or unheard of in Arab children. The frequency of IBD in Israeli Jews is much less than that of European or US Jews. So, even though many of them have the same genetic background, they are not approaching the rate of disease that is seen in North America. There was a recent paper that showed the frequency of inflammatory bowel disease in Manitoba - a province in the middle of Canada that is mostly non-Jewish - is now about one in two hundred fifty people. Once this was a disease that people spoke of in terms of one in fifty thousand, then one in ten thousand, then one in five thousand, and now one in two hundred fifty. Crohn's disease is a disease that is common, not rare. These diseases were essentially unrecognized by very smart doctors up until the 1930's. Then, suddenly, they appear in one population after another, and then around the world in certain situations. Why? The common thing people do when they get sick is to look for something they were exposed to recently. For instance, if you were nauseous late in the day, you might say this was caused by something you ate at lunch. If you felt feverish one night, you might recall having been coughed on several days earlier. Naturally we look to something we did, something we were exposed to. The common thinking had been, up until recently, that IBD is a result of exposure to something; you have a genetic basis for the disease - some of us are prone to getting it - and then either food or food coloring, vaccination, viruses, bacteria, etc. set it off. However, many people have tried to find causes, and nothing has been shown to be associated with inflammatory bowel disease i.e. no particular environmental factor. A few years back our group decided to take a slightly different approach: We said, "let's assume that the problem is not related to exposure to something; rather, due to a lack of exposure to something. What if we are losing something? Is that possible?" The minute we turned the argument around it was as if a light switch turned on. We realized we are losing lots of things. When you go from an agricultural environment (living close to the soil with outhouses), to living in buildings (where the air is filtered, and the water is sterile, and the food is clean, so clean it's almost sterile) there are a lot of things to which a person is not exposed. Some of the things we are not being exposed to are organisms that we traditionally have been raised with. Our stool is roughly fifty percent bacteria - we are teeming with living organisms, both on our skin and within us. These organisms help digest our food, they tone our immune systems, etc. If our gastrointestinal tracts were completely sterile - with no bacteria - we would probably die. All mammals have evolved to have these organisms within them. One interesting group of organisms that we have been losing are a class of parasites we call helminthes (worms). Traditional thought with respect to these parasites has been: they're bad, get rid of them - all the textbooks say this. However, when you start looking at the public health data you see how common they were and that they have very little disease potential. It is not that they cause illness - people simply are afraid of worms. If you look around the world today, there is ample evidence that most children living in Mexico, South America, and Africa, have intestinal worms - it is part of their intestinal fauna. These worms do not cause any harm - much like the bacteria in your intestinal tract (E. Coli, Bacteroides, etc.) What makes the worm an important candidate is that they do something very unique to our immune system: they dampen the TH1 (T helper cell 1) response. The immune system has a variety of cells that react when bacteria or viruses get into our bloodstream, and one important cell is the T-cell. There are various types, classified by the cytokines (type of molecules) they release. One pattern of molecules that comes out of T-cells is called the TH1 pattern - molecules that tend to activate macrophages (cells in our body that chew up, swallow, and kill various bacteria). Theses include interferon gamma (IFN-g), and tumor necrosis factor alpha (TNF-a). Most bacteria, and viruses stimulate a TH1 response. What worms do is dampen this repsonse, and enhance another pathway, called TH2 (T helper cell 2) that involves eosinophils (a type of immune cell), different types of antibodies, and different types of molecules. Inflammatory bowel disease is predominantly a TH1 response. What we hypothesized is that we are no longer being exposed to worms that dampen our TH1 response and stimulate TH2 - this is a very unique property of worms. When we lost our worms, we may have eliminated one of the few environmental factors that dampen TH1 and prevent inflammatory bowel disease. For the first time in our evolutionary history children were being raised without worm exposure beginning in the early 1900s. For instance, Jewish children who lived in New York City in the 1930s wore shoes, traveled on cement sidewalks, did not eat the contaminated pork and therefore did not acquire worms like most other Americans. They were the first to develop IBD. As people became cleaner and cleaner in the North, where the climate is colder and it is easier to avoid these organisms, IBD spread. Then, as the southern part of the United States began cleaning up, people there started getting the disease. In South Korea and Japan there is now an epidemic of IBD. Whites in South Africa are getting it. Israeli Jews but not Israeli Arabs are getting it, etc., etc. If you simply follow IBD around the world, wherever there is de-worming you are seeing a rapid rise in IBD frequency. It occurred to us that worms may be a critical environmental factor - that the loss of this natural dampening influence (of worms) has