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Biomedical subjects

J Heathcote

Publications and source records attributed to J Heathcote.

At least 55 records · Page 3Linked to original sources

Hepatotoxicity: newer aspects of pathogenesis and treatment.

The etiology and the pathogenesis of different forms of hepatotoxicity are discussed; case reports are included to illustrate the importance of history-taking and examination of liver tissue in establishing a specific diagnosis. The role of alcohol as a hepatotoxin as well as an enzyme-inducing agent is stressed. Genetic factors have been identified that may determine susceptibility to alcoholism and the hepatotoxic effects of alcohol and other compounds. Some cases of drug-induced cholestasis may be explained by disturbances in the known pathways of bile acid uptake, transport, and excretion. The importance of small duct destruction in patients with progressive drug-induced cholestasis is discussed. Finally, the potential hepatic complications of some nonprescription remedies used by adherents of "alternative medicine" are described, emphasizing the relevance of thorough etiological inquiry in all patients presenting with hepatic dysfunction.

Acetaminophen↗

Chaparral-induced hepatic injury.

Two patients with hepatic injury after ingestion of chaparral leaf are presented. The first patient, a 71-yr-old man, developed biopsy-proven hepatitis 3 months after ingesting chaparral leaf daily. His illness resolved with discontinuation of the herb and later recurred with rechallenge. The second patient is a 42-yr-old woman who developed hepatitis 2 months after chaparral leaf ingestion and recovered completely after discontinuation of the compound. Both patients have remained well with abstinence from chaparral. These reports provide evidence of the hepatotoxicity of this herb and stress the need for awareness of the potential harm from such nonprescription remedies.

Adult↗

The role of interferon in the treatment of viral hepatitis.

Chronic viral hepatitis, frequently an asymptomatic disease, can persist for decades. Despite the lack of symptoms, prolonged infection can lead to the complications of cirrhosis, liver failure and hepatocellular carcinoma. The goal of therapy is to reduce the risk of developing these complications and to eradicate the infectious pool. Patients with ongoing viral replication appear to be at greatest risk for developing complications. These patients have been targeted for treatment. Numerous randomized studies of interferon treatment of chronic hepatitis B and C have been published in the last 8 years. The experience from these studies and more recent developments will be reviewed.

Hepatitis B↗

Cholestatic liver disease with ductopenia (vanishing bile duct syndrome) after administration of clindamycin and trimethoprim-sulfamethoxazole.

Two patients who developed cholestatic liver disease after exposure to antibiotics are described. One patient who received clindamycin had liver biopsy findings of marked cholestasis, portal inflammation, bile duct injury and bile duct paucity (ductopenia). A second biopsy after clinical improvement showed resolution of cholestasis but persistence of duct paucity. Three years later, treatment with ampicillin caused another episode of cholestatic hepatitis with cholestasis and duct paucity on rebiopsy. The second patient, who developed cholestasis after receiving trimethoprim-sulfamethoxazole, had marked duct paucity in the liver biopsy. This is the first description, to our knowledge, of ductopenia apparently caused by clindamycin. Cross-reactivity between clindamycin and ampicillin is also demonstrated in one patient. This report documents that duct paucity may occur within 10 days of onset of jaundice and appears to be confined to ducts less than 0.03 mm in diameter.

Abscess↗

Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.

PURPOSE: To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection. DATA SOURCES: Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search. STUDY SELECTION: Fifteen randomized controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy. RESULTS: Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels. CONCLUSIONS: Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.

Adolescent↗

Dangers of immunosuppressive therapy in hepatitis B virus carriers.

