Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency

BACKGROUND: Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency in childhood. The aim of the present study is to evaluate the correlation between genotype and exocrine pancreatic insufficiency in CF patients. The special emphasis was put on the analysis of mild CFTR mutations. DESIGN: The study comprised 394 CF patients and 105 healthy subjects (HS). Elastase-1 concentrations were measured in all subjects. RESULTS: Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DeltaF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717-1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DeltaI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 + 1G-A, E92GK, E217G, 2789 + 5G-A. 3849 + 1kbC-T/3849 + 1kbC-T) genotype resulted in high elastase-1-values. However, in case of patients with genotype DeltaF508/3849 + 10kbC-T, 1717-1GA/3849 + 10kbC-T as well as with DeltaF508/R334W, both high and low elastase-1 concentrations were found. Low E1 values were found in a patient with DeltaF508/R347P genotype. CONCLUSION: Patients who carry two 'severe' mutations develop pancreatic insufficiency, whereas those who carry at least one 'mild' usually remain pancreatic sufficient. However, the presence of one mild mutation does not exclude pancreatic insufficiency.     

A highly accurate method for monitoring histological recovery in patients with celiac disease on a gluten-free diet using an endoscopic approach that avoids the need for biopsy: a double-center study

BACKGROUND AND STUDY AIM: Endoscopy with duodenal biopsy is often performed in order to assess histological recovery in patients with celiac disease who are on a gluten-free diet. Use of the "immersion" technique during upper endoscopy allows visualization of duodenal villi or detection of total villous atrophy. In this two-center study, we investigated the accuracy of the immersion technique in predicting histological recovery in patients on a gluten-free diet whose initial diagnosis of celiac disease had been made on the basis of total villous atrophy. PATIENTS AND METHODS: The immersion technique was performed in 62 patients with celiac disease who were being treated and who had been referred for follow-up (26 patients at the Rome center and 36 patients at the Vicenza center). All these patients had an initial diagnosis based on positive antibodies and biopsy-proved duodenal total villous atrophy. At the follow-up examination, the duodenal villi were re-evaluated as present or absent by one endoscopist at each center, and the results were compared with the histology. RESULTS: At the follow-up endoscopy, the duodenal villi were found to be present in 51 patients and absent in 11. The sensitivity, specificity, positive predictive value, and negative predictive value of the immersion technique for detecting the presence or absence of villi were all 100 %. CONCLUSIONS: This study demonstrated the feasibility and the high level of accuracy of the immersion technique in predicting the histological recovery of duodenal villi in patients with celiac disease who are following a gluten-free diet. An endoscopy-based approach that avoids the need for biopsy could be useful for monitoring the dietary adherence and/or response of patients with an initial diagnosis of celiac disease based on total villous atrophy.     

