Correlation of Helicobacter pylori virulence genotype & severity of mucosal inflammation in gastric biopsies from two geographically diverse regions in India

Background: H. pylori-associated gastritis in patients from the high-altitude area of Ladakh showed severe gastritis, mucosal nodularity, atrophy, and cancer in comparison to those from North India. This study served to analyze if differences in the H. pylori virulence genotypes decide the extent of gastric mucosal inflammation. Methods: Fifty gastric biopsies each from patients with H. pylori-associated gastritis from Ladakh and a tertiary care center in North India were included. The presence of H. pylori strain was confirmed with Warthin starry stain and polymerase chain amplification of the H. pylori-specific 16S rRNA. The cagA, vacA s1, s2, and m1, m2 alleles, and dupA virulence genotypes were studied in all archival samples, followed by their histological correlations. Results: cagA (P 0.009) and vacAs1 m1 (P 0.009) genes were distinctly more in H. pylori strains colonizing the biopsies of North Indian patients. In contrast, the cagA -ve vacAs2 m2 strains were significantly more in H. pylori strain colonizing the biopsies from Ladakhi patients. dupA genotype was almost similarly present in strains from both regions. Among these, only cagA and dupA virulence genes were associated with severe mucosal neutrophilic activity and deep infiltration of H. pylori strains in North Indian patients. Conclusions: Differences in virulence genotypes of H. pylori in gastric biopsies from North Indian and Ladakhi patients were found not significant in deciding the severity of H. pylori-associated gastritis.

Association of endotoxaemia & gut permeability with complications of acute pancreatitis: Secondary analysis of data

Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.

A pancreaticographic study of malnutrition-related diabetes mellitus.

Pancreatic involvement is considered to be the hallmark of malnutrition-related diabetes mellitus (MRDM). Of the 2 subgroups of the disease, fibrocalculous pancreatic diabetes (FCPD) is characterized by pancreatic calcification. The nature of pancreatic abnormalities in MRDM have not been studied extensively in Indian patients. The present study was designed to compare pancreatic abnormalities (exocrine and endocrine) including endoscopic retrograde pancreaticography in patients with FCPD and protein deficient pancreatic diabetes (PDPD), in relation to controls. Ten patients each of FCPD and PDPD were studied with regard to clinical features, biochemical exocrine and endocrine pancreatic responses, C-peptide response, islet cell antibody, and pancreatographic changes. Five normal pancreatograms were taken as control. Clinical and biochemical features in patient with FCPD and PDPD were as follows: pain in 8 and 2 patients, respectively; the mean duration of diabetes was similar in both groups (62.28 +/- 71.92 months V. 72 +/- 50.9 months); and faecal fat excretion and insulin requirements were comparable in both groups. The main pancreatic duct was dilated in 6 of 10 patient with FCPD and only 1 of 10 with PDPD on ultrasonography. On pancreatography the duct was dilated in 9 of 10 patients with FCPD and only 1 of 10 patients with PDPD. The number of side branches was reduced in all cases with MRDM; in those with FCPD, these were stunted and dilated while in PDPD side branches are thin and spastic. We conclude that pancreatic ductal changes involving the main duct and side branches are more frequent in patients with FCPD as compared to those with PDPD.

Laparoscopic Nissen fundoplication; results of a prospective pilot study.

Laparoscopic fundoplication is rapidly becoming the surgical procedure of choice in western countries for the management of gastro-oesophageal reflux disease (GERD). Experience with this technique is limited in India. Most operations continue to be performed through the traditional open technique, thus denying the advantage of a minimal invasive approach to patients. This study was done to evaluate the feasibility and short term results of laparoscopic Nissen fundoplication. Between June 2000 and March 2002, a total of 10 patients with GERD refractory to medical therapy or requiring daily treatment underwent laparoscopic Nissen fundoplication. Preoperative evaluation included scoring of symptoms, oesophagogastroduodenoscopy, barium swallow and nuclear scan. The intraoperative and post-operative course of the patients was recorded. At 3 months post-surgery, patients were re-evaluated using pre-operative symptom scores and investigations to assess the benefit of and complications associated with surgery. Laparoscopic nissen fundoplication was successfully completed in all the patients. Follow up ranged from 3 to 18 months with a mean of 5.9 months. The mean symptom score decreased from 10.1 pre-operatively to 1.7 (p value < 0.001). Eight out of 9 patients (88%) had endoscopic resolution of oesophagitis. Seven patients (70%) were off medication following surgery while the remaining 3 (30%) were taking medication intermittently. Overall, 80% of the patients were satisfied with the surgery. One patient required re-exploration due to bleeding from a short gastric vessel. The most frequent post-operative complication was temporary dysphagia in 60% of patients, which improved with conservative management over 2 to 3 weeks. We concluded that laparoscopic Nissen fundoplication is a safe and effective procedure to treat patients with GERD.

