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Biomedical subjects

S A Danner

Publications and source records attributed to S A Danner.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Zidovudine therapy in 141 patients with symptoms of HIV infection; a multicenter study].

We describe the results of treatment with zidovudine in 141 symptomatic HIV positive patients, 119 of whom had AIDS. Total mortality was 30% over a mean observation period of 45 weeks after the start of the treatment. This is much lower than the mortality among AIDS patients in the pre-zidovudine period. During the first 2 months the feeling of wellbeing and the body weight increased, but after 4 months these effects declined. Two months after start of therapy the number of new opportunistic infections declined, but it increased thereafter. Side effects were frequent: after 7 months zidovudine had to be reduced or even stopped in 43% of the patients mostly because of anaemia and/or leukopenia. After 6-7 months 45% of all patients had been given packed cells transfusions with a mean of 16 units. In general tolerability of zidovudine was better in patients with a higher number of circulating CD4-positive cells at the start. These results confirm that the effect of zidovudine in symptomatic HIV infected patients is favourable but only of limited duration.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Can the course of high dose cotrimoxazole for Pneumocystis carinii pneumonia in AIDS be shorter? A possible solution to the problem of cotrimoxazole toxicity.

Fifty consecutive patients with confirmed PCP received a high dose of cotrimoxazole for 14 d, or until development of intolerance, directly followed by reduced dose maintenance therapy. Seven individuals died during the high dose course. Twenty (47%) of the 43 survivors showed toxicity reactions that necessitated dose reduction to maintenance level on average after 9.6 d. Thirteen of these 20 individuals tolerated the reduced dose, and seven did not. No further cases of toxicity were observed. In 43 survivors only one early relapse (day 17) was observed in a patient who had received full dose treatment for 14 d. We conclude (1) that extending high dose cotrimoxazole therapy beyond 2 weeks is usually unnecessary, provided that reduced dose maintenance therapy is given directly, and (2) that dose reduction on appearance of toxicity signs during the second week of treatment is safe and allows two-thirds of patients to be maintained on cotrimoxazole with satisfactory results.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Failure to maintain high-dose treatment regimens during long-term use of zidovudine in patients with symptomatic human immunodeficiency virus type 1 infection.

Long-term tolerance of zidovudine treatment was retrospectively analysed in 97 patients with AIDS or AIDS-related complex. After one year of treatment 68% and after two years 87% of the patients had had at least one dose adjustment during their course of therapy. Myelotoxicity was the most common cause (58% of all cases) of dose reductions and therapy interruptions (dose adjustments). At the time of the first dose adjustment 33 patients (34%) were suffering from anaemia (Hb less than 6.0 g/dl), 20 patients (21%) from leukopenia (leukocytes less than 1.5 x 10(9], and 10 patients (10%) from thrombocytopenia (thrombocytes less than 75 x 10(9]. Fifty-six patients (57%) needed one or more blood transfusions during therapy. The median time from the start of therapy to the time of the first dose adjustment was 14 (range: 2-64) weeks in patients who had a first dose adjustment because of anaemia without co-existing leukopenia or thrombocytopenia, and 37 (range: 6-85) weeks in patients who had a first dose adjustment because of leukopenia without co-existing anaemia or thrombocytopenia (p = 0.01). Peripheral blood CD4 positive lymphocyte counts less than or equal to 100/mm3, anaemia, and CDC classification IV-C1 at the start of treatment were associated with a need for an early dose modification or blood transfusion rather than the need for dose modification per se.

AIDS-Related Complex↗
PubMed1990

Low incidence of anti-interferon-alpha antibodies in patients treated with interferon-alpha-2a for AIDS-associated Kaposi's sarcoma.

Anti-interferon (IFN)-alpha antibodies were determined in the serum of 28 patients treated with high-dose human recombinant IFN-alpha-2a for AIDS-associated Kaposi's sarcoma. After a median treatment duration of 3 months, 3 patients developed anti-IFN-alpha antibodies, of whom 2 showed a long lasting tumour response despite the development of these antibodies. None of 3 patients with tumour progression after an initial treatment response had developed IFN-alpha neutralizing antibodies. In conclusion, a low incidence of anti-IFN-alpha antibodies during treatment with high dose IFN-alpha was found, but the appearance had no detrimental effect on the duration of tumour responses in a small number of patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Antibody response to viral proteins U (vpu) and R (vpr) in HIV-1-infected individuals.

Antibodies to E. coli-produced HIV-1 vpr and vpu were determined by enzyme immunoassay in serial sets of sera from 72 men seroconverting for antibodies to HIV-1 structural proteins, and from 196 initially symptom-free men who were positive for such antibodies at study entry. First detection of vpr- and vpu-specific antibodies always was within 12 months of seroconversion for antibodies to structural proteins. In the combined cohort of 268 men, vpr- and vpu-specific antibodies were found persistently in 26 and 43% of men, respectively. Vpr- and vpu-specific antibodies were transiently detected in 3 and 7%, respectively, and intermittently detected in 18 and 13% of men, respectively. No association was found between the patterns of vpr- or vpu-specific antibody response and clinical outcome. In subjects with different patterns of vpr- and vpu-specific antibody response, no clear temporal relationship existed between the appearance or disappearance of antibodies and the onset of HIV-1-related disease.

