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Biomedical subjects

H C Thomas

Publications and source records attributed to H C Thomas.

At least 343 records · Page 19Linked to original sources
PubMed1980

Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.

A long-term follow-up of at least 10 years or until death of 44 patients taking part in a controlled prospective trial of prednisolone therapy in hepatitis B antigen negative chronic active hepatitis (lupoid hepatitis) has been performed at the Royal Free Hospital, London. Patients presenting between 1963 and 1967 were randomly allocated into control and treatment groups. Ten year life table survival curves showed a significantly improved survival in the treatment group where 63% of patients were alive at 10 years compared with only 27% in the control group (log rank test, P = 0.03). The median survival in the treatment group was 12.2 years compared with 3.3 years in the control group. The mean duration of treatment was 4.5 years. Age, presence of antinuclear factor, cirrhosis, or level of serum transaminases at presentation did not appear to affect survival. Male patients if untreated had a poorer prognosis than females (P = 0.02). The natural history of chronic active hepatitis appeared from clinical, biochemical, and histological findings to be from an active hepatitis or cirrhosis to inactive macronodular cirrhosis. Prednisolone therapy significantly improved survival by reducing mortality in the early active phase of the disease.

Adolescent↗
PubMed1980

HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.

Antibodies, Viral↗
PubMed1980

Viral antibody titres in HBs antigen-positive and -negative chronic active hepatitis.

A comparative study of antibody titres to nine common viruses has been carried out in hepatitis B surface (HBs) antigen-positive and -negative chronic active liver disease. The results show that increased titres of antibody to morbilli virus by complement fixation and to rubella by haemagglutination inhibition are found in HBs antigen-negative but not in HBs antigen-positive chronic active liver disease. There was a significant association of increased morbilli but not of rubella virus antibody titres with the presence of high-titre nuclear antibodies (ANA) but no association with smooth-muscle antibody or the presence of HLA-B8.

Adolescent↗
PubMed1980

Levamisole therapy for HBsAg-positive chronic liver disease.

Eight subjects with HBsAg-positive chronic liver disease received levamisole therapy continuously for 6 to 8 weeks. Depressed T-lymphocyte concentrations, found in all patients before therapy, transiently returned towards normal. All of the three patients who had normal delayed hypersensitivity responses before treatment showed an acute hepatitic reaction manifested by elevation of serum aspartate transaminase (AsT) and HBsAg levels, with transient cell-mediated immunity to HBsAg. This was interpreted as indicating increased lysis of infected hepatocytes. All of the five anergic patients showed no change in AsT or HBsAg levels. The clinical features and hepatic histology were unchanged. In patients with the capacity to mount normal delayed hypersensitivity responses, levamisole enhanced the cell-mediated response to HBsAg, and there was increased lysis of infected cells. Nevertheless, this treatment failed to eradicate the virus, as all patients remained HBsAg-positive.

Adult↗
PubMed1980

Immunological and anti-viral therapy of chronic hepatitis B virus infection.

Although we have reached the stage when we can influence viral replication and some aspects of the immune response to the viral antigens, no practical and effective therapeutic regimen has been evolved. The next few years should, however, see considerable advances in this field, perhaps with combined anti-viral and immunostimulant regimens. The need to consider the infectivity of the patient, the risk of developing clinically significant chronic liver disease and the risk of developing clinically significant chronic liver disease and the risk of developing primary liver cell carcinoma in each patient may dictate that different regimens will be needed for HBe antigen-positive and negative carriers and for patients with chronic active or chronic persistent hepatitis and carriers with normal liver histology.

Adjuvants, Immunologic↗
PubMed1980

Hepatitis B surface antigen and alpha-fetoprotein secreting human primary liver cell cancer in athymic mice.