resulted in many of us becoming hyper-reactive. When we get exposed to bacteria and viruses, we tend to over-respond, and some of the protective immune systems of the gut mucosa that prevent uncontrolled inflammation start breaking down. To test our hypothesis we used several animal models of inflammatory bowel disease, employing intestinal worms to see if they might offer some protection. To our great pleasure, this had a very dramatic effect in mouse models - there was clear protection induced by intestinal worms and worm products. Results were so encouraging that we decided to see if we could get permission to do some limited studies in humans. The first human study was designed as a safety study - we took only a handful of patients, got permission to give them a single dose of a particular agent to see if it had any negative effect at all. We believed this treatment would be something that would be considered relatively safe, and if we could show that it did no harm then that would be a justification for moving on to a subsequent study where we could be more aggressive. We originally chose to use Trichuris suis, known as the pig whipworm, and similar to the human whipworm, Trichuris trichiura. The fact that T. suis is genetically similar to the human worm made it an attractive agent. Why not use the human worm? Well, you cannot grow these things in vitro (in a test tube), so you have to work with an animal that is colonized with the worm to get eggs. This means that you would need humans that were shedding eggs. However, those humans would likely be living in unclean situations and might be carrying hepatitis, or other diseases. This raises safety issues. Secondly, human agents will tend to stay in a person a long time. If you use Trichuris trichiura, it could live inside you for up to two years. The question then is do you want to use an agent that is likely to stick around if you do not like the consequences? Third, as it is a human agent, it has a higher potential for being spread to other humans. This raises issues of confinement and safety within a population - we only want to colonize the sick person, not their neighbors. The pig worm has many advantages: 1) we can produce them in pathogen-free pigs under ultra-clean conditions. The worms are then taken from the pigs - which we cannot do with humans - and then grown in a test tube. Those worms then produce eggs - so, we are not working with pig stool, but simply pure eggs. And, these can then be processed to render them bacteria and virus free. The eggs are very durable - they are extremely stable, and can sit in a refrigerator for a year. 2) The second advantage of the Trichuris is that it is essentially a luminal agent - it lives in the gastrointestinal tract, and does not get into the blood stream, the liver, or any other organs. It tends to colonize the ileum and colon. 3) The third advantage is that this worm does not stay in humans for long - we are not its natural host, and it is eliminated within a few weeks. These worms never reach adulthood, so they never produce eggs - no eggs to be spread into the environment, to other people. Even if they did produce eggs, these could not be spread to people around you and cause infection by hand and mouth as they require an incubation period in soil. T. suis must sit in soil for eight weeks until they mature. The only way you can get the organism is if someone colonized were to defecate in soil and then another person played in that soil. There are several other advantages: 1) We have a drug to get rid of the worm - if it seems to be doing something wrong you take one dose of this agent and you are worm-free. 2) There are no known diseases associated with exposure to these organisms. The natural host of the worm is the pig. Around the United States, there are many pig herds that carry this organism, so farmers have been exposed to these forever. Particularly years ago, most of these herds had this worm. Pigs produce a lot of manure. Farmers shovel that manure. Their hands and boots get dirty - there are literally millions of eggs in the soil around the barn. Farmers have been exposed to this continually in some areas. So, the safety level seemed to be extremely high. And that is why our human investigation committee gave us permission to do this study. The first six patients we treated received a single dose. We staggered the initial dosing for each of the patients - we wanted to watch them singly, over time. Nothing happened for a couple of weeks, and thereafter five of the six patients went into remission. And, by remission, I mean they felt symptom free. These remissions lasted two months to five months, after which the patient gradually relapsed. We then received permission to do some repeat dosing and the patients responded. Ultimately, we received permission to do some maintenance dosing on a regular basis, and we found that if we gave the agent once every three weeks we could sustain remission. A handful of patients have been maintained now out to a year and a half, and have done well. And adverse effects? With a small number of patients, and a few hundred doses, we have had no negative effects that we can attribute to the agent. That is far from saying that this is totally safe. We have treated people beyond a year and a half - almost two years - and we have seen no ill effects of chronic use: no liver abnormalities, no nausea, no abdominal pain, no reactions. When you start treating hundreds or thousands of patients…sooner or later there will be something. Right now there isn't. What leads me to believe that it is going to be very safe is the data on farmers. Some farmers are walking through the soil, swallowing eggs every day, with no illness known to be related to this organism. Thousands of farmers have been exposed