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  1. The following report comes to us from The Sprue-Nik Press, which is published by the Tri-County Celiac Sprue Support Group, a chapter of CSA/USA, Inc. serving southeastern Michigan (Volume 7, Number 6, September 1998). The degree of mucosal damage varies from one celiac patient to another. Also, the amount of the small intestine that is affected also varies, with the damage usually progressing from the beginning of the small intestine and then moving downward toward the end of the small intestine. This may explain the variable symptoms in different patients. For example, when a significant portion of the small intestine is involved, diarrhea, malabsorption, and weight loss result. When damage is isolated to only the top portion of the small intestine, the only affect may be iron deficiency. (Incidentally, when iron deficiency is not corrected by iron supplements, it is highly likely that celiac disease is the cause of the deficiency.) Gluten in a celiacs diet causes the immune system to produce gliadin antibodies in the intestine. Some of these leak into the bloodstream where they can be detected in blood tests. These blood tests are useful for screening for celiac disease, though a small intestinal biopsy remains the gold standard for diagnosing celiac disease (celiac disease). There are few diseases for which diet and nutritional issues are more important than for celiac disease. At this time, the only known treatment of celiac disease is the removal of wheat, barley, rye, and oats from the celiacs diet. On the surface this sounds simple, but complete removal of dietary gluten can be very difficult. Gluten-containing grains are ubiquitous in the Western diet. Also, grain-derived food additives such as partially hydrolyzed vegetable protein [and modified food starch] are widely used in processed foods and oral medications. Content labels are often vague or incomplete regarding these additives. What further complicates matters is a lack of significant experience on the part of physicians and dietitians in the dietary treatment of celiac disease. This is mainly because there are so few celiac patients for anyone practitioner. Therefore the best sources of dietary information for a new patient are other knowledgeable, more experienced celiacs. It is very important that the diet be followed with full and strict compliance. Celiacs, especially if theyve had active celiac disease for a longtime, are at higher than normal risk for GI malignancies.(Fortunately, compliance to a good gluten-free diet returns the risk of malignancy and life expectancy to that of the general population.)Another complication of long-term untreated celiac disease is bone loss, which maybe irreversible in older patients. When a large portion of the small intestine is affected by active celiac disease, the result can be a generalized malabsorption problem, resulting in deficiencies of water- and fat-soluble vitamins and minerals. Folic acid deficiency is particularly common in celiac disease because, like iron, it is absorbed in the upper small intestine [where the highest concentration of celiac-related damage generally occurs]. Folic acid is necessary for DNA replication, which occurs in cell turnover. So a deficiency of folic acid can impair the regenerative ability of the small intestine. Vitamin B12, also essential to DNA synthesis, is not malabsorbed as commonly as folic acid. Magnesium and calcium deficiency are also common in active celiac disease, because of decreased intestinal absorption AND because these minerals tend to bind with malabsorbed fat which passes through the system. It is particularly important for doctors to assess the magnesium status of celiacs, because without correction of a magnesium deficiency, low levels of calcium and potassium in the blood cannot usually be corrected with supplements. In severe cases, magnesium supplementation should be done intravenously because of the tendency of oral magnesium to cause diarrhea. Supplemental calcium generally should be provided to celiacs, possibly with vitamin D, to help restore tissue and bone calcium levels to normal. The exact dose of calcium is not known. Dr. Fine usually recommends 1500-2000 mg of elemental calcium per day, divided into two doses, for several years and sometimes indefinitely. [4], [5], [6] Zinc is another mineral that often becomes depleted in patients with chronic malabsorption. Zinc supplementation (usually the RDA via multi-vitamin and mineral supplements) helps avoid skin rashes and restores normal taste. Up to 20% of celiacs will continue to experience loose or watery stools even after going on a gluten-free diet. Sometimes this is due to inadvertent gluten in the diet, but a recent study at Dr. Fines medical center showed that in these cases other diseases epidemiologically associated with celiac disease are present.