Cross-Sectional Studies↗
PubMed1990

Therapy for cytomegalovirus polyradiculomyelitis in patients with AIDS: treatment with ganciclovir.

Six AIDS patients with progressive cytomegalovirus (CMV) polyradiculomyelitis were treated with ganciclovir in an open study. The diagnosis was based on the presence of a distinct clinical syndrome with progressive flaccid paraparesis, preserved proprioception and urinary retention with specific cerebrospinal fluid (CSF) findings. Ganciclovir therapy, 5-10 mg/kg per day, instituted 3-6.5 weeks after onset of symptoms, was ineffective in four patients with severe paraparesis. One patient developed CMV polyradiculomyelitis while receiving ganciclovir and further deteriorated during foscarnet therapy. One patient however, showing minor paresis of one leg, improved after institution of ganciclovir therapy 1 week after onset of symptoms. It is concluded that a presumptive diagnosis of CMV polyradiculomyelitis can be made on the basis of distinct clinical findings and CSF pleocytosis with predominance of polymorphonuclear leukocytes in patients with AIDS. Ganciclovir therapy does not appear to be beneficial for patients with advanced paresis in the doses used. Further investigations are needed in order to determine if early intervention with ganciclovir, when paresis is mild, or higher doses in advanced paresis, might be of some benefit.

Acquired Immunodeficiency Syndrome↗
PubMed1990

HIV seropositivity and tuberculosis in a large general hospital in Malawi.

The incidence of the acquired immunodeficiency syndrome (AIDS) in Malawi is one of the highest in Central Africa. Since tuberculosis is an important initial manifestations of the disease, consecutive patients admitted to the tuberculosis (TB) wards of Zomba General Hospital, Malawi, were asked for permission to undergo a human immunodeficiency virus (HIV)-antibodies test. In addition, two other studies were done: from September 1986 all medical in-patients, clinically suspected for immune deficiency and from April 1988 all blood donors were tested for HIV seropositivity. Seventy-five percent of the TB patients volunteered; 32 out of 125 (26%) were seropositive. In the high-risk age groups (20-40 years) this percentage rose to 32. Among the medical in-patients suspected of immune deficiency the seropositivity rose sharply from April 1987 to October 1988. Among the blood donors tested, 20% were seropositive.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[AIDS and tuberculosis; a retrospective study in 225 patients with AIDS].

Of 225 patients in whom AIDS was diagnosed in the period January 1982 to March 1988 at the Academic Medical Centre, Amsterdam, the tuberculosis incidence and the clinical and demographic characteristics were recorded retrospectively. Tuberculosis was diagnosed in 18 patients (8%). The most frequent risk factor of AIDS-tuberculosis patients was intravenous drug abuse. The chest X-ray was frequently atypical and there were more extrapulmonary locations in comparison to patients with tuberculosis without AIDS. On September 1, 1988, 13 of the 18 patients had died. The response to tuberculostatic therapy was good. Our results are in agreement with comparable studies elsewhere. The expectation is that the tuberculosis incidence among AIDS patients will increase as more intravenous drug users become part of the whole AIDS patient population.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment.

OBJECTIVE: To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN: Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING: An academic centre for AIDS. PATIENTS: 196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS: Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES: Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS: The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS: The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.

AIDS Dementia Complex↗
PubMed1989

Glomerular lesions and opportunistic infections of the kidney in AIDS: an autopsy study of 47 cases.

AIDS-associated nephropathy (AAN) causing acute renal failure has been described in patients with AIDS. It is characterized by massive proteinuria and focal segmental glomerulosclerosis. From 1982 until 1987, 177 patients with AIDS were seen in our center. Most of them were homosexual or bisexual men. One patient was also an intravenous drug addict. One patient was a black female. None suffered from a nephrotic syndrome or needed hemodialysis during their illness. In 47 of the 110 patients who died an autopsy was performed. On microscopical examination of kidney tissue obtained at autopsy, no abnormalities were seen in 12 patients and slight abnormalities were found in 35 patients. Glomerular changes, mostly fibrous caps in Bowman's space, were present in 22 patients. Mesangial and intracapillary lesions were seen in only 5 patients. Tubular atrophy was found in 14 patients and sparse interstitial inflammation in 15 patients. A renal localisation of disseminated opportunistic infections was found in 11 patients: CMV (n = 4), tuberculosis (n = 2), Mycobacterium avium intracellulare (n = 1) and Cryptococcal infection (n = 4). In one patient a renal localisation of a Kaposi sarcoma and in another patient a renal localisation of a disseminated non-Hodgkin lymphoma was found. In conclusion the clinical picture of AAN with acute renal failure was not found in our center. As is the case with heroin associated nephropathy, AAN seems to be confined to certain areas in the USA, suggesting that racial or local co-factors, are important for the pathogenesis of AAN in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Low antigenicity of HIV-1 rev: rev-specific antibody response of limited value as correlate of rev gene expression and disease progression.

