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Biomedical subjects

F Degos

Publications and source records attributed to F Degos.

At least 109 records · Page 6Linked to original sources

Hepatitis B vaccine: randomized trial of immunogenicity in hemodialysis patients.

In order to determine whether reinforced vaccinations improve the immune response among uremic patients, three vaccination schedules with hepatitis B surface antigen vaccine (Institut Pasteur Production) were compared. A total of 215 hemodialysis patients treated in HBV free units were randomly allocated to Group I (3 injections of 1 ml), Group II (3 injections of 2 ml) and Group III (4 injections of 1 ml). Immune response was evaluated in 204 patients. The percentages of responders within 12 months after the first injection (greater than = 10 mIU/ml on 2 successive blood specimens) were: 45.6%, 75.0% and 69.4% in Group I, Group II and Group III respectively. The geometric mean peak values of anti-HBs observed 6 months after the first injection among the responders were: 60, 192 and 268 mIU/ml respectively. One month after a booster dose given to 182 patients 14 months after the first injection, anti-HBs levels were 144, 1123, 524 mIU/ml respectively, and the frequency of patients with an anti-HBs titer greater than = 50 mIU/ml was 68%, 82% and 75% respectively. These results led us to discard the use of Protocol I for these immuno-depressed patients while it is quite satisfactory in healthy subjects; they also show that Protocol II and III give better results than Protocol I, but that they cannot be statistically differentiated. We conclude that response rates and anti HBs antibody titers can be significantly improved in chronic hemodialysis patients with reinforced vaccination protocols.

Antibodies, Viral↗

Relationship between liver histopathological changes and HBsAg in 111 patients treated by long-term hemodialysis.

We studied liver biopsies performed between January 1972 and June 1980 in 111 patients receiving regular dialysis treatment. Biopsies were performed either because of suspected liver disease (61 patients) or routinely during abdominal surgery or kidney transplantation (50 patients). Repeat biopsies were done in 14 cases. Hepatitis B virus markers, assayed every 3 months during the observation period, were detected at some time in 71 patients (64%); 51 remained persistently positive. Histological examination showed normal liver in 39 cases, lobular hepatitis in 15, chronic persistent hepatitis in 36 and chronic active hepatitis in 21. All patients with chronic active hepatitis were chronic HBsAg carriers, and repeated biopsies showed aggravation only in these patients. The course was remarkably asymptomatic, with lesions leading to fibrosis despite the lack of histopathological patterns of severe necrosis and/or inflammation, which were conspicuously absent in this series.

Biopsy↗

Serial transmission of hepatitis B like non-A, non-B hepatitis and associated markers to chimpanzees successfully immunized against HBV.

In order to demonstrate that the HBV like strain of NANB hepatitis bred true as non-B together with its associated markers, 2 chimpanzees with high titer anti-HBs (45 and 125 AUSAB RU respectively) immunized with the Pasteur HB vaccine received 1 ml IV of a NANB inoculum. Two neighbour captive animal served as controls. The inoculum was the serum of a leukemic patient in remission for over 3 years with NANB chronic active hepatitis which serum contained HBV like particles and was found positive for NANBe Ag and anti-NANBc whereas in the liver typical numerous "SHIMIZU" dense soft edge aggregated intranuclear structures were demonstrated by electron microscopy. After 4 weeks portal inflammation and hepatocyte necrosis with significant aminotransferase elevation lasting for over 10 weeks developed in the 2 infected chimpanzees. No change in anti-HBs titer was seen and HBs, HBc, HBe Ag and/or AB could neither be detected in serum by RIA nor in liver by immunofluorescence during the 6 month follow up period. By contrast NANBc Ag became clearly demonstrable by immunofluorescence in the liver nuclei together with anti-NANBc in the serum after the 6th week and both persisted for over 4 months. Double unit structures similar to those of NANB/F strain were demonstrable in the cytoplasm at the acute phase. None of these changes was seen in the two control animals. Inoculation of the acute phase serum in the 2 previous control animals was again followed by the same sequence of events. Hybridization studies with HBV DNA of liver biopsies of infected chimps were negative.

Animals↗

[In vitro supplementation of pyridoxal phosphate for the optimisation of the determination of the catalytic activity of alanine aminotransferase and aspartate aminotransferase in kidney transplant patients (author's transl)].

Pyridoxal phosphate (PLP) is the coenzyme of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Thus, in vitro supplementation with PLP is important for the optimisation of the determination of catalytic activity of both enzymes. It patients with kidney transplants, stimulation by PLP is very important for ALT activity, which could be affected by plasma PLP deficiency. Furthermore, in this population catalytic activities are more frequently found increased using methods with PLP supplementation than without PLP supplementation (56% and 71% of patients for AST and ALT, respectively). These differences are not related to HBs antigen.

Adolescent↗

Regulatory T cell-subset imbalance in chronic active hepatitis.