A human primary liver cancer cell line which retains the property of synthesizing hepatitis B surface antigen has been successfully transplanted into nude (athymic) mice. The morphology of the heterotransplanted tumor is similar to that of a well-differentiated human primary liver cell cancer. It produces hepatitis B surface antigen, but there is no evidence of hepatitis B virion production: Hepatitis B core antigen is not detected in the PLC tissue, and serum is negative for hepatitis B e antigen. The nude mouse exhibits a resistance to the transplantation of the human primary liver cancer cells which can be modified by sublethal total body irradiation, suggesting involvement of an immunologic rejection mechanism. The heterotransplanted primary liver cell cancer also produces alpha-fetoprotein, as did the original tumor in vivo, although this marker was not detected during in vitro cell culture. The serum level of alpha-fetoprotein rises exponentially, enabling quantitative evaluation of tumor growth. The human primary liver cell cancer in nude mice provides an in vivo model for determination of tumor response to chemotherapeutic agents.

Animals↗
PubMed1980

Bile duct carcinoma: a late complication of congenital hepatic fibrosis. Case report and review of literature.

Bile duct carcinoma is reported in a 50-year old man as a rare late presentation of congenital hepatic fibrosis (CHF). A survey of the world literature suggests that carcinoma occurs with increased frequency in congenital biliary dilatation. It appears to be a particular risk in patients with prolonged survival but is rare in CHF, where portal hypertension and renal insufficiency make the long-term prognosis poor. In this patient the absence of both gastroesophageal varices and renal disease may have permitted longevity with development of carcinoma. The finding of carcinoma arising in the bile ducts distal to the basic lesion of CHF suggests that active carcinogens may be present in the bile in CHF. The tumor in this patient was unusual in producing mucinous biliary obstruction and terminal hypercalcemia.

Adenocarcinoma, Mucinous↗
PubMed1980

Immune function in patients with extrahepatic portal venous obstruction and the effect of splenectomy.

Abnormalities of cell-mediated immunity-anergy to delayed hypersensitivity skin testing, diminished T-lymphocyte concentrations and mitogen responsiveness, and the presence of serum inhibitors--have been shown to be present in patients with portal venous obstruction and normal hepatic function. In contrast, tests of humoral immunity--antibody titiers to viral and bacterial antigens and immunoglobulin concentrations--were normal. These abnormalities in cell-mediated immunity are probably the result of the development of portal hypertension, portosystemic shunting, and congestive splenomegaly. These studies raise the possibility that qualitatively similar defects in patients with chronic liver disease and portal hypertension may, in part, be attributable to the same mechanisms.

Adolescent↗
PubMed1980

Complement metabolism in chronic liver disease: catabolism of C1q in chronic active liver disease and primary biliary cirrhosis.

The fractional catabolic rate of C1q was increased markedly in primary biliary cirrhosis, and in HBsAg-positive chronic liver disease. In 3 out of 4 patients with HBSAg-negative chronic active liver disease C1q catabolism was normal. The rate of synthesis of the protein was increased in primary biliary cirrhosis, but it was normal in patients with chronic active liver disease. The fractional catabolic rate and synthetic rate of albumin were normal in these subjects. These data provide further evidence for the activation of the classical pathway of complement in primary biliary cirrhosis and HBsAg-positive chronic active liver disease. In HBsAg-negative chronic active liver disease, the presence of C1q binding macromolecules was not associated with increased C1q catabolism.

Adult↗
PubMed1979

Reduction of immune complexes and immunoglobulins induced by D-penicillamine in primary biliary cirrhosis.

Penicillamine has an effect on immune complexes and immunoglobulins both in vivo and in vitro. We therefore studied the effect of penicillamine on immune complexes and immunoglobulins in primary biliary cirrhosis. Twenty-eight patients were randomly allocated into a treatment group receiving 600 to 900 mg of penicillamine, or a control group, and followed for a maximum of 24 months. After 12 and 24 months, serum immune complexes had fallen significantly in treated patients as compared to controls (P less than 0.05, P less than 0.01). Treatment reduced IgA, IgG and IgM concentrations, with IgM being significantly different from controls at six, 12 and 24 months (P less than 0.01). Over 24 months, serum aspartate transaminase levels fell in treated patients but rose in controls (P less than 0.01). Bilirubin concentrations increased at a slower rate in treated patients. Penicillamine may favorably influence the course of primary biliary cirrhosis by its immunologic action in addition to its copper-chelating action.

