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Background the rare occurrence of collagenous gastritis (CG) makes its epidemiology difficult to investigate. We designed a study to determine the demographic and clinical characteristics as well as the associations of CG with other upper gastrointestinal diseases in a large national clinicopathological database. Methods from the IDEA database we extracted all patients with histopathologically documented CG and, in a case-control study, we compared 168 subjects with and 1,286,165 subjects without CG using odds ratios (OR) with their 95% confidence intervals (CI). Results the prevalence of CG was 13 per 100,000 EGDs. CG was significantly more common among female than male patients (OR: 1.69, 95% CI: 1.20–2.39) and was characterized by a bi-modal age distribution (first peak in patients aged 10–19, second peak primarily in females aged >60 years). CG patients presented with diarrhea (18%), anemia (12%), weight loss (11%), and vomiting (10%). CG was significantly associated with other lymphocytic disorders of the upper gastrointestinal tract, including celiac sprue (2.12, 1.55–2.88), duodenal intraepithelial lymphocytosis (3.71, 2.30–5.98), and lymphocytic gastritis (23.2, 10.9–49.5). CG persisted in 69% of patients who underwent multiple consecutive endoscopies. Conclusions the epidemiologic features of collagenous gastritis reflect on different etiologies contributing to its occurrence in children and adults.

The present work proposes an improved multi-gate designs (MGDs) in sand casting process, using both experimental and simulation (FLOW 3D) approaches, aiming to produce defect-free component. In this regard, the variant MGDs were developed and compared with the existing designs reported in the previous studies. Accordingly, the following new MGDs: side sprue serial connection (SSSC), centre sprue serial connection (CSSC), side sprue parallel connection (SSPC), centre sprue parallel connection (CSPC) and centre sprue runner extension parallel connection (CS-RE-PC) were modelled for both techniques. The experimental set-ups were developed for the aforementioned designs to study the flow behaviour of aluminium alloy and water. The validity of aluminium alloy flow characteristics in closed mould condition was checked with the water mould experimentation. The quality of the casting was examined by visual inspection, optical microscopy, ultrasonic and X-ray tests. From the results obtained, it was evident that CS-RE-PC mould set-up or design was most suitable with a runner system for four-cavity application. This design exhibited best flow rate, as a nearly defect-free casting component was produced. Comparison of the FLOW 3D simulation results with similar experimental findings provided potential opportunity to reduce both cast product rejection rate and rework, and consequently it aids enhancement of the productivity and profitability in a manufacturing/casting industry.

The opportunity to improve the quality of metal castings by enabling fabrication of complex gating systems via 3D Sand-Printing (3DSP) has been recently established. Among the different components of a gating system (often called rigging), sprue design offers a major opportunity to exploit the unlimited geometric freedom offered by 3DSP process. In this study, conventional principles of casting hydrodynamics is advanced by validated novel numerical models for novel sprue designs to improve melt flow control. Computational flow simulations demonstrate that conical-helix sprue satisfy the critical velocity condition by reducing the ingate velocity below 0.5 m/s. Multiple approaches to integrate 3DSP into conventional manufacturing to fabricate complex gating systems through “Hybrid Molding” are presented. 3DSP molds featuring two optimized sprue profiles and a benchmark straight sprue are fabricated to pour 17-4 stainless steel. Computed tomography scans (CT) shows that parabolic sprue casting (PSC) and conical-helix sprue casting (CHSC) reduced overall casting defects by 56% and 99.5% respectively when compared to straight sprue casting (SSC). Scanning electron microscopy (SEM) analysis confirms the presence of globular oxide inclusions and that PSC and CHSC exhibits 21% and 35% reduced inclusion when compared to the SSC. Three point flexural testing reveals that CHSC and PSC exhibits an increase of 8.4% and 4.1% respectively in average ultimate flexural strength than SSC. The findings from this study demonstrate that numerically optimized gating systems that can only be fabricated via 3DSP have the potential to significantly improve both mechanical and metallurgical performance of sand castings.

