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Biomedical subjects

Gourdas Choudhuri

Publications and source records attributed to Gourdas Choudhuri.

At least 19 recordsLinked to original sources

Slow acetylator genotype of N-acetyl transferase2 (NAT2) is associated with increased susceptibility to gallbladder cancer: the cancer risk not modulated by gallstone disease.

This study comprised 124 consecutive cases of proven GBC and 147 healthy controls. NAT2 polymorphisms were carried out using PCR-RFLP method. The NAT2 slow acetylator genotype was significantly associated with risk of GBC (OR 3.4, 95% CI =1.9-5.7 p = 0.000007). The NAT2 2*6 and 2*7 allele frequencies were higher in GBC and conferred significant risk of cancer (OR 1.9, 95% Cl = 1.2-2.9, p= 0.006; OR, 2.9, 95% Cl = 1.6-5.2, p = 0.0001). The haplotypes 2, 1, 1 and 1, 2, 1 were significantly higher (OR 3.7 95% Cl 2.1-7.0, p = 0.00001; OR 1.8 95% Cl =1.1-2.8, p = 0.008) in GBC. The risk of slow acetylator phenotype in GBC patients with or without gallstones was similar. These results suggest that NAT2 slow acetylator phenotype influences the susceptibility of gallbladder cancer and the risk is not modulated by gallstone disease.

Acetylation↗

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Acute Disease↗

Association of lipoprotein receptor, receptor-associated protein, and metabolizing enzyme gene polymorphisms with gallstone disease: A case-control study.

INTRODUCTION: To identify high risk alleles for gallstone disease, we analyzed association of LDLRAvaII, LRPAP1 insertion/deletion, CETPTaqI B, and LPLHindIII polymorphisms with gallstone disease. METHODS: In DNA samples of 214 gallstone patients and 322 age and sex matched controls, specific region containing polymorphisms was PCR amplified and digested with restriction enzymes except for LRPAP1 insertion/deletion polymorphism. RESULTS: LRPAP1 gene insertion/deletion polymorphism was found to be significantly associated with gallstone disease. Genotype II was conferring significant risk for gallstone disease in females only (P=0.019; OR 2.577, 95% CI 1.144-5.806). LDLRAvaII, CETPTaqI B, and LPLHindIII polymorphisms were not found to be associated with gallstone disease either at genotype or allele level. CONCLUSIONS: LRPAP1, II genotype carrier females may have increased risk for gallstone disease. On the other hand, LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms may not be associated with gallstone disease.

Journal Article↗

Association of low density lipoprotein receptor related protein-associated protein (LRPAP1) gene insertion/deletion polymorphism with gallstone disease.

BACKGROUND AND AIM: Gallstones are byproducts of cholesterol supersaturated bile. Various studies have indicated that there might be a genetic predisposition to the disease. Receptor-associated protein (RAP) is a molecular chaperone for low density lipoprotein receptor-related protein (LRP), which plays a key role in cholesterol metabolism. Intron 5 insertion/deletion polymorphism of RAP gene (LRPAP1) has been implicated in other diseases sharing etiology with gallstone disease (GSD). METHODS: To analyze the association of insertion/deletion polymorphism in GSD, 130 gallstone patients and 202 healthy subjects took part in the present study. For genotyping, polymerase chain reaction was followed by 2% agarose gel electrophoresis. RESULTS: The results showed that frequencies of D and I allele were 65.77% and 34.23% in patients, 76.24% and 23.76% in controls, respectively. Frequency of I allele was significantly higher in the patient group than in the control group (P = 0.003). CONCLUSION: In the present study I (insertion) allele was found to be associated with GSD.

