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    New Testing Procedure for Intestinal Permeability


    Scott Adams


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    This was posted to the Celiac Listserv by Don Wiss.

    Testing for intestinal permeability is a sensitive and accurate way to screen for celiac disease, with fewer false positive and false negative results than other commonly used screens. Intestinal permeability reflects the ability of the intestinal lining to absorb nutrients while keeping undesirable chemical substances out of the body. In patients with celiac disease who are consuming gluten, even small amounts of damage to the intestine will allow certain large chemical molecules to leak into the bloodstream, from which they may be excreted by the kidneys into the urine. The available permeability test requires that the individual drink a solution which contains two sugars, neither of which is metabolized or changed in the body. One sugar is usually mannitol, which is readily absorbed from the intestine and excreted in the urine. The other sugar is lactulose, which is hardly absorbed at all under normal conditions. Any lactulose that is absorbed is excreted unchanged in the urine within 5 to 6 hours. Both sugars are safe to be taken, even by small children. When a person with celiac disease drinks the lactulose/mannitol mixture, an excessive amount of lactulose will appear in the urine, unless the person is on a strict gluten-free diet. If the person has enough celiac disease to create malabsorption, then the mannitol level in urine will be low. The ratio of lactulose to mannitol in urine is the most sensitive index of active celiac disease. An elevated lactulose to mannitol ratio in urine may be due to conditions other than celiac disease, such as intestinal infection, severe food allergy or Crohns disease, but a normal ratio indicates either that the person does not have celiac disease or is in complete remission due to strict adherence to a gluten-free diet. Information about this test can be obtained from the one laboratory that presently offers it, Great Smokies Diagnostic Laboratory in Asheville, NC. Their number is 1-800-522-4762.

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  • Related Articles

    Scott Adams
    The following article was published in The Sprue-nik Pres, Volume 9, Number 1 January 2000, Published by the Tri-County Celiac Sprue Support Group, a chapter of CSA/USA, Inc. serving southeastern Michigan. Members receive this newsletter, a shopping guide, and a new member packet full of articles and useful information. Mail-in subscriptions are welcome. For subscription information, send a note to tccssg@yahoo.com.
     