Introduction and aims: Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. Materials and methods: A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: ‘celiac disease’ OR ‘celiac sprue’ AND ‘colorectal’ OR ‘colorectal neoplasia’ OR ‘colorectal adenoma’. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. Results: The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I2 = 26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). Conclusion: Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association. Resumen: Introducción y objetivos: No se ha evaluado de manera extensa si la enfermedad celiaca incrementa o no el riesgo de presentar adenoma colorrectal. Esta cuestión se hace relevante al considerar los métodos de cribado tempranos en pacientes con esta enfermedad. El objetivo de nuestro artículo fue determinar el riesgo de adenomas colorrectales en los pacientes con enfermedad celiaca. Materiales y métodos: Se realizó una búsqueda electrónica en las bases de datos MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library y Google Scholar, integrando el periodo de tiempo de 1966 a diciembre de 2016. La estrategia de búsqueda consistió en los siguientes términos MESH: «enfermedad celiaca» O «esprue celiaco» Y «colorrectal» O «neoplasia colorrectal» O «adenoma colorrectal». Se empleó el uso de modelos de efectos fijos para los análisis. El primer análisis trató sobre la prevalencia de todas las presentaciones de adenoma colorrectal en pacientes con enfermedad celiaca y el segundo, sobre la prevalencia de adenomas avanzados. Los desenlaces se describieron como razones de momios (RM) con sus intervalos de confianza al 95%. Resultados: La búsqueda identificó 480 citas bibliográficas, de las cuales 17 se escogieron para ser evaluadas. Catorce de aquellos estudios se rechazaron, dejando un total de 3 estudios para el análisis. Estos estudios incluían 367 casos de enfermedad celiaca y 682 controles. No se observó heterogeneidad significativa (I2 = 26%). Al compararse con los controles, no se encontró un incremento en la prevalencia de adenomas colorrectales en los pacientes con enfermedad celiaca (RM: 0.94 [0.65-1.38]), y no se observaron diferencias significativas al valorar la prevalencia de adenomas avanzados (RM: 0.97 [0.48-1.97]). Conclusión: La enfermedad celiaca no se asoció con el incremento de riesgo de adenomas colorrectales. Sin embargo, debido a la evidencia disponible limitada, se requiere de más estudios para determinar si existe una asociación real. Keywords: Celiac disease, Colorectal adenoma, Colonoscopy, Palabras clave: Enfermedad celiaca, Adenoma colorrectal, Colonoscopia

In the present work, in-situ microwave casting was analyzed for higher efficiency while aluminum casting at 2.45 GHz and 1400 W. Models of setup with different insulation arrangements were generated using a software tool. Simulation was carried out to find the optimum casting conditions. Results revealed that complete insulation of mold assembly enhances energy saving and reduces melting time; however, higher mold preheating results in longer solidification time and coarse grains in the cast. Mold assembly without insulation showed poor efficiency. Optimum results were obtained in a mold assembly consisting insulated pouring basin and charge with bare mold and sprue.

Sprue-like enteropathy associated with the angiotensin II receptor blocker (ARB) olmesartan was first described in 2012, and a number of cases have since been reported. This syndrome is characterized by severe diarrhea and sprue-like histopathologic findings in the intestine, often with increased subepithelial collagen. The incidence of this adverse drug reaction is not entirely clear, although it is thought to be rare. It is also not well established if other ARBs cause such a syndrome, although case reports suggest they can. The histopathologic features of olmesartan-related injury have only been described in a limited number of cases, and there are no guidelines regarding the histopathologic distinction of olmesartan-associated enteropathy from other causes of sprue (eg, celiac disease, tropical sprue). Herein, we review the histopathologic changes and clinical observations described in recent reports of olmesartan-associated sprue-like enteropathy comprising case series and isolated reports, other relevant literature, and our experience at a referral center specializing in small intestinal disorders. We will review recent literature suggesting other ARBs can be associated with a similar phenotype. Lastly, we will discuss the histopathologic differential diagnosis and provide clues to distinguish this entity from other entities which can cause sprue-like histopathology.

Chronic diarrhoea is a common clinical problem in gastroenterology practice and often it is difficult to diagnose the cause. Villous atrophy is not specific and the rarer possibility of drug-induced enteritis should always be considered. Olmesartan has recently been described as a cause of drug-induced enteropathy characterized by chronic diarrhoea and varying degrees of duodenal mucosa atrophy resembling celiac disease.We describe two cases of sprue-like enteropathy in patients treated with olmesartan for arterial hypertension several years before the onset of symptoms. Patients presented severe diarrhoea and significant weight loss, and both had histological evidence of intestinal villous atrophy. The clinical signs completely resolved after drug withdrawal.Olmesartan-induced enteropathy is a new clinical entity that must be included in the differential diagnosis of villous atrophy with negative celiac serology. The clinical and histological alterations easily and completely resolve after drug discontinuation, restoring quality of life to patients and avoiding unnecessary investigation.

Small bowel tumors (SBTs) are rare. Their diagnosis by small bowel capsule endoscopy (SBCE) is usually made during the evaluation of obscure gastrointestinal tract bleeding or unexplained iron-deficiency anemia. SBCE has a good sensitivity for the detection of SBT. However, submucosal tumors, large or proximally located SBTs, have a higher risk of being missed by SBCE. SBCE should be considered in patients with complicated or refractory celiac sprue and those with advanced melanoma, as these patients are at risk for SBT. The retention rate of a video capsule in patients with SBT is slightly higher than in those with obscure gastrointestinal tract bleeding, but rarely causes obstruction and typically can be resolved during resection of the tumor. In patients with familial adenomatous polyposis and duodenal adenomas, SBCE is useful in detecting additional intestinal polyps, although a beneficial effect on clinical outcome has not yet been demonstrated. SBCE in the surveillance of Peutz-Jeghers syndrome is feasible and well tolerated, although MR enterography seems to have a higher accuracy.

