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Biomedical subjects

M S Gottlieb

Publications and source records attributed to M S Gottlieb.

At least 55 records · Page 3Linked to original sources
PubMed1989

The relationship between medical and psychological status in newly diagnosed gay men with AIDS.

We assessed current medical and psychological status in 50 homosexual/bisexual males who were within 3 months of the diagnosis of AIDS. Subjects had typically impaired cellular immunity, relatively well-maintained physical performance capacity, and reported surprisingly good current health status, in spite of significant numbers of medical symptoms. While as a group they reported moderate levels of psychological distress, intact self-esteem, and a high quality of life, a significant minority reported high psychological distress, low self-esteem, and low quality of life. Psychological distress was correlated with subjective, but not objective, measures of current health status.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Documentation of an AIDS virus infection in the United States in 1968.

The acquired immunodeficiency syndrome was first recognized as a clinical entity in the United States in the early 1980s; however, the issue of when human immunodeficiency virus, the causative agent of the acquired immunodeficiency syndrome, was introduced into at-risk populations in the United States is unresolved. Previously, we reported the case study of a 15-year-old black male who was admitted to St Louis City Hospital in 1968 for extensive lymphedema of the genitalia and lower extremities. Chlamydial organisms were widely disseminated and isolated from numerous body fluids and organs. Over a 16-month clinical course his condition progressively deteriorated, and at autopsy there was widespread Kaposi's sarcoma of the aggressive, disseminated type. Recently performed Western blot and antigen capture assays on serum and autopsy tissue specimens frozen since 1969 have disclosed that this sexually active teenager was infected with a virus closely related or identical to human immunodeficiency virus type 1. The clinical and immunologic findings together suggest that an immunosuppressive retrovirus existed in the United States before the late 1970s.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Clinical drawbacks of total lymphoid irradiation: the cons.

Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.

Humans↗
PubMed1987

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

AIDS-Related Complex↗
PubMed1987

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

AIDS-Related Complex↗
PubMed1987

Mechanism of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. II. Normal antibody-dependent cellular cytotoxicity (ADCC) mediated by effector cells defective in natural killer (NK) cytotoxicity.

Our studies and other investigations have shown that NK effector cells can also mediate antibody-dependent cellular cytotoxicity (ADCC) through the use of the Fc gamma receptor on the NK cell membrane. Peripheral blood lymphocytes (PBL) derived from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex exhibit a poor NK activity due to a defective "trigger" required for activation in the lethal hit stage of the NK lytic pathway. Consequently, it was important to delineate whether the defect in AIDS NK cells affected the ADCC function. By using the 51Cr-release assay, the ADCC cytotoxic activity of AIDS PBL was found to be within the normal range, despite the absence of significant NK activity. Several experiments corroborated that the same effector cells mediate both NK CMC and ADCC. Depletion of Fc gamma R-bearing cells resulted in elimination of both the ADCC and NK cytotoxic functions. Single cell analyses, using one- and two-target cell conjugates, revealed that the frequency of ADCC effector:target conjugates and the frequency of killer cells from AIDS PBL were comparable to the frequencies seen in the normal controls. However, when mixtures of NK and ADCC targets were used to form mixed two-target conjugates, the AIDS effector cells lysed only the bound ADCC target, whereas the normal effector cells lysed both the bound NK and ADCC targets. These results demonstrate clearly that the same NK/K effector cells from AIDS PBL, defective in NK activity, are not impaired in mediating ADCC activity. These findings were supported by the demonstration that AIDS PBL stimulated with ADCC targets, but not with NK targets, released NK cytotoxic factors, postulated mediators of the NK CMC reaction. These findings indicate that the NK/K cells in AIDS are triggered normally for ADCC activity but are not triggered for NK activity. Furthermore, the results indicate that the lytic machinery is not impaired in the AIDS NK/K cells.

AIDS-Related Complex↗
PubMed1987

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

AIDS-Related Complex↗
PubMed1987

Treatment of cytomegalovirus retinopathy with ganciclovir.

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Response of AIDS-related thrombocytopenia to intravenous and oral azidothymidine (3'-azido-3'-deoxythymidine).