Adult↗

Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is commonly associated with overweight and insulin resistance. Aerobic exercise is known to reduce insulin resistance. We studied the effect of regular aerobic exercise on serum aminotransferase levels in patients with NASH. METHODS: Sixty-five (mean age 38.7+/-9.5 years; 46 [78%] males) out of 94 patients diagnosed with NASH participated in the study. Each patient was advised regular aerobic exercise for 30 min duration per day, and trained to achieve a heart rate of 60-70% of his/her maximal heart rate for at least 5 days a week. In addition, those with a high body mass index (BMI) were advised a moderately energy-restricted diet. Patients were followed up monthly for at least 3 months by BMI, waist-hip ratio (WHR), waist circumference (WC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Forty-three (72.8%) patients had a high BMI. Central obesity (WHR >or=0.90 cm in men and >or=0.85 cm in women) was present in 58 (98.3%) patients and metabolic syndrome in 12 (20.3%) patients. In the 44 patients who complied regularly with the exercise program, serum ALT normalized in 20 (45%; P<0.05), and mean AST and ALT values declined from 70.5 and 104.0-41.5 (P<0.001) and 63.2 (P<0.001), respectively. Overweight patients lost a mean 3.1 kg (range 0-13 kg) weight and showed a decline in BMI (28.7 vs 27.5; P<0.001) and WC (99.4 cm vs 96.1 cm; P=0.001). Serum ALT did not normalize in any of the 15 patients who failed to comply with the exercise program; their pre- and post-AST (82.8 and 81.2, respectively) and ALT (98.0 and 96.1, respectively) levels, BMI (27.5 and 27.6, respectively) and WHR (0.99 cm and 0.99 cm, respectively) did not show any significant change at 3 months, and also for an extended mean follow-up period of 5.3 months. CONCLUSION: Moderate intensity aerobic exercise helps in normalizing ALT levels in patients with NASH.

Adult↗

Gastric adenocarcinoma presenting with intestinal pseudoobstruction, successfully treated with octreotide.

Intestinal pseudoobstruction has been reported as a paraneoplastic manifestation of several cancers, including those of gastrointestinal tract. Octreotide, a somatostatin analogue, has been used successfully in the treatment of idiopathic and scleroderma-associated intestinal pseudoobstruction. We report a 65-year-old man with carcinoma stomach presenting with intestinal pseudoobstruction, which responded to octreotide.

Adenocarcinoma↗

High rates of early HBeAg seroconversion and relapse in Indian patients of chronic hepatitis B treated with Lamivudine: results of an open labeled trial.

BACKGROUND: The use of Lamivudine in chronic hepatitis B (CHB) is well known, however the reported rate of HBeAg sero-conversion and its durability post-treatment have varied considerably. We undertook the present study to study the effect of Lamivudine on HBeAg loss and seroconversion rates in Indian patients of CHB in relation to frequency, predictors and durability. METHODS: We treated 60 patients of e antigen positive CHB (with active viral replication and ongoing necro-inflammatory activity) with Lamivudine. They were followed up by monthly aminotransferases, and 3 monthly HBeAg and anti-HBe. Those who attained HBeAg sero-conversion were advised to discontinue Lamivudine after 6 months and followed up every 3 months thereafter, to see for relapse. Treatment was given for maximum of 3 years if not sero-converted. RESULTS: The annual incremental loss of HBeAg in patients receiving Lamivudine was 25 (41.6%) at end of 1st year, 33 (55%) at 2nd year and 35 (58.3%) at 3rd year. The corresponding rates for full sero-conversion were 17/60 (28.6%), 22/60 (36.6%) and 24/60 (40%) in the 3 years. HBeAg loss correlated with increased pre-therapy ALT levels (p = 0.002) and decreased pretreatment HBV-DNA levels (p = 0.004). The presence of cirrhosis had no influence on the rate of HBeAg loss. Relapse occurred in 35% (7/20) post-treatment at median time of 6 months. CONCLUSION: Indian patients showed a higher rate of HBeAg sero-conversion in the first year of Lamivudine treatment. This correlated with baseline ALT and inversely with HBV-DNA levels. Relapse rate after treatment was high and occurred soon after stopping treatment.

Adolescent↗

Autoimmune hepatitis in India: profile of an uncommon disease.