[7] These include microscopic colitis, exocrine pancreatic insufficiency, lactose intolerance, selective IgA deficiency, hypo- or hyperthyroidism, and Type I diabetes mellitus. When diarrhea continues after beginning a gluten-free diet, a search for these associated diseases or others should be undertaken and treated if found. The use of cortico steroids has been advocated in celiacs when the response to the gluten-free diet is sluggish or absent. This is necessary more often in older than in younger patients. However, pancreatic enzyme supplements (prescribed by a doctor) may be needed to help digestion and resolve ongoing malabsorption in some patients. The endomysial antibody blood test is highly accurate and specific for detecting celiac disease. However, the current method of detecting these antibodies involves an operator looking through a microscope and observing the antibody binding on monkey esophagus or human umbilical cord tissue substrates. The correct interpretation of results is highly dependent on the skill and experience of the technician interpreting the fluorescence pattern through the microscope. Moreover, determination of the amount of antibody present relies upon repeat examinations following dilutions of the blood serum, with the last positive test being reported as a titer. A new discovery was reported by a research group in Germany.[8] The antigen substrate of the endomysial antibodies has been identified. This allows the development of a new test that can detect and measure serum endomysial antibodies in one, chemically-based test run [thus greatly reducing the potential for human error and significantly reducing the time needed for each test--ed.] These new tests should be available for clinical use shortly. In a recent study, Dr. Fine found that the frequency of positive stool blood tests was greater in patients with total villous atrophy relative to partial villous atrophy, and all tests were negative in treated patients without villous atrophy.[9] This suggests that fecal occult blood may be a non-invasive and inexpensive method of following the response of the damaged intestine to treatment. Also, it should be noted that the high frequency of positive tests due to villous atrophy will decrease the accuracy of the tests when used for cancer screening in this same patient population (which is how these tests are normally used by health care providers). There have been two recent reports touting the lack of deleterious effects when 50 grams of oats per day are added to the diet of celiac patients. Although this finding is exciting for celiacs, both studies possess certain limitations. In the first study, published by a Finnish group, the exclusion criteria for symptoms and histopathology were somewhat strict, so that patients with more mild forms of celiac disease seemingly were selected for study. And though no damage to duodenal histology occurred after one year of oats consumption, no physiologic or immunologic parameters of disease activity were measured. Furthermore, several patients in the treatment group dropped out of the study for reasons not mentioned in the article.[10] The second and more recent study involved only 10 patients, studied for twelve weeks. The favorable results of this study must be interpreted with caution because of the small sample size and short study period.[11] Even the one-year treatment period in the Finnish study may be too short to observe a harmful effect, as it is known that small intestinal damage sometimes will not occur for several years following there introduction of gluten to a treated celiac. At the worst, an increase in the incidence of malignancy may result from chronic ingestion of oats, an effect that could take decades to manifest. Therefore, this issue will require further study before oats can be recommended for the celiac diet. 3. From the September 1998 newsletter of the Houston Celiac-Sprue Support Group, a chapter of CSA/USA, Inc. 4. Ciacci C, Maurelli L, et el, Effects of dietary treatment on bone mineral density in adults with celiac disease; factors predicting response, Am J Gastroenterol, 1997; 92 (6): 992-996. 5. Mautalen C, Gonzalez D, et al, Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac patients, Am J Gastroenterol, 1997; 2 (2):313-318. 6. Corazza gluten-free, Di Sario A, et al, Influence of pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease, Bone, 1996; 18 (6):525-530. 7. Fine, KD, Meyer RL, Lee EL, The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet, Gastroenterol, 1997; 112 (6):1830-1838. 8. Dieterich W, Ehnis T, et al, Identification of tissue transglutaminase as the autoantigen of celiac disease, Nat Med, 1997; 3 (7):797-801. 9. Fine KD, The prevalence of occult gastrointestinal bleeding in celiac sprue, N Engl J Med, 1996; 334 (18):1163-1167. 10. Janatuinen EK, Pikkarainen PH, et al, A comparison of diets with and without oats in adults with celiac disease, N Engl J Med, 1995; 333 (16):1033-1037. 11. Srinivasan U, Leonard N, et al, Absence of oats toxicity in adult coeliac disease, BMJ, 1996; 313 (7068):1300-1301.
