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Biomedical subjects

A M Lever

Publications and source records attributed to A M Lever.

At least 91 records · Page 5Linked to original sources

Human lymphoblastoid interferon does not increase survival when added to mitozantrone in the treatment of hepatocellular carcinomas.

Human lymphoblastoid interferon, in an initial dose of 2.5 MU m-2 weekly i.m., was given with mitozantrone 12 mg m-2 i.v. every 3 weeks to 15 patients with hepatocellular carcinoma. The survival curve for these patients was worse than that of 15 patients previously treated with mitozantrone alone; there were more long-term survivors in those not given interferon; more side-effects were seen in the group given interferon. The addition of interferon to mitozantrone in the management of hepatocellular carcinoma is not recommended.

Adolescent↗

Immunity to rubella among women of child-bearing age.

The results of testing for rubella antibodies in over 6000 sera from women of child-bearing age are reported and analysed according to pregnant state, age, country of origin and social class. There was no difference between the rubella seroprevalence rates in women who were pregnant and in those who were contemplating pregnancy in the future. Likewise, women (either pregnant or non-pregnant) who were young enough to have been offered rubella vaccine at school were not more likely to be immune to rubella than were older women. Rubella seropositivity rates were not influenced by social class but significantly higher rates were found in women born in European or Arabian than in African or Asian countries. We conclude that the national scheme for rubella immunization has not reduced the number of women susceptible to rubella entering pregnancy in this Health District and that greater attention should be paid to immunization of women of child-bearing age from African or Asian countries.

Adolescent↗

Increased half-life of gammaglobulin after prolonged intravenous replacement therapy.

The half-life of total IgG and antibodies to cytomegalovirus and pneumococcal polysaccharide type III was consistently prolonged after a 9 month course of intravenous gammaglobulin treatment in three patients with 'primary' hypogammaglobulinaemia. The half-life of antibody to tetanus toxoid showed no consistent pattern. These data are at variance with the traditional dogma that IgG half-life is inversely related to serum IgG concentration. They suggest that patients on intravenous gammaglobulin therapy are likely to need less, rather than more, infusions when their serum IgG has risen to within the physiological range.

Adult↗

Homology between HBV-DNA and a sequence regulating the interferon-induced antiviral system: possible mechanism of persistent infection.

Treatment of hepatitis B virus (HBV)-infected hepatocytes with lymphoblastoid alpha-interferon (IFN) leads to an increased expression of the core antigen (HBcAg) and reduced expression of surface antigen (HBsAg). We have identified the presence of a nucleotide sequence at the start of the HBc gene in the hepatitis B virus genome similar to a consensus sequence known to occur upstream from genes induced by IFN in mammalian cells. It is possible that interferon influences the expression of the viral genes because of the presence of this homologous sequence. This sequence in the viral genome may determine the site of integration of the virus and could influence the ability of the cell containing the integrated viral sequence to respond to interferon. This "neutralisation" of the interferon system by viral integration might not only facilitate persistent infection but might also adversely affect response to alpha-interferon therapy.

Biopsy↗

Identification of factors influencing response rate to antiviral therapy of chronic hepatitis B virus infection. A review of the efficacy of adenine arabinoside and lymphoblastoid interferon in the Royal Free Hospital studies.

We have reviewed the results of treating over 100 HBV carriers with adenine arabinoside, adenine arabinoside monophosphate and lymphoblastoid interferon. In the homosexual group of carriers, adenine arabinoside and its monophosphate have no value. However, in this group, lymphoblastoid interferon will produce a response in over 50% of cases. The lack of effectiveness of adenine arabinoside monophosphate in this group may stem from its immunosuppressant properties. In heterosexual carriers both adenine arabinoside monophosphate and lymphoblastoid interferon are effective in approximately 50-60% of cases. However, the response rate is different in the various racial groups. Northern European and Mediterranean people appear to respond whereas those from the Far East do not. This may reflect the fact that there are at least 2 mechanisms by which the chronic carrier state may arise. In 5-10% of adults, a relative deficiency of alpha-interferon production exists and this defect is found in the majority of HBV carriers in Western Europe. In these, interferon acts as a replacement therapy and excellent results may be obtained if the patient is treated early in the course of the disease. It would appear that as the duration of the infection increases, the virus may integrate into interferon-reactive consensus sites and prevent the cell from responding to interferon. In patients infected at birth, transplacental anti-HBc appears to modulate the immune response and along with immaturity of the immune system at this age, results in failure to lyse infected cells. These patients do not benefit from interferon treatment: some form of immune manipulation is required.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Relationship of HLA protein display to activation of 2-5A synthetase in HBe antigen or anti-HBe positive chronic HBV infection.