Monitoring nonresponsive patients who have celiac disease

Because of the wide variations in the clinical presentation of celiac disease and because treatment exists that is effective in most cases, screening of the general population for celiac disease has been considered. There is still no evidence that patients who have symptom-free celiac disease are at increased risk of small intestinal lymphoma or other complications. Prevention of osteoporosis seems to be the strongest indicator for widespread screening today [22].The major cause of failure to respond to a gluten-free diet is continuing ingestion of gluten, but other underlying diseases must be considered.Many different drugs (eg, anti-tumor necrosis factor [TNF]-alpha) have been used in patients who have RCD [23]. Steroid treatment has been reported to be effective even in patients who have underlying early EATL.Histologic recovery in patients who have celiac disease usually takes several months but can take up to 1 year, even if the patient remains on a strict gluten-free diet. Some patients report celiac-related symptoms for months after a single gluten intake.The definitions for RCD in literature vary. The authors consider the definition give by Daum and colleagues [24] suitable. They defined true RCD as villous atrophy with crypt hyperplasia and increased IELs persisting for more than 12 months in spite of a strict gluten-free diet.If a patient is not responding well to a gluten-free diet, three considerations are necessary: (1) the initial diagnosis of celiac disease must be reassessed;(2) the patient should be sent to a dietician to check for errors in diet or compliance problems, because problems with the gluten-free diet are the most important cause for persisting symptoms; (3) other reasons for persisting symptoms (eg, pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, protein-losing enteropathy,T-cell lymphoma, fructose intolerance, cavitating lymphadenopathy, and tropical sprue) should be considered.Other causes for villous atrophy are Crohn's disease, collagenous sprue, and autoimmune enteropathy.Abdulkarim and colleagues [25] examined 55 patients who had a diagnosis of nonresponsive celiac disease. He found that 6 did not have celiac disease, and25 still had some gluten ingestion.Tursi and colleagues [26] reported 15 patients who had celiac disease with persisting symptoms. Because histology improved in all patients after several months, RCD was excluded. Of the 15 patients, 10 had small intestinal bacterial overgrowth, 2 showed lactose malabsorption causing the described symptoms, 1 had mistakenly taken an antibiotic containing gluten, and 1 patient each had Giardia lamblia and Ascaris lumbricoides. Thus, other entities must be considered in patients who have celiac disease and ongoing symptoms.In a follow-up clinical trial, 158 patients who had celiac disease underwent follow-up small intestine biopsies within 2 years after starting a gluten-free diet.Eleven patients (7.0%) with persisting (partial) villous atrophy were considered to have RCD; 5 of them developed EATL [27].RCD type I is characterized by normal expression of T-cell antigens and polyclonal TCR gene rearrangement.RCD type II is characterized by an abnormal IEL phenotype with the expression of intracytoplasmic CD3e, surface CD103, and the lack of classic surface T-cell markers such as CD8, CD4, and TCR-alpha/beta. This clonal IEL population can be considered crypt IEL [24]. RCD II has a poor prognosis, which is a problem for therapy.Clonal TCR gene rearrangements and loss of T-cell antigens such as CD8 and TCR-beta in IELs may indicate the development of an EATL in patients who have RCD.The markers for an overt EATL are a positive stool blood test, increased lactate dehydrogenase, or beta2-microglobulin [24]. If an overt lymphoma is suspected, upper and lower endoscopy, an ear, nose, and throat work-up, CT scan, capsule endoscopy, and possibly double-balloon enteroscopy should be performed.Most reports of the difficulties in treating patients who have true RCE are casereports. Turner and colleagues [28] reported on an induction of remission by useof the anti-TNF-alpha antibody infliximab and maintenance with prednisoloneand azathioprine. Olaussen and colleagues [29] and Mandal and colleagues [30]tried a nonimmunogenic elemental diet.Gillet and colleagues [31] reported successful treatment of a patient who hadRCD using anti-TNF-alpha antibodies (infliximab) for induction and azathioprinefor maintenance.Maurino and colleagues [32] studied seven consecutive patients diagnosed ashaving refractory sprue and no response to oral or parenteral steroids. Aftertreatment with azathioprine (2 mg/kg/d) and oral prednisone (1 mg/kg/d), fivepatients had a complete clinical remission. Two patients who did not respond totreatment at any time died.Goerres and colleagues [33] described 18 patients who had RCD, 10 of whomhad type I RCD, and 8 of whom had type II RCD. Treatment consisted ofazathioprine combined with prednisone for 1 year. Consistent with reports byother investigators, the response rates in the two groups differed. Eight of the10 patients who had type I RCD had a histologic response. Seven of the eightpatients who had type II RCD died, and six of the eight developed a lymphoma.At present there is no effective treatment for type II RCD.Fig. 3 presents a proposed algorithm for monitoring patients who have ce-liac disease.     

Collagenous sprue: a case description

Collagenous sprue (CS) is a rare disease of the small bowel, which is characterized by complete atrophy of mucosal villi and excessive subepithelial collagen deposition. The authors describe a 40-year-old patient, who was examined for severe malabsorption syndrome. The diagnosis of celiac disease was based upon serological and histological data, but gluten-free diet was not effective and only treatment with prednisolone led to positive changes. Another histologic study revealed a focal deposit of collagen under the epithelium in addition to signs of intestinal mucosal atrophy, and the diagnosis of CS was made. The case is discussed from the positions of known information of CS.     

Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis

BACKGROUND: We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. METHODS: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. RESULTS: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from approximately 15% of patients without CD. CONCLUSION: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.     

Relevance of the barium follow-through examination in the diagnosis of adult celiac disease

Significant changes on a standard barium follow-through examination in celiac disease have been determined by comparison with functional changes (irritable bowel syndrome), malabsorption without a villous lesion (chronic pancreatitis), and a villous abnormality without malabsorption (dermatitis herpetiformis). Patients with iron deficiency anemia formed the control group. Slight jejunal dilatation (26–30 mm) was found in 15% of the celiacs and 17% of the irritable bowel patients. Dilatation in excess of 30 mm and/or effacement of jejunal fold pattern occurred only with an abnormal jejunal biopsy, in 54% of the celiacs and 33% of the dermatitis herpetiformis patients. Patients with malabsorption by itself and 46% of the celiacs could not be distinguished from those with irritable bowel syndrome. The concept of a malabsorption pattern is considered invalid, and the diagnosis of celiac disease can be reliably established only by peroral jejunal biopsy.     