Summary Background Within the present era of worldwide travel, it is important for all clinicians to consider the possibility of tropical sprue (TS) in returning patients with persistent diarrhoea after travel. The symptoms and histologic findings of TS can resemble but also be confused with celiac disease (CD). Material and method Patients at our institute diagnosed with CD or TS in the period January 2000–December 2010 were eligible for inclusion. Of all patients, demographic, clinical, laboratory and endoscopy data on admission and in follow-up were collected retrospectively. Results 28 CD and 7 TS patients were included. There were no differences in baseline clinical characteristics, duration of stay in a tropical region or in laboratory findings on admission. However, in the majority of CD patients antibodies against endomysium (EMA) or tissue transglutaminase (tTG) were present at presentation but absent in all TS patients at presentation. Conclusions In returning travellers with persistent diarrhoea, a diagnosis of CD is unlikely in case of absence of anti-EMA or anti-tTG antibodies but conversely increases the likelihood of TS. This distinct immunoserological profile may be of help in selecting the optimal treatment in returning travelers with chronic diarrhoea after staying in a tropical region.

Celiac disease is an enteropathy due to gluten intake in genetically predisposed persons (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Celiac disease is extremely various and anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may be the only revealing symptoms. Diagnosis releases on evidence of histological villous atrophy in proximal small bowel and presence of specific serum antibodies. Treatment relies on eviction of gluten. Gluten free diet allows prevention of malignant complications such as small bowel adenocarcinoma and lymphoma and osteopenia. The main cause of resistance to gluten free diet is its bad observance. On the contrary, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T-cell lymphoma need to be screen.

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent symptoms of malabsorption and intestinal villous atrophy. Diagnosis of this condition, defined as refractory celiac disease (RCD), is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal (type 1 RCD [RCDI]) or abnormal phenotype of intraepithelial lymphocytes (IEL) (type II RCD [RCDII]). The latter condition, called clonal refractory celiac sprue, is considered a low-grade intraepithelial lymphoma and has a very poor prognosis, leading to intractable ulcerative duodenojejunitis, gastrointestinal and extraintestinal dissemination of the abnormal IEL, and to their frequent transformation into a high-grade lymphoma. We review here the clinical and pathological features of RCD as well as the recent pathogenic findings in RCDII, which offers a model to study how inflammation can drive T-cell lymphomagenesis.

Summary Celiac disease or celiac sprue is predominately a disease of the small intestine in susceptible individuals who ingest grains containing gluten. Celiac disease is frequently associated with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders and diabetes mellitus. Cardiomyopathy associated with celiac disease is reported infrequently. We described a patient with cardiomyopathy and who is serologic celiac marker's positive. Our case had neither gastro-intestinal symptoms nor manifestations of malabsorption and the cardiac function improved substantially after treatment with a gluten-free diet.

Background Duodenal biopsies are frequently obtained to investigate malabsorption, diarrhoea, and aneamia. The proportion of patients who have duodenal biopsies and their diagnostic yield are unclear. Aims To determine what proportion of patients undergoing esophagogastroduodenoscopy in a private setting has duodenal biopsies and to evaluate the diagnostic yield relative to clinical indications and endoscopic findings. Methods Records of patients who had duodenal biopsies diagnosed at a United States gastrointestinal pathology laboratory in a single year were analysed. Results 28,210 patients with and 75,175 without duodenal biopsies were studied. Duodenal biopsy patients were younger (52 years versus 58 years, p

Selective IgA deficiency is the most common primary immunoglobulin deficiency. The clinical manifestations of selective IgA deficiency, including gastrointestinal (GI) complications, are rare and typically milder than those seen with common variable immunodeficiency or X-linked agammaglobulinemia. We present a rare case of selective IgA deficiency that shows a number of interesting histological features in the GI tract, including diffuse nodular lymphoid hyperplasia involving the entire small and large intestine, celiac disease-like and collagenous sprue-like changes in the small intestine, as well as lymphocytic colitis pattern. However, this patient had no particular GI symptoms suggestive of celiac sprue or microscopic colitis. These findings suggest that the GI tract in patients with selective IgA deficiency can show peculiar histologic changes that mimic celiac disease, collagenous sprue, or lymphocytic colitis, which may be a pattern of injury related to infection or immunoglobulin immunodeficiency-associated autoimmune phenomena.

Endocytoscopy (EC) is a novel technique that allows magnified live inspection of the intestinal mucosa.To evaluate EC for the detection of key pathological findings in patients with celiac sprue.A total of 166 EC recordings were prospectively acquired. Matched videos, images, and biopsy specimens were obtained by duodenal argon beamer labeling of the respective sites.Academic tertiary referral center.Forty patients (mean age 51.5 years, 70% women) with established (n = 32) or suspected (n = 8) celiac disease (CD).A validated scoring system (Marsh classification) was used to assess disease activity. EC criteria were independently evaluated by 2 gastroenterologists and 1 pathologist.The primary endpoint was to examine EC correlation with conventional CD histology.Of 166 duodenal biopsy sites, 23% were classified as Marsh III (moderate to severe), 10% as Marsh I (mild), and 67% as Marsh 0 (normal). Using the 450x magnification, we found that identification of crypts was diagnostic for celiac pathology. Four criteria were significant predictors of Marsh III pathology when adjusted by multivariate analysis: low number of villi per visual field (3; odds ratio [OR] 9.1; 95% CI, 1.3-62.0), confluence of villi (OR 37.1; 95% CI, 1.3-1021.2), irregular epithelial lining (OR 10.9; 95% CI, 2.5-46.7), and inability to delineate loop capillaries (OR 14.9; 95% CI, 3.3-67.0). None was a good predictor of Marsh I pathology.Single-center experience. No prospective validation of the criteria in an independent patient population.EC at 450x magnification accurately identifies mucosal histopathology of advanced CD, but not early morphological changes.