    Ann gave us TIPS: Five food tips, five health tips, five quickie tips, and five things to look forward to, always in a Lets Be Positive mode.
    Food Tips:
    Concentrate on what you CAN eat, not what you cant. Try not to blow the gluten-free (gluten-free) diet out of proportion. If you take processed foods out of the equation, you can eat almost anything: fruits, vegetables, beans, meat, fish, rice, corn, etc. When you eat plain food, you start to really taste food the way you never tasted before. What we can eat is good for us. Get used to the fact that you have to do more cooking and baking. Turn this factor into an asset and become a good gluten-free cook. Eat
    simply. For breakfast Ann eats eggs, yogurt, fruit, Jowar (sorghum) Jo Crisps Cereal, or even vegetables. For lunch you can eat leftovers. Leftover rice mixed with a vegetable is always a good idea; you can keep bags of frozen peas,
    corn, or broccoli in the freezer. One of Anns favorite lunches is to put plain peanut butter on a rice cake and slice apples on top.
    For snacks try fruit, Jell-O, or home-popped popcorn, all of which can be quickly prepared.
    In a restaurant, first check the menu to see what you can eat without question, what you might be able to eat if you ask questions, what youd better stay away from, and what you might want to look into a little bit. Try not to make an issue of it and dont be embarrassed or afraid to ask questions. Ann says she figures whatever the gathering is for, its not to discuss her diet
    Forget about getting dietary advice from your doctor. A gastroenterologists primary job is to diagnose your illness and then send you on to a dietitian and a support group. Please dont get mad at doctors for not knowing all the details of the gluten-free diet. Dietitians, too, may not know a lot about the gluten-free diet. We celiacs need to partner with dietitians to get them up to speed and help those we educate teach other dietitians. There are many pieces of the celiac pie that need to be improved, and adopting and educating dietitians is an important step toward getting more reliable
    information to more people.
    Join a support group. The best place to get information about the disease and the gluten-free diet is from a support group because the leaders and members deal with diet issues every day. Celiacs need to support their group leaders and volunteer assistance. Ann says she feels strongly about all of us giving something back to society for the richness that we have managed in our own personal lives. So if you are really interested in making celiac disease your thing, you can volunteer to work with a support group
    Accept that there are very few absolutes and very many points of disagreement about what is and is not gluten-free or what is and is not appropriate for celiacs. We know with certainty that the things we should not eat are wheat, barley, rye, oats, spelt, triticale and kamut. The next thing we need to find out is where those grains actually are, not necessarily where they might be. We should have a basic diet we can rely on before we waste valuable time and effort looking for needles in haystacks. In her research Ann has discovered that a lot of the things we celiacs believe but have
    never checked out are not necessarily true in the real world. Misinformation takes hold in the celiac community and then we are left trying to disprove something that should never have been proposed in the first place. In other words, we are left trying to prove a negative.
    For example, research shows that canola oil is gluten-free, so it should be appropriate for any celiac except those with a special sensitivity to it. Since it is gluten-free, any sensitivities to canola oil cant be gluten problems. But it has been publicized that canola oil is not appropriate for any celiac, so everyone (especially food vendors) has been forced to decide what to do about this product, which actually happens to be a healthy oil. Canola oil did not belong on any list of products that all celiacs should avoid in the first place. Celiacs need to make their own judgments and realize that no one can tell them what they cannot eat without explaining and/or proving that it is dangerous. You have to do the best you can with the diet, but try to stay away from any gluten-fearing paranoia that exists. Try to know your sources and the reasons why you should be avoiding something.
    Health Tips:
    Eat a varied diet, which will provide a wider variety of vitamins and minerals for better nutrition. Iron, calcium and folic acid are the three nutrients most frequently malabsorbed by celiacs, so be sure you eat the foods that contain them. Whatever your age and whatever your sex, do get a bone density test. Many celiac experts say that most celiac patients have some degree of abnormal bone loss, often serious, at diagnosis. If your doctor is not up to speed on celiac disease, you may have to firmly request the simple, noninvasive bone density test. The treatments for osteoporosis include hormone therapy and some new drugs, primarily Fosamax. There are 10 million Americans today who have osteoporosis, and 18.5 million more who have some early signs of osteoporosis. The cost of treating these problems is enormous. Yet if a person has osteoporosis and also has hidden celiac disease, and is taking osteoporosis medications and eating calcium-rich foods, the treatment will probably not be optimum if the patient is malabsorbing the calcium she is eating and perhaps even the medications. Since the celiac connection to osteoporosis is the malabsorption of calcium, treating the cause of the malabsorption--the gluten-free diet --needs to come before consideration of Fosamax or other drugs.
    Celiacs need to eat dairy products because they are a prime source of calcium. Calcium, which has such a strong connection with osteoporosis, is one of the most malabsorbed nutrients in celiac disease. Some celiacs have difficulty eating dairy products because of associated lactose intolerance, but it is extremely important to get dairy products into your body in whatever way works. Of all the dairy products available, one of the best is yogurt; its low fat, easily digested (even for some who are lactose intolerant), and readily available.
    Have an annual physical exam that includes a complete blood count (CBC) and stool testing, according to Dr. Joseph Murray of the Mayo Clinic. He thinks you should have thyroid testing every other year, but if you already have thyroid disease, more frequent testing might be advantageous. The experts also say you should have serology antibody testing once a year to test for compliance with the gluten-free diet. A positive result almost always means some gluten has been inadvertently ingested. Dr. Murray says you then have to: Check your diet, check your diet again, and check your diet a third time. He also recommends taking one good multi-vitamin a day that includes 100 percent of the recommended
    daily amount of B-complex vitamins, iron, folate and other vitamins and minerals.
    Whatever other supplements you take will depend on your own personal needs. You will need to investigate the possible gluten content in everything you ingest, including (and especially!) vitamins and medications. We have to be careful of everything that goes into our mouths, but especially of anything we take every day.
    Encourage your first-degree relatives to get screened for celiac disease. Usually these relatives are not comfortable with your request because they dont want to follow your diet, but 10% of them will probably have celiac disease, and of the 10% who have it, 50% will have no symptoms but will have flat intestinal villi. How can we get our relatives tested? First of all, dont make an issue of your diet around them. Make them drool over the delicious gluten-free dishes you are eating. Keep the current complexities about the diet to yourself. And dont nag!
    If you can, send donations to the University of Maryland Prevalence Study, which is testing first-degree relatives (and others) to try to find out what the true prevalence of celiac disease is in the United States. If it turns out that celiac disease is not rare, then the FDA and food manufacturers will have to pay more attention to our problems. Please make checks payable to the UM Foundation, Inc. Center for Celiac Research, Attn: Pam King, 700 W. Lombard St., Room 206, Baltimore, MD 21201. These funds are administered by the University of Maryland Foundation, Inc.
    The very best thing you can do for yourself is to have a life beyond celiac disease. Dont let having this disorder stop you from doing anything! Make sure you have other interests. Make sure you exercise. Make sure you get out and eat with gluten-eating people. Make sure you travel. Make sure you stay all-around healthy.
    Five Quick Tips:
    Buy your own toaster or toaster oven. This is an easy way to avoid cross contamination. Try not to complain about the cost of gluten-free products. They are expensive for a reason. The manufacturers have to pay more to get supplies, pay more to process the food, and they have to pay more to market it because they dont have normal marketing avenues. We have to pay more because we have to order a lot by mail. It helps to remember that we usually dont have to take expensive medications as treatment for gluten sensitivity and, unlike medications, the foods we eat have no side effects.
    Buy a bread machine. When you bake your own bread, it is ultimately cheaper than any ready-made bread. Plus it usually tastes better.
    Not everyone can do this, but it helps to avoid processed food. Even when you investigate products over the phone or get a letter from the manufacturers or consult some of the commercial product listings that are available, you are still not totally sure the product is safe. Life is simpler and safer when you avoid processed foods--or eat them as infrequently as possible.
    Remember that Europe is well ahead of the U.S. in dealing with celiac disease. We know physicians there have been diagnosing celiac disease for a longer time
    and celiacs have been on a gluten-free diet longer in Europe than here. Yes, several European countries do allow a small amount of wheat starch in international products, but their research has not shown an increased morbidity or mortality rate in their celiac population. Ann says she tends to think of this when she hears Americans going nuts about potential (versus actual) trace amounts of scientifically immeasurable gluten in certain ingredients.
    Unfortunately, we dont have our act together in the U.S. when it comes to celiac disease and the gluten-free diet. All U.S. celiacs have a lot in common and we all need to pull together, not apart, for our common good.
    Five Things to Look Forward To:
    A good possibility that doctors will be able to diagnose celiac disease without the biopsy in the years to come. The Celiac International Conference in August 2000 in Baltimore. Those who attend can plan a nice east coast vacation around the dates (August 10-13) if theyd like. gluten-free food that gets better and more varied as the number of vendors grows. Hopefully our specialty foods will be more easily available locally. In the meantime, ask your supermarket managers to stock specific products in their stores. You might be surprised at how quickly they agree to do so. More awareness of celiac disease, especially in terms of research, doctors understanding, availability of gluten-free food, and interest from the federal government and FDA. We need to make celiac disease a household word because it impacts so many peoples lives. A united U.S. effort to support celiacs!!