Inhibition of endogenous pancreatic enzyme secretion by oral pancreatic enzyme treatment

BACKGROUND: The existence of a feedback mechanism for exocrine pancreatic secretion in humans is controversial. Exclusion of proteases from the duodenum stimulates exocrine pancreatic secretion. Conversely, addition of exogenous enzymes could reduce the enzyme secretion. Further investigation of the feedback mechanism should be performed under the most physiological conditions. In the present study we investigated exocrine pancreatic function by measuring fecal enzyme output in healthy volunteers consuming a normal diet, before and during a time course of exogenous pancreatic enzyme supplementation. MATERIAL AND METHODS: Twenty-five healthy subjects (HS) were given two different doses (30 and 60 FIP proteases kg(-1) d(-1)) divided by the number of meals. In all subjects, fecal elastase-1 (E1) concentrations and chymotrypsin (ChT) activities were measured without and with enzyme supplements after 7 days of treatment. In eight subjects, E1 concentrations and ChT activities were measured daily for 10 consecutive days. The subjects were given a dose regimen of 100 FIP proteases kg(-1) d(-1)(divided by the number of meals) for the first 7 days. RESULTS: Oral pancreatic treatment dose-dependently inhibited endogenous pancreatic secretion measured with the use of E1 concentrations. In both regimen groups, the differences were statistically significant. The exogenous enzymes, which interfere with colorimetric method for ChT, dose-dependently increased ChT output. However, only the higher dose resulted in a statistically significant difference. In the subgroup of eight HS, time-dependent changes of fecal enzyme output occurred with a decrease of E1 concentrations and an increase of ChT activity from the second up to eighth or ninth day of the experiment. CONCLUSION: Exogenous applied pancreatic enzymes, dose- and time-dependently inhibited endogenous pancreatic secretion. The obtained results strongly support the existence of a protease mediated feedback mechanism in humans.     

Case Report: Revisiting Celiac Disease

Abstract

Celiac disease (CD) is an autoimmune disorder that causes varying degrees of villous atrophy and chronic malabsorption in genetically predisposed persons. Once considered a rare disease affecting children, younger adults, and persons of European ancestry, CD is increasingly recognized in all demographic groups with a prevalence rate in the United States of almost 1%. We offer an overview of the evaluation and management of CD vis-à-vis the case of a 41-year-old man who was hospitalized after presenting with the classic symptoms of chronic abdominal complaints, diarrhea, iron-deficiency anemia, and weight loss. Celiac disease remains an underdiagnosed condition in the United States, which is unfortunate given the potential treatment with a gluten-free diet.     

Frequent causes of diarrhea: celiac disease and lactose intolerance

Celiac disease and lactose intolerance are both relatively frequent diseases with symptoms occurring after ingestion of certain food components.In celiac disease wheat gluten and related proteins of other cereals induce an inflammatory disease of the small intestine in predisposed individuals, leading to gastrointestinal and extraintestinal symptoms. Moreover, there is an association with many other diseases and besides classic symptoms (diarrhea, weight loss, malabsorption) atypical courses with less or lacking gastrointestinal symptoms exist. The prevalence is about 1 : 100 (Europe, USA) and higher than supposed earlier. Diagnostic criteria include serologic tests (tissue transglutaminase antibody, endomysial antibody) and characteristic small bowel histology (lymphocytic infiltration, villous atrophy). Therapy is a strict and lifelong gluten-free diet. Rarely, refractory disease or lack of compliance are associated with increased risk of malignancy and worse prognosis.Lactose intolerance is attributed to low intestinal lactase levels, due to reduced genetic expression or mucosal injury and consequent intolerance to dairy products. The frequency is varying in different ethnic groups, occurring in 10-15% of Northern European people. Intensity of clinical symptoms (diarrhea, abdominal pain, bloating) depends on the amount of ingested lactose and individual activity of intestinal lactase. The capacity of lactose malabsorption can be measured using the noninvasive lactose breath hydrogen test. The treatment is based on a reduced dietary lactose intake or in case of secondary form treatment of the underlying disease.     