SummaryNew tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for noninvasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized noninflammatory gluten peptide analogs in which key Gln residues are replaced by Asn or His. Like their proinflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2, or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.

Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration in the epithelial membrane and the lamina propria, and expression of multiple cytokines and other signaling proteins. The disease leads to inflammation, villous atrophy, and crypt hyperplasia in the small intestine. In addition to the intestinal symptoms, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits. Gluten-free diet is currently the only effective mode of treatment for celiac disease, but better understanding of the mechanism of the disease is likely to add other choices for therapy in the future.

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with intestinal gluten sensitivity. Epidermal transglutaminase (TGe) and closely related tissue transglutaminase (tTG) are considered to be autoantigens in DH, because a majority of DH patients have IgA specific for TGe and for tTG. It is unknown where and how these autoantigen-specific IgAs are generated in DH. Results reported in this paper on nine DH patients on a gluten containing diet demonstrate that the levels of circulating anti-tTG IgA and anti-TGe IgA in DH are correlated with each other and that both appear to be correlated with the degree (extent) of enteropathy. An analysis of 15 untreated celiac sprue (CS) patients demonstrated that approximately 33% of CS patients had elevated levels of anti-TGe IgA. These results would indicate that intestinal damage is associated with the production of anti-tTG IgA and anti-TGe IgA in DH patients.

Objective To describe a patient with osteoporosis who was treated with alendronate and developed hypocalcemia, which ultimately led to the diagnosis of celiac sprue. Methods We present the clinical and laboratory findings in a patient with osteoporosis, in whom hypocalcemia developed after treatment with alendronate. This patient was subsequently diagnosed with celiac sprue. The pertinent literature regarding orally administered bisphosphonate-induced hypocalcemia is reviewed. Results A 79-year-old man who was diagnosed with osteoporosis was treated with alendronate. He was subsequently found to have asymptomatic hypocalcemia (serum calcium concentration, 8.3 mg/dL), which resolved after alendronate therapy was discontinued. He was then treated with calcium, vitamin D, and calcitonin nasal spray, which did not cause hypocalcemia. Because of his reduced bone density, however, he was subsequently referred for endocrine consultation. Evaluation at that time showed normal levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, 25-hydroxyvitamin D, thyrotropin, and parathyroid hormone as well as 24-hour urine calcium excretion. An endomysial antibody titer was dramatically elevated. Upper endoscopy showed villous atrophy, and small bowel biopsy confirmed the presence of villous blunting and chronic inflammation, consistent with celiac sprue. He was treated with a gluten-free diet and then subsequently treated with orally administered risedronate, which he tolerated well without evidence of hypocalcemia. Conclusion To the best of our knowledge, this is the first report of orally administered bisphosphonate-induced hypocalcemia, which subsequently led to the diagnosis of previously unrecognized, otherwise asymptomatic celiac sprue. Patients with unexplained hypocalcemia should be screened for celiac sprue, even in the absence of gastrointestinal symptoms. (Endocr Pract. 2007;13:403-407)

SummaryCeliac sprue (also known as celiac disease) is an inheritable, gluten-induced enteropathy of the upper small intestine with an estimated prevalence of 0.5%–1% in most parts of the world. The ubiquitous nature of food gluten, coupled with inadequate labeling regulations in most countries, constantly poses a threat of disease exacerbation and relapse for patients. Here, we demonstrate that a two-enzyme cocktail comprised of a glutamine-specific cysteine protease (EP-B2) that functions under gastric conditions and a PEP, which acts in concert with pancreatic proteases under duodenal conditions, is a particularly potent candidate for celiac sprue therapy. At a gluten:EP-B2:PEP weight ratio of 75:3:1, grocery store gluten is fully detoxified within 10 min of simulated duodenal conditions, as judged by chromatographic analysis, biopsy-derived T cell proliferation assays, and a commercial antigluten antibody test.

Background Capsule endoscopy (CE) is a new device that enables visualization of areas of the small bowel that were previously inaccessible through other noninvasive procedures. The purpose of this study is to evaluate this new diagnostic tool and its efficacy in finding occult GI tract pathology. Methods A single-institution retrospective review was completed on patients undergoing CE from January 2002 to September 2004. Data evaluated included indications for CE, results of previous studies, CE findings, and complications of the CE study. Results A total of 702 CE studies in 652 patients were performed during the study period. Suspicious GI bleeding presenting as anemia, guaiac positive stools, or history of gross bleeding were the most common reasons to perform CE (75.8%). Other indications included abdominal pain (11.5%), diarrhea (3.1%), or others (9.5%). In studies performed for GI bleeding (N = 532), a source was found in 49.3% of CE studies. Arteriovenous malformation (AVM) was the most common reported finding (43.9%), followed by ulcer (24.1%), colon or gastric pathology (14.1%), mass/tumor (9.1%), and stricture (6.9%). Patients with abdominal pain (n = 81) had findings 46.9% of the time including edema/ulcer (47.4%), stricture (10.5%), mass/tumor (26.3%), gastric pathology (10.5%), AVM (2.6%), or sprue (2.6%). Patients with diarrhea (n = 22) had findings 45.5% of the time including edema/ulcer (75%), mass/tumor (12.5%), or sprue (12.5%). A total of 66 patients underwent operative exploration after a CE study at this institution either because of the observed findings or for other reasons. There were 12 (1.7%) CE studies in which the capsule was retained and required surgical removal. Pathology at the retention site included benign strictures or adhesions (n = 9, 75%), Crohn’s stricture (n = 1, 8.3%) carcinoid tumor (n = 1, 8.3%), and villous adenoma (n = 1, 8.3%). Conclusions CE is an accurate study to locate abnormalities in the GI tract that may have either been missed by previous diagnostic studies or cannot be observed through other non-invasive means. When used for diagnostic challenges such as GI bleeding with no apparent source, CE can be helpful in guiding surgical decisions in patients and thus should be integrated as part of the diagnostic workup.

