Elevated Liver Enzyme Activities Research Articles

Hepatic Effects of Inhaled Plutonium Dioxide in Beagles

The effects of inhaled 238PuO2 deposited in the liver of dogs were studied in beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung. Approximately 20% of the initial lung deposition was translocated to the liver by 1500 days after exposure. Life-span observations revealed that the liver contained 40% of the final body burden of plutonium, second only to the skeleton. Elevated serum liver enzyme activities were observed in dogs with final liver depositions of > or = 0.4 Bq/g, cumulative dose to the liver of > or = 0.18 Gy and annual dose rate > or = 0.02 Gy/year. Enzyme elevations were seen at one dose level lower than that in which bone or lung tumors were observed. Linear regression analysis revealed strong to moderate correlation between cumulative dose and dose rate and time to observed increases in liver enzyme activities. Liver tumors were late-occurring neoplasms observed at lower exposure levels where life span was not shortened by lung and bone tumors.

Ciclosporin metabolite pattern in blood and urine of kidney graft patients in relation to liver function

Ciclosporin, an immunosuppressant, is metabolized by the liver cytochrome P450 system. Changes in the pattern of its metabolites in blood and urine in patients with disturbed liver function have been studied. Forty seven kidney graft patients receiving 2.9 mg/kg/d ciclosporin b.i.d., and no additional medication that would interfere with ciclosporin metabolism, were allocated to three groups according to liver function: I with normal liver function (n = 19), II with elevated liver enzyme activity or bilirubin concentration in serum (n = 20), and III with cholestasis (n = 8). Ciclosporin and 17 metabolites were determined in blood and 24 h-urine. In blood the trough concentrations of metabolites M19 and M1A were significantly higher in group III than in groups I and II. The total quantity of metabolites excreted in 24 h-urine was significantly different for H230, M4N69 and M1A (group III greater than I = II). Renal excretion of the daily dose of ciclosporin in patients in group I was 2.7%, group II 3% and group III 5.7%. In group III compared to group I the ciclosporin metabolite pattern was shifted to a relatively higher concentration of M19 in blood and of H 230, M19 and M1A in urine. Since high ciclosporin metabolite concentrations appear to be associated with nephrotoxicity, the metabolite pattern in patients with impaired liver function should be monitored.

Tolerance of mefloquine alone and in combination with sulfadoxinepyrimethamine in the prophylaxis of malaria

A randomized double blind study was performed to evaluate the tolerance and the acceptance of mefloquine alone (Lariam ®) compared to a combined drug regimen consisting of mefloquine, sulfadoxine and pyrimethamine (MSP; Fansimef ®) in the prophylaxis of malaria. 175 Europeans travelling to different malaria endemic areas received either mefloquine alone (250 mg/week) or its combination with sulfadoxine (500 mg/week) plus pyrimethamine (25 mg/week). One person taking mefloquine and two taking MSP discontinued the drug intake because of moderate clinical side effects. Mild and moderate adverse clinical reactions predominantly concerning the gastro-intestinal tract and the autonomous nervous system were reported with a significantly higher occurrence in the MSP group. With both prophylactic regimens, reversibly elevated liver enzyme activities (glutamate oxalate transaminase and glutamate pyruvate transaminase [GPT]) were observed after prophylaxis. The increase of GPT serum activity correlated significantly with relatively high GPT levels before prophylaxis in both groups. This finding suggests a limited use of both regimens in cases of liver dysfunction. One case of mefloquine-resistant Plasmodium falciparum malaria was observed from West Africa; this patient was cured by a standard regimen of chloroquine.

Classification of diseases in student health with ICD-9.

Abstract In order to evaluate the progress of a health service, certain criteria (indices) should be established and monitored. If any health center wishes to compare its situation with others, a valid instrument for measuring morbidity is required, and the criteria must be in conformity with national and/or international standards. This paper details methods of producing health indices from medical diagnoses. It is based on experience in a health service for students. Three systems are offered to cover centers with and without computer facilities: 1) a minimum for student health services; 2) the “minima” requested by the World Health Organization; 3) a classification of conditions of special interest in student health. It is strongly recommended that the International Classification of Diseases (ICD-9) of the World Health Organization be accepted as the local and international basis for these diagnostic categories. “Epidemic Non-A, Non-B Hepatitis in Nepal: Recovery of a Possible Etiologic Agent and Transmission Studies in Marmosets,” MARK A. KANE, et al. An epidemic of non-A, non-B hepatitis occurred in Kathmandu Valley, Nepal, during 1981–1982, with approximately 7.6% of households and 1.4% of individuals affected. Cases occurred preponderantly in the 15- to 34-year-old age group (70%), with most cases (75%) occurring in males. A high mortality rate (21%) occurred in pregnant women admitted to the hospital. No single water source was implicated, but epidemic peaks occurred during monsoon rains, and multiple opportunities for enteric transmission existed. One of eight patient stools examined by immune electron microscopy revealed aggregated, antibody-coated, 27-nm viruslike particles when convalescent serum samples were used as sources of antibody. Inoculation of two chimpanzees and four marmosets with a suspension of this stool resulted in elevated liver enzyme activity in three marmosets. Fecal excretion of 27-nm particles during the acute phase of disease (with temporally coincident antigen activity by radioimmunoassay) was observed in one marmoset, which also developed convalescent antibody against the particles in the original inoculum. (Journal of the American Medical Association 1984;252:3140–3145.) “High-dose Vitamin C Versus Placebo in the Treatment of Patients with Advanced Cancer who Have Had No Prior Chemotherapy; A Randomized Double-Blind Comparison,” CHARLES G. MOERTEL, et al. It has been claimed that high-dose vitamin C is beneficial in the treatment of patients with advanced cancer, especially patients who have had no prior chemotherapy. In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy. (New England Journal of Medicine 1985;312:137–41.)

Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets.

An epidemic of non-A, non-B hepatitis occurred in Kathmandu Valley, Nepal, during 1981-1982, with approximately 7.6% of households and 1.4% of individuals affected. Cases occurred preponderantly in the 15- to 34-year-old age group (70%), with most cases (75%) occurring in males. A high mortality rate (21%) occurred in pregnant women admitted to the hospital. No single water source was implicated, but epidemic peaks occurred during monsoon rains, and multiple opportunities for enteric transmission existed. One of eight patient stools examined by immune electron microscopy revealed aggregated, antibody-coated, 27-nm viruslike particles when convalescent serum samples were used as sources of antibody. Inoculation of two chimpanzees and four marmosets with a suspension of this stool resulted in elevated liver enzyme activity in three marmosets. Fecal excretion of 27-nm particles during the acute phase of disease (with temporally coincident antigen activity by radioimmunoassay) was observed in one marmoset, which also developed convalescent antibody against the particles in the original inoculum.