BACKGROUND: Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. METHODS: Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. RESULTS: Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the duration of symptoms was 20.3 (20.5) months. Nineteen (50%) of them presented with chronic hepatitis, 13 (34.2%) as cirrhosis, 5 (13.1%) with acute hepatitis and 1 (2.6%) with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%), pedal edema and hepatomegaly in 17 (44.7%), splenomegaly in 13 (34.2%), encephalopathy, abdominal pain in 9 (23.6%) and fever in 8 (21%). Twelve had esophageal varices and 3 had bled. Biochemical parameters were ALT 187 (360) U/L, AST 157 (193) U/L, ALP 246 (254) U/L, globulin 4.1 (1.6) g/dL, albumin 2.8 (0.9) g/dL, bilirubin 5.2 (7.4) mg/dL, prothrombin time 17 (7) sec and ESR 47 (17) sec. The autoimmune markers were SMA (24), ANA (15), both SMA and ANA (4), AMA (1), rheumatoid factor (2), pANCA (1), and Anti-LKM in none. Thirty (79%) patients had definite AIH and eight (21%) had probable AI hepatitis. Associated autoimmune diseases was seen in 15/38 (39.4%), diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2, rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular syndrome III in 1. Viral markers were positive in two patients, one presenting as acute hepatitis and HEV-IgM positive and another anti-HCV positive. CONCLUSION: In India, autoimmune hepatitis is uncommon and usually presents with chronic hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation was earlier but clinical parameters and associated autoimmune diseases were similar to that reported from the west. Primary biliary cirrhosis is rare. Type II AIH was not observed.

Adolescent↗

Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance.

BACKGROUND: Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE PRESENTATION: During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery.

Adult↗

Mutational spectrum of K-ras oncogene among Indian patients with gallbladder cancer.

BACKGROUND AND AIM: Gallbladder cancer (GBC) is a common abdominal malignancy in India with an obscure etiology. However, long-standing stones and chronic infection in gallbladder have been suspected as possible etiologic factors. As carcinogenesis complicating chronic inflammation proceeds through the stages of dysplasia and metaplasia, mutation in the K-ras gene may be an important marker for GBC. The aim of the present study was to detect K-ras mutation in cytological smears from GBC. METHODS: Malignant cells were marked on slides of cytological smears obtained from 39 patients with cytologically proven GBC. Marked cells were scraped off and DNA was extracted. Polymerase chain reaction coupled with restriction fragment length polymorphism (RFLP) analysis was performed to detect the point mutation in codon 12 of the K-ras gene. RESULTS: Mutation in codon 12 of K-ras oncogene was detected in eight (38%) of 21 PCR amplified samples by this technique. Six of eight specimens with K-ras (codon 12) mutation corresponded to coexisting gallstone disease. Five patients with K-ras (codon 12) mutation were found to have stage IV malignancy. CONCLUSIONS: Mutation in codon 12 of the K-ras oncogene occurs in more than one-third of GBC in northern India. Its detection from fine-needle aspirates may prove useful as an adjunct to cytological examination. The presence of this mutation suggests that chronic inflammation may play an etiologic role in gallbladder carcinogenesis.

Adult↗

Severe ulcerative colitis: prospective study of parameters determining outcome.

BACKGROUND: One-third of patients with exacerbations of ulcerative colitis (UC) require colectomy and 1% die. Although several studies have reported parameters associated with failure of medical treatment, studies using multivariate analysis of various predictors are scanty. METHODS: Demographic, clinical and laboratory parameters within 48 h of admission of 50 consecutive patients (55 episodes) were prospectively recorded. Each episode was treated with intravenous hydrocortisone, antibiotics and fluid administration. The data of patients who failed to respond, deteriorated, developed complications requiring emergency surgery or died within 7 days of hospitalization, were compared with the data of those who responded during this period using Mann-Whitney U-test or chi-squared tests. Variables found to be significant on univariate analysis were entered into a multivariate model. RESULTS: Medical treatment failed in 10 of 55 episodes; eight had surgery (one died), another died with bowel perforation and peritonitis and one left hospital in a moribund state. Younger age, pedal edema, transverse colonic diameter >5 cm on abdominal radiograph, low hemoglobin, low serum albumin, high C-reactive protein, presence of fibrin degradation product (FDP) in serum, low serum fibrinogen, prolonged prothrombin time, Truelove-Witt's fulminant disease, and high clinical activity index were associated with failure of medical treatment on univariate analysis. All the above variables were significant by multivariate analysis except age, serum albumin level and presence of FDP. CONCLUSION: It may be possible to predict the failure of medical treatment in exacerbations of UC using a scoring system based on clinical parameters and simple laboratory tests.