Background & Aims: We sought to determine whether prolyl endopeptidase (PEP) treatment of food gluten would obviate the intestinal dysfunction produced by small amounts of dietary gluten supplement in patients with celiac sprue. Methods: Twenty asymptomatic patients with histologically proven celiac sprue completed a randomized, double-blind, cross-over study involving two 14-day stages. Each patient consumed a low dose of a gluten supplement daily (5 g; equivalent to 1 slice of bread) in 1 stage and gluten pretreated with PEP in the other stage. Patients completed a daily symptom questionnaire and a D-xylose urine excretion and a 72-hour quantitative fecal fat were monitored before and after each stage. Results: Despite clinical remission at baseline, 40% of patients had at least 1 abnormal celiac antibody, 20% had an abnormal urine xylose, and 63% had an abnormal fecal fat test result. There was no difference in symptoms as a function of the type of gluten consumed. In response to gluten not treated with PEP, an appreciable proportion of patients developed malabsorption of fat (7 of 17, 41%) or xylose (8 of 14, 57%). When the gluten was pretreated with PEP, fat malabsorption was avoided in 5 of 7 and xylose malabsorption in 4 of 8 of these same patients. Conclusions: A significant proportion of asymptomatic patients with celiac sprue have abnormal celiac antibodies and fat or carbohydrate malabsorption. Pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who developed fat or carbohydrate malabsorption after a 2-week gluten challenge.

Background & Aims: Undiagnosed patients with symptoms of celiac sprue often present to physicians after establishing dietary gluten exclusion. Although they must resume a gluten-containing diet for evaluation, there are no guidelines regarding duration of the gluten challenge, gluten dose, or monitoring parameters. We investigated the effects of a short-term gluten challenge in asymptomatic treated adult celiac patients on intestinal absorption and celiac antibody tests. Methods: Eight adult asymptomatic celiac patients consumed either 5 or 10 g of partially hydrolyzed gluten per day in an orange juice mixture for 21 days while maintaining their usual gluten-free diet. A symptom questionnaire, serum antibodies (antigliadin immunoglobulin [Ig]A and antitransglutaminase IgA and IgG), D-xylose urine excretion test, and 72-hour quantitative fecal fat test were monitored. Results: Two patients (25%) had at least 1 abnormal celiac antibody test at baseline. There was no increase in antibodies during gluten exposure compared with baseline for any of the patients (P > .05). At baseline, 1 patient had abnormal urine xylose excretion, and 3 patients had abnormal fecal fat values. At day 15 of gluten challenge, all patients had reduced xylose absorption compared with baseline (P = .0019), and 5 of 8 participants (63%) reduced their xylose excretion to the abnormal range. Seven of 8 patients (88%) had increased fecal fat excretion at day 15 (P = .026), and 6 of these (75%) had steatorrhea by day 15. Conclusions: Short-term gluten challenge in asymptomatic adult celiac patients produces carbohydrate and fat malabsorption but does not increase transglutaminase and antigliadin antibody titers.

Summary Objective The behavior of molten titanium in molds of complicated shape is still insufficiently understood; consequently, definite spruing criteria are not yet available for titanium RPD frameworks. This study investigated the influence of sprue design on porosity in pressure-cast titanium circumferential clasps. Methods The patterns of 90 circumferential clasps were sprued with three directions (0, 30 and 60°, as measured between the sprue and the symmetry plane of the clasp assembly) and three sprue diameters (1.5, 2.0 and 2.5 mm). CPTi was cast in a one-chamber pressure casting machine. Pore number and size were assessed on radiographs of the castings. Statistical analysis was done by two-way analysis of variance (ANOVA), followed by Fisher's PLSD post hoc test. Results The porosity in lingual arms increased significantly with increase of sprue diameter and sprue angle, while the porosity in minor connectors had an inversely proportional distribution. Very low porosity, uninfluenced by sprue design, was found in buccal arms. In conclusion, internal porosity in titanium circumferential clasp arms can be minimized through sprue design: the 0° sprue direction produced the least porosity, while for the 30 and 60° directions, 1.5 mm diameter sprues produced lower porosity than 2.0 and 2.5 mm diameter sprues. Significance In this study, the lowest porosity in titanium circumferential clasp arms was obtained with sprues attached perpendicularly to the minor connectors, regardless of sprue diameter. Conventional sprue directions produced significantly higher porosity in clasp lingual arms, the amount of porosity increasing with sprue diameter.

