Search PubMed⌕ Search

Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 307 records · Page 17Linked to original sources
PubMed1983

Relationship between HBV-specific DNA polymerase and HBe antigen/antibody system in chronic HBV infection: factors determining selection of patients and outcome of antiviral therapy.

The sera of 23% of HBe antigen positive patients with chronic hepatitis are HBV-DNA polymerase negative. These patients are probably undergoing spontaneous seroconversion from a state of high to low viral replication and do not require antiviral therapy. In chronic HBV infection rapid changes in viral replication as a result of antiviral therapy are reflected by changes in HBV-DNA and HBV-DNA polymerase but not by changes in HBe antigen concentrations. Disappearance of HBe antigen from serum may be delayed for 180 days after permanent inhibition of HBV replication with adenine arabinoside or its monophosphate derivative.

DNA-Directed DNA Polymerase↗
PubMed1983

Acute type A, B, and non-A, non-B hepatitis in a hospital population in London: clinical and epidemiological features.

The aetiology of acute viral hepatitis in 172 patients admitted to an infectious diseases hospital in North London was: hepatitis A in 88 (51%), hepatitis B in 58 (34%), Epstein-Barr (EB) virus in four (2%) and non-A, non-B in 22 (13%). NANB hepatitis was a milder disease than that associated with the other viruses. It predominantly occurred in young men (77%). In half of the cases there was evidence of parenteral transmission. It was not transmitted by sexual contact.

Acute Disease↗
PubMed1983

Approaches to the treatment of chronic hepatitis B viral infection.

In HBeAg positive patients with a high level of viral replication, antiviral therapy is the treatment of choice. The most promising agents at the moment are ARA-AMP and Interferon and both are being assessed in controlled clinical trials. In the anti-HBe positive patients in whom continued HBs antigenaemia is due to the presence of clones of cells containing integrated virus, some form of immune manipulation may be necessary. In rare cases in whom continuing inflammatory activity is related to an autoimmune reaction, low dose prednisolone may be beneficial. Treatment for delta infection has yet to be evaluated but antiviral agents such as interferon which inhibit both DNA and RNA viruses may prove effective. Although these forms of therapy are currently experimental, some are now entering phase III clinical trials. It seems probable that the ultimate regimen will include antiviral drugs and immune manipulation to adequately eliminate hepatocytes containing replicating and integrated virus. The latter is essential if we are to deal with the problem of neoplasia as well as infectivity and inflammatory liver disease.

Acyclovir↗
PubMed1983

Recent advances in viral hepatitis.

In the space of one decade we have come to understand the mode of replication of the hepatitis B virus and something of the mechanisms by which it produces liver cell damage and primary liver cell cancer. Although several drugs have been shown to be effective in inhibiting the replication of this virus, none are completely satisfactory. Our knowledge of the mode of replication of the virus now enables us to design new trials to selectively inhibit the enzymes involved in the replication of the virus. Although these advances will be of great benefit to the individual patient, clearly the problem is best dealt with, world-wide, by effective prophylaxis and the availability of a safe and effective vaccine now makes this possible. However, although the problems of Type B hepatitis infection are being overcome the problem of non-A, non-B hepatitis remains.

Animals↗
PubMed1983

Epidemiology and clinical course of delta infection in Britain.

This study demonstrates the presence of serological markers of delta infection in HBsAg positive patients throughout the years 1976-1982. As in other Northern European countries, delta infection in Britain is predominantly found in drug addicts and haemophiliacs. delta Ag was detected transiently in serum in a minority of patients presenting with acute hepatitis. In the others and those presenting with chronic liver disease, anti-delta was the only serological evidence of delta infection. Our findings also confirm that delta infection is associated with a more severe and rapidly progressive liver disease.

Acute Disease↗
PubMed1982

A rapid one-step radiometric assay for hepatitis B surface antigen utilizing monoclonal antibodies.

A two-site antigen assay for HBsAg has been developed that employs 3 monoclonal antibodies. The antibodies were selected for their high affinity and their particular epitope specificity to establish an assay with a sensitivity for the antigen comparable with that of a conventional assay with heterologous antisera. In addition, by selecting a monoclonal antibody for use as a tracer which does not compete for antigenic binding sites with the solid-phase monoclonal antibodies, it has been possible to perform a two-site assay in a single 1 h incubation step, achieving the same degree of sensitivity. This principle of using monoclonal antibodies in a one-step assay therefore gives advantages of speed and simplicity over assays using heterologous antisera and would be applicable to a variety of antigen assays for which appropriate monoclonal antibodies are available.

Animals↗
PubMed1982

Genetic and sex-linked factors influencing HBs antigen clearance. I. Nonimmune clearance in inbred strains of mice.

Differences in the clearance values of polyvinylpyrrolidone (KPVP) and HBs antigen (KHBs) were seen in several strains of inbred mice. In addition, in all strains studied KHBs was greater in females than in males, while KPVP was not significantly different in the two sexes. In the strain with the lowest KHBs values, the incidence of HBs antibody formation was lower than in the other strains. These data indicate that genetic and sex-linked factors influence nonimmune clearance of HBs antigen in mice. If similar factors exist in man they may explain some of the variation in clinical manifestation of HBV infection.

Animals↗
PubMed1982

Analysis of hepatitis virus DNA in the liver and serum of HBe antigen positive chimpanzee carriers.

Hepatitis B viral DNA present in the liver of HBe antigen positive chimpanzee carriers is in the form of viral molecules (3.2 Kb) and no integration into host DNA was observed. The 3.2 Kb form was not detected in the serum. Other discrete HBV DNA species with faster mobilities than the major 3.2 Kb were consistently detected both in the liver and in the serum and their possible significance is discussed.