Adolescent↗

Apolipoprotein B-100 XbaI gene polymorphism in gallbladder cancer.

Genetic polymorphisms in the apolipoprotein B (apoB) gene have been reported to be associated with altered serum lipids and susceptibility to cholesterol gallstones (GS). Gallstones are among the well-known risk factors for carcinoma of the gallbladder (GBC). In the present study, the association between the XbaI polymorphism of the apo B gene was examined in patients with GBC and GS and in normal controls in a north Indian population. DNA samples from patients with GBC (n=153), GS (n=117) and healthy subjects (n=137) were analysed for the apoB- XbaI polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism. The genotype X+/- was less frequent in patients with GBC (39.2%) than in those with GS (68.3%) and in normal subjects (66.4%; P<0.00001). In contrast, there was an increase in the homozygous X-/- genotype in patients with GBC (54.9%) as compared with those with GS (23.9%) and normal subjects (25.5%; P<0.00001). The frequency of the X- allele was found to be significantly increased in GBC patients with or without GS (odds ratio=2.3 and 1.7, respectively). We suggest that the apoB-XbaI gene polymorphism confers susceptibility to carcinoma of the gallbladder under specific environmental conditions.

Adult↗

Dapsone induced cholangitis as a part of dapsone syndrome: a case report.

BACKGROUND: Dapsone can rarely cause a hypersensitivity reaction called dapsone syndrome, consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. Dapsone syndrome is a manifestation of the DRESS (drug rash with eosinophilia and systemic symptoms) syndrome which is a serious condition that has been reported in association with various drugs. Cholangitis in dapsone syndrome has not been reported so far in the world literature. CASE PRESENTATION: We report a patient who presented with fever, exfoliative dermatitis, jaundice and anemia within three weeks of starting of dapsone therapy. These features are typical of dapsone syndrome, which is due to dapsone hypersensitivity and is potentially fatal. Unlike previous reports of hepatitic or cholestatic injury in dapsone syndrome we report here a case that had cholangitic liver injury. It responded to corticosteroids. CONCLUSION: We conclude that cholangitis, though unusual, can also form a part of dapsone syndrome. Physicians should be aware of this unusual picture of potentially fatal dapsone syndrome.

Adult↗

Piperacillin induced bone marrow suppression: a case report.

BACKGROUND: Piperacillin (and piperacillin/tazobactam) is a commonly prescribed antibiotic and is generally considered safe. We report a case of piperacillin induced bone marrow suppression. CASE PRESENTATION: A 19-year-old boy was being treated with piperacillin followed by piperacillin/tazobactam for infected pancreatic pseudocyst. After 21 days of treatment, he developed neutropenia and thrombocytopenia. These reversed promptly after stopping piperacillin/tazobactam. The time course of events suggested that piperacillin was the cause of bone marrow suppression in this patient. CONCLUSION: Bone marrow suppression is a serious adverse effect of piperacillin, which should be kept in mind while treating patients with this drug.

Adult↗

Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.

BACKGROUND & AIMS: Tropical calcific pancreatitis (TCP) is a chronic pancreatitis unique to developing countries in tropical regions. The cause of TCP is obscure. Whereas environmental factors, such as protein energy malnutrition and ingestion of cassava, have been implicated, a genetic predisposition to the disease also may be important. In the present study we report on mutations in the serine protease inhibitor, Kazal type 1 (SPINK1) gene in north Indian patients with TCP. METHODS: We studied 66 unrelated TCP patients (44 men, 49 with diabetes, and 6 with family history of TCP), 25 relatives, and 92 healthy control subjects. Samples were analyzed for SPINK1 variants (-53C>T, L14P, N34S, P55S, and 272T>C) and cationic trypsinogen (PRSS1) variants (A16V, K23R, N29I, and R122H) by melting curve analysis. RESULTS: Twenty-nine patients (44%) carried the N34S missense mutation, of whom 9 (14%) were homozygotes. In contrast, only 2 (2.2%) control subjects were N34S heterozygotes (prevalence ratio 20.2; 95% confidence interval 5.0-81.8; P < 0.0001 vs. TCP). The severity of pancreatitis did not differ between TCP patients with or without N34S, or among those heterozygous or homozygous for N34S. Among TCP patients with or without diabetes, the frequency of N34S carriers (43% vs. 47%) and N34S homozygotes (14% vs. 12%) was similar. CONCLUSIONS: TCP is highly associated with the SPINK1 N34S mutation. The high prevalence of N34S in TCP patients with and without diabetes suggests that these 2 subtypes have a similar genetic predisposition. The genetic predisposition to TCP resembles, at least in part, the idiopathic chronic pancreatitis found in industrialized countries.

