Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet.

The aim of this study was to investigate the relation between Celiac disease (CD) and unexplained dysfunctional uterine bleeding (DUB) in celiac women. The celiac patients were selected from women who were referred to celiac department. Controls were selected from those women without any signs of celiac disease and matched with age. Meanwhile, a trained physician was ready to explain the study, and then in case of their allowance, a questionnaire was completed by the physician. 24 % of celiac women reported a past history of at least one menstrual cycle disorder vs 10 % of controls reported these problems (p=0.038) and higher percentage of unexplained DUB has been observed in celiac women. All celiac patients were undertaking gluten free diet for at least 3 months and the celiac patients who reported the history of DUB were again interviewed for any signs of unexplained DUB. From 12 celiac women with DUB, 10 patients reported no more unexplained DUB after getting gluten-free diet (83.3 %). The occurrence of a significant correlation between CD and DUB suggests the possibility of considering CD as one of the potential causes of abnormal uterine bleeding. Therefore, celiac disease must be seriously considered in the screening of patients with reproductive disorders (Tab. 2,Ref. 23).

Celiac disease hidden by cryptogenic hypertransaminasemia mistaken for fatty liver.

A variety of signs and symptoms have been reported in regards to the typical and atypical presentations of CD. It is now well recognised that its onset may occur at any age and that atypical forms of CD are much more prevalent than its classic form (1).In this case, where the patient presented with high BMI and evidence of grade I of fatty liver disease, CD was suspected due to mildly abnormal bloating, cryptogenic hypertransaminasemia, abnormal LFT and poor response to fatty liver treatment. This presentation type is not uncommon; diagnosis was confirmed by the presence of subtotal villous atrophy in the biopsy specimen, positive specific antibody screening (AGA, tTG and EMA antibodies), negative antibody screening and normalization of liver enzymes on a gluten-free diet (Tab. 2, Ref. 13).

Epidemiology of celiac disease in iran: a review.

Celiac disease (CD) was traditionally believed to be a chronic enteropathy, almost exclusively affecting people of European origin. Celiac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. The availability of new, simple, very sensitive and specific serological tests has shown that CD is as common in Middle Eastern countries as in Europe, Australia and New Zealand where the major dietary staple is wheat. A high prevalence of CD has been found in Iran, in both the general population and the at-risk groups, i.e. patients with type 1 diabetes or irritable bowel syndrome (IBS). In developing countries, serological testing in at risk groups is necessary for early identification of celiac patients. Clinical studies show that presentation with non-specific symptoms or a lack of symptoms is as common in the Middle East as in Europe. Wheat is a major component of the Iranian diet and exposure to wheat proteins induces some degree of immune tolerance, leading to milder symptoms that may be mistaken with other GI disorders. The implementation of gluten free diet (GFD) is a major challenge for both patients and clinicians in Iran, especially since commercial gluten-free products are not available in this area.

Microscopic enteritis: novel prospect in coeliac disease clinical and immuno-histogenesis. Evolution in diagnostic and treatment strategies.

The diagnosis of coeliac disease has traditionally depended on symptoms and intestinal biopsies; nowadays, the diagnosis has been expanded to include an array of serological markers and subtle microscopic lesions. The most important advance in classifying mucosal lesions in coeliac disease was forwarded by Marsh (1992), who provided the biological explanation of how the small bowel reacts to a variety of environmental antigenic challenges including gluten. In the modified version of this classification (Arnhem 1998-1999) autoantibodies have integrated into Marsh's histopathological scheme. As a large part of the coeliac 'iceberg' remains unrecognised, the difficulties in diagnosis continue to challenge clinicians and researchers. Advances in immuno-histochemistry and discovery of the other sensitive markers have acquainted us with so-called Microscopic enteritis, the distinctive subtle abnormalities behind the atypical gluten sensitivity symptoms that often remain unrecognised. Current diagnostic pathways do not always include facilities for looking for this common histological feature in atypical cases. This is essential since improving of the detection rate has been shown to be directly proportional to recognition of cases with milder or minimal mucosal abnormalities. In this revision, we will define and characterise microscopic enteritis as the entity behind a wide range of unexplained gastrointestinal symptoms. Screening for this subtle and distinctive presentation in small bowel pathology will open a new prospect in recognising the most common but unrecognised atypical forms of symptomatic gluten related enteropathies.

