Midodrine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study.

BACKGROUND & AIMS: Splanchnic arterial vasodilatation plays an important role in cirrhotic ascites. The aim of this study was to evaluate the effects of long term administration of midodrine on systemic hemodynamics, renal function, and control of ascites in patients with cirrhosis and refractory or recurrent ascites. METHODS: Forty cirrhotic patients with refractory or recurrent ascites were prospectively studied after long term administration of midodrine plus standard medical therapy (n=20) or standard medical therapy alone (n=20) in a randomized controlled trial at a tertiary centre. RESULTS: A significant increase in urinary volume, urinary sodium excretion, mean arterial pressure, and decrease in plasma renin activity (p<0.05) was noted after 1 month of midodrine administration. There was also a significant decrease in cardiac output and an increase in systemic vascular resistance after midodrine therapy at 3 months (p<0.05). There was no change in glomerular filtration rate and model for end-stage liver disease (MELD) score. Midodrine plus standard medical therapy was significantly superior to standard medical therapy alone in the control of ascites (p=0.013) at 3 months. The mortality rate in the standard medical therapy group was significantly higher than the midodrine group (p<0.046). There was no significant difference in the frequency of various complications at the end of follow-up. CONCLUSIONS: The results of this randomized pilot study suggest that midodrine plus standard medical therapy improves the systemic hemodynamics without any renal or hepatic dysfunction in these patients and is superior to standard medical therapy alone for the control of ascites.

Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India.

BACKGROUND AND AIM: There is scanty data on the occurrence of celiac disease in patients with type 1 diabetes mellitus in South Asia. Our aim was to study the prevalence and clinical profile of celiac disease in patients with type 1 diabetes mellitus in a tertiary care referral centre in north India. METHODS: Consecutive patients of type 1 diabetes mellitus attending the Endocrine clinic of our institute between January 2002 and December 2008 were screened using anti-tissue transglutaminase antibodies (tTGAb), and those positive were subjected to duodenal biopsy. Clinical profile of these patients was recorded. RESULTS: Out of 189 patients of type 1 diabetes mellitus, 21 (11.1%) were diagnosed to have celiac disease on the basis of positive serology (tTGAb) and duodenal histology. The mean age at diagnosis of diabetes was 10.81 ± 7.3 years and that of celiac disease was 13.74 ± 5.71 years, with a difference of 5.18 ± 4.75 years between the two. Only 2/21 patients with celiac disease had been diagnosed before detection of diabetes mellitus. Short stature was the commonest (52.3%) manifestation of celiac disease, followed by anemia (47.3), weight loss (42.8%), diarrhea (28.6%) and abdominal pain (14.2%). After initiating gluten free diet, 14/16 symptomatic patients had reversal of anemia, weight loss and diarrhea. Growth rate velocity improved from 2.3 ± 1.0 cm/year to 5.5 ± 2.4 cm/year in those with short stature. CONCLUSION: Celiac disease is highly prevalent in patients with type 1 diabetes mellitus (11.1%) and majority of them (90.5%) were diagnosed on screening. Routine screening is required for early diagnosis and combat associated co-morbidities.

Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study.

OBJECTIVES: Intravenous albumin has been used to prevent paracentesis-induced circulatory dysfunction (PICD) in cirrhotics; however, its use is costly and controversial. Splanchnic arterial vasodilatation is primarily responsible for PICD. There are no reports of use of midodrine in the prevention of PICD. In this pilot study, we evaluated midodrine and albumin in the prevention of PICD. METHODS: Forty patients with cirrhosis underwent therapeutic paracentesis with midodrine or albumin in a randomized controlled trial at a tertiary center. Effective arterial blood volume was assessed by plasma renin activity. RESULTS: Plasma renin activity at baseline and at 6 days after paracentesis did not differ in the two groups (43.18 +/- 10.73 to 45.90 +/- 8.59 ng/mL/h, P= 0.273 in the albumin group and 44.44 +/- 8.44 to 41.39 +/- 10.21 ng/mL/h, P= 0.115 in the midodrine group). Two patients had an increase in plasma renin activity of more than 50% from baseline in the albumin group, and none in the midodrine group. A significant increase in 24-h urine volume and urine sodium excretion was noted in the midodrine group. Midodrine therapy was cheaper than albumin therapy. CONCLUSIONS: The study suggests that midodrine may be as effective as albumin in preventing PICD in cirrhotics, but at a fraction of the cost, and can be administered orally. Midodrine also resulted in an increase in 24-h urine volume and sodium excretion.