Animals↗
PubMed1982

The detection of HBV-DNA in serum by molecular hybridisation: a more sensitive method for the detection of complete HBV particles.

Existing methods for detecting complete virus particles in the serum of patients with chronic HBV infection are either insensitive or indirect. A method is described in which Dane particle-associated DNA is extracted from a small volume of serum and detected by molecular hybridization using 32P-labeled cloned HBV-DNA or HBV-DNA extracted from the serum of an immunosuppressed patient, followed by autoradiography and densitometry. There was a positive correlation between the amount of HBV-DNA detected using HBV particle-derived and cloned HBV-DNA probes. The amount of HBV-DNA detected in serum samples showed a positive correlation with the HBV-DNA polymerase. The method was more sensitive than the DNA polymerase and HBeAg assays in detecting complete virus particles. It may be useful in determining the level of infectivity in patients and in monitoring response to antiviral therapy.

Cloning, Molecular↗
PubMed1982

The pathology of hepatitis A in man.

Liver biopsies from 17 patients with serologically established hepatitis A were examined by light microscopy. Biopsies were taken from 2 to 27 weeks after onset of symptoms. All showed acute hepatitis, usually with centrilobular lesions but also commonly with a striking portal and periportal inflammatory reaction, resembling that seen in chronic active hepatitis. The infiltrate was rich in plasma cells. Centrilobular cholestasis was common and occasionally severe. Neither cholestasis nor the periportal lesion appeared to be related to patient age or to the timing of liver biopsy. All patients made a full recovery and none developed chronic liver disease. The histological changes differed from those reported in children and in chimpanzees in the presence of centrilobular lesions, but resembled them in that the latter two groups also had periportal lesions. These lesions may lead to a false impression of impending chronicity if the aetiology of the hepatitis is not known at the time of liver biopsy.

Adult↗
PubMed1982

Effects of prednisolone/azathioprine in chronic hepatitis B viral infection.

Changes in markers of hepatitis B viral replication and standard liver function tests were studied in 30 patients with HBsAg positive chronic liver disease starting or stopping prednisolone/azathioprine therapy, and compared with those occurring in 15 patients who did not receive therapy. On stopping prednisolone/azathioprine, 10 out of 11 HBeAg positive patients and one out of three patients negative for HBeAg and anti-HBe, lost HBV-DNA polymerase activity (p less than 0.01), five lost HBeAg, three developed anti-HBe and HBsAg concentration decreased (p less than 0.01). Only one out of seven untreated HBeAg positive patients lost HBeAg and there were no significant changes in DNA polymerase activity. In the anti-HBe positive patients, 14 starting therapy and eight untreated, there were no significant changes in the markers of viral replication - although two patients developed DNA polymerase activity on high maintenance doses of prednisolone - but a significant decrease (p less than 0.05) in aspartate transaminase in the treated group. It is concluded that the cessation of prednisolone/azathioprine therapy in HBeAg positive patients will result in a reduction in viral replication. In anti-HBe positive patients such therapy may be beneficial.

Azathioprine↗
PubMed1982

Successful treatment of HBs and HBeAg positive chronic liver disease: prolonged inhibition of viral replication by highly soluble adenine arabinoside 5'-monophosphate (ARA-AMP).

In eight HBs and HBe antigen positive patients with chronic active liver disease, adenine arabinoside 5'-monophosphate (ARA-AMP) given, intravenously or intramuscularly, six or 12 hours, produced inhibition of viral replication. In five patients given a short course of therapy with 10 or 15 mg/kg/day this effect was transient and in two thrombocytopenia occurred. In three further consecutive cases given a longer course with 5 mg/kg/day after five days of the high dose, thrombocytopenia was not seen and inhibition of viral replication for up to 13 months occurred. These patients lost HBV-DNA polymerase activity, serum viral DNA and HBeAg, developed anti-HBe, and HBsAg concentrations decreased. A course of twice daily intramuscular ARA-AMP given for three to five weeks as an outpatient may be expected to produce a long-term reduction in infectivity.

Adult↗
PubMed1982

T cell subset abnormalities in tissue lesions developing during autoimmune disorders, viral infection, and graft-vs.-host disease.

The authors review a large body of contemporary immunohistologic findings on the tissue distribution of T lymphocytes in normal and pathological conditions. The suggestions for technological advances in this field are: signal amplification using mixtures of monoclonal antibodies directed against different epitopes on the same antigen (e.g. OKT4A+B+D), triple layer amplification systems using hapten-labelled antibodies, and informative double staining methods with combinations of antibodies labelled with different fluorochromes or enzymes. Review of histological observations in a series of human diseases suggests that imbalances of OKT4+ and OKT8+ subsets of T lymphocytes may represent different types of immunoregulatory disorders. Rheumatoid arthritis and sarcoidosis appear to involve a high level of OKT4+ subpopulation response coupled with an associated appearance of a special type of HLA-DR+ macrophages. It remains to be seen whether normal or self-limited immunological responses (early stages of bacterial infection or delayed-type hypersensitivity reactions) produce OKT4+ and macrophage responses that are characteristically different. Meanwhile, excessive levels of OKT8+ cells have been found in a wide range of recognized or presumed immunoregulatory disorders including: graft-vs.-host reaction and viral infections. These disorders, as well as primary biliary cirrhosis and lichen planus, appear to possess both overlapping and disparate clinical characteristics, and the immunohistological observations may reflect the functional heterogeneity of OKT8+ populations in these diseases. These studies show that histologically meaningful heterogeneity can already be demonstrated for the OKT8+ lymphocyte group.

Animals↗