S. Dasarathy

Prospective study of plasma fibronectin in fulminant hepatitis: association with infection and mortality.

BACKGROUND/AIMSnPlasma fibronectin is an opsonic glycoprotein, normally synthesized by the liver, which decreases subsequent to severe liver damage and low levels of which may contribute to reticuloendothelial system dysfunction by compromising opsonic activity. This may result in an increased frequency of infection and death. The present study was conducted to evaluate the association of plasma fibronectin activity with infection and mortality in patients with fulminant hepatic failure.nnnMETHODSnPlasma fibronectin was estimated serially in 69 consecutive patients with fulminant hepatic failure, nine patients with uncomplicated acute viral hepatitis and 32 normal volunteers.nnnRESULTSnPlasma fibronectin levels in patients with fulminant hepatic failure (85.6 +/- 75.8 micrograms/ml) were significantly lower than in patients with uncomplicated acute viral hepatitis (295.5 +/- 88.5 micrograms/ml) and healthy volunteers (362.6 +/- 69.2 micrograms/ml). Forty-nine (72%) patients with fulminant hepatic failure died. The initial values of fibronectin in fulminant hepatic failure did not correlate with mortality. Patients with fulminant hepatic failure who survived showed a progressive rise in the fibronectin levels compared to the absence of an increase in fibronectin levels in the non-survivors. The mortality in patients with fulminant hepatic failure with infection (24/27) was significantly higher (p < 0.05) compared to those without infection (25/42). Initial fibronectin levels in patients with infection (70.3 +/- 54.2 micrograms/ml) were significantly lower (p < 0.05) than in those without infection (92.3 +/- 64.4 micrograms/ml). We conclude that plasma fibronectin levels in patients with fulminant hepatic failure are decreased compared to healthy subjects and the absence of an increase in levels indicates a poor prognosis. Low levels of fibronectin are associated with an increased incidence of infection, which increases the mortality in these patients.

Endoscopic diagnosis of segmental colonic tuberculosis

We report colonoscopic findings in 29 proven cases of segmental colonic tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy biopsies enabled a histologic diagnosis to be made on the basis of typical granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and bacteriologic evaluation established the diagnosis in 60% of patients. We conclude that even though target biopsy is an effective method of diagnosis, anti-tuberculous chemotherapy may be started on the basis of the endoscopic appearance if there is a high clinical suspicion of tuberculosis.

Magnitude of hepatitis C virus infection in India: prevalence in healthy blood donors, acute and chronic liver diseases

An enzyme immunoassay (EIA) was developed in‐house for the detection of anti‐hepatitis C virus (HCV) antibody against the prevailing genotypes in India. The specific reactivity of the test was compared with commercial second and third‐generation EIAs and reverse transcription nested polymerase chain reaction (RT‐nested PCR). Fifteen thousand nine hundred twenty‐two healthy blood donors at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, were screened for anti‐HCV antibody. Two hundred ninety‐five (1.85%) of these donors were positive. The screening was also used to determine how many patients with acute hepatitis and chronic liver diseases were positive for anti‐HCV antibody. Five hundred sixty‐four chronic liver disease patients were screened for anti‐HCV antibody and 78 (13.83%) were found positive. Two hundred forty‐seven sporadic acute viral hepatitis patients were screened for viral infection markers. Hepatitis B and E viruses (HBV and HEV) were the major etiologic agents. HCV was associated with 9% of the acute cases. Anti‐HCV core IgM with HCV RNA detection were found to be helpful for the diagnosis of acute HCV infection. J. Med. Virol. 51:167–174, 1997.

