A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease.

BACKGROUND: The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown. AIM: To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients. METHODS: We performed a multicenter, case-control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259). RESULTS: Smoking was associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) but not among those PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Compared to controls, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT; OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (OR, 1.6; 95% CI 1.2-2.3). PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6) and grilled/barbecued meat (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well done (OR, 1.3; 95% CI 1.2-1.5). CONCLUSIONS: IBD (rather than PSC) is associated with smoking. Women with PSC are more likely to have recurrent urinary tract infections and less likely to receive HRT. Dietary intake and methods of food preparation differ in PSC patients when compared to controls.

A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

Self-expanding metal oesophageal endoprostheses, covered and uncovered: a review of 30 cases.

OBJECTIVE: Oesophageal self-expanding metal endoprostheses (SEMS, or stents) are recognized as a safe means of palliating dysphagia caused by malignancy. Stent designs that have covered or uncovered walls are now available. The purpose of this study was to compare the outcome of use of these two designs. DESIGN: Thirty consecutive cases were reviewed. All the patients had been referred over a period of 25 months for palliation of dysphagia caused by malignant obstruction. Either a covered or an uncovered stent was placed in each patient. Palliation of dysphagia, 30 day mortality, mean survival time, and the number of endoscopic re-interventions required, were assessed. RESULTS: Uncovered Ultraflex stents were used in 14 patients, and Schneider Wallstents were used in 16 patients. Dysphagia improved by one grade or more in 69% of patients. The 30 day mortality was 27%, with an overall mean survival time of 99 days. There was no significant difference between the two groups for these three parameters. Ten patients needed a total of 28 repeat endoscopic procedures to maintain stent patency, with overall rates for each group of 1.64 procedures per patient, for uncovered stents, compared with 0.31 for covered stents (significant at the P < 0.05 level). The number of repeat procedures increased with survival time. CONCLUSION: The use of covered self-expanding metal oesophageal endoprostheses is associated with a significant reduction in the need for endoscopic reintervention after stent placement.

Randomised study of endoscopic biliary endoprosthesis versus duct clearance for bileduct stones in high-risk patients.

BACKGROUND: The value of an endoprosthesis for long-term management of bileduct stones has not been formally established. The main theoretical advantage of endoprosthesis insertion (BE) over conventional endoscopic duct clearance (DC) is the prevention of stone impaction, with obstruction and consequent cholangitis or pancreatitis. In a randomised study we compared the results of these two methods in patients with symptomatic bileduct stones who were at high risk because of old age (> 70 yr) or serious debilitating disease. METHODS: 43 high-risk patients were randomised to BE with a 7F double-pigtail endoprosthesis and < 0.75 cm sphincterotomy, and 43 to DC with standard 1.25-1.50 cm sphincterotomy and stone extraction by balloon or basket, with or without mechanical lithotripsy. The principal endpoint was the rate of biliary related complications. FINDINGS: In the BE group biliary drainage was achieved in the first session in all but one patient (who required 2 sessions). In the DC group, 24 patients had duct clearance at the first attempt and 35 (81%) after a median of 2 sessions (range 2-4); eight of this group had an endoprosthesis inserted to maintain long-term drainage. At 72 h the complication rates were 7% in the BE group and 16% in the DC group (p = 0.18). However, the long-term complication rate for BE was higher: by Kaplan-Meier analysis, at a median of 20 months the proportions free of biliary complications were 64% BE and 86% DC (p = 0.03, log-rank test). INTERPRETATION: For immediate bileduct drainage, endoprosthesis insertion proved a safe and effective alternative to duct clearance. Because of the risk of subsequent cholangitis, its use as a definitive treatment should be confined to highly selected cases.

Ultrasonic evaluation of portosystemic collateral circulation in portal hypertension.

The aim of the study was to evaluate portosystemic collateral circulation in relation to (1)individual etiological groups of portal hypertension., (2) Presence and size of esophageal varices, (3) esophageal sclerotherapy and (4) ascites. A prospective study of 101 patients of portal hypertension was carried out. Patients were divided into 4 etiological groups: Alcoholic cirrhosis (ALD) (38), Non-alcoholic cirrhosis (NALD) (35), non cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Esophageal varices were assessed and graded endoscopically into 3 categories: no varix, small varices and large varices. Evaluation of portosystemic collateral circulation, other than esophageal varices was done ultrasonically. "Other" portosystemic collaterals (lienorenal, gastrorenal, dilated paraumbilical and umbilical veins, paraduodenal and gall bladdes varices) were seen in 26 out of 101 patients and more commonly in the non-cirrhotic groups (50%) [NCPF: 57.14%, EHPVO: 42.86%] than in the cirrhotic group (16.44%) [ALD: 13.5%, NALD: 20%]. Gall bladder varices were the only form of ectopic (extra esophagogastric) varices visualised with an overall incidence of 3.96%. Collateral shunts were seen more frequently in patients without varices (100%), than in patients with small varices (34.88%) or large varices (7.84%), and in patients having undergone esophageal sclerotherapy (57.14%). Collateral circulation did not contribute to the development of ascites. 37 patients with ascites did not have collateral shunts. We conclude portosystmic circulation plays a decompressive role in portal hypertension and prevents formation of esophageal varices or prevents them from increasing in size. It is seen more frequently in noncirrhotic patients and in those having undergone sclerotherapy and does not contribute to development of ascites.