    Scott Adams
    Like many people with celiac disease, I spent a lot of years and money to go through many tests and misdiagnoses before doctors finally found my problem. Because of the large variety of symptoms associated with celiac disease, diagnosis can be very difficult. Most medical doctors are taught to look for classic symptoms and often make a wrong diagnosis, or no diagnosis at all.
    During my doctor visits my diet was never discussed, even though most of my symptoms were digestive in nature. My symptoms included abdominal pain, especially in the middle-right section while sleeping, bloating, and diarrhea (off and on over a period of several years). A simple (and free!) exclusionary diet would have quickly revealed my problem. An exclusionary diet involves eliminating wheat, rye, oats, barley, dairy products, soy and eggs for several weeks, and recording any reaction as one slowly adds these foods back to their diet.
    It took two years for the doctors to discover that I had celiac disease. During that time I was misdiagnosed with Irritable Bowel Syndrome (IBS), told that I could have cancer or a strange form of Leukemia, treated for a non-existent ulcer with a variety of antibiotics that made me very ill, and was examined for a possible kidney problem. I also underwent many unnecessary and expensive tests including CAT Scans, thyroid tests, tests for bacterial infections and parasites, ultrasound scans, and gall bladder tests. Luckily I ended up reading something about celiac disease in a book on nutrition, which led me to ask my doctor to test me for it. I was finally diagnosed via a biopsy of my small intestine (which is not as bad as it sounds). Although the biopsy is still considered the gold standard of diagnosis, there are also several blood tests for celiac disease.
    I decided to create this Website to help others avoid a similar ordeal. I also want to provide people who know they have the problem with information which will improve their quality of life, and broaden their culinary horizons. To do this, I have compiled information from a large variety of sources including medical journals, books, doctors, scientists and the Celiac Listserv News Group, and posted it all right here. Please remember that I am not a doctor, and none of this information should be considered expert medical advice....enjoy! - Scott Adams