to the agent with no disease. Odds are it will have a very high safety profile, particularly once we learn more about it. As with all experiments it takes time to optimize, understand, know how to use, determine frequency of use - these are all unknown at present. We are walking slowly in the dark, trying not to make any mistakes. I suspect we will have a long journey of improvement, which is good. If we can get this result with one blind shot in the dark, what happens when we finally get the opportunity and the resources to optimize it? The potential will be even better. For the initial patients, were the results dramatic? The first five of the six, went into complete remission - no diarrhea, no abdominal pain, no joint problems. These are people who were chronically ill for years. The one patient who did not go into remission got somewhat better. That same patient re-entered into the open label, maintenance phase, with twenty-five stools per day (all diarrhea), arthralgias, and a fistula. After three doses (within a couple of months) this patient was in complete remission, gained weight, had no signs of arthralgias, and is now running five miles a day. So, where do I sign up? I know this sounds incredible. However, these patients went from chronic illness to complete sustained remission. What is latest status of the study? We closed the open label study - as we understood how to use the agent, we have an impression that it does work, and we have some long-term data suggesting its not just a one shot affair. We have started several double-blind projects where neither the investigator nor the patient knows what they are receiving. This includes a protocol for Crohn's disease, a protocol for ulcerative colitis, and a pediatric protocol. Are any patients excluded? With the first patients we were very strict: we only took patients who were refractory patients, who did not respond to standard therapy, as we were concerned. We did not want to choose someone who might otherwise benefit from other treatments. In this trial, we will take all patients within the right age group, and with defined disease. For Crohn's disease the only exclusion might be history of extensive bowel resection. We also want patients mostly from our geographical area, as the biological agent is not available all over the world, only in Iowa. This is only being done in Iowa? Yes, at the current time. To set up study centers around the country is a very expensive and difficult process. We are not a biotech company. We're not Merck - we cannot afford to spend millions of dollars trying to set up study centers to treat one patient here and one there. So, we would prefer to have patients within easy reach of us, who can come here to be dosed, be examined, and then go home. We would occasionally consider a patient further away, but it would have to be a very exceptional circumstance that would be easy to manage - we do not want to get into the difficulty of distances. We are in the process now of exploring setting up a study center in Europe - that is currently in negotiations. And, we are considering the possibility of developing a study center in Canada as well. How many patients are currently in this double-blind study? We are trying to solicit appropriate patients for two studies - we need roughly 64 patients for the Crohn's disease study, and 50 to 60 for the ulcerative colitis study. Has the study started? Yes. We assess patients as they come along. An appropriate candidate would be someone who is neither too sick, nor too well, and we certainly want people who are committed to completing the study. Individual patients can enter at any time. The study is designed such that patients get either the active agent or placebo for twelve weeks. At the end of that period, all patients switch to the other agent. So, everybody gets the agent sooner or later. Most patients do not wish to go untreated in a study - this allows everybody to get the agent, but no one will know whether they received the placebo or active agent for the first twelve weeks, or the second twelve weeks. At the end of the twenty-four week interval, those who benefited from the agent will be permitted to continue using it indefinitely. The National Institutes of Health (NIH), Thomas Irwin Memorial Fund, and the Crohn's and Colitis Foundation of America (CCFA), funded the first study. Who is funding this latest study? These clinical studies have funding from the Crohn's and Colitis Foundation of America, some funding from our local university, and some from private donors. If people would like to help contribute to the study it would be greatly appreciated - this is not a commercial operation; there are no investors, and no money from any companies. Do you have information on how one can make a donation? If people would like to email me I can refer them to the appropriate party: Click Here To Email Dr. Weinstock Fax: (319) 353-6399 Phone: (319) 356-2132 What is it about T. suis that is operative in evoking a TH2 response? Antigens? Secretory proteins? I know culturally some people may be averse to ingesting worms - is there work being done to determine this? Looking into the crystal ball - research will go in two directions. We need to perfect the biological agent. People are not swallowing wiggly little worms. What they are swallowing is microscopic eggs. We give this to the patient in Gatorade - a few ounces with something in it, which they cannot see. There are no side effects that have been reported to date - no diarrhea, no cramps, nothing. People drink a glass of milk that contains more living organisms than there are eggs in one of our Gatorade doses. People do not think twice about getting a flu shot, or immunizing their children against disease, and much of the time we are putting live organisms