  2. Dr. Peter Green is a gastroenterologist and the director of the GI Endoscopy Unit at Columbia-Presbyterian Medical Center in New York City. He has a large celiac patient base. On September 29th, Dr. Green spoke to the Westchester Celiac Sprue Support Group and presented an excellent review of the medical care an adult Celiac patient should receive. What follows is a summary of Dr. Greens presentation, compiled by Sue Goldstein, a past president of the Westchester group. Initial Assessment Dr. Green sees a lot of patients who, either through their own frustration or because of physician advice, have started a gluten-free (gluten-free) diet without obtaining a biopsy-proven diagnosis of celiac disease (celiac disease). However, the need for a biopsy to establish a diagnosis of celiac disease must be emphasized. celiac disease is a lifelong illness with serious potential implications. In addition, sensitivity to gluten doesnt go away, and a radical lifestyle change is involved. You also need to be certain of the diagnosis because celiac patients families should be screened. The initial biopsy is also needed to serve as a baseline because one doesnt know what the future may involve. Basic blood work is also included in the initial assessment. Such things as anemia and liver function need to be looked for. But its very important to go further than that, and knowledge of the physiology of the small intestine should lead a physician to measure those nutrients that could be malabsorbed. celiac disease involves the small intestine, where iron, folic acid, calcium, fat soluble vitamins (K, A, D, and E) and zinc are absorbed. These nutrients should be measured in the initial assessment and also during the course of the illness. Physicians will see patients who present with malabsorption of just one of these nutrients. If they are aware of the consequences of all these nutrient deficiencies, it will help them consider celiac disease as a possible diagnosis. The patient should also have the celiac antibodies blood testing, but the diagnosis is still established on the biopsy pathology. In Dr. Greens experience, about 30% of celiacs have negative antibodies at diagnosis, so positive antibodies are not required to make the diagnosis. Antibodies testing often helps establish the need for a biopsy, but they also have great value in establishing a baseline so that an assessment can be made on how the patient is doing later on. All the antibodies should normalize, in time, when gluten is eliminated from the diet. What about the patient who seeks a diagnosis, but has already eliminated gluten from the diet? It is very difficult for many patients to go back on a gluten-containing diet to secure a biopsy-proven diagnosis. This can often take three to six months or longer. Columbia-Presbyterian has been talking about setting up alternative means of securing a diagnosis, such as a rectal challenge. The physician can take a biopsy of rectal tissue, and then instill gliadin extract into the rectum and do a repeat biopsy a certain number of hours afterward to demonstrate an inflammatory response similar to that in the small bowel. However, interpreting the results of the gluten challenge would require a pathologist who is very experienced, and sophisticated immunology on the cells of the rectal biopsy may be needed. Follow-up Care Soon after diagnosis and adhering to a gluten-free diet, patients will often report an increased feeling of well-being. How well they feel--and how quickly--will also depend on what the manifestations of their disease were. For example, if the patient was iron-deficient, it will take time for the iron stores to be restored. An assessment of vitamin and mineral levels should be part of the follow-up care. Specific deficiencies need to be addressed, treated, and monitored. Patients have been seen who have been ingesting too much of the fat-soluble vitamins, with resulting problems such as liver disease (from vitamin A toxicity), and hypercalcemia (from vitamin D toxicity) which can cause confusion, constipation, and kidney problems. Certain vitamins and minerals may need to be administered, but the patient should be under a physicians guidance as to how much should be taken. After a diagnosis of celiac disease, a bone mineral density test should be performed to assess the condition of the bones. Reports have shown that between 50-100% of people at initial diagnosis of celiac disease will have osteopenia or osteoporosis. Ostopenia is thinner bones, usually less than 2 standard deviations from normal. Osteoporosis involves an even greater deviation from normal.. In Dr. Greens experience, nearly 100% of the celiac patients at diagnosis will have osteoporosis. Surveys of celiac patients have shown an increased incidence of fractures prior to diagnosis and after diagnosis. If the bone mineral density is low, the patient should be referred to a bone mineral expert for assessment and specific individual treatment. For example, calcium and vitamin D needs will be addressed and monitored, and exercise and hormone replacement (in post-menopausal women) will be considered. At diagnosis, patients should get a Pneumovax, because it is very common for celiacs to have poor splenic function, which puts them at risk of developing certain bacterial infections such as pneumoccal pneumonia and meningitis. Since there is a genetic predisposition to celiac disease, another important issue in the follow-up is screening family members for celiac disease. Children and other first-degree relatives should have their antibodies status measured. About 10-15% of first-degree relatives have positive antibodies, and the bulk of the people with positive