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Biomedical subjects

J Gerstoft

Publications and source records attributed to J Gerstoft.

At least 109 records · Page 6Linked to original sources

HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features.

All 51 cases of HIV-related malignant lymphoma in Denmark diagnosed from 1983 to 1989 were reviewed. There were 12 Burkitt-type lymphomas, 30 immunoblast-rich lymphomas and 9 other lymphomas. Patients with immunoblast-rich lymphomas had significantly lower CD4 cell counts (median 60 vs. 188 x 10(6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0.10). Compared with EBV DNA-negative tumours EBV DNA-positive tumours were associated with lower CD4 cell counts (median 39 vs. 188 x 10(6)/l, P = 0.01). It is concluded that two main types of HIV-related malignant lymphoma exist. One is associated with severe immunosuppression, is often of immunoblast-rich morphology, and may be linked to EBV, whereas the other may occur in the absence of immunosuppression, is often of Burkitt-type morphology, and is probably not linked to EBV. In addition to these two main types, other non-Hodgkin lymphomas and Hodgkin's disease do occur.

Adult↗

Cellular profiles in bronchoalveolar lavage fluid of HIV-infected patients with pulmonary symptoms: relation to diagnosis and prognosis.

Bronchoalveolar lavage (BAL) cell differentials and T-lymphocyte subpopulations were analysed in 95 HIV-infected patients with pulmonary symptoms to determine whether the type of cellular inflammatory response could be useful in diagnosis or as a prognostic marker. Patients with Pneumocystis carinii pneumonia (PCP) had more BAL fluid lymphocytes, mainly comprising CD8+ cells, and patients with bacterial infection had more neutrophils than other patients. Neither of these changes were mirrored in peripheral blood. Seven patients who died after their acute episode of PCP had significantly higher BAL fluid neutrophils than 53 patients with PCP who survived (P = 0.002). There seems to be correlation between BAL fluid neutrophilia, PCP and concomitant bacterial infection since four out of seven patients with a fatal outcome had coinfection with bacteria, whereas only one patient with PCP and bacterial coinfection survived (P = 0.0007).

Acquired Immunodeficiency Syndrome↗

The prognosis in HIV-infected patients with pneumonia. Relation to microbiological diagnoses.

Ninety consecutive first-time fiberoptic bronchoscopies (FB) were performed on HIV-infected patients with pulmonary symptoms and radiographic evidence of active pneumonitis. Microbiological data were analysed for acute and long-term prognostic significance. 56/90 (63%) patients had one type of microbiological agent recovered from FB, 22/90 (24%) patients had more types recovered, and 12/90 (13%) patients had no types recovered. Nine patients (10%) died during the acute episode of pneumonia. A prognostic factor of a fatal outcome of the acute episode of pneumonia was concurrent multiple pulmonary infections (p = 0.002), mainly ascribed to patients with Pneumocystis carinii pneumonia (PCP) and concomitant bacterial pneumonia (p = 0.003). Specific microbiological findings at FB did not influence long-term survival of patients, and, when omitting patients who died during the acute episode of pneumonia (n = 9), no difference in survival was observed between patients with a) no agent, b) one type of agent or c) more types of agents recovered from FB. Only non-pulmonary parameters such as CD4-count, haemoglobin and age were found to be prognostic parameters. Thus, increased attention should be paid to co-pathogens presenting in HIV-infected patients with pulmonary infection and appropriate therapy instituted.

Acquired Immunodeficiency Syndrome↗

[HIV infected women in Copenhagen. Risk factors and sex behavior].

A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty-five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV-positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test.

Denmark↗

The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group.

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.

Acquired Immunodeficiency Syndrome↗

Opportunistic infections and malignancies in 231 Danish AIDS patients.

We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS, and that the frequencies of particular diseases may change with calendar time.

Acquired Immunodeficiency Syndrome↗

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Acquired Immunodeficiency Syndrome↗

Effects of isoprinosine treatment of HIV-positive patients on blood mononuclear cell subsets, NK- and T-cell function, tumour necrosis factor, and interleukins 1, 2, and 6.

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV-infected individuals. To elucidate the mechanism of action, eight HIV-positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment. Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu-8, and HLA-DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL-2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN-alpha), IL-2, or indomethacin. Neither did isoprinosine affect the in vitro production of (IL-1) alpha or beta, IL-2, IL-6, or tumour necrosis factor (TNF).

Adult↗

Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

Contraceptive Devices, Male↗

Pulmonary pathogens in HIV-infected patients.

On well defined criteria a total of 102 fiberoptic bronchoscopies (FB) were done on HIV-infected patients with pulmonary symptoms. A microbiological agent was identified in 85 patients (83%). Pneumocystis carinii (PC) was histologically verified in 61 patients, bacteria cultured in 22 patients, and cytomegalovirus (CMV) cultured in 17 patients. A histological diagnosis of CMV was only established in 2/17 patients. In the present study, a CMV positive culture from bronchial lavage fluid did not appear related to the clinical picture. Patients with P. carinii pneumonia (PCP) had significantly higher IgA, lower CD4-count, more commonly dyspnea and an X-ray showing diffuse interstitial infiltration than patients without PCP. Patients with bacterial pneumonia had significantly higher CD4-count, lower IgA, more commonly productive cough and an X-ray showing focal infiltration. In more than 75% of the patients, microorganisms identified were responsible for the pulmonary symptoms leading to bronchoscopy. Mainly PC and bacterial pathogens, both of which are treatable, were responsible for these infections. Pulmonary infections of clinical relevance besides PCP and bacterial infections were rare (3%, 95% confidence limit 1-8%).

