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J Gerstoft

Publications and source records attributed to J Gerstoft.

At least 145 records · Page 8Linked to original sources
PubMed1987

Stages in LAV/HTLV-III lymphadenitis. II. Correlation with clinical and immunological findings.

The aim of the present study was to investigate the relation between the histopathological findings in LAV/HTLV-III lymphadenitis and immunological, clinical, and serological variables. The study group included 38 consecutive homosexual men with persistent generalized lymphadenopathy (PGL) in whom lymph node biopsy was performed. The histopathological lymph node changes were grouped into three stages. Opportunistic infections at the time of biopsy and their development during follow-up were significantly associated with stage III histology (follicular depletion). Analysis of blood from 10 patients with stage III histology revealed significantly (P less than 0.01) decreased proliferative responses of lymphocytes to mitogens and reduced absolute number of CD5+ and CD4+ lymphocytes compared with 17 patients with stage I histology (follicular hyperplasia), whereas patients with stage II histology (follicular involution) had intermediate values. The absolute number of CD8+ lymphocytes was increased in all three stages, as was IgG, while increase in IgM and IgA was restricted to stage III. No difference was observed between the different histopathological stages with respect to the specificity of the anti-LAV/HTLV-III antibody as measured by immunoblotting. In conclusion, the defects of lymphocytes from the blood of LAV/HTLV-III infected persons reflect alterations in secondary lymphoid tissue. Further, there is a close correlation between these alterations and the clinical status of the patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Quantification of CD8-positive lymphocytes in lymph node follicles from HIV-infected male homosexuals and controls.

The number of CD8-positive cells in follicular centres of hyperplastic lymph nodes from 20 Danish and Swedish homosexual men with persistent generalized lymphadenopathy and 43 control patients were enumerated in frozen tissue sections immunostained with monoclonal antibody reactive with the CD8-antigen ("cytotoxic-suppressor" T-cell antigen). All the homosexuals were seropositive for HIV and histology showed changes characteristic of the early stage of HIV lymphadenitis. A significant increase (p much less than 0.001) of CD8-positive cells was demonstrated (mean 1,307 per mm2 follicular centre, SD 639) in HIV-related lymphadenopathy compared with the controls (mean 161 CD8-positive cells per mm2 follicular centre, SD 169). The results of this study show that the immunohistological demonstration of a significant increase of CD8-positive cells in the follicles of hyperplastic lymph nodes is suggestive of HIV-related lymphadenopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The immunological and clinical outcome of HIV infection: 31 months of follow-up in a cohort of homosexual men.

T-cell subsets, antibodies (Ab) against human immunodeficiency virus (HIV) and clinical status were evaluated during a 31 (24-35) month follow-up study of homosexual men. The study group included 50 homosexual men, with many sexual partners, who by 1982-83 were without symptoms and had a prevalence of HIV Ab of 38%. Among the men who were seropositive on the initial investigation a significant decrease occurred in the absolute number of CD4+ lymphocytes (p less than 0.01). 88% of these men experienced a decrease, and by follow-up 59% had CD4+ lymphocytes below the normal range. Also the men who seroconverted during the study had a significant decrease in CD4+ lymphocytes, while no changes were observed in the seronegative group. None of the subgroups had significant changes in CD8+ lymphocyte number. AIDS or AIDS related complex developed in 33% of the men seropositive at inclusion. None of these clinical syndromes developed in the seroconverting or the seronegative group. The men who eventually developed clinical symptoms did not differ significantly from the healthy HIV Ab positive persons, with respect to lifestyle parameters, presence of lymphadenopathy and isolation of cytomegalovirus. However, they had significantly lower CD4+ cells and CD4/CD8 ratio (p less than 0.01) at inclusion. It is concluded that in the majority of persons infected with HIV, phenotypic T-cell alterations will occur with a latency of years, but it remains to be seen if the alterations necessarily will result in clinical manifestations. Further, T-cell subset determination among healthy HIV Ab positive persons will provide prognostic information.

AIDS-Related Complex↗
PubMed1987

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunological studies in acquired immunodeficiency syndrome: effect of TCGF and indomethacine on the in vitro lymphocyte response.

We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls. While low amounts of TCGF reduced the response of peripheral blood mononuclear cells (PBMC) to allogeneic cells in both healthy controls and AIDS patients, large amounts of TCGF augmented the response in both groups, although the response of the patients' cells were still subnormal. By depleting the PBMC for either CD4-positive or CD8-positive cells, the effect of TCGF on suboptimally mitogen-stimulated PBMC from controls was shown to be due to an increased response in both the CD4-positive and the CD8-positive cells. In contrast, with patient cells, TCGF only increased the response of the CD4-positive cells, while that of the CD8-positive cells was largely unchanged. Thus, the lack of normalization of the mitogen response of patient cells upon addition of TCGF may be largely due to unresponsiveness of CD8-positive cells to TCGF. This observation further supports the idea that CD8-positive cells are abnormal. To investigate the role of the inhibitor of TCGF production, PGE2, in AIDS, indomethacine was added to cultures of mitogen-stimulated PBMC from controls and patients. No differences were found between the three groups: the responses to PHA were slightly increased and those to Con A were unchanged.

AIDS-Related Complex↗
PubMed1986

Immunological studies in the acquired immunodeficiency syndrome. II. Active suppression or intrinsic defect--investigated by mixing AIDS cells with HLA-DR identical normal cells.

The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Interleukin 1 activity in the acquired immunodeficiency syndrome.