An enzyme immunoassay based on an E. coli-produced HIV-1 rev gene product was used to detect rev-specific antibodies in longitudinally collected serum samples from 196 initially symptom-free men who were seropositive for antibodies to HIV-1 structural proteins and 72 men who seroconverted for such antibodies. In 61% of men no rev-specific antibodies were detected at all, 30% had persistently detectable rev-specific antibodies, and in 9% rev-specific antibodies were only transiently or intermittently detected. When a persistent rev-specific antibody response occurred in subjects who seroconverted to structural proteins, it was always, with one exception, found within 12 months of seroconversion. The rev-specific antibodies were also studied in a transectional sample of sera from the men who remained symptom-free and from those who developed AIDS-related conditions or AIDS, as well as in sera from 31 other men with AIDS-related conditions and in sera from 6 of these men at the time they developed AIDS. The rev-specific antibodies were found in 34% of symptom-free men, in 28% of patients with AIDS-related conditions, and in 16% of patients with AIDS. The low incidence of rev-specific antibodies early after infection may be due to low antigenicity of rev. The lower prevalence of rev-specific antibodies in sera from patients with AIDS, compared with patients with AIDS-related conditions and symptom-free HIV-1-infected individuals, may be explained by a progressive HIV-1-induced immunodeficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1989

Lack of activity of zidovudine in AIDS-associated Kaposi's sarcoma.

The efficacy of zidovudine (AZT) for treatment of patients with Kaposi's sarcoma as the initial manifestation of AIDS was determined in a non-randomized, phase-II clinical trial. Twenty-two patients were treated with zidovudine (300 mg 4 times daily for 8 weeks). In patients with stable disease or showing a response, treatment was continued. After 12 weeks the total daily dose was changed to 1000 mg. Only two of all 22 evaluable patients achieved a response (one complete and one partial response), of only brief duration (2 and 4 months, respectively). There was no such association between antiretroviral activity, increase in CD4+ cells and tumour response, as was reported during treatment with human recombinant interferon alpha (IFN-alpha). These findings do not support the use of zidovudine as a first-line treatment for patients with AIDS-associated Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cellular and humoral immunity in various cohorts of male homosexuals in relation to infection with human immunodeficiency virus.

The relationship between infection with human immunodeficiency virus (HIV) and various immunological parameters was studied in: (a) healthy controls; (b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; (c) idem, but with anti-HIV antibodies; (d) patients with persistent generalized lymphadenopathy (PGL); (e) patients with AIDS-related syndrome; (f) patients with AIDS and opportunistic infections. In each group, consisting of 15-20 individuals, the following parameters were studied: absolute numbers of CD4+ and CD8+ cells; ratio CD4+/CD8+; cellular immune responses as measured in vivo by delayed-type hypersensitivity (DTH) and in vitro; and antibody response in vivo after immunization with a low dose of keyhole limpet haemocyanin. Healthy HIV antibody-positive individuals and patients with persistent generalized lymphadenopathy already showed a decreased CD4+/CD8+ ratio, mainly due to an increase in the number of CD8+ cells. The ratio in the AIDS-related syndrome and AIDS groups was even lower, but this was now due to low numbers of CD4+ cells while the number of CD8+ cells was normal. The lymphocyte proliferative response was low in the HIV antibody-positive group, normal in the group with persistent generalized lymphadenopathy and profoundly decreased in the AIDS-related syndrome and AIDS groups. DTH was enhanced in the PGL group and diminished in both ARC and AIDS. Compared to healthy controls, the antibody response upon immunization with a low dose of keyhole limpet haemocyanin was depressed (although not absent) in all groups studied, even in HIV antibody-negative homosexuals. In the HIV antibody-positive group, the severity of the impairment of the various parameters of immunocompetence was not related to the presence of HIV antigenaemia.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma.

The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients with stable disease or showing a response, treatment was continued three times weekly until a complete response was achieved or there was progression. 12 of the 26 evaluable patients achieved a major response; 5 of these showed histologically confirmed complete responses. There was a significant increase in OKT4-positive cells in the responders and a significant decrease in HIV antigen (HIV-Ag) in the 7 responders with initially detectable HIV-Ag. Interferon-alpha is thus an effective treatment. The increase in OKT4-positive cells and the decrease in HIV-Ag seem to be significantly related to patients with tumour responses.

Acquired Immunodeficiency Syndrome↗