Three monoclonal anti-T-cell antibodies, specifically directed against total T cells (OKT3), inducer-helper T cells (OKT4) and suppressor/cytotoxic T cells (OKT8), were used in this study to analyze peripheral T-cell subsets in hepatitis B surface antigen (HBsAg)-positive and -negative chronic active hepatitis (CAH) patients. Results showed that a clear-cut difference exists in the distribution of peripheral T cells of these two groups of subjects. HBsAg-positive CAH patients had a numerical predominance of peripheral T lymphocytes expressing the characteristics of cytotoxic/suppressor T cells. In contrast, patients with "autoimmune" HBsAg-negative CAH exhibit a predominance of OKT4 cells, namely, the helper-inducer T-cell subset. In addition, high numbers of circulating double labeled cells (expressing both the OKT4 and the OKT8 xenoantigens) were detected in some of the HBsAg-positive and HBsAg-negative CAH patients studied.

Adult↗

Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state.

The detection of hepatitis B virus (HBV) DNA in the liver and the serum permits direct study of the interaction between the virus and the liver cell. 40 HBV chronic carriers were studied by the blot technique of Southern to detect HBV DNA, and the results were compared with the serological status and histological status of the patients. It was possible to define two different chronic carrier states. The first is characterised by free viral DNA in the liver, with viral DNA and hepatitis B e antigen (HBeAG) in the serum; integrated HBV DNA is also present, at least in some patients. The second carrier state is characterised by the presence of only integrated HBV DNA sequences in the liver: viral DNA and HBeAg are not present in the serum. In one HBeAg-negative patient, however, free HBV DNA was detected in the liver and HBV DNA was present in the serum. The hybridisation technique appears to be a very sensitive test which could reflect viral multiplication better than HBeAg radioimmunoassay. Since a needle biopsy sample provides sufficient tissue for the Southern blot technique, it should be useful in understanding chronic hepatitis, the selection of patients for antiviral therapy, and the estimation of its efficiency.

Autoradiography↗

Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients.

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.

Adult↗

Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in French haemodialysis units: I, Medical staff.

A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.

Clinical Trials as Topic↗

Chronic active hepatitis and giant multinucleated hepatocytes in adults treated with clometacin.

The authors report the cases of 2 adults who became jaundiced during prolonged administration of clometacin, a new analgesic drug. Jaundice and serum aminotransferase activity progressively increased while the drug administration was continued but quickly decreased when it was eventually interrupted. 1 patient resumed the intake of clometacin and died with jaundice and ascites. In both patients, liver lesions were those of severe chronic active hepatitis with numerous giant multinucleated hepatocytes.

Aged↗

Is renal transplantation involved in post-transplantation liver disease? A prospective study.

Various lesions of the liver commonly observed in renal transplant recipients are usually considered as a consequence of the transplantation procedures (immunosuppression, drug toxicity, alteration of immune responses to various viruses). A group of 64 patients all treated with corticosteroids and azathioprine was studied prospectively, and serial liver biopsies were performed on the day of transplantation and at 1 and 3 years after transplantation. Chronic hepatitis was already present in 40% of the patients on the day of transplantation and an increase of only 15% in the frequency of this condition was observed 3 years later. The presence of HBsAg in 45% of the patients at the time of transplantation was significantly associated with liver lesions. In about 3% of the cases, transplantation was directly responsible for a liver disease (peliosis hepatitis). During the followup period an evolution from chronic persistent hepatitis to chronic active hepatitis was observed with an abnormally high frequency (25%). We conclude that most of the liver diseases observed in transplant recipients are the consequence of events before transplantation and probably related to hemodialysis.

Alanine Transaminase↗

[Ineffectiveness of corticosteroids in cholestatic forms of chronic active hepatitis].

Four cases of chronic active hepatitis with cholestasis resembling primary biliary cirrhosis are reported. Two patients were women and two were men; their age ranged from 18 to 52 years. They had recurrent jaundice with pruritus, and, in two cases, xanthelasma or xanthomas. All patients had hyperbilirubinemia, a moderate increase in serum aspartate aminotransferase activity, an increase in serum alkaline phosphatase activity and immunoglobulins G levels. Hepatitis B surface antigen was present in one patient. Histological examination of the liver revealed active chronic hepatitis with cholestasis. Moderate doses of prednisone had no effect on clinical or biochemical signs in any of the patients.

Adolescent↗

[Alcoholic ketoacidosis (author's transl)].

Chronic alcoholism is a frequently unrecognized cause of ketoacidosis in nondiabetic patients. Seven episodes of alcoholic ketoacidosis were observed in three patients. No consciousness disturbances were present. Semi-quantitative tests for ketones were strongly positive in urine, weakly positive in serum. The anion gap was between 25 and 41 mEq/l; serum lactate was between 0.9 and 9.0 mEq/l, and, in all cases, below the anion excess. Blood glucose ammonia was increased. Massive fatty liver was documented in all patients. All ketosis episodes followed an increase of alcohol ingestion associated with one to four week-starvation and vomiting; however, at the time of admission, alcohol was weakly increased in blood. In the four episodes where diagnosis was correct, ketoacidosis was rapidly corrected without insulin administration. In conclusion, in some nondiabetic subjects, the occurence of alcohol prolongated ingestion together with starvation and vomiting is responsible for ketoacidosis; because alcoholic ketoacidosis has often a mild clinical expression, its true prevalence is underestimated; insulin administration is not required.

Acidosis↗