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Biomedical subjects

A J Pinching

Publications and source records attributed to A J Pinching.

At least 145 records · Page 8Linked to original sources

Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis.

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

AIDS-Related Complex↗

Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate).

Three patients with biopsy diagnosed invasive cytomegalovirus infection of the colon have been seen in the context of the acquired immune deficiency syndrome (AIDS). Cytomegalovirus colitis presented with fever, abdominal distention, bloody diarrhoea and weight loss. Plain abdominal radiographs showed generalised large bowel dilatation in one patient. Cytomegalovirus infection was shown histologically, but the virus could not be cultured from the stool; no other gastrointestinal pathogens could be demonstrated. The patients were treated with a 14 day continuous infusion of Foscarnet 0.08 mg/kg/min (phosphonoformate, Astra Pharmaceuticals). One patient showed a partial response to therapy, but the cytomegalovirus colitis relapsed; the second patient had a symptomatic response only and the third patient died of non-cytomegalovirus opportunist infection while on treatment. Two other patients with biopsy proven cytomegalovirus ulceration of the oesophagus were seen, presenting with dysphagia, fever and weight loss. Invasive infection of the gastrointestinal tract with cytomegalovirus is now a major clinical problem in AIDS. Treatment with Foscarnet may be initially effective, but does not eliminate cytomegalovirus infection.

Acquired Immunodeficiency Syndrome↗

Diagnosis of lung disease in acquired immune deficiency syndrome: biopsy or cytology and implications for management.

One hundred and twenty consecutive bronchoscopic examinations were carried out on 80 patients with acquired immune deficiency syndrome (AIDS) between January 1982 and December 1986. Ninety one paired biopsy and cytology specimens from 72 of these patients were analysed. There was no significant difference between biopsy and cytology in diagnosing Pneumocystis carinii pneumonia (0.95 greater than p greater than 0.1). In 10 cases P carinii pneumonia was diagnosed by biopsy but not cytology and in seven cases by cytology but not biopsy. Nineteen patients had multiple infections or Kaposi's sarcoma. Biopsy was more useful than cytology in the diagnosis of other infections (n = 20) and Kaposi's sarcoma (n = 2) with positive cytological correlation in only three of the infections. Biopsy and cytology together have a diagnostic yield of 78.3%. We conclude that all patients presenting with respiratory disease who have, or are in a high risk group for, AIDS should be examined by bronchoscopy at an early stage with both cytology and biopsy.

Acquired Immunodeficiency Syndrome↗

New microbial and host factors in disseminated gonococcal infection: case report.

Disseminated gonococcal infection was diagnosed in an immunocompromised patient who presented with oliogoarthropathy and tenosynovitis. The gonococcal isolate was prototrophic, showed intermediate resistance to penicillin, and belonged to serogroup WII/III. An isolate from the patient's sexual contact showed similar characteristics. The patient had a Saccharomyces opsonin defect, which is associated with childhood infections and has not been reported previously in association with disseminated gonococcal infection. The pathogenetic importance of the unusual isolate and the underlying host defence defect is considered.

Adolescent↗

Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update.

Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.

Acquired Immunodeficiency Syndrome↗

Microbicidal activity of monocyte derived macrophages in AIDS and related disorders.

We have examined the ability of monocyte-derived macrophages from patients with AIDS and other HIV-related disorders to kill the intracellular pathogen Toxoplasma gondii. We have also examined the capacity of peripheral blood mononuclear cells from these patients to produce macrophage-activating and other lymphokines. The capacity to produce interleukin 2 and gamma interferon decreases from controls through asymptomatic seropositive subjects and lymphadenopathy groups A (benign) and B (prodromal) to AIDS. The decrease did not correlate precisely with the decrease in CD4+ cells in these patients. Monocyte-derived macrophages from asymptomatic HIV-infected subjects and lymphadenopathy patients showed a decreased ability to kill T. gondii after activation with recombinant gamma interferon; paradoxically, this was most striking for PGL group A. The defect was largely overcome by using Concanavalin A stimulated autologous supernatants. It was notable that macrophages from AIDS patients showed normal killing with recombinant gamma interferon, but that the supernatants from AIDS patients had reduced activity with normal macrophages. These studies confirm that functional defects of both lymphocytes and macrophages are found in HIV-infected subjects; they serve to emphasize the heterogeneity of the clinical and biological responses to this retrovirus, responses which have important implications in the pathogenesis and treatment of the immunodeficiency.

AIDS-Related Complex↗

Decline of anti-p24 antibody precedes antigenaemia as correlate of prognosis in HIV-1 infection.