Antigen-Antibody Complex↗
PubMed1979

Humoral immunity before and after thymectomy in myasthenia gravis.

Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p less than 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p less than 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.

Adult↗
PubMed1979

Monomeric (7S) IgM in chronic liver disease.

Monomeric (7S) IgM was detected by polyacrylamide/agarose gell immunodiffusion and Sephadex G200 gel filtration in 33% of sera from patients with primary biliary cirrhosis (PBC) and 5% of patients with HBsAg-negative chronic active liver disease (CALD). It was not found in the sera of patients with extrahepatic cholestasis, alcoholic liver disease (ALD), HBsAg-positive CALD and normal control subjects. In the PBC group the presence of 7S IgM was associated with significantly higher IgM concentrations and Clq binding activity (P less than 0.001; P less than 0.01 respectively). The antibody specificity of the 7S IgM is unknown. Its presence in patients with high serum IgM concentrations probably reflects failure of complete polymerisation of 7S IgM because of an increased rate of synthesis of the protein. The association of the presence of 7S IgM and high total IgM with immune complexes suggests that the increased rate of synthesis of IgM and formation of immune complexes probably are a result of the same antigenic (or mitogenic) stimulus.

Cholestasis↗
PubMed1979

The immunological effects of thymectomy in myasthenia gravis.

Thymus-derived (T) lymphocytes in the peripheral blood and cellular immune function have been studied in ten patients with myasthenia gravis and in fifteen different myasthenic patients more than 10 years after thymectomy. The results were compared with those of a normal control population. The non-thymectomized myasthenic patients had normal T lymphocyte concentrations measured by rosetting with native sheep red cells. These patients also showed normal sensitization and recall of delayed hypersensitivity, phytohaemagglutinin (PHA) induced lymphocyte transformation and antibody-assisted (K cell) cytotoxicity; however, PHA-induced cytotoxicity was markedly reduced (P less than 0.001). The thymectomized group exhibited a lower mean percentage and absolute number of E-rosette-forming cells, which returned toward normal after in vitro treatment with thymosin. PHA-induced lymphocyte cytotoxicity, however, was normal in the patients who had undergone thymectomy, as were lymphocyte transformation, antibody-assisted cytotoxicity and sensitization to dinitrochlorobenzene (DNCB); there was a decrease in recall of established delayed hypersensitivity. Adult thymectomy in man, therefore, produces a partial and dissociated decrease in T cell responses and it is unlikely that the beneficial effect of this operation in myasthenia gravis is related to immunosuppression.

Adolescent↗
PubMed1978

HBsAg-positive chronic liver disease: inhibition of DNA polymerase activity by vidarabine.

Four patients who had chronic liver disease and were positive for hepatitis B surface antigen (HBsAg) were treated with vidarabine, a synthetic purine nucleoside that inhibits DNA polymerase activity in vitro and in vivo. Before treatment all had raised serum DNA polymerase concentrations. Three also had hepatitis B e (HBe) and were shown by electron microscopy to have hepatitis B virus (Dane) particles in their serum. In all patients 10 days' treatment with vidarabine resulted in an immediate loss of DNA polymerase activity. In three patients the activity returned when treatment was stopped. In those three patients Dane particles and HBe antigen persisted during and after treatment; in the fourth patient, who remained negative for DNA polymerase, HBsAg titres fell. Although vidarabine inhibited virus replication, virus particles did not disappear from the blood in these patients, presumably because the particles were cleared only slowly. Similar results with interferon suggest that the virus disappears, and HBsAg titres fall, some weeks after the fall in DNA polymerase activity. Continued treatment may therefore have a sustained effect on viral replication. Whether vidarabine can permanently clear HBsAg and so arrest chronic liver disease remains to be seen, but at the very least it could reduce the spread of infection.

Adult↗