Functional and morphological alterations in small intestine mucosa of chronic alcoholics.

BACKGROUND AND AIM: Alcohol-related diseases constitute the third largest health problem after heart disease and cancer in the world. The objective was to study the effects of chronic alcohol intake on small bowel cellular functions with focus on brush border enzymes, membrane enzymes, cellular enzymes and their relationship with structural changes in small bowel mucosa of chronic alcoholics. METHODS: Duodenal biopsies were obtained by upper gastrointestinal endoscopy of chronic alcoholics having alcoholic liver disease (ALD) with and without cirrhosis. The biopsies were then processed for enzymatic assays to analyze the status of cellular functions. Light microscopy, transmission electron microscopy, and scanning electron microscopy were done to study the morphological alterations. Control group consisted of nonalcoholic gastroesophageal reflux disease patients reporting for routine endoscopy. RESULTS: The experimental group consisted of ALD patients which showed significant difference (P < 0.01) in cellular functions when compared with controls. The light microscopy showed partial villous atrophy, increase in lamina propria infiltrate, and intraepithelial lymphocytes as main findings in the alcoholic group. Ultrastructural evaluation revealed changes like widened intercellular junction, distorted microvilli, increased rough endoplasmic reticulum, and increased and dilated mitochondria. The enzyme parameters correlated positively with the mucosal morphology parameters indicating a direct relationship. CONCLUSION: The study brought out the changes in small bowel of chronic alcoholics having ALD at both cellular and subcellular levels which correlated significantly.

Brush border enzyme activities in relation to histological lesion in pediatric celiac disease.

BACKGROUND AND AIM: In celiac disease (CD), abnormalities of brush border enzyme activities have been detected in the course of the disease activity. There are conflicting results on intestinal mucosal enzyme activities and its correlation to mucosal injury in CD. The aim of the present study was to evaluate the brush border enzyme activities (disaccharidases and alkaline phosphatase) in the duodenal mucosa of North Indian children with CD and to examine their correlation to duodenal mucosal morphological alterations. METHODS: This prospective study included 71 children with CD and 29 controls (patients with gastroesophageal reflux disease) in whom upper gastrointestinal endoscopy was performed and distal duodenal biopsies were taken for histological assessment, and estimation of disaccharidases and alkaline phosphatase activities. Each biopsy sample was classified according to the modified Oberhuber classification. Lactase, sucrase, maltase and alkaline phosphatase activities were estimated in duodenal biopsy homogenates from patients with CD and from controls. The association between enzyme activities and duodenal morphology was examined. RESULTS: The mean age of the 71 patients with CD (M:F, 43:28) was 6.0 +/- 0.3 years and mean age of onset of symptoms was 2.7 +/- 0.4 years. Sixty-four of 71 (90.1%) CD patients showed type 3 (destructive) lesion, whereas it was grade 0 in all patients with gastroesophageal reflux disease. In CD and patients with gastroesophageal reflux disease, the mean level (IU/g protein) of lactase was 12.1 +/- 0.9 versus 24.4 +/- 1.0 (P < 0.001), mean level of sucrase was 25.9 +/- 1.9 versus 42.5 +/- 1.9 (P < 0.001), mean level of maltase was 56.6 +/- 3.5 versus 76.1 +/- 13.0 (NS), and mean level of alkaline phosphatase was 602.8 +/- 56.2 versus 1359.3 +/- 51.2 (P < 0.001), respectively. The mean disaccharidases and alkaline phosphatase levels were not significantly different in patients with milder lesions (type 2 and type 3a) compared with those of control. However, mean lactase, sucrase and alkaline phosphatase levels were significantly lower (P < 0.001) in CD patients with moderate (type 3b) and severe (type 3c) lesions compared with control. CONCLUSIONS: A generalized decrease of disaccharidases and alkaline phosphatase activity was seen in the duodenal mucosa of children with CD. The depressed activities of lactase, sucrase and alkaline phosphatase were well correlated with the histological grade of duodenal mucosal lesions in children with CD.