Interleukin 1 (IL-1) is a monocyte-derived mediator that participates in the regulation of various T-lymphocyte activities, among them IL-2 production. Since IL-2 deficiency is a central feature in the immunological profile of the acquired immunodeficiency syndrome (AIDS), the production of IL-1 from peripheral blood monocytes from male homosexuals with AIDS was investigated at the same time as the IL-1 responsiveness of monocyte-depleted mononuclear cells (MDC) from the same patients. The IL-1 was produced by lipopolysaccharide-stimulated monocytes and assayed by the capacity of monocyte supernatants to amplify the proliferation of phytohaemagglutinin-stimulated allogeneic MDC from healthy donors as well as murine thymocytes. The IL-1 responsiveness was measured by measuring the enhancing effect of an IL-1 standard on the proliferative response of patients' MDC. The IL-1 production was not reduced compared to the IL-1 production in a control group, but the IL-1 responsiveness of the patients' MDC was depressed. The results indicate that depressed IL-1 production is not one of the immunological disturbances in AIDS, but that the T-lymphocyte accessory properties of IL-1 are affected.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Immunological studies in homosexual men with and without antibodies to human T-cell lymphotropic virus type III.

T-cell subsets were studied in 559 homosexual or bisexual men attending outpatient clinics for AIDS-screening in Copenhagen during the period July 1984 to April 1985. Of the 559 individuals studied, HTLV III antibodies were found in 161 (29%). Persistent generalised lymphadenopathy (PGL) defined as the presence of lymph nodes greater than 1 cm in diameter at two or more extrainguinal sites for at least three months were found in 91 patients, 72 (79%) of whom had HTLV III antibodies. The seropositive group had lower counts of T-helper/inducer cells (p less than 0.001), higher counts of T-suppressor/cytotoxic cells (p less than 0.001), lower T-helper/T-suppressor ratios (p less than 0.001) and higher levels of IgG (p less than 0.001), compared to the seronegative group. Compared to seropositive men without PGL, seropositive men with PGL had higher levels of IgA and IgG (p less than 0.05) and lower T-helper/T-suppressor ratios (p less than 0.05), the latter primarily caused by an elevated number of T-suppressor/cytotoxic cells. It is concluded that HTLV III infection is accompanied by a number of immunological abnormalities, including depletion of T-helper/inducer cells and B-lymphocyte activation. A subgroup of patients is characterised by having PGL and increased serum concentrations of IgA and IgG. The clinical and prognostic importance of PGL and B-cell activation is unknown. To study this more closely, prospective studies are needed.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The LAV/HTLV-III screening in Copenhagen. Epidemiological results from four clinics over the period 1 July 1984 to 1 April 1985.

Over the nine month period from 1st July 1984 to 1st April 1985, 737 persons attended the four AIDS-screening clinics in Copenhagen. The attendance was unconditional, and the examination free of charge. All were examined clinically and serologically for LAV/HTLV-III infection. Ninety-seven percent were males; 490 (68%) and 198 (28%) described themselves as homosexual or bisexual respectively. This study presents epidemiological data on that group. As in other studies, we found a relationship between anti-LAV/HTLV-III and male homosexual promiscuity, i.e. trends towards higher antibody prevalences, the higher the number of different sexual partners annually and the number of previous sexually transmissible diseases. The occurrence of 18 percent seropositivity in a group with no previous sexually transmissible disease indicate a dissemination of the infection to a subpopulation of Danish homosexuals with a nonpromiscuous lifestyle. Night sweats and lymph node enlargement as subjective complaints along with lymphadenopathy and anal pathology on objective examination were significantly (p less than 0.025) related to positive LAV/HTLV-III serology. Fifty-one percent (337 persons) had neither subjective symptoms nor objective signs, and 50 of these (28% of this asymptomatic group) were seropositive. At this stage of the AIDS epidemic, it is important for surveillance purposes that anti-LAV/HTLV-III testing is made available to all members of risk groups. The establishment of the screening clinics with unconditional attendance and ensured anonymity seems to be an important step in this effort.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Prognosis in glomerulonephritis. II. Regression analyses of prognostic factors affecting the course of renal function and the mortality in 395 patients. Calculation of a prognostic model. Report from a Copenhagen study group of renal diseases.

The course of the renal function and mortality were analysed in 395 patients with biopsy-proven glomerulonephritis (GN), using Cox's proportional hazards model. Seventeen clinical, biochemical and histopathological parameters were analysed for prognostic information. The patients were grouped according to their serum creatinine levels. Increase in serum creatinine, decrease in serum creatinine, cure and death were used as endpoints for the analysis. Caplan Meyer curves were made for 7 transitions between different groups and the variables were reduced by a step-wise procedure to a final model. Thirteen of the variables considered offered significant prognostic information (p less than 0.05) for at least one of the transitions. Short duration of disease, young age, non-nephritic urinary sediment and preceding streptococcal infection were predictors of cure. Extracapillary, membranoproliferative and unclassifiable GN, old age and arterial hypertension predicted increase in serum creatinine in patients with low serum creatinine, while male sex, short duration of disease and pathological electrocardiogram favoured a further increase in patients with high serum creatinine. A later decrease in serum creatinine was signified by a preceding streptococcal infection, short duration of disease, absence of arterial hypertension and low urinary protein excretion. Death without uremia was predicted by high age, connective tissue disease and extracapillary GN. Using these parameters and the models, it is possible to make a prognostic forecast for the individual GN patient. Examples of such a forecast are described.

Adult↗