Magnification endoscopy and chromoendoscopy are two new endoscopic techniques which have been introduced into clinical practice over the past decade with uses in patients both with and without inflammatory bowel disease. Specific uses for these techniques in patients without inflammatory bowel disease include evaluating for celiac sprue and tropical sprue, detection of squamous cell esophageal cancer, detection of Barrett’s esophagus and its associated neoplasia, as well as assisting in the detection of colorectal neoplasia for which specific pit pattern appearances have been described. In patients with ulcerative colitis, magnification endoscopy and chromoendoscopy have been shown to significantly increase the overall detection of colorectal neoplasia, particularly in flat colorectal lesions, as compared with conventional endoscopy. In addition, pit pattern analysis has allowed these techniques to be highly accurate in predicting neoplasia at histology. Thus, with magnification endoscopy and chromoendoscopy, targeted biopsy during colorectal neoplasia surveillance in ulcerative colitis may become feasible in the not too distant future. Finally, magnification endoscopy and chromoendoscopy have been shown to be significantly more accurate than conventional endoscopy in predicting the extent of ulcerative colitis and in predicting mild histologic disease. These techniques do not appear to be helpful in predicting severe histologic disease, and it is unclear at this time if they will be useful for predicting moderate histologic disease. Specific trials using magnification endoscopy and chromoendoscopy to predict response to therapy have not yet been done to determine whether these findings will translate into any significant clinical advantage.

In this study, physical properties of a commercial investment casting sprue wax (B97) have been improved by the addition of some additives so that it can be used as a pattern wax. For this purpose, some chemicals and soybeans of different varieties, which their positive effects oil the properties of B97 had been observed in our previous studies, have been used in combination. Two or more of these chemicals and soybean flours have been added to the wax composition and it has been shown that Surface roughness, solidification shrinkage, apparent viscosity, hardness, tensile strength and wettability properties of a sprue wax can be improved by these additives to such an extent that it has properties superior to those of a commercial investment casting pattern wax (B140). (C) 2003 Elsevier Ltd. All rights reserved.

Gluten-sensitive enteropathy, otherwise known as celiac sprue, is characterized by an abnormal proximal small intestinal mucosa arising as a result of an inappropriate inflammatory response to ingested gluten antigens present in wheat in genetically susceptible individuals. This immune response is directed to a 33-mer peptide of the alpha gliadin component of gluten. The generation of an epitope for the recognition by CD4+ T cells requires deamination of the protein by tissue transglutaminase (tTG). Moreover, IgA anti tTG is highly sensitive and is specific serologic marker (95-99%) of celiac disease. They can be easily determined quantitatively, by ELISA of an accurate and relatively inexpensive technique. Therefore, tTG can be used as the first line diagnostic test in the work-up of celiac disease, as well as for screening purposes. Finally, tTG may contribute to future strategies in treating celiac disease either by producing nontoxic wheat or by generating oral vaccination that can prevent the disease.

In this article, disease of the small intestine will be discussed, with particular reference to those conditions leading to malabsorption and malnutrition. The work up of these entities will be emphasized, with focus on bacterial overgrowth, celiac sprue and nonsteroidal-induced enteropathy.

The literature review and the recommendations therein were prepared for the American Gastroenterological Association (AGA) Clinical Practice and Practice Economics Committee. The paper was approved by the Committee on September 23, 2000, and by the AGA governing board on November 12, 2000. GASTROENTEROLOGY 2001;120:1526-1540

Zusammenfassung Die Zoliakie (Synonym: einheimische Sprue, glutensensitive Enteropathie, Herter-Heubner-Syndrom) ist eine chronische Verdauungsinsuffizienz aufgrund einer Unvertraglichkeit gegenuber dem in Getreideprodukten vorkommenden Gluten bzw. Gliadin. Es besteht eine genetische Disposition mit familiarer Haufung der Erkrankung. Charakteristisch ist eine Atrophie der Dunndarmzotten, die zu Malabsorption und Maldigestion fuhrt. Die Erkrankung betrifft etwa einen von 1000 Einwohnern und mehr Frauen als Manner. Typische Symptome sind Diarrho, Flatulenz, Gewichtsverlust sowie Eisenmangelanamie. Oligosymptomatische Verlaufe mit dem Bild eines Reizdarmes oder isolierter Erhohung der Lipase sind jedoch nicht selten. Die Diagnose kann uber eine tief duodenal entnommene Schleimhautbiopsie und den Nachweis von Antikorpern gegen Gewebs-Transglutaminase gestellt werden. Die Therapie besteht in einer konsequent glutenfreien Ernahrung. Selten ist immunsuppressive Therapie notwendig. Eine Spatkomplikation der unzureichend behandelten Sprue sind T-Zell-Lymphome des Dunndarms.