A cohort of 84 homosexual men presenting with persistent generalized lymphadenopathy (PGL) was studied between March 1982 and March 1987. A progression rate to AIDS of 5% per year was seen in those who were infected with HIV. Certain clinical features and routine laboratory investigations were significantly associated with an increased risk of disease progression, but had only limited predictive value. Two hundred and fifty-two serial sera from 57 patients were analysed for the p24 antigen (Abbott), the principal core protein of HIV and antibody against p24 by direct enzyme-linked immunosorbent assay (ELISA). Patients who remained well retained a high titre of anti-p24 antibody compared with those who progressed to AIDS-related complex (ARC) or AIDS. HIV antigen was detectable in 40% of AIDS patients 2 years before diagnosis, but antigenaemia was preceded by loss of anti-p24 antibody by up to 18 months and preceded AIDS by up to 40 months. ARC patients tended to be negative when tested for both alpha-p24 antibody and antigen, suggesting a transitional state. Analysis of the humoral response against gag proteins appears to correlate closely with clinical status and may be an earlier and more consistent way of predicting disease progression than p24 antigenaemia, or clinical and routine laboratory investigations.

AIDS-Related Complex↗

Three-year prospective study of HTLV-III/LAV infection in homosexual men.

170 symptom-free homosexual men were recruited in London in 1982-83 and 133 were evaluable in 1983-85. Of the 33 who were seropositive to HTLV-III/LAV at entry, 4 (12%) progressed to AIDS, 16 (48%) progressed to persistent generalised lymphadenopathy (PGL), and 13 (40%) remained symptom-free. A further 15 men seroconverted during the study (7% per annum), of whom 8 progressed to PGL. Serial estimations of T lymphocyte subsets showed progressive reduction in T4 numbers in the seropositive groups, but these indices also varied widely in the seronegative group. Counts of T4 and T8 cells or T4/T8 ratio at entry were not of prognostic value. Seronegative subjects were as likely as seropositives to have abnormal immunological tests. Serial measurement of T lymphocyte subsets seems to be of little prognostic or clinical value in the monitoring of populations infected with the HTLV-III/LAV virus. The strongest association with prognosis was an episode of sexually transmitted disease in the six months before entry to the study. This supports the hypothesis that intercurrent infection may be an important co-factor in the acquisition of HTLV-III/LAV infection, and in subsequent disease progression.

Acquired Immunodeficiency Syndrome↗

Whipple's disease with unusual clinical, bacteriologic, and immunologic findings.

A middle-aged man was found to have Whipple's disease after episodes of nephritis and arthralgia. While on antibiotic therapy, and in the absence of worsening of the histologic appearances of the jejunum, aortic valve endocarditis developed, presumably due to Whipple's disease. Observations during the course of his illness included the isolation of Corynebacterium bovis from an inguinal lymph node, and detection of circulating antibodies against material within the characteristic abnormal macrophages present in the gastrointestinal mucosa. This antigen-antibody reaction was specifically blocked by the monosaccharide rhamnose, a component of the polysaccharide surface coat of many bacteria, including C. bovis.

Antibody Formation↗

Factors affecting seropositivity to human T cell lymphotropic virus type III (HTLV-III) or lymphadenopathy associated virus (LAV) and progression of disease in sexual partners of patients with AIDS.

Fifty four sexual partners of homosexual men with the acquired immune deficiency syndrome (AIDS) were studied, of whom 32 were seropositive and 22 seronegative for human T cell lymphotropic virus type III or lymphadenopathy virus (HTLV-III/LAV) antibody, which showed that repeated exposure by anal intercourse does not necessarily lead to seroconversion. Seropositivity to HTLV-III/LAV was not associated with the absolute number of sexual partners, receptive anal intercourse, or the use of recreational drugs, but was associated with a history of other sexually transmitted diseases (STDs), particularly in the year preceding the patient's initial examination. Acquisition of an STD after the date of last sexual contact with a person with AIDS was strongly associated (p less than 0.001) with the development of persistent generalised lymphadenopathy (PGL). Concurrent or recent STDs would seem to be an important cofactor in developing antibody to HTLV-III/LAV and in the progression of infection from a person being asymptomatic to having PGL.

Acquired Immunodeficiency Syndrome↗

HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS.

The presence of core antigens of retrovirus HTLV-III/LAV, referred to as "AIDS-related virus" (AV), has been sought in lymph node samples of patients with persistent generalized lymphadenopathy (PGL, 28 patients), prodromal AIDS (1 patient) and AIDS with Kaposi sarcoma (3 patients). In 30 patients the deposition of viral antigens, detected by monoclonal antibodies to HTLV-III and LAV, could be observed within the germinal centers (GCs) primarily within the extracellular network of immune complexes, and the two patients who were negative were atypical. No AV could be found in normal tonsil or in samples with follicular hyperplasia of unknown etiology (20 cases). These findings, taken together with the ultrastructural identification of typical retrovirus particles in all 9 PGL and 2 AIDS cases studied, indicates that the network of follicular dendritic (FD) cells is an important reservoir of AV virus antigen at this site. The persistence of this retrovirus inside the GCs helps explain how the follicular hyperplasia affecting FD cells and B blasts in PGL may in progressive cases be accompanied by destruction of FD cells and gradual development of T4+ lymphopenia. T4+ T cells may circulate through the GCs and become infected with AV there. In addition, the identification of retrovirus antigen in situ may be of diagnostic value.

Acquired Immunodeficiency Syndrome↗