Therapy of acquired immunodeficiency syndrome.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Masur.
Explore the source record for details and available documents.
To evaluate the ability of a mouse monoclonal antibody, 2G2, directed against human Pneumocystis carinii, to detect the organism in clinical specimens, a prospective study of the antibody in an indirect immunofluorescent assay was undertaken. P carinii was rapidly detected in thirteen of fourteen bronchoalveolar lavage specimens positive by toluidine-blue-O stain, none of eleven lavage specimens negative by toluidine-blue-O, neither of two impression smears of histologically negative open-lung biopsy specimens, and both of two impression smears of histologically positive necropsy specimens. Immunofluorescence with monoclonal antibody 2G2 is a rapid, simple, and specific technique for detection of P carinii in clinical specimens.
Eight patients with cytomegalovirus retinitis in one or both eyes were treated with 9-(1,3 dihydroxy 2-propoxymethyl) guanine. Of the 14 eyes with retinitis, eight demonstrated more than 90% resolution, four had partial improvement, one failed to respond, and one could not be evaluated. Two of the eight patients had chemotherapy-induced immunosuppression and had ocular remissions for at least several months. The remaining six patients had AIDS or probable AIDS and relapsed in five weeks or less after discontinuation of therapy. Dihydroxy propoxymethyl guanine appears to be effective biologically in treating human cytomegalovirus retinitis without the development of unacceptable side effects but a single course of therapy is not capable of eradicating the virus.
Pulmonary infiltrates in the patient with acquired immunodeficiency syndrome (AIDS) may be associated with a spectrum of unusual neoplastic and infectious process. Transbronchial biopsy frequently reveals the cause of these infiltrates; however, when transbronchial biopsy is nondiagnostic or contraindicated, or if the patient fails to improve after a diagnostic transbronchial biopsy, further investigation is warranted to direct appropriate therapy. Efficacy of 23 open-lung biopsies in 19 AIDS patients with pulmonary infiltrates was evaluated to define the indications for and the diagnostic yield of open-lung biopsy. Pulmonary infiltrates were recognized for a mean duration (+/- standard error) of 16 +/- 2 days before open-lung biopsy and were associated with fever and cough. These patients did not have prior transbronchial biopsy, and open-lung biopsy was diagnostic in all of these. Prior transbronchial biopsy performed in the remaining 16 patients was nondiagnostic in 10. Open-lung biopsy was diagnostic in 70% of these patients (Pneumocystis carinii pneumonia, 2 patients; Kaposi's sarcoma, 3 patients; Kaposi's sarcoma and Legionella pneumophila, 1 patient; cytomegalovirus, 1 patient). The other 6 patients having a previous diagnostic transbronchial biopsy failed to improve with therapy, and open-lung biopsy resulted in a therapeutic change in 67% of these patients. Two deaths were attributable to open-lung biopsy in patients with postoperative thrombocytopenic hemorrhage. Open-lung biopsy should be performed in AIDS patients when transbronchial biopsy is nondiagnostic or contraindicated, or in patients who fail to improve with appropriate therapy after diagnostic transbronchial biopsy, especially in patients with Kaposi's sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)
The human T-cell leukemia/lymphotropic virus type III (HTLV-III), the causative agent of the acquired immunodeficiency syndrome (AIDS), has been isolated from the tears of five AIDS patients. When combined with data from our previous study, 5 of 16 samples from patients with AIDS or AIDS-related complex (ARC) showed positive isolates for HTLV-III from the tears. Normal control tears were negative for HTLV-III. Based upon these findings, the Centers for Disease Control (CDC) has issued precautions to prevent any possible spread of the virus by this route. Although there is no evidence to suggest transmission of HTLV-III by contact with the tears, until more is known about the possible transmissibility and infectious dose of this virus, such precautions should be taken during ophthalmic examination.
Whole body Ga-67 scans revealed increased uptake in lymph nodes accessible for biopsy in three patients with the acquired immunodeficiency syndrome (AIDS) infected by Mycobacterium avium-intracellulare (MAI). In diagnostically difficult cases where the usual methods for diagnosing MAI are not helpful, Ga-67 studies may be of value.