The increased incidence of gastrointestinal lymphoma and adenocarcinoma in patients with celiac sprue is well recognized, with 10% to 15% developing a gastrointestinal malignancy. Somatostatinomas are rare neuroendocrine tumors that occur most commonly within the pancreatic head or duodenum. Although fewer than 100 cases have been reported, somatostatinomas are often associated with multiple endocrine neoplasia-1 syndrome and von Recklinghausen's disease. The unusual case of a 43-year-old woman with celiac sprue in which a somatostatinoma involving the ampulla of Vater was identified and resected is presented. To our knowledge, somatostatinomas have not been previously reported in patients with celiac sprue.

Summary Background Adult refractory sprue is a poorly defined disorder. We did a multicentre national study of patients with refractory sprue to characterise their clinical and pathological profile and outcome, and to assess the frequency and prognostic significance of phenotypic and molecular abnormalities in the intraepithelial T-cell population. Methods Patients with severe symptomatic villous atrophy mimicking coeliac disease but refractory to a strict gluten-free diet, and with no initial evidence of overt lymphoma, were diagnosed at gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes (IEL). TCR γ gene rearrangements were assessed on frozen biopsy samples by multiplex fluorescent PCR. Findings There were 21 patients with refractory sprue and 20 controls with coeliacs disease. 16 (84%) of 19 assessed patients had an aberrant intraepithelial lymphoid intestinal population expressing intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCR γ gene rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed) had clonal dissemination to the blood. The 16 patients with an aberrant phenotype all had uncontrolled malabsorption; three subsequently developed overt T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal IEL made a complete clinical and histological recovery with steroid therapy plus a gluten-free diet. Interpretation An immunophenotypically aberrant clonal intraepithelial T-cell population (similar to that of most cases of enteropathy-associated T-cell lymphoma) can be found in up to 75% of patients with refractory coeliac sprue; its identification by simple diagnostic techniques represents a marker of poor outcome (including occurrence of overt T-cell lymphoma). We suggest that refractory sprue associated with an aberrant clonal IEL may be the missing link between coeliac disease and T-cell lymphoma and may be classified as cryptic enteropathy-associated T-cell lymphoma.

Background : The aim of this study was to determine in patients with sprue whether jejunal endoscopy improves the diagnostic yield or provides information that may modify management, when compared with evaluation limited to the duodenum. Methods : From January 1994 to June 1998, a total of 31 patients (6 men, 25 women, mean age 41 years) were prospectively evaluated by push enteroscopy. They were divided into two groups: (1) celiac disease at different stages of activity (n=23) and (2) refractory sprue (n=8). The endoscopic and histologic findings in the duodenum and in the jejunum were compared. Results : Celiac disease: In 19 patients, endoscopic and histologic findings in the duodenum and jejunum were similar; in four patients villous atrophy was more severe in the duodenum than in the jejunum. Refractory sprue: In 5 of 8 patients, enteroscopy revealed ulcerative jejunitis, whereas ulcerations were found in the duodenum in only one case. Conclusion : In refractory sprue, push enteroscopy with jejunal biopsies was of diagnostic value in 50% of cases demonstrating ulcerative jejunitis, whereas it did not modify the management of patients with responsive celiac disease.

There is, of course, always a need to have universally accepted criteria, conveniently called a gold standard, for the diagnosis of any disease. In general, the better defined the condition in terms of its clinical course, pathogenesis, clinical presentation, and histology, the simpler it becomes to define a precise gold standard. For some conditions, best exemplified by malignant neoplasms, histology is required even when the clinical and radiologic appearances are highly characteristic. For other conditions, histology is not pathognomonic but only characteristic; therefore, conditions with similar presentation must be excluded by additional measures. Thus, the gold standard for the initial presentation of celiac sprue is not only characteristic of small bowel histology but also a response to a gluten-free diet. For other conditions, histology is not key for the diagnosis; for example, the diagnosis of collagen-vascular disease is conventionally established by recognition of a clinical syndrome in conjunction with positive serum antibody tests, which together provide the gold standard. Whereas the diagnosis of chronic pancreatitis can be established histologically, in clinical practice obtaining tissue is only possible by resection of a portion of the pancreas, and in most instances this is not indicated. The histologic finding of pancreatitis, however, is not a complete diagnosis because it states a consequence of a cause, not the cause itself. For example, a patient with a pancreatic neoplasm initially may present clinically with chronic pancreatitis, and indeed a needle biopsy may show chronic pancreatitis until resective surgery is performed. Histology alone, although an important criterion in some patients who present with pancreatic disease, is not only usually unavailable but in certain circumstances is insufficient in isolation to establish a gold standard. Chronic pancreatitis is not a single, well-defined entity. Rather, it is a condition with multiple causes; a complex, not well-defined pathogenesis; and a variety of clinical presentations. Because it is not a simple, well-defined entity, a single test frequently does not provide a gold standard. As is apparent from the following discussion, we generally do not have a problem with the diagnosis of chronic pancreatitis in most patients. Those situations in which the diagnosis is challenging are threefold: (1) patients who present with pain alone, often atypical pain; (2) patients in whom the diagnosis of chronic pancreatitis cannot be differentiated confidently from pancreatic malignancy; and (3) patients who present with an episode of acute pancreatitis (AP), and the issue is whether this in fact represents AP or is the first clinical manifestation of chronic pancreatitis. What we attempt to outline in this article, therefore, are the criteria that we believe are necessary to establish the diagnosis of chronic pancreatitis. To do so, we consider the causes, pathogenesis, clinical presentation, and currently available structural and functional tests used in the diagnosis of pancreatic disease, with a major emphasis not only on their use but also on their limitations.