    Scott Adams
    Wahab PJ, Meijer JW, Mulder CJ.
    Department of Gastroenterology and Hepatology, Rijnstate Hospital Arnhem, The Netherlands.
    Am J Clin Pathol 118(3):459-463, 2002
    Celiac.com 10/28/2002 - The following study strongly supports follow-up care and testing for people with celiac disease. As the study found, over 10% of people with diagnosed celiac disease have still not fully recovered even after five years of treatment.
    To assess histologic recovery in response to gluten withdrawal in celiac disease, 158 patients seen in our hospital during a 15-year period underwent follow-up small intestine biopsies (SIBs) within 2 years after starting a gluten-free diet; further SIBs were done if villous atrophy was present. A modified Marsh classification was used (IIIA, partial villous atrophy; IIIB, subtotal villous atrophy; IIIC, total villous atrophy). Of patients with Marsh IIIA, IIIB, or IIIC lesions, histologic remission was seen in 65.0% within 2 years, 85.3% within 5 years, and 89.9% in long-term follow-up. Eleven patients (7.0%) with persisting (partial) villous atrophy had symptoms and signs of malabsorption and were considered to have refractory celiac disease; 5 of them developed an enteropathy-associated T-cell lymphoma. Children recovered up to 95% within 2 years and 100% in the long-term. Histologic recovery in celiac disease after starting a gluten-free diet takes time and is incomplete or absent in a substantial subgroup of patients (10.1% villous atrophy after 5 years). Systematic follow-up of patients with celiac disease and the malabsorption syndrome and secondary complications is needed.

    Jefferson Adams
    Celiac.com 03/18/2015 - Getting high-quality biopsy specimens is key to making accurate celiac disease diagnoses. Endoscopists may take either a single- or double-biopsy specimen with each pass of the forceps.
    Does it matter whether they take one or two? Is two better than one?
    A team of researchers recently set out to answer those questions, by comparing the quality of biopsy specimens obtained with the single-biopsy and double-biopsy techniques.
    The research team includes M. Latorre, S.M. Lagana, D.E. Freedberg, S.K. Lewis, B. Lebwohl, G. Bhagat, and P. H. Green of the Celiac Disease Center, Department of Medicine, Columbia University, New York, New York, USA.
    Their prospective cohort study looked at patients undergoing upper endoscopy with confirmed, suspected, or unknown celiac disease status. A total of 86 patients enrolled in the study, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status.
    In each case, patients received four biopsy specimens from the second portion of the duodenum. Two were made using the single-biopsy technique of 1 bite per pass of the forceps, and two more using the double-biopsy technique, which takes 2 bites per pass of the forceps.
    Specimens were blindly reviewed to determine orientation, consecutive crypt-to-villous units, and Marsh score. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01).
    Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).
    Now, this is just a single-center trial, so results need to be compared with results from additional cities.
    Interestingly, these results suggest that one bite is actually better than two, because the single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens.
    For best results, the endoscopists should consider taking only one biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.
    Source:
    Gastrointest Endosc. 2015 Jan 29. pii: S0016-5107(14)02380-3. doi: 10.1016/j.gie.2014.10.024.

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023

    Jefferson Adams
    Celiac.com 06/13/2018 - There have been numerous reports that olmesartan, aka Benicar, seems to trigger sprue‐like enteropathy in many patients, but so far, studies have produced mixed results, and there really hasn’t been a rigorous study of the issue. A team of researchers recently set out to assess whether olmesartan is associated with a higher rate of enteropathy compared with other angiotensin II receptor blockers (ARBs).
    The research team included Y.‐H. Dong; Y. Jin; TN Tsacogianis; M He; PH Hsieh; and JJ Gagne. They are variously affiliated with the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston, MA, USA; the Faculty of Pharmacy, School of Pharmaceutical Science at National Yang‐Ming University in Taipei, Taiwan; and the Department of Hepato‐Gastroenterology, Chi Mei Medical Center in Tainan, Taiwan.
    To get solid data on the issue, the team conducted a cohort study among ARB initiators in 5 US claims databases covering numerous health insurers. They used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy‐related outcomes, including celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy. In all, they found nearly two million eligible patients. 
    They then assessed those patients and compared the results for olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. They found unadjusted incidence rates of 0.82, 1.41, 1.66 and 29.20 per 1,000 person‐years for celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy respectively. 
    After PS matching comparing olmesartan to other ARBs, hazard ratios were 1.21 (95% CI, 1.05‐1.40), 1.00 (95% CI, 0.88‐1.13), 1.22 (95% CI, 1.10‐1.36) and 1.04 (95% CI, 1.01‐1.07) for each outcome. Patients aged 65 years and older showed greater hazard ratios for celiac disease, as did patients receiving treatment for more than 1 year, and patients receiving higher cumulative olmesartan doses.
    This is the first comprehensive multi‐database study to document a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, though absolute rates were low for both groups.
    Source:
    Alimentary Pharmacology & Therapeutics

    Jefferson Adams
    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.
    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.
    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 
    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.
    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.
    Source:
    Gut. 2017 Feb;66(2):250-257. &nbsp;doi: 10.1136/gutjnl-2015-310148.