Adolescent↗

Clinical course of primary HIV infection: consequences for subsequent course of infection.

OBJECTIVE: To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN: Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS: 86 Men in whom seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE: Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS: Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively). CONCLUSION: The course of primary infection may determine the subsequent course of the infection.

Acquired Immunodeficiency Syndrome↗

Antibodies against the major core protein p24 of human immunodeficiency virus: relation to immunological, clinical and prognostic findings.

In 79 homosexual men positive for antibody to human immunodeficiency virus (HIV), the titer and avidity of p24 antibody was determined by an indirect ELISA and the serum tested for the presence of HIV antigen. Results were examined for a possible correlation with clinical, immunological and prognostic findings. High titers and low avidity of p24 antibodies correlated significantly with a normal pokeweed mitogen response, early lymph node changes, and an asymptomatic and stable clinical condition. In HIV antigen negative patients, low titers and high avidity of p24 antibodies correlated significantly with a progressive clinical condition. The finding of primarily high avidity antibodies against p24 antigen in patients with more advanced immunodeficiency indicates that a decline of p24 antibodies during the clinical course of HIV infection may not be explained exclusively by an increased production of viral proteins.

Acquired Immunodeficiency Syndrome↗

Effects of antineoplastic treatment of HIV-positive patients with testicular cancer.

Among 101 patients with testicular cancer referred to the Department of Oncology ONB, Finsen Institute, four were proven HIV-positive before admission. Three of these patients were treated with cisplatin, 4-epi-podophyllotoxin (VP-16, Etoposide) and bleomycin. One patient with stage I of the testicular cancer was observed, after orchiectomy, without medical antineoplastic treatment. In the HIV-positive patients treated with cytotoxic drugs, leucopenia was seen after one (8%), fever after three (23%) and thrombocytopenia after two (15%) courses. Amongst patients not proven HIV-positive leucopenia, fever and thrombocytopenia were seen after 11 (9%), 21 (18%) and 27 (29%) courses. Two patients had stage II and two patients stage III of the HIV infection prior to treatment. The clinical stage of the disease did not change during the course of chemotherapy. We suggest that HIV-positive patients (stage II and III) with germ cell tumours should be treated with the same aggressive chemotherapy as given to other patients, not proven HIV-positive.

Adult↗

The development of AIDS or AIDS-related conditions in a cohort of HIV antibody-positive homosexual men during a 3-year follow-up period.

One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes less than 0.5 x 10(9) l-1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes less than 0.3 x 10 l-1 and elevated serum level of IgA were significantly associated with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy. When adjusted to the probable year of infection, these results are in accordance with previous cohort studies. It is concluded that most, or all, subjects seropositive for HIV will develop progressive loss of CD4 lymphocytes followed by clinical signs of immune deficiency, and that differences among previous cohorts with respect to disease progression are probably due to differences in the duration of infection.

AIDS-Related Complex↗

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging.

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

Biomarkers↗

The value of lymph node histology in human immunodeficiency virus related persistent generalized lymphadenopathy.

Histological changes in lymph nodes were evaluated in a prospective study of 124 homosexual men who presented with generalized lymphadenopathy. The histological changes were classified according to a classification system with three stages. HIV antibodies were present in 88% of the patients. The finding of one of the three histopathological stages was highly indicative--although not absolutely pathognomonic--for HIV infection. The subsequent course of HIV infection after biopsy was significantly correlated to the histopathological changes, but it was not possible to evaluate if the biopsy added new information to that already available. Among the group of HIV infected, immediate clinical consequences of lymph node biopsy were not observed (95% confidence limits 0-3.3%). In a retrospective investigation of 123 consecutive AIDS patients, it was found that lymph node histopathology had been able to identify secondary infections and neoplasms among 10%. It is concluded that lymph node biopsy is indicated in the HIV infected patients with unexplained generalized symptoms or with atypical enlargement of the lymph nodes. The prognostic significance of lymph node histology compared to other prognostic parameters of HIV infection, remains to be determined.

AIDS-Related Complex↗

Hepatitis B in symptomless Danish homosexual men.

Forty eight symptomless homosexual men attending a sexually transmitted disease (STD) clinic and found by screening to have hepatitis B surface antigen (HBsAg) were followed up for a median of 10 (range six to 26) months to characterise their liver disease. Initially 33/50 (66%) of the men had increased serum liver enzyme activity and 19/47 (40%) had increased serum immunoglobulin G concentrations. Liver biopsy specimens showed acute hepatitis B in 12 (39%) and chronic hepatitis B in 19 (61%) of the 31 patients who underwent liver biopsy. The course of the infection was: acute hepatitis B in 14/48 (29%), chronic persistent hepatitis B in 23/48 (48%), chronic aggressive hepatitis B in 8/48 (17%), and cirrhosis in 3/48 (6%) of the patients. Antibodies against human immunodeficiency virus (HIV) were present in 16/45 (36%) of the patients, but the presence of antibodies to HIV did not influence the course of hepatitis B in the observation period.

Adult↗