Adult↗

Prospective study of pancreatic b-cell and exocrine function following duct decompression in tropical calcific pancreatitis.

Tropical calcific pancreatitis (TCP) is a chronic, nonalcoholic pancreatitis, which is limited to developing countries. In this condition, surgical decompression of the pancreatic duct consistently leads to relief of abdominal pain. However, no data are available on the effect of such intervention on pancreatic function. The aim of the present study was to prospectively evaluate b-cell and exocrine function following ductal drainage in patients with TCP. We studied 14 consecutive TCP patients who underwent ductal decompression for abdominal pain (longitudinal pancreaticojejunostomyin 12 patients, endoscopic sphincterotomy and ductal stenting in 2 subjects). Six patients who refused similar intervention served as controls. Patients were evaluated prospectively (median follow-up 13 months) for pain score, fasting and oral glucose stimulated plasma C-peptide, serum trypsin, and fecal chymotrypsin. After intervention, 1 patient died 2 months after surgery, and 2 others were lost in follow-up. The pain score improved significantly following duct decompression (median 8.0 vs. 0, p < 0.01), while in the control group there was no change in pain score (7.0 vs. 7.0). There was no change in b-cell function after intervention (fasting plasma C-peptide [mean +/- SEM] 0.41 +/- 0.08 vs. 0.42 +/- 0.05 nmol/l; peak plasma C-peptide 2.24 +/- 0.20 vs. 2.32 +/- 0.24 nmol/l). Fecal chymotrypsin was diminished in all patients prior to intervention (1.9 +/- 0.7 U/g), and did not normalize after ductal drainage in any subject. Serum trypsin levels were variable, being elevated in 29% and diminished in 47% of subjects. All 4 subjects with elevated baseline trypsin levels had a sharp fall after intervention (1020 vs. 175 ng/ml). However, serum trypsin did not normalize after ductal drainage in any patient with a diminished baseline value. In conclusion, patients with TCP have significant reduction in abdominal pain after decompression of the main pancreatic duct. However, there is no significant change in b-cell function. A fall in elevated serum trypsin suggests that there may be relief of subclinical inflammation after intervention; however, there is no improvement in exocrine function after a follow-up of 1 year.

Abdominal Pain↗

Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity.

BACKGROUND: Serological tests may fail to identify hepatitis B virus (HBV) infection as a cause of liver cirrhosis in a proportion of patients. The frequency of such occult infection in regions with intermediate HBV endemicity is not known. Such cases may be diagnosed by incremental testing for IgG anti-HBc, serum HBV DNA, and HBV DNA in liver tissue. METHODS: We tested sera of 111 patients with cirrhosis, including 39 with history of significant alcohol ingestion, for HBsAg, anti-HBc and serum HBV DNA. In addition, in a subset of 14 patients, HBV DNA was looked for in liver tissue. RESULTS: On HBsAg and anti-HBc testing, 66 patients had HBV infection. Serum HBV DNA testing identified HBV infection in 13 additional cases. Of 18 patients labeled as 'cryptogenic' on serological testing, HBV DNA was detected in the serum in 7 patients. Of 14 patients in whom paired liver tissue and serum specimens were tested, 4 additional patients with HBV infection were detected after liver biopsy analysis. CONCLUSIONS: Serological tests for HBsAg and anti-HBc antibody are insensitive in identifying HBV infection in patients with liver cirrhosis. HBV DNA testing in serum and liver can help in establishing HBV infection as etiology, either alone or in addition to another cause.

Adult↗