OBJECTIVE: To identify the risk of hepatic failure in hepatitis B virus (HBV) carriers given intermittent immunosuppressive therapy. DATA SOURCES: The key words "immunosuppression" and "hepatitis B" were used to search MEDLINE for relevant articles in English published from 1970 to 1990; the bibliographies of these articles were reviewed for additional publications. Also included were articles published in 1991. STUDY SELECTION: Articles were included if they documented the use of immunosuppressive drugs to treat chronic hepatitis B or another condition in patients at high risk for the HBV carrier state. RESULTS: Long-term immunosuppressive therapy has not improved the survival of patients with chronic hepatitis B. The withdrawal of such therapy from HBV carriers has resulted in a flare-up of potentially fatal hepatitis in 20% to 50%, regardless of whether underlying liver disease was present. The presence of replicating viral DNA in the serum of HBV carriers may identify those who are at high risk of the deleterious effects of immunosuppressive therapy. CONCLUSIONS: Long-term immunosuppressive therapy is not advised for liver disease in HBV carriers. For other conditions in such people continuous rather than intermittent therapy is safer. Patients at high risk for hepatitis B should be screened for this virus when immunosuppressive therapy is contemplated.

Carrier State↗

The use of nuclear magnetic resonance imaging in monitoring total body iron in hemodialysis patients with hemosiderosis treated with erythropoietin and phlebotomy.

Two hemodialysis patients with hemosiderosis were treated with combined erythropoietin and repeated phlebotomy. Serial nuclear magnetic resonance (NMR) imaging and serum ferritin levels were used to monitor the efficacy of treatment. This treatment modality has definite advantages over chronic deferoxamine therapy. NMR image-derived parameters offer an objective, accurate, and noninvasive indication of tissue iron stores.

Adult↗

The demography of primary biliary cirrhosis in Ontario, Canada.

The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty-five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody-positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty-nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable.

Autoantibodies↗

Multiple hepatic abscesses: cholangiographic changes simulating sclerosing cholangitis and resolution after percutaneous drainage.

A 59-yr-old man developed multiple hepatic abscesses following an episode of diverticulitis. A percutaneous transhepatic cholangiogram (PTC) showed changes typical of sclerosing cholangitis complicated by multiple hepatic abscesses. No biliary tract stones were seen either on ultrasound or PTC. A single drain left in the right biliary tree and a course of intravenous antibiotics resulted in complete normalization within 14 days of the previously involved biliary tree.

Bacteroides Infections↗

Interferon-associated lymphocyte 2',5'-oligoadenylate synthetase in acute and chronic viral hepatitis.

Basal levels of the interferon-associated enzyme 2',5'-oligoadenylate synthetase were studied in lymphocytes of 46 patients with acute viral hepatitis and in 46 patients with chronic hepatitis B. Measurement of in vitro production of 2',5'-oligoadenylate synthetase following overnight incubation of lymphocytes with exogenous interferon was used to assess functional capacity of the lymphocyte interferon system. In acute hepatitis patients, an early but transient elevation of 2',5'-oligoadenylate synthetase was observed; the mean level at 1 week was significantly greater than the mean level at 4 weeks after the onset of their illness (p less than 0.01). Serial 2',5'-oligoadenylate synthetase levels did not identify those patients who were to progress to chronic hepatitis. Patients with chronic hepatitis B infection, regardless of background liver histology, generally had normal basal lymphocyte 2',5'-oligoadenylate synthetase levels. In both acute viral hepatitis and chronic hepatitis B, there was an inverse correlation between basal 2',5'-oligoadenylate synthetase level and 2',5'-oligoadenylate synthetase response to overnight incubation with interferon, a finding that suggested a transient down-regulation of interferon responsiveness. These findings provided no support for the hypothesis that there is an inherent or persistently induced deficiency in the interferon system in acute or chronic hepatitis B.

2',5'-Oligoadenylate Synthetase↗

Being a boss.

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Family Practice↗

Settling in.

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England↗

New patients.

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Family Practice↗

Hepatic arterial infusion of mitoxantrone in the treatment of primary hepatocellular carcinoma.