In this study we have examined the density of HLA class I protein display on the hepatocytes of patients with HBe antigen (HBeAg) or anti-HBe (HBeAb) positive chronic hepatitis B virus (HBV) infection and related this to the level of interferon activation of these cells determined by measuring hepatic oligo 2-5A synthetase activity. In HBeAg positive patients the density of HLA class I (HLA-I) protein was not significantly increased above that found in uninfected liver, but levels of 2-5A synthetase were twice normal. In anti-HBe positive patients, HLA-I density was markedly increased in the presence of normal 2-5A synthetase activity. These data are consistent with type I (alpha or beta) interferon activation of the hepatocytes in HBeAg positive patients and type II (gamma) interferon activity in anti-HBe positive subjects.

2',5'-Oligoadenylate Synthetase↗

Viral hepatitis.

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Chronic Disease↗

Serum factors for opsonisation of non-typable Haemophilus influenzae.

Neutrophil chemiluminescence was used to assess the opsonins required for phagocytosis of non-typable Haemophilus influenzae isolated from sputum samples of patients with hypogammaglobulinaemia. Immunoglobulin was the major opsonin, whereas complement was relatively unimportant. Evidence was found for a heat-labile opsonin other than complement that enhanced phagocytosis of these organisms. Tuftsin was shown to aid phagocytosis of H. influenzae without triggering chemiluminesence.

Agammaglobulinemia↗

Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells.

Low-density cells (LDC) of dendritic morphology from the blood of patients with common variable (late-onset) hypogammaglobulinaemia (CVH) did not induce allogeneic immunoglobulin production by normal B cells unlike LDC from normal blood. When LDC from patients were treated with pokeweed mitogen (PWM), a lower allogeneic secretion of IgM and IgG was induced in normal B cells than that induced by allogeneic normal LDC treated with PWM. B cells from hypogammaglobulinaemic patients were non-responsive to both normal and patient LDC treated with PWM under all conditions tested.

Agammaglobulinemia↗

Non-A, non-B hepatitis occurring in agammaglobulinaemic patients after intravenous immunoglobulin.

Acute non-A, non-B hepatitis developed in twelve patients with primary hypogammaglobulinaemia during treatment with intravenous gammaglobulin prepared by Cohn fractionation of pooled plasma. The illness was clinically and histologically identical to the short-incubation non-A, non-B, hepatitis observed in haemophilic patients receiving factor VIII concentrates. Most of the patients were symptomless, but 10 months after onset ten of the twelve still had abnormal liver function. The occurrence of non-A, non-B hepatitis in agammaglobulinaemics indicates that humoral mechanisms are not essential for production of hepatocyte necrosis in this infection. This outbreak emphasises the need for a screening test to identify the agent in blood products, and shows that Cohn fractionation of plasma does not always inactivate the agent. Furthermore, the finding that the virus can be transmitted in IgG concentrates suggests either that the general population has a very low level of antibodies to the putative virus or that such antibodies are not virus-neutralising.

Agammaglobulinemia↗

Nifedipine enhances the bronchodilator effect of salbutamol.

Ten male asthmatic volunteers each inhaled two puffs (200 micrograms) of salbutamol on two separate days 30 minutes after double blind oral administration of either 20 mg nifedipine or identical placebo. FEV1 was recorded before and at intervals for four hours after inhalation of salbutamol. Overall the FEV1 was significantly greater during the four hour period after premedication with nifedipine (p less than 0.025) and the difference between the effects of placebo and nifedipine was greatest four hours after salbutamol (p less than 0.005). These results suggest that nifedipine prolongs the bronchodilator action of salbutamol in vivo.

Adult↗

Persistent immunoglobulin deficiency after prednisolone and antiepileptic therapy in a C2 deficient patient with lupus-like syndrome.

A homozygous C2 deficient patient with a lupus-like syndrome developed hypogammaglobulinemia soon after treatment with prednisolone together with phenytoin, replaced subsequently by carbamazepine. She suffered from recurrent chest infections and her lupus symptoms continued unabated. In vitro tests of immunoglobulin production by her Epstein Barr virus transformed B cells showed typical patterns of reduced IgA and IgG production seen in common variable hypogammaglobulinemia. An opsonisation defect to Hemophilus influenzae was also demonstrated which could be reversed by the addition of pooled human gammaglobulin. Serum IgM and IgG levels returned to normal 2 years after withdrawal of phenytoin and prednisolone, but 3 years later, she remained IgA deficient and the in vitro abnormalities persisted.

Adult↗

Acute polyarthritis following the use of Corynebacterium parvum vaccine (Coparvax) for malignant pleural effusion.

A 77-year-old man with a malignant pleural effusion was treated by aspiration of fluid and injection of Corynebacterium parvum vaccine for pleurodesis. Within 24 hr he had developed a temperature and a neutropenia followed by an acute crippling polyarthritis of his hands and wrists which subsequently responded to oral steroids and non-steroidal antiinflammatory drugs.

Acute Disease↗