Celiac disease and Hp infection association in Iran.

BACKGROUND: we assessed the prevalence, the related symptoms, and the endoscopic and histologic gastric features of celiac disease (CD) in patients with Helicobacter pylori (Hp). METHODS: 450 dyspeptic patients were studied. Biopsies of gastric antrum and duodenum, CD serology, and total IgA were obtained. Histological findings were scored with the Marsh-Rostami criteria. RESULTS: 411 (91.3%) patients were Hp positive. Duodenal histology was normal in 385 (85.6%) patients, 124 (27.5%) had duodenitis and 28 (6.2%) showed duodenal abnormalities (Marsh I-IIIc). Twenty three/28 (82.1%) patients with malabsorption pattern were also Hp positive. Serological analysis: 12 of 31 (38.7%) positive patients had abnormal histology (Marsh I,-IIIc). Nine out 450 patients were IgA deficient; none of them was serologically positive for CD. CONCLUSION: although a high prevalence of Hp infection was found in this study, the relationship between Hp infection and CD was similar to that reported in other geographic areas.

Some studies of alpha-amylase production using Aspergillus oryzae.

The extracellular alpha-amylase production by Aspergillus oryzae was studied in submerged fermentation using an Adlof-Kuhner orbital shaker. The effect of initial pH values in the range of 4 to 7.5 on enzyme production was investigated and initial pH medium of 6.2 +/- 0.1 resulted in enhanced alpha-amylase production. The effect of carbon and nitrogen source and composition was examined and it has been observed that corn starch concentration of 15 g L(-1) has sound effect on enzyme production. The medium containing corn starch, sodium nitrate resulted in considerable higher enzyme production. Further, the yeast extract of 2.5 g L(-1) in the medium produced higher enzyme in view to other organic nitrogen sources. The effect of temperature on alpha-amylase production from 20 to 40 degrees C has been studied and at 35 +/- 1 degrees C higher alpha-amylase has been obtained. The effect of shaker's speed on alpha-amylase production from 50 to 200 rpm was investigated. And at about 180 rpm higher enzyme production has been observed. In the present study, it has been found that glucose has repressing effect on a-amylase production using A. oryzae PTCC5164.

Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder?

About 10,000 years ago domestication and farming of wheat and other cereals developed in the 'Fertile Crescent', an area including modern Turkey, Iraq and Iran. Agriculture then slowly spread from Middle East to Europe. Coeliac disease is the permanent intolerance to dietary gluten, the major protein component of wheat. It has been until relatively recently hypothesised that wheat consumption exerted a negative selective pressure on genes predisposing to coeliac disease, eventually leading to higher coeliac disease frequency in Northeastern Europe because of lack of exposure to cereals. This theory is at variance with recent studies showing that coeliac disease is as common in Middle Eastern countries as in Europe. High prevalence of coeliac disease has been found in Iran, in both the general population and at-risk groups, e.g. patients with irritable bowel syndrome or type 1 diabetes. Clinical manifestations of coeliac disease vary markedly with the age of the patient, the duration and the extent of disease. Clinical studies showed that presentation with non-specific symptoms or no symptoms is as common in the Middle East as in Europe. Wheat represented a major component of the Iranian diet for many centuries and it may be argued that the continuous and high level of exposure to wheat proteins has induced some degree of immune tolerance, leading to milder symptoms that may be misdiagnosed as irritable bowel syndrome or unexplained gastrointestinal disorders. The gluten-free diet represents a real challenge to both patients and clinicians in this area. This is particularly difficult in the absence of any supply for gluten-free diet in Middle Eastern countries.

Enzyme mass-transfer coefficient in aqueous two-phase systems using static mixer extraction column.