Toxic effects of chronic fluoride ingestion on the upper gastrointestinal tract

In a prospective case controlled study, we evaluated the adverse effects of long-term fluoride ingestion on the gastrointestinal tract. Ten patients with otosclerosis who were receiving sodium fluoride 30 mg/day for a period of 3-12 months, and 10 age- and sex-matched healthy volunteers were included. They were all evaluated clinically and subjected to a real time ultrasound examination, upper gastrointestinal endoscopy, and biopsies from the gastric antrum and duodenum. The biopsies were subjected to a rapid urease test as well as light and electron microscopic examinations. Ionic fluoride was estimated in the serum, urine, and drinking water using an ION 85 Ion Analyzer. Seven subjects (70%) ingesting fluoride had abdominal pain, vomiting, and nausea. Petechiae, erosions, and erythema were seen on endoscopy in all the subjects, but not in the controls. Histological examination of the gastric antral biopsy showed chronic atrophic gastritis in all the subjects but in only one (10%) healthy volunteer. Scanning electron microscopic examination showed cracked-clay appearance, scanty microvilli, surface abrasions, and desquamated epithelium in the subjects ingesting fluoride, but not in the controls. We conclude that long-term fluoride ingestion is associated with a high incidence of dyspeptic symptoms as well as histological and electron microscopic abnormalities.

A prospective randomized study to evaluate propranolol in patients undergoing long-term endoscopic sclerotherapy

A prospective randomized double-blind study was conducted to evaluate the efficacy of propranolol in patients with portal hypertension undergoing long-term endoscopic sclerotherapy (EST) for recurrent variceal bleeding. Consecutive patients with portal hypertension (Childs class A or B) due to cirrhosis (n = 72), non-cirrhotic portal fibrosis (n = 29) and extrahepatic portal venous obstruction (n = 13) attending the liver clinic of a tertiary care center were included in the study. All patients had had at least one documented episode of variceal bleed in the previous 4 weeks. Fifty-eight patients received propranolol and 56 received placebo in addition to weekly EST. Rebleeding occurred in 12 (21%) patients in the placebo group and 10 (17%) patients in the propranolol group during a mean follow-up period of 24.4 +/- 10.4 months in the former and 23.8 +/- 9.2 months in the latter group (P > 0.1). The number of episodes of rebleeding (14 in the placebo and 12 in the propranolol group) were also similar (P > 0.1). The median bleeding-free period was more than 40 months in both treatment groups (P > 0.1). The mean transfusion requirements and the number of hospital admissions for rebleeding were also similar in the two treatment groups (P > 0.1). Complete obliteration of varices was achieved in 44 (78.9%) patients in the placebo group and 43 (75.5%) patients in the propranolol group (P > 0.1). Recurrence of new varices was seen in two patients in the placebo and in three of those in the propranolol group. Seven patients in the placebo group and five in the propranolol group died (P > 0.1). Complications related to EST were similar in the two treatment groups but additional adverse effects were observed in the propranolol group. The cumulative incidence of rebleeding in the placebo group was 12.7 and in the propranolol group it was 11.2 per 100 patient years of follow-up. It is concluded that the addition of propranolol in patients with portal hypertension and fair hepatic function on long-term EST does not confer any additional benefit.

Gastroduodenal manifestations in patients with skeletal fluorosis

A prospective case-controlled study was performed to evaluate the gastrointestinal symptoms and mucosal abnormalities occurring in patients with osteofluorosis. Ten patients with documented osteofluorosis and ten age- and sex-matched healthy volunteers were included in the study. Clinical evaluation, real-time ultrasound, and upper gastrointestinal endoscopy and biopsy from the gastric antrum and duodenum were performed in all subjects. The biopsies were subjected to a rapid urease test and light and electron microscopic examinations. Ionic fluoride levels were estimated in the drinking water, serum, and urine using an ION 85 ion analyzer. All patients with osteofluorosis had gastrointestinal symptoms, the most common being abdominal pain. Endoscopic abnormalities were found in seven patients with osteofluorosis. In all 7 of these patients, chronic atrophic gastritis was seen on histology. Electron microscopic abnormalities were observed in all 10 patients with osteofluorosis. These included loss of microvilli, cracked-clay appearance, and the presence of surface abrasions on the mucosal cells. None of the control subjects had any clinical symptoms or mucosal abnormalities. It was concluded that gastrointestinal symptoms as well as mucosal abnormalities are common in patients with osteofluorosis.