Lymphocytic gastritis and celiac disease in indian children: evidence of a positive relation.

OBJECTIVES: Lymphocytic gastritis (LG) is characterized by the presence of > or = 25 lymphocytes/100 epithelial cells in the gastric surface and pit epithelium. An association of LG with Helicobacter pylori infection or celiac disease (CD) has been suggested. The aim of this study was to verify the relation of LG with CD, with and without H pylori infection, in children. PATIENTS AND METHODS: A total of 164 children with CD diagnosed between June 2003 and October 2005, in whom gastric and duodenal biopsies were performed simultaneously, were enrolled prospectively. The control group was composed of 164 children without CD, matched for sex and age, who were undergoing upper digestive endoscopy. H pylori was searched for in gastric biopsy specimens sectioned and stained with hematoxylin and eosin, and a modified Giemsa stain for H pylori was performed for confirmation. The Student t test was used to compare quantitative measurements between groups. RESULTS: LG was found in 69 (42.1%) patients with CD. Positive cases had a mean of 43.9 +/- 1.5 intraepithelial lymphocytes per 100 surface epithelial cells, compared with a mean of 13.4 +/- 0.4 in negative cases and 7.8 +/- 0.5 in non-CD control children (P<0.0001). Patients not showing LG did, however, show significantly increased gastric intraepithelial lymphocytes compared with the control children. Nine of 164 CD patients, and 4 of 69 patients with LG, had positive results for H pylori. CONCLUSIONS: This study supports a pathogenetic relation between CD and LG. CD without LG also showed increased gastric intraepithelial lymphocytes. H pylori infection may be another cause of LG in children.

Prevalence of coeliac disease in healthy blood donors: a study from north India.

BACKGROUND: Blood donor screening can help predict prevalence of coeliac disease in population. METHODS: Between December 2010 and June 2011, healthy blood donors were screened using anti-tissue glutaminase antibodies. Those positive underwent duodenoscopy. Their age, gender, body mass index and haemoglobin and histological changes were recorded. RESULTS: Of the 1610 blood donors screened, 1581 (98.2%) were males. The mean age of donors was 31.51 ± 9.66 years and the mean body mass index was 22.12 ± 4.24 kg/m(2). Nine (0.56%) men were seropositive. Endoscopic features included reduced fold height (9), scalloping (8), grooving (7) and mosaic mucosal pattern (3). Eight had Marsh IIIa changes whilst one had IIIb change. The prevalence of coeliac disease was 1:179 (0.56%, 95% confidence interval 1/366-1/91, 0.27-1.1%). None of the 9 patients had any symptoms. Their mean haemoglobin and body-mass index was similar to rest of the cohort. CONCLUSION: The prevalence of coeliac disease amongst apparently healthy blood donors was 1:179 (0.56%).

Prevalence and predictors of abnormal bone mineral metabolism in recently diagnosed adult celiac patients.