Significance of radioisotope bone marrow uptake on 99m technetium sulphocolloid scan in portal hypertension.

A prospective study of 101 consecutive patients of portal hypertension was carried out to study the possible relationships between bone marrow activity on 99m technetium labelled sulphocolloid scan and severity of liver disease, etiology of portal hypertension and cirrhosis, as well as presence and extent of collateral circulation, including esophageal varices. The patients were divided into 4 etiological groups: alcoholic cirrhosis (ALD), (38) non-alcoholic cirrhosis (NALD) (35) non-cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Patients of cirrhosis were categorised according to modified Child-Pugh's classification. Esophageal varices were graded endoscopically as (1) no varix (2) small varices (< 5mm) (3) large varices (> 5mm). All patients underwent radionuclide imaging using 99m Technetium labelled sulphocolloid and bone marrow activity was studied. Evaluation of portasystemic collaterals was done ultrasonically. We found that 16.6%, 44.6% and 72.72% patients with Child A, B and C cirrhosis respectively, had increased marrow activity (p < 0.05). There was no significant difference between marrow activity of patients with ALD (52.6%) and NALD (40%). None of the non-cirrhotic patients demonstrated bone marrow uptake of radioisotope. There was no significant difference between bone marrow uptake presence of lienorenal collaterals and presence or size of esophageal varices. We thus conclude the bone marrow activity on radioisotope scanning depends only on the severity of liver disease and does not vary a according to the etiology of cirrhosis, or presence and extent of portasystemic collaterals, including esophageal varices.

Evaluation of splenomegaly in portal hypertension.

Splenomegaly is obvious in portal hypertension, but controversy still exists over the relationship between splenic size or size of esophageal varices. Previous methods to assess spleen size are less accurate than ultrasonic estimation of spleen size by splenic volumetric index (SVI). In a prospective study, we evaluated 101 consecutive patients with portal hypertension for spleen size measured ultrasonically by SVI, presence and size of esophageal varices, and etiology of portal hypertension. A total of 219 age-matched controls were evaluated ultrasonically to define a normal SVI. Splenomegaly defined by 1 or 2 standard deviations of normal SVI had high accuracy in predicting portal hypertension, presence of esophageal varices, and provided a clue to the etiology of portal hypertension. However, there was no correlation between spleen size and size of esophageal varices.

Tuberculous abscess of the liver associated with HIV infection.

Tuberculosis is an AIDS-defining illness in HIV-seropositive patients. Though disseminated tuberculosis is common in HIV-seropositive patients, hepatic involvement in the form of abscess formation is rare. We report such a patient.

Hepatitis C virus infection in chronic liver disease in Bombay.

To find out the prevalence of antibody of hepatitis C virus (anti-HCV) in patients with chronic liver disease in Bombay, sera from 126 patients (93 men, 33 women; aged 9-70 years, mean 39.7) with chronic liver disease (cirrhosis 103, cirrhosis with hepatocellular carcinoma 3, chronic active hepatitis 20) were tested for HBsAg and anti-HCV antibody. HBsAg positive sera were tested for anti-delta antibody and IgM anti-HBc. All the tests were carried out by ELISA. Of 126 patients, 51 (40.5%) were HBsAg positive, 49 (38.8%) alcoholic and 21 (16.6%) anti-HCV positive. The prevalence of anti-HCV in HBsAg positive, alcoholic and cryptogenic (HBV negative and no alcohol) liver disease patients was 13.7%, 14.7% and 20.5% respectively. Of 21 anti-HCV antibody positive patients, 8 (38%) had received blood transfusions previously. HCV is present in 15-20% of patients with chronic liver disease in Bombay.

Bilateral optic nerve infarction following acute systemic hypotension and anemia--a case report.

Presented here are case reports of two patients who became completely blind in both eyes following acute systemic hypotension - in one following bouts of vomiting and in the other after repeated gastrointestinal bleeding. Both patients had severe degree of anemia. There were no other risk factors for vascular disease such as arteriosclerosis or vasculitis.

Carotid sinus syndrome associated with carcinoma of the pyriform fossa.

A patient who developed syncope due to carotid sinus syndrome is described. The patient was suffering from carcinoma of the pyriform fossa for the past one year and received radiotherapy in the region of the neck for the same. Demand pacing was ineffective in alleviating syncopal episodes. The patient responded to oral administration of an anticholinergic (belladonna) and a sympathomimectic agent (orciprenaline).