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Biomedical subjects

J Gerstoft

Publications and source records attributed to J Gerstoft.

At least 37 records · Page 2Linked to original sources

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

Humoral and cellular responses to Pneumocystis carinii, CMV, and herpes simplex in patients with AIDS and in controls.

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Acquired Immunodeficiency Syndrome

Cytostatic treatment of glomerular diseases. V. Treatment of glomerulonephritis with cyclophosphamide plus prednisone, azathioprine plus prednisone and cyclophosphamide as monotherapy. A comparative study. A report from a Copenhagen Study Group of Renal Diseases.

Thirty-two patients suffering from biopsy-proven glomerulonephritis with proteinuria greater than or equal to 1.2 g/24 hours and/or creatinine clearance less than 50% of normal value were treated for 6 weeks with prednisone plus cyclophosphamide (C+P), azathioprine (A+P) or cyclophosphamide as a monotherapy (C). The effect of the treatment was evaluated after 6 and 16 weeks. The results were entered consecutively in a sequential analysis. The three treatment regimes were compared mutually as well as with the results of 16 weeks' treatment with C and placebo, published previously. Six weeks' treatment with C+P or A+P was superior to C and at least as efficient as 16 weeks' C treatment. C treatment for 6 weeks was less efficient than 16 weeks' C treatment. The side-effects of the 6 weeks' A+P or C+P treatment were fewer and less serious than those reported from the long-term C treatment.

Adult

Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection.

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (less than 0.5 X 10(9)/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.

AIDS-Related Complex

Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies.

To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk of a worsened clinical condition was 55 times higher in seropositive men whose responses to pokeweed mitogen were low than in other seropositive men. The corresponding relative risks for low transformation responses to cytomegalovirus and for a decreased absolute count of CD4 positive lymphocytes were 18 and six. The relative response to pokeweed mitogen is therefore a very sensitive short term predictive marker of the clinical condition of seropositive patients who have a CD4:CD8 ratio of less than 1.0.

AIDS-Related Complex

An enzyme labelled nuclear antigen immunoassay for detection of cytomegalovirus IgM antibodies in human serum: specific and non-specific reactions.

A mu-capture enzyme linked immunosorbent assay was developed for detection of IgM antibody to cytomegalovirus (CMV). Virus-specific IgM was detected using horseradish peroxidase labelled nuclear CMV antigen (CMV-ELA). False-positive reactions caused by Paul-Bunnell-Davidsohn (PBD) positive sera and antinuclear antibody (ANA) positive sera were identified in a combination assay employing enzyme labelled nuclear control antigen (CO-ELA) in parallel to the CMV-ELA. Four of five PBD positive and 30 of 31 ANA positive sera reactive with the CMV-ELA were identified as false positive reactions in the combined ELA-assay. The reactivity in PBD-positive sera could not be explained by antigenic cross reactivity between CMV and Epstein-Barr virus, and the results further suggested that different cell specified components of the CMV-ELA were responsible for the reactivity of PBD-positive as compared to ANA-positive sera. One of 314 healthy blood donors, 12 of 12 patients with primary CMV infection, and 11 of 15 patients with secondary CMV infection had detectable CMV IgM antibodies. Comparison of different CMV-ELAs revealed that pronounced differences in specificity as well as sensitivity may exist.

Antibodies, Antinuclear

Systemic lupus erythematosus: follow-up study of 148 patients. I: Classification, clinical and laboratory findings, course and outcome.

The present paper is a description of 148 patients with circulating antinuclear antibodies and multisystemic disease filed during 18 years by one of the authors and followed up to date in 1981-83. Seventy-eight per cent of the patients satisfied the 1971 ARA criteria for the classification of systemic lupus erythematosus and 92 per cent fulfilled the 1982 ARA criteria. Eighty-five per cent were women, the mean age at onset of SLE was 32 years. Malar rash and arthritis were early manifestations in 80 per cent of the patients whereas the onset of nephropathy, CNS manifestations, serositis, and peripheral cytopenia was delayed in about half of the patients. Nephropathy and thrombocytopenia were observed particularly in the youngest patients. The mean duration of the observation period was 8 years. The 10-year-survival was 80 per cent. Half of the deaths were presumably unrelated to SLE. The mean ages at entry of patients who died of SLE and of unrelated causes were 30 and 52 years respectively. Eighteen per cent of the deaths were caused by uremia and 18 per cent by infections. The total and the SLE related mortalities were evenly distributed throughout the observation period. The morbidity (incidence of new ARA criteria and other findings indicating active disease) decreased during the first year of observation but rarely subsided completely during the following years. All patients observed for more than 10 years showed evidence of active disease during the rest of the observation period and most showed evidence of renal disease.

Adolescent

Systemic lupus erythematosus. Follow-up study of 148 patients. II: Predictive factors of importance for course and outcome.

The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.

Adolescent

A biotin-avidin-amplified inhibition enzyme immunoassay for detection of CMV antibodies in human serum.

In this inhibition immunoassay undiluted serum reacts in solution with crude cellular CMV antigen in wells of microtestplates coated with hyperimmune CMV-reactive monkey IgG. CMV antibodies in the serum under test block (completely or partial) the fixation of antigen to the capture layer. Unblocked antigenic activity is in subsequent steps measured by the use of biotinylated CMV-reactive monkey IgG and peroxidase-conjugated avidin. The assay was evaluated in comparison with the CF test and was found superior both in terms of qualitative and quantitative detection of CMV antibodies. The results were uninfluenced by the presence in the sera of rheumatoid factor or autoantibodies (antinuclear antibodies). A characteristic feature of this inhibition immunoassay was the absence of equivocal results as demonstrated by analysis of 500 donor sera which were classified in two distinct separate groups: reactive and nonreactive. The assay is simple and reproducible and provides for a good reagent economy. Crude antigen can be used without sacrifice of specificity. Antigen from one Roux bottle proved sufficient for 25,000 duplicate tests.

Animals

Stages in LAV/HTLV-III lymphadenitis. I. Histological and immunohistological classification.

Lymph nodes from 40 homosexuals with persistent, generalized lymphadenopathy were studied for histological and immunohistological changes and classified into histological stages based on the progressive destruction of lymph node follicles in association with progression of the disease. Three patterns were recognized: stage I was characterized by follicular hyperplasia, mantle zone depletion, and follicular fragmentation in the absence of vasculitis, stage II by signs of follicular involution, and stage III by depletion of follicles and dendritic reticulum cells with development of diffuse pattern. The T zone was gradually depleted of CD4-positive lymphocytes, but on further progression, lymphocytic depletion (which also involved the CD8-positive cells) and fibrosis prevailed. The 40 lymph nodes from homosexuals were classified as stage I in 18 cases, stage II in 11, and stage III in 10. One case did not fulfil our histological criteria for LAV/HTLV-III lymphadenitis, although this patient was seropositive. Convincing correlation was found between histological stages and clinical and laboratory data. The triad of follicular hyperplasia, mantle zone depletion, and follicular fragmentation, in the absence of vasculitis, appears pathognomonic for the early disease. The diffuse pattern, however, may be seen in different disease entities.

Acquired Immunodeficiency Syndrome