into the body this way. It has become accepted as an appropriate thing to do. So, one possibility is that the biological agents can be put in a gel capsule, kept in a refrigerator, and taken once every two or three weeks - what ever we ultimately determine to be the correct dosage. All with no side effects, and no problems - that would be a dream. It could be as simple as that. Also, it is possible this is not the ultimate organism - we simply tried something, gave it to people, and it seemed to work. Perhaps we may be able to bioengineer these things and make them better. Also, what about children? Perhaps children need to be exposed to these organisms, similar to vaccinations. Perhaps intestinal colonization when children are three, four, or five may be healthy for them, and lessen the risk of future development of immunological diseases. In addition, these organisms probably do produce factors - not necessarily antigens or proteins - that do modulate the immune system. This is an area that is very poorly explored. We are undergoing some early investigations to try to identify potential drugs that could be produced by these organisms that could be taken as pills, IV infusion, etc. to modulate or effect immune responses. Both directions need to be explored. Both need to be developed. My prediction is that both will have a role. Some may need biological agents, some may need pills - depending upon what you wish to accomplish. Now, I have studied helminthes for twenty-five years. They stimulate the host to produce certain molecules such as transforming growth factor beta (TGF-b), interleukin-10 (IL-10), but they do a lot more than that. How they work is still a mystery, how they trigger the TH2 response is a mystery. You have to remember that these worms need us to survive - we are their homes. As such, we have co-evolved throughout the existence of humans and worms. As our immune systems have evolved, they have evolved. And, they have been in intimate contact with our immune systems throughout our evolution. They probably know our immune systems better than we do. They know how to play our immune systems, they know how it works, and they probably have a variety of ways of affecting our immune responses so that they can survive appropriately within our bodies. They probably have various tricks for affecting various immune regulatory pathways, some of which we have not even discovered. The immune system is very complicated, with many overlapping molecules that tend to do the same thing. If you block one molecule, it may be important, but others will compensate. For instance, if you use anti-IL-10 and it does not work it may be that the researcher did not use it properly, or they did not use enough of it, or some other molecule takes over. This happens commonly in the immune system. Occasionally we find an Achilles heel, where you do one thing and it produces a dramatic effect. However, evolution has dictated that such Achilles heels must be very rare. Otherwise, some smart bug would have come along a million years ago, a hundred thousand years ago, and wiped us all out. By some genetic mutation it would take advantage of that little hole in our defense and suddenly we would not be able to respond, and goodbye human race. That is one of the reasons we evolved to have such complexity. Selection pressure has dictated that our immune systems must have redundancy, and various ways of dealing with certain issues. When the wiring goes crazy, when things get out of control, very often the immune system is easily deviated back - without the need for some sledgehammer. It does deviate back in IBD, and people with Crohn's disease and ulcerative colitis are not always symptomatic - disease does spontaneously remit. That tells us something: that the immune system is capable of shutting down the process. We are just not smart enough yet to know how that works. If we did, then we should be able to induce remission. Do you think it matters when one becomes infected or takes the organism? Is there a training of the immune system when one is young? I suspect that our immune systems learn as we learn. We learn to read, write, walk. Our exposures to antigens in the environment develop our immune system. T-cells and other cells remember all the things you have been exposed to since childhood. Therefore, our immune systems are not all the same - they develop and change as we get older. What we are exposed to as a child could ultimately affect how our immune system develops. If we are not being exposed to the right things, it could lead to the development of immunological diseases. That has not been proven, but we do see this in mice. If mice are kept in certain environments, they can be more prone to inflammatory bowel disease, less prone, healthier, less healthy, etc. We have seen this for years in mice, and have not paid attention to it. And, people are doing it to themselves. Perhaps we are not raising our children quite right - this lack of environmental exposure is leading to the emergence of immunological diseases. When we moved into "clean" environments, life expectancy increased. People used to die from various infectious diseases - hepatitis, salmonella, cholera, etc. Overall, cleaning up our environment has been good for us. However, when we clean up we just throw out everything. I suspect that to rid ourselves of the five, ten, fifty organisms that were not good for us, we also threw out many other organisms that were important for us. Where I think research is needed, is to try to understand how humans interact with their environment, and to remember that we evolved in an environment very different from what we live in today. Our bodies are adapting to situations that they were not geared to adapt to. We may need to re-institute some exposures to