BACKGROUND AND AIMS: This study aimed to evaluate the prevalence of low bone mineral density (BMD) in recently diagnosed adult celiac patients and to identify the factors associated with this. METHODS: We investigated 54 newly diagnosed adult celiac patients between February 2008 and April 2009. BMD was measured in all patients and its correlation with clinical and biochemical parameters was analyzed. RESULTS: Fifty-four (24 male) newly diagnosed celiac patients with a mean±SD age of 30.6 ± 9.3 years (range 18-50) were included. Thirty-nine (72.2 %) presented with intestinal symptoms, and the rest with extraintestinal symptoms. Low vitamin D levels were seen in 11 (20.3 %) patients and elevated iPTH (secondary hyperparathyroidism) in 12 (22.2 %) patients. Twenty-one (39 %) patients had normal BMD, 23 (43 %) had osteopenia (T-score -1 to -2.5), and 10 (18 %) patients had osteoporosis (T-score <-2.5). A statistically significant association was seen between BMD and age of onset, duration of illness, serum tTGA levels, serum vitamin D levels, and histopathological changes. CONCLUSIONS: Low BMD is common in newly diagnosed adult celiac patients with approximately one fifth of them having osteoporosis. BMD should be measured in all newly diagnosed celiac patients and calcium and vitamin D supplementation included in the treatment regimen.

Clinical presentation of celiac disease among pediatric compared to adolescent and adult patients.

BACKGROUND: Celiac disease (CD) is being increasingly recognized in adults though a majority of patients continue to be diagnosed in childhood. AIM: To compare the clinical presentation and profile of newly diagnosed pediatric and adolescent/adult CD patients. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with CD between year 1997 and 2007 in the pediatric group, and between year 2000 and 2007 in the adolescent/adult group was done for clinical presentation, endoscopic findings and duodenal histology. RESULTS: A total of 434 children and 298 adults were studied. The mean age of diagnosis was 6.5 ± 2.5 years (1-11 years) in children and 29.3 ± 13.3 years (6-73 years) in adolescent/adults. The mean duration of symptoms before diagnosis was 3.5 ± 2.5 years in children and 4.9 ± 4.6 years in the latter. Diarrhea as the presenting symptom was seen in 74 % of children and 58.7 % of adolescent/adults. Anemia (on investigations) was seen in 84 % of children and 94 % of adolescent/adults. CONCLUSIONS: Pediatric patients of CD present more often with typical features than adults. Atypical presentations are more common in adults and the latent period for diagnosis is also longer in adolescent/adults. There is a need for increasing awareness about CD, both among pediatricians and physicians caring for adult patients.

Hepatobiliary disorders in celiac disease: an update.

This communication reviews recent literature and summarizes hepatobiliary abnormalities that may complicate the clinical course of celiac disease. A wide spectrum of hepatobiliary diseases has been described, including asymptomatic elevations of liver enzyme levels, nonspecific hepatitis, nonalcoholic fatty liver disease, and autoimmune and cholestatic liver disease. Moreover, in the majority of patients, liver enzyme levels will normalize on a gluten-free diet. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Because many celiac patients do not have overt gastrointestinal symptoms, a high index of suspicion is required. Simple methods of detecting celiac disease such as serum antibody tests help in the early identification of the disease, thus preventing serious complications of the disorder. The IgG DGP antibody test and IgA tTG antibody test used in combination are an excellent screening test for suspected cases of celiac disease.

Celiac disease suspected at endoscopy in patients with chronic liver disease.

Endoscopic findings of celiac disease have high specificity and sensitivity. We evaluated records of 137 consecutive patients who had endotherapy for variceal hemorrhage, and who had features of celiac disease at endoscopy; patients who had such markers at endoscopy had undergone duodenal histology and serology. Thirty-one patients had changes of portal hypertensive vasculopathy in the duodenum, 8 had scalloping, and 6 had mosaic pattern; 3 patients also had decreased fold height or sparse folds in the descending duodenum. Six of these 8 patients had positive serology and histology suggestive of celiac disease. Endoscopic evaluation resulted in diagnosis of CD in 4.37% patients of chronic liver disease undergoing endotherapy.