antibodies will have the disease, even though 50% of those people will be asymptomatic, even with a flat biopsy. What annual follow-up care should the celiac patient be getting? The most important thing is a good physical examination. Blood work, x-rays, CAT scans, mammograms and PSA tests, while valuable, do not replace a physical examination. The physical exam should include a breast exam for women, prostate exam for men, and a rectal exam for everyone. Blood work should include measurements of folic acid, calcium, and iron, and antibodies testing. Bone mineral density testing should be repeated annually for those with abnormal results, and every several years for those with normal results. Finally, patients with celiac disease should have at least one follow-up biopsy to confirm response--normalization of the biopsy sample. Patients who are non-responders, or whose clinical situation is somewhat confusing, may need more repeated biopsies at intervals. Non-responders What about the non-responders or people who relapse? The first thing is to check the diet with antibodies testing. People may be ingesting gluten, such as in medications, and not be aware of it. They may be getting gluten from licking stamps or envelopes. They may have misinformation from food labels or manufacturers. However, the antibodies can normalize and the biopsy still look quite flat, so once again, the antibodies have only a limited value--but they are still important to measure. It is also important to check the original biopsy to make sure of the diagnosis. Not all pathologists are experienced enough to properly diagnose celiac disease. Pathology departments, by law, have to keep the biopsies for a lengthy period of time--some keep them for 50 years. So it is important for the physician to review the biopsy sample with a pathologist who understands the spectrum of celiac disease. The pathologist needs to know, for example, how to identify latent celiac disease and different subtle aspects of the biopsy, such as increased intraepithelial lymphocytes. A problem that comes up in non-responders is other food sensitivities. Its very rare for people with celiac disease to also have sensitivities to other foods that result in the abnormal biopsy. There are, however, reports of ingestion of soy protein or egg or some kind of meats that cause the biopsy not to normalize. There are other conditions that can co-exist with celiac disease and confuse physicians. For example, pancreatic insufficiency can cause diarrhea and steatorrhea (malabsorption of fat), and bacterial overgrowth can affect absorption of nutrients. Patients may have colonic pathology. Having one disease doesnt mean you cant have another disease, and other conditions need to be investigated in the celiac disease patient who is not doing well. When there is no improvement in the biopsies, patients remain at the risk of developing or maintaining bone disease and vitamin deficiencies, and they are at a higher risk for malignancy. Patients who are refractory may need other therapies such as corticosteroids or immunosuppressent drugs such as cyclosporin. One doesnt engage in these therapies lightly (for example, steroids will thin the bones); being closely evaluated while on these drugs is important. Prognosis for the Celiac Patient The studies that have indicated increased mortality in celiac disease are from other countries where people have different smoking and dietary habits. It is hard to extrapolate these studies to our patient population. Dr. Green believes existing studies indicate that the mortality rate among adult celiacs is about two to three times that of the general population, and the increased mortality is found mainly in the first five years after diagnosis. After that, the mortality rate approaches that of the normal population. That tends to suggest that it is the continued ingestion of gluten that is responsible for the increased mortality. This is especially so in regard to malignancies, where the risk of diagnosis of malignancy such as lymphoma is usually highest in the first year after diagnosis, and then decreases in incidence downward until it equals that of the normal population after about five years. There is certainly the suggestion that adhering to a gluten-free diet reduces the risk of developing a malignancy. A Final Word--Looking For Celiac Disease Traditionally, the incidence of celiac disease in this country, based upon epidemiological work, suggests that celiac disease occurs in about 1 in 4,600 people. Certainly its much more common than that. Serology testing of blood donors by Dr. Fasano suggests the same prevalence as in European countries, about 1 in 300 people. Dr. Green, who does a lot of endoscopies, has found an incidence of celiac disease in about 1 in 280 patients who were having endoscopies for reasons other than suspicion of celiac disease. It is important, therefore, for the gastroenterologist to have a higher suspicion for the possibility of celiac disease, and for physicians to screen for celiac disease, particularly among their patients who have associated diseases such as Insulin Dependent Diabetes, Sjogrens, and Autoimmune Thyroid Disease.
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