BACKGROUND: Celiac sprue is a malabsorption disease, which carries an increased risk of gastrointestinal malignancy, often underestimated. The purpose of this study was to examine the management of patients with gastrointestinal neoplasms complicating celiac disease. PATIENTS AND METHODS: The pathology database at our institution was searched from 1986 to present; and the literature from 1966 to 1997 was reviewed to identify reports of celiac sprue complicated by malignancy. A total of 82 cases were available for analysis. RESULTS: Two thirds of patients had carried the diagnosis of celiac sprue for a mean of approximately 10 years. The remaining one third were diagnosed with celiac disease and gastrointestinal malignancy simultaneously. Jejunal T-cell lymphoma was the most common malignancy. There was also an increased frequency of small intestinal adenocarcinoma and squamous cell carcinoma of the esophagus. Prognosis was generally poor, related to the histologic type and stage of the disease. CONCLUSIONS: Gastrointestinal malignant neoplasms, especially small bowel lymphomas, can occur in patients with celiac sprue. Patients with known celiac disease who present with exacerbation of symptoms should be promptly investigated for occult gastrointestinal malignancies, and considered for early surgical exploration.

Celiac disease is a chronic disorder of gluten sensitivity associated with a spectrum of mucosal lesions termed preinfiltrative, infiltrative, hyperplastic, destructive, and atrophic. The symptoms are not related to the degree of mucosal pathology but to the extent of the mucosal lesion. Neoplasms constitute the major complication of celiac disease, and EATCL is the most common neoplasm in this category. There is evidence that a strict gluten-free diet is protective against the complications of celiac disease; hence it is important that even the subclinical forms be diagnosed early. Small bowel biopsy remains the gold standard for diagnosis of celiac disease; however, antibody tests are a useful adjunct in deciding whom to biopsy and for screening groups at high risk before initiating a lifelong gluten-free diet.

Background & Aims: The etiology of refractory sprue is unclear. To gain insight into its pathogenesis, the phenotype and T-cell receptor (TCR) gene rearrangement status of intestinal lymphocytes were analyzed in a group of patients with clinical or biological features of celiac disease but either initially or subsequently refractory to a gluten-free diet. Methods: Intestinal biopsy specimens were obtained from 26 adults: 6 patients with refractory sprue, 7 patients with active celiac disease, and 13 normal controls. The phenotype of intestinal lymphocytes was studied by immunohistochemistry and, in 3 patients with refractory sprue, by cytometry of lymphocytes purified from intestinal biopsy specimens. TCR rearrangements were assessed by studying TCRγV-J junctional regions from DNA extracted from intestinal biopsy specimens and purified intestinal lymphocytes. Results: In the 6 patients with refractory sprue, but not in normal controls or patients with active celiac disease, the intestinal epithelium was massively infiltrated by small lymphocytes that lacked CD8, CD4, and TCR, contained intracytoplasmic but not surface CD3ϵ chains, and exhibited restricted TCRγ gene rearrangements. Conclusions: Refractory sprue is associated with an abnormal subset of intraepithelial lymphocytes containing CD3ϵ and restricted rearrangements of the TCRγ chain but lacking surface expression of T-cell receptors. GASTROENTEROLOGY 1998;114:471-481

Background : Occult gastrointestinal blood loss is generally investigated with colonoscopy and esophagogastroduodenoscopy in patients with iron-deficiency anemia. The aim of this study was to prospectively measure the additional diagnostic yield of examining the jejunum at the time of upper endoscopy in patients with iron-deficiency anemia. Methods : Asymptomatic patients with newly diagnosed iron-deficiency anemia who had no identifiable source of blood loss at colonoscopy underwent standard esophagogastroduodenoscopy with the Olympus SIF100L enteroscope followed by overtube-assisted enteroscopy. Upper tract and jejunal sources of blood loss were noted. Biopsy samples from the small bowel were taken when a bleeding lesion was not identified. Results : Thirty-one consecutive patients (13 men, mean age 71) with no gastrointestinal symptomatology were studied. Eleven patients (35%) had a bleeding source that required only esophagogastroduodenoscopy for identification; 8 patients (26%) had a source only in the jejunum; 2 patients (6%) (one with sprue) had a source in upper tract as well as jejunum. The enteroscopy was rated as causing minimal or mild discomfort in 25 of 31 patients (81%). Using Medicare reimbursement figures, a strategy of performing esophagogastroduodenoscopy first would have cost $656 per patient, whereas the strategy of performing esophagogastroduodenoscopy with enteroscopy as the initial test in all patients costs $467 per patient. Conclusions : Performance of push enteroscopy along with esophagogastroduodenoscopy increases the diagnostic yield from 41% to 67% when evaluating the upper gastrointestinal tract of asymptomatic patients with iron-deficiency anemia and, because of a lower cost, should be the preferred initial diagnostic test. (Gastrointest Endosc 1998:47:144-48)