Susceptibility testing and serotyping were performed on 57 isolates of Mycobacterium avium-M. intracellulare from patients with acquired immunodeficiency syndrome (AIDS) and 75 isolates from patients without AIDS. Susceptibility patterns and serotypes of AIDS isolates were significantly different from those of non-AIDS isolates. These results may partially explain the poor therapeutic response of M. avium-M. intracellulare infections in AIDS patients.
Studies were designed to examine skin test responses to leishmanial antigens in American visceral leishmaniasis (AVL) in Brazil. We found that after recovery from AVL, patients had positive delayed hypersensitivity reactions to Leishmania. Different amounts of a soluble extract obtained from Leishmania donovani chagasi promastigotes were compared with whole L. d. chagasi promastigotes in persons with past AVL. The most effective soluble preparations tested contained 25 and 50 micrograms leishmanial protein. These produced positive responses in 95%-100% of the individuals with past AVL. The 25 micrograms protein dose was used in further studies. This preparation produced no positive responses in either normal controls, tuberculosis patients, or schistosomiasis patients, and less than 5% positive responses in persons with Chagas' disease. The same amount of soluble extract prepared from L. mexicana amazonensis produced 82% positive skin test responses in persons with past AVL. When persons living in an area endemic for AVL were skin tested with the 25 micrograms preparation of L. d. chagasi extract, 34.1% yielded positive tests with a low number of positive responses in young children and 48% positive in adults. Only 3.1% of the population studied had a history of AVL. We have found that positive delayed hypersensitivity response to a soluble Leishmania extract is a sensitive and specific indicator of previous infection with AVL.
Eight immunosuppressed homosexual men with cytomegalovirus viremia--seven with serious bilateral retinitis, one with colitis in addition to retinitis, and one with pneumonitis only--were treated with a new acyclovir derivative, 9-(1,3-dihydroxy-2-propoxymethyl) guanine, which has excellent in-vitro activity against cytomegalovirus. All patients had virologic and clinical improvement, but substantial leukopenia developed in three patients. Both clinical relapses and viral relapses occurred frequently, usually within 30 days after cessation of treatment. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine represents the first clinically and virologically effective agent for the treatment of cytomegalovirus disease, but more effective and less toxic therapeutic regimens for both acute and chronic use must be developed.
To assess the risk of nosocomial transmission of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), we prospectively evaluated a cohort of 531 health care workers. One hundred fifty of these employees reported percutaneous or mucous membrane exposures to blood or body fluids from a patient with the acquired immunodeficiency syndrome (AIDS) during the treatment of 238 such patients since 1981. None of these 150 employees had serologic evidence of HTLV-III/LAV infection on follow-up from 6 to 46 months after exposure. Of the 150, 46 were studied immunologically and 29 had lymphocytes cultured for HTLV-III/LAV. Results of all studies were normal. Of the 531 employees, 3 (0.56%) had serologic evidence of HTLV-III/LAV infection. All were seropositive at the time of study entry; none reported adverse nosocomial exposures. All acknowledged membership in one or more established risk groups for AIDS. This study provides strong evidence that the risk of nosocomial transmission of HTLV-III/LAV is extremely low.
Explore the source record for details and available documents.
The human T-cell leukemia/lymphotropic virus type III (HTLV-III), the causative agent of the acquired immunodeficiency syndrome (AIDS), has been isolated from the conjunctival epithelium of a 33-year-old woman with AIDS, suggesting that an important reservoir of the virus may be the ocular surface epithelial cells. The tears and conjunctival epithelium from normal controls were negative for HTLV-III. The finding of HTLV-III in the tears and conjunctival epithelium indicated that HTLV-III may be ubiquitous in bodily cells and fluids. Repeated contact with the tears and ocular surface epithelium of patients with AIDS may possibly facilitate transmission of HTLV-III, and precautions are advisable during routine ophthalmologic procedures such as glaucoma testing and contact-lens fitting.
Human T-lymphotropic virus type III (HTLV-III) was isolated from the tears of 1 out of 7 patients with the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex. The tears from 5 healthy individuals did not show HTLV-III. The recovery of HTLV-III from tears suggests that they may harbour free virus or contain virus-positive cells and is consistent with the recovery of HTLV-III from other body fluids. Although casual contact with such fluids has not been shown to cause AIDS, direct contact with the tears of AIDS patients, including contact during routine ophthalmologic procedures, should be minimised.