Gallbladder abnormalities in acute viral hepatitis: A prospective ultrasound evaluation

We carried out a prospective case controlled study to evaluate the temporal sequence of sonographic abnormalities in acute viral hepatitis (AVH) and their resolution patterns. Correlations were established between the sonographic abnormalities and the clinical and biochemical profiles. Fifty-six patients within 2 weeks of onset of illness (37 within 1 week and 19 between 1 and 2 weeks) underwent real-time ultrasound at weekly intervals until clinical and biochemical resolution. Abnormal sonographic patterns were found in 55 of 56 (98.2%) patients. The wall thickness was abnormal (6.1 +/- 4.3 mm) in 55 (98.2%) cases, luminal abnormalities observed in 33 (58.9%) cases, and alterations in volume in 14 (25%) cases. Complete resolution took place in 53 (96.4%) cases by 12 weeks. A wall thickness of greater than 7 mm and abnormal luminal contents were more frequent in patients studied within 1 week of illness than later (p less than 0.05). No other correlations could be established between the different sonographic patterns and the clinical and biochemical profiles at any stage of the illness. We conclude that sonographic abnormalities are common in patients with AVH, with resolution as the rule with clinical recovery.

Hepatitis G virus in India.

disease. Two of these three had evidence of dual infection; one had antibody to HCV and another was a hepatitis B surface antigen carrier. The third patient was infected with HGV alone but had clear laboratory evidence of chronic liver disease. All five were negative for HCV RNA. Two patients had evidence of circulating HGV RNA without biochemical evidence of liver disease. We conclude that hepatitis G is present in Pakistan and is responsible for liver disease. Five of the first 43 sera tested were reactive (12%) so the prevalence may be high in patients with chronic active hepatitis in Pakistan. Our observation adds support to the urgency of making affordable tests available for hepatitis G and for effective blood bank screening in countries such as Pakistan.

A prospective randomized double blind trial comparing prednisolone and 4‐aminosalicylic acid enemas in acute distal ulcerative colitis

A prospective double blind and randomized study was conducted to compare 4‐aminosalicylic acid (4‐ASA) and prednisolone‐21‐phosphate enemas in inducing remission in patients with acute distal ulcerative colitis. Patients with ulcerative colitis distal to the splenic flexure as assessed by flexible colonoscopy, barium enema and histology were included in the study. Of 40 consecutive patients, 20 were randomized to each of the two treatment groups. Clinical evaluation was done weekly; sigmoidoscopy and histology were performed at entry and at the end of 4 weeks. Therapy was discontinued in four patients treated with prednisolone enemas due to worsening of symptoms. The clinical improvement was significant in the remaining patients (P<0.001) and was similar in the two groups P > 0.1). Sigmoidoscopic and histological improvement were better with 4‐ASA than with prednisolone enemas. No adverse effects were observed in any of the patients treated. The present study suggests that 4‐ASA is a safe and effective treatment for inducing remission in acute distal ulcerative colitis.

Fluoride as a possible aetiological factor in non‐ulcer dyspepsia

A prospective case controlled study was conducted to evaluate the role of fluoride as a possible aetiological factor for non‐ulcer dyspepsia (NUD). Twenty patients with NUD and 10 age and sex matched healthy controls were subjected to clinical evaluation, upper gastrointestinal endoscopy and biopsies from the gastric antrum and duodenum. The antral and duodenal mucosa was subjected to a rapid urease test for Helicobacter pylori and histological and electron microscopic examinations. Fluoride levels in the drinking water, serum and urine were estimated using a ION 85 ionanalyser. These levels were significantly higher in patients with NUD than in controls (P < 0.05). Histological abnormalities in the antral and duodenal mucosa were seen in 14 patients (70%) with NUD and 1 control subject (10%) (P < 0.05). Electron microscopic abnormalities in the mucosal cells were seen in all patients with NUD but in none of the controls (P < 0.01). The fluoride levels in serum and urine correlated with the symptoms, histological and electron microscopic abnormalities (P < 0.05). It was concluded that chronic exposure to fluoride may result in NUD and should be considered in patients where other known causes of dyspepsia have been excluded.