A pancreatography study of chronic calcific pancreatitis of the tropics.

Chronic Calcific Pancreatitis of Tropics is a disease of unknown aetiology and is characterised by chronic pancreatitis with calcification in young persons who present with pain, diabetes, and/or steatorrhoea. ERCP performed on 42 patients with this condition revealed changes compatible with chronic pancreatitis. These changes were however, more marked and somewhat different from those seen in the alcoholic chronic pancreatitis. Cystic dilatation, tortuosity, and obstruction of the main pancreatic duct were similar to that in alcoholic pancreatitis. The features of CCPT that were different from those of latter, were large pancreatic calculi, absence of strictures/stenosis and absence of irregularity of the ductal wall. The calculi were predominantly in the head region of the pancreas causing maximal dilatation of the main pancreatic duct in the head of pancreas. The secondary branches were stunted, short and scanty but revealed a lower grade of changes, than the changes documented in the main pancreatic duct. The pancreatic ductal changes in CCPT seems to be different from that seen in chronic alcoholic pancreatitis and may be due to the difference in the pathophysiology of the underlying disease.

Profile of lower gastrointestinal bleeding in children from a tropical country.

Eighty five children were evaluated endoscopically for recurrent lower gastrointestinal (GI) bleeding. The male: female ratio was 2.4:1 with a mean age of 6 years (range 8 months to 2 years). After adequate bowel preparation endoscopic evaluation was done using olympus CF 101 colonoscope. Sedation was given only in two patients. Full length colonoscopy had been done in 16 cases only, to look for extent of disease in 8 cases and to ascertain site of bleeding when no lesion could be seen on sigmoidoscopy. Juvenile polyps were seen in 40 cases, amoebic ulcer in 20, solitary rectal ulcer in 4 and polyposis syndrome in 5 cases. Sigmoidoscopy alone could establish the diagnose in 76 cases. We conclude that flexible sigmoidoscopy alone is safe and adequate in ascertaining the cause of prolonged recurrent lower GI bleeding.

Management of foreign bodies of the upper gastrointestinal tract.

The use of flexible endoscopes had made removal of foreign bodies in the upper gastrointestinal tract easier and safer. We describe our experience of 49 cases of foreign bodies of the upper gastrointestinal tract. Majority (67%) of the patients were children and only 4 patients (8%) were above 45 years of age. The most common foreign bodies encountered were coins (25), fruit stones (4) and dentures (3). In 29 patients foreign bodies were lodged in the oesophagus and in 15 cases in the stomach. Forty one patients were considered for endoscopic removal of the foreign bodies and 40 could be managed successfully. There were no procedure related complications. We conclude that endoscopic removal of the foreign bodies of the upper gastrointestinal tract is a safe and effective technique.

Plasma lipid profile in gallstone patients from North India.

One hundred and thirty five patients with gallstones along with eighty nine matched controls were studied ultrasonographically to look for any association with hyperlipidemias. Plasma cholesterol and triglycerides were estimated by colorimetric methods and lipoproteins were classified according to Beaumont's classification. Male to female ratio in gallstone patients was 1:3. Mean plasma cholesterol and triglyceride values were higher in male gallstones patients as compared to controls (166.40 +/- 54.21 vs 40.26 +/- 32.80 mg/dl, p <0.01 and 182.65 +/- 84.49 vs 133.18 +/- 52.37 mg/dl, p <0.01 respectively). In female gallstone patients, on the other hand, only plasma triglyceride levels were raised as compared to control (182.65 +/- 84.49 vs 133.18 +/- 52.32 mg/dl, p <0.01). Prevalence of type IIb and type IV was 24.32% and 29.72% in male gallstone patients and 13.2 and 39.70% respectively in female gallstone patients. Thus, more than half of our gallstone patients had hyperlipidemia, the commonest types amongst them being type IIb and type IV.