Recent technical advances in aqueous two-phase systems (ATPS) have made this a sound technique for the extraction of biomacromolecules. The extraction of alpha-amylase was investigated using aqueous two-phase systems formed by sodium sulphate-polyethylene glycol (PEG) in water in a 47-mm inner diameter spray column packed with three types of static mixers. The effects of dispersed-phase flow rate, phase composition, column height and diameter were studied. The extraction column was operated in a semi-batch manner. It was found that the hold-up and volumetric mass transfer coefficients increased with an increase in dispersed (PEG-rich) phase velocity and decreased with increasing phase composition. Empirical correlations were developed for fractional dispersed-phase hold-up and volumetric mass transfer coefficients.

Coeliac disease and reproductive disorders: a neglected association.

Coeliac disease is a chronic disease caused by a permanent intolerance to ingested gluten resulting in immunologically mediated inflammatory damage of the small-intestinal mucosa. The wide spectrum of clinical symptoms is partly due to the malnourished state caused by the malabsorption of macro- and micronutrients. Fertility problems, sexual dysfunction and obstetrical complications are more frequently observed in patients with coeliac disease. These reproductive disorders may be a consequence of the endocrine derangements caused by selective nutrient deficiencies. Nowadays, the early diagnosis and treatment of coeliac disease is possible and not very costly. Therefore, coeliac disease must be seriously considered in the preconceptional screening and treatment of patients with reproductive disorders.

Should relatives of coeliacs with mild clinical complaints undergo a small-bowel biopsy despite negative serology?

BACKGROUND AND OBJECTIVES: Small intestinal lesions in coeliac disease (CD) have a variable severity. Early diagnosis of CD is important because treatment allows a normal psycho-physical development, especially in children, and can avoid associated disorders. The aim of this study was to evaluate the predictive value of screening parameters for the detection and estimation of CD prevalence in first-degree relatives. METHODS: The screening was performed in 338 first-degree relatives of 134 coeliac families. Questionnaires and a physical examination followed by haematological analyses and serologyfor IgA anti-endomysium (EMA)/IgA antigliadin (AGA) antibodies were used in orderto selectthe candidates for small-bowel biopsy. The small-bowel biopsy was indicated on the basis of clinical complaints, laboratory tests and serology performed in 96 (28%) of the study group. RESULTS: CD was diagnosed in 17/96 cases. Six of the 17 showed total villous atrophy (VA) (Marsh IIIc), five subtotal VA (Marsh IIIb) and six partial VA (Marsh IIIa). EMA and AGA were strongly positive in the six patients whose intestinal biopsy showed total VA. However, only one coeliac out of the six patients with partial VA had positive EMA and AGA. CONCLUSION: A significant proportion of coeliacs may be missed if cases are screened by serology only. Although endomysial antibody assay has been reported as a highly sensitive and specific test for detection of CD, we argue that using only EMA and AGA in screening is not enough for investigation of the true prevalence of CD. A combination of clinical parameters as described in this study and laboratory/serological tests is an important and practical contribution to improving the detection rate of CD.

The relationship between anti-endomysium antibodies and villous atrophy in coeliac disease using both monkey and human substrate.