bring things back into balance - I think that is the most important message. I believe inflammatory bowel disease is seventy percent environment, and thirty percent genetic. Not a particular gene - I do not think we are going to find a single gene for either Crohn's disease or ulcerative colitis. I think we have many genes that lead us to be hyper-reactive, and some more so than others. Uniformly, over thousands of years there have been factors that dampen this reactivity, and we have removed these factors. Now these genes start manifesting themselves, and that's what leads to IBD. Environment is the key to understanding inflammatory bowel disease. I think it might be the key to understanding multiple sclerosis. What are we doing to our environment that is causing these diseases to move from 1 in 100,000 to 1 in 10,000 to 1 in 250? To your knowledge is anyone working on a similar application for multiple sclerosis (MS)? Are you? Yes, we have a project looking at early stages of MS. There are also a number of groups that have started addressing aspects of this issue. I am starting to see papers and discussions, and I suspect there will be a lot more on this issue in the next couple of years. And for those who are infected with various helminthes in the underdeveloped world…big problem, no problem? We know that this is not a disease as epidemiological data in the United States showed in the 1930's twenty-five percent of the American population had Trichanella, which causes trichinosis. But, trichinosis is a very rare disease. School surveys that had been performed, where parents were asked to bring in a stool sample from their child to be examined for eggs, showed that seventy percent of the children had eggs in their stool. Now those kids were healthy. We know that they had helminthes, and none of them were having diarrhea, cramps, abdominal pain - it was just there. Immigrant children who come into the United States from Southeast Asia and Mexico - legal immigrants - when you check their stool one year after entrance roughly seventy percent are positive for worms. These are healthy kids. We know that the pathogenic potential of many of the intestinal helminthes is pretty low. Some worms do cause illness. Occasionally there are people who do get sick with worms. Approximately a billion people are colonized with Ascaris lumbricoides, which is a worm that lives in the GI tract and is about a foot long. There are few diseases associated with that worm, even though it is so long. People have E. coli (bacteria), and some get abdominal abscesses from it. You can get diverticular disease, inflammation of the intestine, and abcess of the liver, all from your intestinal bacteria. There are going to be occasional cases where people get in trouble with their intestinal organisms, but for the most part they are good for us and we need them. The benefit of having intestinal organisms certainly outweighs the risk. Twenty-five percent of the American population has allergic rhinitis (a disorder infrequent in Mexico, and in South America), one in every two hundred fifty people are getting inflammatory bowel disease, and multiple sclerosis is on the rise - obviously the risk from these organisms is far less than the risk of these diseases. We have to find the right balance. What are your thoughts on probiotics? Probiotics may be doing something that the worms are doing, but they may only be doing part of it. I believe worms are the ultimate - they go all the way. That is the secret. Are you still doing research on somatostatin and Substance P? Absolutely. We have a very extensive basic science program in this area. At least in mice, we showed that these molecules are extremely important regulators of the TH1 response. When do you anticipate we will hear some of the results of your latest trial? The next major advance will be in about a year. We have to finish the study. We do know that there are patients going into remission, but we do not know if they are getting the treatment or placebo. When the study is done, we will look at the data, and determine whether the results were spectacular, good, or poor - that is a double blind. The open label suggests it will work, and we know that the probability of it not working at all is pretty slim. Whether the results will be magnificent, a major breakthrough, or a pretty good adjuvant we'll have to see as time goes on. Thank you Dr. Weinstock for sharing your thoughts on helminthic therapy for inflammatory bowel disease. Interview posted: January 10, 2001 Source: 
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Herckleperckle
Member
11-20-2003
| Friday, August 12, 2005 - 10:32 am
Before and after treatment with pig worm!
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Metoo
Member
02-22-2005
| Wednesday, October 26, 2005 - 12:35 pm
(bumping up...don't want to lose this!) Hi HP, Zachsmom, Watching2, Luvmyjrt, Landi...how's everybody doing? Anyone else dealing with Crohn's??
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Auntiemike
Member
09-17-2001
| Tuesday, December 20, 2005 - 12:50 pm
Well, I'm reading up on it as I'm trying to self-diagnose my extreme pain in lower abdominal area right above groin, on right hand side. I've had gastro-intestinal bypass so my body does not always absorb what it needs. I also have severe hemorhoids....I keep putting off a visit regarding those! So, I now have an appointment with my primary care doctor this afternoon to check out the pain. Who knows what he will say/diagnose? Will keep you posted.
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Herckleperckle
Member
11-20-2003
| Monday, January 16, 2006 - 8:14 pm
Auntie Mike, so what's the story, hon? Were you referred to a gastro doc for further testing?
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