Gall bladder dysmotility in diabetes mellitus--an ultrasound study.

Fifty two diabetic patients and 15 healthy control subjects were prospectively studied for their gall bladder function by ultrasound examination. The fasting gall bladder volume (FGBV) was calculated by using ellipse formula from the dimension of gall bladder shadow seen on ultrasound screen in two different cuts. The contractility of gall bladder was measured by calculating post prandial ejection fraction (EF) of the gall bladder. The mean FGBV and EF in 52 diabetic patients was found to be 20.7 +/- 10.7 cc and 47.5 +/- 20.1%, which was not significantly different from that in normal controls. Age, sex, obesity, diabetic control and presence of dyspeptic symptoms had no impact in FGBV and EF. Diabetic symptoms had no impact in FGBV and EF. However, diabetics with longer duration of disease had poorer gall bladder contractility (p < 0.05). Patients with autonomic neuropathy (AN) had significantly larger FGBV but normal contractility. Our results suggest that (a) long standing diabetics may have poor gall bladder emptying predisposing to gall stone formation (b) patients with autonomic neuropathy have reduced tone of fasting gall bladder but normal contractility.

Lupus anticoagulant and anticardiolipin antibodies in systemic lupus erythematosus.

BACKGROUND. Lupus anticoagulant and anticardiolipin antibodies are antiphospholipid antibodies which have been independently associated with a high incidence of thrombotic diseases. However, the importance of their combined occurrence has not yet been examined. METHODS. We investigated 70 patients with systemic lupus erythematosus for the presence of anticardiolipin antibodies paying particular attention to a history of thrombosis and abortion. Lupus anticoagulant was detected using the kaolin clotting time, its mixing tests with normal plasma and the inosithin neutralization test. Anticardiolipin antibodies were detected using the ELISA technique. RESULTS. Lupus anticoagulant was detected in 11 patients (16%) and anticardiolipin antibodies in 13 (19%). Six patients were positive for both lupus anticoagulant and anticardiolipin antibodies. These patients had a higher incidence of thrombosis or recurrent abortion (5 of 6) compared to those with lupus anticoagulant (2 of 5) or anticardiolipin antibodies alone (1 of 7). The amount of inosithin required to neutralize lupus anticoagulant was greater [mean (SD) 27.5 (20.5) micrograms] in patients with both lupus anticoagulant and anticardiolipin antibodies than in patients with lupus anticoagulant alone [mean (SD) 4.0 (5.4) micrograms]. CONCLUSION. The presence of lupus anticoagulant is associated with thrombosis and recurrent abortion which are more frequent when both lupus anticoagulant and anticardiolipin antibodies are present and these patients probably have more severe disease as the amount of inosithin required to neutralize the lupus anticoagulant was greater.

Platelet function disorders in north India.

BACKGROUND. Platelet function disorders are a fairly common cause of bleeding manifestations. Although their relative types and incidence are well documented, data from India are lacking. METHODS. Between 1970 and 1991, we studied the clinical and laboratory features of 144 north Indian patients who presented to our hospital with a bleeding diathesis in whom coagulation disorders, von Willebrand's disease and a history of drug ingestion were absent. RESULTS. Isolated platelet factor 3 availability defect was the commonest (56 cases) followed by the thrombasthenias (49 cases), arachidonic acid pathway defect (26 cases), storage pool disease (8 cases) and the Bernard-Soulier syndrome (3 cases). Isolated platelet factor 3 deficiency was rare (2 cases). Two varieties of thrombasthenia were seen--the classical Glanzmann's (13 cases) and thrombopathic (36 cases). The latter was characterized by absent or sub-normal platelet aggregation with agonists along with a reduced (to less than 50% of normal) total platelet factor 3 content. This has not been reported from western countries. Patients with classical Glanzmann's thrombopathic thrombasthenia with absent platelet aggregation and isolated platelet factor 3 deficiency were severe bleeders. Their family history suggested an autosomal recessive transmission in Glanzmann's and thrombopathic thrombasthenia and a possible autosomal dominant transmission in isolated platelet factor 3 availability defect and isolated platelet factor 3 deficiency. CONCLUSION. The frequency of various types of platelet function disorders in Indians is similar to that in western populations except that the incidence of thrombopathic thrombasthenias is higher in India.