Thirty consecutive patients with the acquired immune deficiency syndrome were treated with intramuscular human lymphoblastoid interferon for Kaposi's sarcoma. Patients were divided into three groups receiving 7.5 million units/m2 per day, 15 million units/m2 per day, or 25 million units/m2 per day for 28 days. Because of dose-limiting toxicity in the highest dose group, all patients received between 6 and 15 million units/m2 per day. There were three partial responses and four minor responses. The responses were not dependent on drug dose, but did correlate with higher total lymphocyte and OKT4-positive lymphocyte numbers and absence of prior opportunistic infection. Patients who had endogenous acid-labile alpha-interferon prior to therapy were more likely to have progressive disease during interferon administration.
The present study was designed to determine whether there was a significant correlation between the clinical presentation of patients with AIDS or AIDS-related illnesses and the degree of their underlying immunologic abnormalities. In 17 patients who presented with opportunistic infections, the mean number of T4 lymphocytes was 34/mm3 and the mean proliferative response to phytohemagglutinin 26,000 cpm; in 12 patients who presented with Kaposi's sarcoma alone, the mean number of T4 cells was 231/mm3 and the mean proliferative response to phytohemagglutinin, 32,809 cpm; and in nine patients with the lymphadenopathy syndrome, the mean number of T4 cells was 703/mm3 and the mean proliferative response to phytohemagglutinin, 49,317 cpm. These findings suggest that those patients who present with opportunistic infections as their initial clinical manifestation of AIDS may represent a subgroup with a more severe immunologic derangement prior to clinical diagnosis. Thus, in those who have a predisposition to Kaposi's sarcoma, this disease will often develop, prior to the development of T cell dysfunction, to the degree of that in those who present with opportunistic infections. This finding is of importance in attempts to understand the pathogenesis of this syndrome and in the design of therapeutic trials.
A 30-year-old homosexual man presented with widespread Burkitt's lymphoma. On the basis of immunologic and viral studies, he was suspected of having the acquired immune deficiency syndrome. Following chemotherapy that included intrathecal cytosine arabinoside and methotrexate, brain stem edema, paraplegia, and an elevated cerebrospinal fluid level of myelin basic protein developed. Autopsy revealed vacuolar demyelination of spinal cord, brain stem, and cerebellum. The pathologic findings were similar to those reported to occur in myelopathy associated with intrathecal chemotherapy, but far more extensive. The contribution of the suspected acquired immune deficiency syndrome is unknown.
Analysis of serum samples from patients with the acquired immunodeficiency syndrome (AIDS) was performed by high-resolution zone electrophoresis. A high incidence of monoclonal and oligoclonal immunoglobulins was detected in the sera of 24/27 patients with Kaposi's sarcoma and in 2/15 patients with opportunistic infections. The presence of monoclonal bands was independent of whether or not the patients had experienced an opportunistic infection. These findings indicate a monoclonal or oligoclonal B-cell activation occurring in a much higher frequency in AIDS patients with Kaposi's sarcoma, thus suggesting that similar mechanisms may be operative in the malignant or pseudomalignant proliferation of B-cells and endothelial cells in patients with AIDS.
Titers of circulating interferon (IFN) and the activity of 2'-5' oligoadenylate (2-5A) synthetase, an enzyme specifically induced by IFN, were measured in 28 homosexual men with acquired immunodeficiency syndrome (AIDS) who received one- to six-month courses of antineoplastic therapy with IFN-alpha and in homosexual and heterosexual controls. Fifteen of the patients and two of seven healthy homosexual men had high endogenous levels of 2-5A synthetase. IFN therapy induced further increases in this enzyme in only 10 of the 28 patients with AIDS. Furthermore, peripheral blood cells from all but one of the patients with AIDS and homosexual controls tested were markedly deficient in their ability to respond to IFN in vitro, as measured by increased levels of 2-5A synthetase. We did not find a statistical correlation between cytomegalovirus viremia and pretherapy endogenous circulating IFN, nor any apparent correlation between disseminated infection with cytomegalovirus and either basal levels of 2-5A synthetase or changes in enzyme level during therapy. Pretherapy circulating IFN was significantly correlated with progressive Kaposi's sarcoma during therapy, but rises in levels of 2-5A synthetase were not sufficient to predict a good clinical response.