A patient with AIDS-related thrombocytopenia (ART) was treated with the new anti-retroviral agent azidothymidine (AZT, Retrovir, zidovudine) by the intravenous and oral routes for a period of 20 weeks. After a 6 week period of initial treatment, the platelet count rose from 38,000 to 140,000/mm3. AZT was intentionally discontinued for three weeks over which the platelet count declined to 70,000/mm3. After reinstitution of AZT, the platelet count rose once again and remained near normal levels for over one year. We conclude that AZT may have efficacy against the thrombocytopenia observed in some patients infected with human immunodeficiency virus (HIV). The pathogenesis of ART and the mechanisms of action of AZT in this condition remain unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Treatment of the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) are sequelae of immune system injury initiated by a novel human retrovirus [human T-lymphotrophic virus strain III/lymphadenopathy-associated virus (HTLV III/LAV)]. The resulting spectrum of immune deficiency sets the stage for opportunistic infection and malignancy. In this review, we consider progress made in the treatment and prevention of AIDS and HTLV III/LAV infection. Immunomodulator and antiviral approaches are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Illness concerns, attitudes towards homosexuality, and social support in gay men with AIDS.

High levels of illness-related psychologic distress, marked social stigmatization and loss of social support, and negative internalized feelings towards homosexuality have previously been reported in homosexual men with the diagnosis of acquired immune deficiency syndrome (AIDS). We assessed 50 homosexual or bisexual men who were within 3 months of their AIDS diagnosis with respect to medical status, illness concerns, attitudes towards homosexuality, and social support. Subjects reported levels of illness-related concerns comparable to previously studied cancer patients. Their attitudes towards homosexuality were similar to previously studied healthy homosexual males. Their social support needs were variable, as was their satisfaction with specific types of social support. Their social networks were moderately small. In this AIDS subject group, illness concerns, attitudes toward homosexuality, and social support satisfaction were significantly correlated with each other, and with previously reported levels of psychologic distress and subjective (but not objective) measures of health status.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome.

We report on a patient with cytomegaloviral epididymitis and the acquired immune deficiency syndrome. The diagnosis was suggested by epididymitis that was refractory to antibiotics, and by isolation of cytomegalovirus from the urine and semen. The definitive diagnosis was made with immunohistochemical staining for cytomegaloviral antigens in the epididymal ductal cells. Because of the ineffectiveness of antimicrobial agents in this disorder, epididymectomy is the current treatment of choice.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Immunologic aspects of the acquired immunodeficiency syndrome and male homosexuality.

The acquired immunodeficiency syndrome (AIDS) is the most common and best characterized disorder of T cells leading to enhanced susceptibility to infection. Current hypotheses hold that infection with human T-cell lymphotropic virus type III/lymphadenopathy virus (HTLV-III/LAV) is a necessary but not a sufficient condition for the development of AIDS, and that a variety of cofactors participate in the pathogenesis of the syndrome. This article reviews the immunologic aspects of AIDS and the AIDS-related syndromes, as well as concepts of etiology and pathogenesis. Predisposing factors for this disease in the homosexual or bisexual host are emphasized.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Chemiluminescence of lung macrophages and blood leukocytes in sarcoidosis.

A luminol-enhanced chemiluminescence assay was used to measure light elaborated by peripheral blood polymorphonuclear leukocytes (PMNs) and by pulmonary alveolar macrophages (PAMs) from 14 healthy, normal subjects and 16 patients with sarcoidosis. Resting peripheral blood PMNs (incubated only in medium) from patients with sarcoidosis generated substantially more chemiluminescence than PMNs from normal control subjects (p = 0.002). With zymosan stimulation, greater chemiluminescence was produced by PMNs from untreated patients with sarcoidosis than from normal subjects (p less than 0.05), whereas no differences were noted with latex stimulation. Chemiluminescence for resting PAMs was not different between normal subjects and patients with sarcoidosis. However, PAMs from untreated patients with sarcoidosis had higher chemiluminescence with latex particle ingestion than PAMs from normal subjects (p less than 0.05), but no differences in PAM chemiluminescence were found when zymosan was the phagocytic particle. Increased chemiluminescence by PMNs and PAMs from patients with sarcoidosis may reflect phagocyte activation in the disease process.

Adult↗