BACKGROUND/OBJECTIVE: Circulating antibodies offer a noninvasive diagnostic screening test in patients with coeliac disease with severe histopathological abnormalities. This study assesses for the first time the sensitivity and reliability of anti-endomysium in screening for coeliac disease in patients with milder forms of villous atrophy using human umbilical cord and monkey ileum. MATERIALS AND METHODS: Serum from 124 adults and children > 2 years old including 33 patients with coeliac disease on a gluten-free diet and 91 patients referred to the laboratory for screening was studied. The presence of IgA-anti-gliadin (AGA) (ELISA) and IgA-anti-endomysium (EMA) was detected in the serum using monkey ileum and human umbilical cord (HUC) substrates. Patients with abnormal serology results or severe clinical complaints were invited to attend for a small-bowel biopsy. The prevalence of EMA detected on monkey ileum and HUC was compared with the histopathological features of coeliac disease at presentation. Fifty-three of the 91 patients screened for coeliac disease underwent a small intestinal biopsy. RESULTS: Twenty-three of the 91 patients suspected of having coeliac disease had coeliac disease. The EMA test was positive in 18 of 23 using both monkey ileum and HUC (sensitivity 78%). Partial villous atrophy (PVA) was seen in four of the five EMA-negative patients, and subtotal/total villous atrophy (SVA/TVA) was demonstrated in 18 of the 23 cases with positive EMA. Both substrates detected identical positive cases. There was an excellent concordance between EMA sensitivity evaluated on HUC and those on monkey ileum. One patient was EMA-negative on monkey ileum but positive on HUC and one patient who was EMA-positive on monkey ileum was EMA-negative on HUC. Only one of 33 coeliac disease patients on gluten-free diet for more than one year with persisting TVA had positive EMA. The rest of the cases had a negative EMA on both HUC and monkey ileum. CONCLUSION: A negative result for EMA in coeliac disease patients with a normal IgA value does not exclude the diagnosis of coeliac disease. A positive EMA is seen mostly in those coeliac disease patients with severe tissue damage (SVA/TVA). EMA has a low sensitivity in coeliac disease patients with PVA in spite of use of different substrates.

High prevalence of celiac disease in apparently healthy blood donors suggests a high prevalence of undiagnosed celiac disease in the Dutch population.

BACKGROUND: In the last few years the prevalence of celiac disease (CD) seems to have increased. It is clear that subclinical and silent CD exist in a large subgroup of the celiac population. METHODS: The aim of this study was to evaluate the prevalence of CD in an apparently healthy population. Blood samples were obtained from 1000 apparently healthy blood donors at Arnhem and Nijmegen Blood Donation Centers from January 1997 through April 1998. Sera from 660 blood donors were assayed for total IgA. By means of immunofluorescence, antibodies, including those to endomysium (EMA), were determined. Serum immunoglobulin levels (IgA) were assayed by means of nephelometry. All donors who had positive serology for EMA underwent small-intestinal biopsy. RESULTS: Of the 1000 healthy blood donors 3 had positive EMA. Small-intestinal biopsy of two of these showed subtotal villous atrophy (Marsh IIIb), and the third had intraepithelial lymphocytosis and crypt hyperplasia (Marsh II). The prevalence of gluten sensitivity was 1 of 330. Low IgA (0.60-0.23 g/l) in our study group was found in 9 of 660 (1%), but no one showed an IgA < or = 0.02 g/l. CONCLUSION: Our study shows that the prevalence of gluten-sensitivity in apparently healthy blood donors is 3 of 1000, which suggests a high prevalence of CD in the Dutch population, in contrast to the results of the last published Dutch epidemiologic studies. The recorded prevalence will increase further with greater recognition of subclinical and asymptomatic forms detected by screening tests.

Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice.

OBJECTIVE: We have undertaken a study to assess the efficiency of serological tests in the diagnosis of celiac disease (CD) during the period January 1, 1994 to January 7, 1997. Our aim was to evaluate the sensitivity of IgA antiendomysium (EMA) and IgA antigliadin (AGA) with regard to the degree of histological abnormality in biopsy specimens of small intestine in untreated celiac disease patients and first-degree relatives. METHODS: The study population comprised 101 cases: 85 untreated celiac patients and 16 first-degree relatives with a mean age of 42 yr (range, 2-76 yrs). Sixteen of 85 were excluded from study because they did not satisfy the study or diagnostic criteria of CD. EMA and AGA have been compared with the degree of villous atrophy (VA) in 69 celiac patients and 16 relatives according to the Marsh criteria of 1992. We divided the Marsh III histology into three subgroups as follows: Marsh IIIa (partial VA), Marsh IIIb (subtotal VA), and Marsh IIIc (total villous atrophy). RESULTS: The specificity and positive predictive value of EMA for CD was excellent, because all EMA-positive patients (n = 42) were diagnosed with CD. The sensitivity of EMA, however, differed between CD subgroups; in patients with total VA, the sensitivity of EMA was 100% (17/17). However, in patients with partial VA (Marsh IIIa), the sensitivity of EMA was disappointing, only 9/29 (31%). Three of 72 celiacs with Marsh IIIb and Marsh IIIc had IgA deficiency and were excluded from the study. Elevated AGA has been detected in the sera of 39 of 69 (62%) patients. A combination of EMA and AGA tests showed a sensitivity of 76% (53/69). None of 16 first-degree relatives with Marsh I-II had positive EMA. CONCLUSIONS: Interpretation of negative serology needs great awareness. Although EMA sensitivity in total villous atrophy is excellent, in partial villous atrophy the sensitivity of EMA appears to be disappointing. Our experience shows that EMA and AGA have only limited value in screening programs for CD.

SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality.

UNLABELLED: The aim of this study was to assess the correlation of sugar absorption test (SAT) using Lactulose/Mannitol/Sucrose (LMS), with IgA-endomysium (EMA), and IgA-gliadin (AGA) antibodies in relation to the severity of the intestinal mucosal damage in adult coeliacs. We have differentiated the Marsh classification in partial villous atrophy (VA) (III a), subtotal VA (III b), and total VA (III c). Twenty-nine untreated adults coeliacs, with a mean age of 47 years, range 20-76 yrs were studied over 3 years. SAT, IgA-AGA and IgA EMA were performed in 29 consecutive coeliac patients with villous atrophy on a gluten containing diets. RESULTS: Histopathological evaluation of small intestinal mucosa showed a partial VA in 14/29, subtotal VA in 10/29 and total VA in 5/29. All coeliacs with total VA had positive EMA (5/5 100%). However in coeliacs with partial VA sensitivity of EMA was poor (4/14 29%). Sensitivity of EMA in patients with subtotal VA was 50% (5/10). AGA was raised in 3/14 (21%), 6/10 (60%), and in 4/5 (80%) coeliacs with partial, subtotal and total VA respectively. AGA was raised in 13/29 (sensitivity 45%). SAT was abnormal in 26/29 (sensitivity: 89%). One patient had abnormal SAT, EMA and AGA. Eleven of 29 patients (38%) were negative for AGA and EMA, but SAT was abnormal in 10 of them. One patient was positive for EMA, negative for AGA, normal for SAT. EMA and/or AGA were positive in 18/29 (sensitivity 62%). Our study suggests that negative predictive value of serology should be interpreted cautiously since coeliacs with partial VA are negative in serology. Over the last ten years SAT and EMA have been accepted as screening tools for CD. SAT seems to be more sensitive than serology. However there is no standardized agreement in the literature for serology and SAT. A combination of SAT and serology may provide a good sensitivity in order to detect that subgroup of coeliacs with milder histopathological abnormality.

New evidence and new hope concerning endothelial seeding of vascular grafts.

Endothelial cell (EC) seeding of prosthetic bypass grafts has been promoted as a method of improving graft patency. However, an efficient and reliable method of seeding vascular prostheses with ECs is lacking due to inefficient harvesting of ECs and poor attachment and proliferation of cells on the prosthetic surfaces. To investigate the effect of a commonly used prosthetic surface on EC attachment and proliferation, we measured the attachment and proliferation of ECs on polytetrafluoroethylene (PTFE) grafts uncoated or coated with gelatin, laminin, fibronectin, collagen type I and/or III, or RGD (arginine-glycine-aspartate)-containing peptide. EC attachment and proliferation were both significantly decreased on the untreated PTFE graft surface. Conversely, coating of PTFE with fibronectin, RGD, laminin, or gelatin significantly (p less than 0.05) improved the attachment of ECs, with the most striking increases occurring with laminin and gelatin. Similarly, all matrix components in this study improved EC proliferation compared with untreated PTFE, with RGD and gelatin producing the most significant improvement. PTFE adversely effects EC attachment and proliferation. These properties can be improved by treating PTFE graft surfaces with extracellular matrix components in relatively low concentrations. Future investigations are needed to determine whether there are combinations and concentrations of matrix components that will optimize these cellular functions on vascular prostheses.