Endoscopic markers of villous atrophy are not useful for the detection of celiac disease in patients with dyspeptic symptoms

BACKGROUND AND STUDY AIMS: Celiac disease can manifest with nonspecific symptoms, including functional gastrointestinal disorders such as dyspepsia. The aim of our study was to assess the usefulness of duodenal endoscopic markers of villous atrophy for the selection of dyspeptic patients for histological assessment. PATIENTS AND METHODS: Esophagogastroduodenoscopy was performed in dyspeptic patients, in patients considered to be at risk of having celiac disease, and in healthy controls. At least three duodenal biopsies were performed for histological assessment of villous atrophy in all patients and controls. We looked for the following four duodenal endoscopic markers of celiac disease: reduction in the number of folds, scalloping of folds, mosaic-pattern mucosa, and nodular mucosa. RESULTS: A total of 175 people were enrolled (75 patients with dyspepsia; 75 patients who were "at risk" of having celiac disease; and 25 healthy volunteers, or "controls"). Of the dyspeptic patients, four had endoscopic markers of celiac disease with no histologically confirmed villous atrophy, while one patient without endoscopic markers was found to have Marsh type I villous atrophy. Of the patients at risk of having celiac disease, 16 had at least one endoscopic marker and 10/16 were found to have histological villous atrophy. In this group, the sensitivity and specificity of the endoscopic markers were 100 % and 90.8 % respectively. "At-risk" patients with two or more endoscopic markers all had histologically confirmed villous atrophy. Neither endoscopic markers nor villous atrophy were found in any of the control patients. CONCLUSIONS: Additional endoscopic markers are valuable for diagnosis in patients with clinical symptoms suggestive of celiac disease. In contrast, endoscopic markers of villous atrophy are not useful for selecting a subgroup of dyspeptic patients for screening for celiac disease by duodenal histological assessment. These patients should be screened using other protocols.     

Hereditary pancreatitis in a young adult: Acute to chronic

This report investigates an unusual case of recurrent pancreatitis. A 22-year-old female was admitted to the emergency room for severe abdominal pain, nausea, and weight loss. She reported having these symptoms since she was a toddler. The clinician ordered fecal pancreatic elastase-1, fat-soluble vitamins, molecular studies, and imaging of the pancreas by computed tomography. The screening test result for fecal pancreatic elastase-1 revealed severe pancreatic exocrine insufficiency, and the concentrations of fat-soluble vitamins were also low. Imaging showed scattered calcifications in the pancreas. These findings supported a diagnosis of chronic pancreatitis. Due to the rarity of chronic pancreatitis in young adults, molecular studies were performed. The patient was found to be homozygous for a mutation in the SPINK1 gene, which is associated with hereditary pancreatitis. This case report discusses hereditary pancreatitis and highlights data on the utilization of fecal pancreatic elastase-1 to assess pancreatic exocrine insufficiency.     

Fecal elastase-1 as a test for pancreatic function: a review.

Pancreatic elastase-1 is a specific human protease synthetized by the acinar cells. Immunoreactive elastase-1 cannot be detected in either porcine or bovine pancreatic enzyme preparations. It is very stable and, in contrast to fecal chymotrypsin, elastase is unaffected by exogenous pancreatic enzyme treatment, and correlates well with exocrine pancreatic function tests. The measurement of this proteolytic enzyme in stool by means of an enzyme-linked immunosorbent assay (ELISA) is a sensitive, specific, and relatively inexpensive non-invasive test. It is an accurate function test for patients with chronic pancreatitis confirmed by endoscopic retrograde cholangiopancreatography and computerized axial tomography. It shows higher sensitivity and specificity for exocrine pancreatic insufficiency than fecal chymotrypsin determination and is comparable to oral pancreatic function tests such as the pancreolauryl test.     

Fecal chymotrypsin and elastase-1 determination on one single stool collected at random: diagnostic value for exocrine pancreatic status

OBJECTIVE: The secretin-cholecystokinin test is the "gold standard" to evaluate exocrine pancreatic function. But this direct duodenal intubation test is invasive, particularly in children, time-consuming, and expensive. For several years, indirect noninvasive tests of pancreatic insufficiency have been developed, such as fecal chymotrypsin (FChT) and fecal elastase-1 (FEL-1) measurements. Generally, elastase-1 is truly admitted to be the most relevant test of exocrine pancreatic status. However, so far, no consensus for stool collection protocol exists. The aim of our study was to investigate the diagnostic advantage from measuring fecal proteases in stool samples collected for two or three consecutive days in comparison to one single stool sample collected at random. DESIGN: A total of 69 children were divided into group A (stool samples collected for three consecutive days) and group B (stool samples collected for two consecutive days). These two groups included pancreatic-sufficient patients (PS) and severe pancreatic-insufficient patients (PI). One single determination of fecal chymotrypsin activity and of fecal elastase-1 concentration was realized on each stool. RESULTS: The same relatively important intraindividual variability of fecal proteases was observed in group A and B (mean coefficients of variation (CVs) 36% vs. 40.2% for chymotrypsin, 22.2% vs. 26.8% for elastase-1). No significant PS or severe PI diagnostic discordance was observed between 1, 2, or 3 days of stool collections. CONCLUSION: Our study clearly shows that the determination of fecal proteases on one single stool collected at random is sufficient to evaluate pancreatic exocrine status for PS and severe PI.     