Twenty-three patients (16 male, seven female) with hepatocellular carcinoma (HCC) were treated by hepatic arterial infusion (HAI) of mitoxantrone every 4 weeks. At each treatment, a catheter was inserted percutaneously into the main hepatic artery via the femoral artery under image intensification. Treatment consisted of a 24-hour continuous HAI of mitoxantrone, 6 mg/m2/d X 3 (eight patients) or 10 mg/m2/d X 3 (14 patients) without heparin. Eight patients had only one infusion, nine patients four infusions, five patients three infusions, two patients two infusions, and one patient five infusions. A partial response was seen in six patients, with a median duration of 20 weeks (range, 18 to 38 weeks). Five patients achieved stable disease, with a median duration of 20 weeks (range, 11 to 42 weeks). The median survival of the overall group was 22 weeks. Survivals of responding, stable, and nonresponding patients were 32 weeks, 24 weeks, and 9 weeks, respectively. Complications of catheter placement included asymptomatic dissection of the hepatic artery (one patient), and asymptomatic thrombosis of the hepatic artery (five patients). Three patients experienced mild nausea and vomiting, and six patients had mild to moderate alopecia. Granulocytopenia was frequent at both dose schedules. The granulocyte nadir was greater than 1,000/microL in 34% of evaluable courses, 500 to 1,000/microL in 32%, and less than 500/microL in 34% of courses. Two patients developed neutropenia-associated fever. A platelet nadir below 100,000/microL was seen after only 10% of courses, and only two patients had platelets below 50,000/microL. Seven patients received doxorubicin after progression on mitoxantrone. Four received systemic doxorubicin, 50 mg/m2, and three HAI of doxorubicin, 25 mg/m2, for three days. Two patients achieved partial response (18 weeks and 32 weeks) to HAI doxorubicin. Mitoxantrone has activity in HCC and is well tolerated when administered by HAI. It is not entirely cross-resistant with doxorubicin.

Adult↗

Acute hepatitis in Crigler-Najjar syndrome.

We describe a 23-yr-old man with congenital unconjugated hyperbilirubinemia secondary to uridine diphosphate glucuronosyltransferase deficiency, and who cannot readily be classified as type I or type II Crigler-Najjar syndrome. After an episode of kernicterus in childhood he was treated with phenobarbital with a resultant marked decrease in his serum bilirubin concentration. Herein we describe his course after developing acute hepatitis secondary to infectious mononucleosis. He was treated acutely with plasmapheresis with prevention of any neurological sequelae despite having previously suffered from kernicterus.

Acute Disease↗

Pharmacokinetic disposition of isoxicam in hepatic cirrhosis.

To determine the effect of liver dysfunction on the absorption and disposition of isoxicam, we administered a single oral dose of 200 mg to 8 patients with alcoholic cirrhosis, and followed the plasma concentration-time curve for 96 h. The calculated isoxicam disappearance t 1/2 of 30 +/- 19.1 h in these patients was not different from the mean value of 31 +/- 5.7 h obtained in 10 normal subjects studied earlier by our group; however, interindividual variation was larger. No differences in lag time (0.42 +/- 0.3 vs 0.49 +/- .2 h) or time to peak concentration (9.0 +/- 2.5 vs 10.0 +/- 2.9 h) were observed. However, the peak plasma isoxicam concentrations and the areas under the plasma concentration-time curves (AUC) were reduced 32% (p less than 0.01) and 41% (p less than 0.01), respectively. Plasma protein binding of isoxicam studied by equilibrium dialysis was 80 +/- 16% in the cirrhotic patients compared with 96 +/- 1.4% in the normal volunteers (p less than 0.02), again with larger interindividual variation noted in patients with cirrhosis. The binding did not correlate significantly with any laboratory tests of liver function or with the AUC for plasma isoxicam. As compared to the normal subjects, these cirrhotic patients had decreased plasma isoxicam binding, peak plasma isoxicam concentrations and AUC, without a significant change in the apparent disappearance half-life of total plasma isoxicam after a single oral dose.

Anti-Inflammatory Agents, Non-Steroidal↗