The Occurrence and Effects of Human Vitamin E Deficiency: A STUDY IN PATIENTS WITH CYSTIC FIBROSIS

The role of vitamin E in human nutrition was studied by investigation of patients with cystic fibrosis (CF) and associated pancreatic insufficiency. Vitamin E status was assessed by measurement of the plasma concentration of the principal circulating isomer, α-tocopherol. Results of such determinations in 52 CF patients with pancreatogenic steatorrhea revealed that all were deficient in the vitamin. The extent of decreased plasma tocopherol varied markedly but correlated with indices of intestinal malabsorption, such as the serum carotene concentration and percentage of dietary fat absorbed. Supplementation with 5-10 times the recommended daily allowance of vitamin E in a water-miscible form increased the plasma α-tocopherol concentrations to normal in all 19 CF patients so evaluated.     

Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up

OBJECTIVE: This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease. RESEARCH DESIGN AND METHODS: In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD. RESULTS: In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6-16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA(1c) remained unchanged (P = 0.311) during follow-up. CONCLUSIONS: This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes.     

Improving outcomes in patients with cystic fibrosis

Cystic fibrosis (CF) is the most common fatal inherited disease in Caucasian people. Inheritance follows an autosomal recessive pattern. Recent data indicate that there are more than 9,000 patients with CF in the UK. At a cellular level there is an abnormal CF transmembrane conductance regulator (CFTR), a protein essential for chloride and sodium homoeostasis, caused by a mutation in the CF gene. The consequence of this abnormal protein is thick, viscous secretions in the lungs and GI tract, which lead to recurrent lung infections and pancreatic insufficiency with intestinal malabsorption. Most patients present in early childhood with classic CF. They show one or more of the typical CF phenotypic characteristics (chronic pulmonary disease, GI symptoms and malabsorption, nutritional abnormalities and sinus disease). A minority of patients have atypical CF. They tend to present at an older age, often in adulthood, are mainly pancreatic sufficient, have milder disease and a better prognosis. When CF is suspected the diagnosis can be confirmed by measuring sweat chloride concentration and by looking for CFTR mutations. Immunoreactive trypsinogen is measured in blood taken from a heel prick in all neonates, and is a marker of pancreatic injury consistent with (but not specific for) CF.     

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201–995 in acromegalic patients

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.     

Évaluation endoscopique des patients atteints de maladie coeliaque

Celiac disease is an autoimmune disorder of the small bowel triggered by the exposure to gliadine, a storage protein of wheat and similar grains, occurring in genetically predisposed patients. The diagnosis of celiac disease typically requires the presence of both anti-tissue transglutaminase antibodies in the serum and specific histological features on small bowel mucosal biopsies, such as villous atrophy. The goals of the endoscopist in the management of patients with known or suspected celiac disease is to obtain contributive histological samples, knowing that mucosal lesions may be patchy among the small bowel, and to diagnose potential complications, such as ulcerative jejunitis, refractory sprue, or enteropathy-associated T lymphoma. We reviewed the respective contribution of the various endoscopic diagnostic tools in the management of patients with celiac disease.     

Cardiomyopathy associated with celiac disease

Celiac disease or celiac sprue is predominantly a disease of the small intestine characterized by chronic malabsorption in genetically susceptible individuals who ingest grains containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon, celiac disease may be present in up to 1% of the general population. Celiac disease is associated frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy associated with celiac disease is a serious and potentially lethal condition. However, with early diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may be completely reversible.     

Advances in the diagnosis and management of cystic fibrosis

Cystic fibrosis (CF), the most common lethal genetic disease affecting Caucasians, is a multi-system illness, most frequently characterized by childhood chronic obstructive pulmonary disease, pancreatic exocrine insufficiency, and abnormal sweat electrolyte concentrations. The diagnosis of CF is based on a combination of the above clinical findings and/or a positive family history of the illness in conjunction with an abnormal sweat test. The quantitative pilocarpine iontophoresis test is the sole acceptable method for diagnostic confirmation of the clinical suspicion of CF. A recent advance in the diagnosis of CF has been in the development of methods for neonatal detection. The immunoreactive trypsinogen (IRT) detection test is practical, adaptable to large scale screening of dried neonatal blood spots, relatively inexpensive, and promising for the detection of newborns with CF who have pancreatic insufficiency. However, the reliability and validity of this method have not yet been adequately established. Major advances in the treatment of patients with CF have emerged in the last decades, particularly in supportive pulmonary and nutritional care.