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Biomedical subjects

H Masur

Publications and source records attributed to H Masur.

At least 145 records · Page 8Linked to original sources
PubMed1990

Problems in the management of opportunistic infections in patients infected with human immunodeficiency virus.

Opportunistic infections ultimately occur in most patients infected with human immunodeficiency virus (HIV) and are responsible for 90% of deaths. Over the decade since the acquired immunodeficiency syndrome (AIDS) was first recognized, important advances have been made in reducing the morbidity and mortality of opportunistic infections in patients infected with HIV. These include an improved understanding of the relationship between immunologic parameters and infection, allowing the occurrence of infectious complications to be more predictable; development of prophylactic regimens and chronic suppressive regimens that are effective, well tolerated, and convenient; and emphasis on earlier diagnosis and therapeutic intervention of those infectious processes that are not prevented. These advances have allowed the quality and duration of patient survival to improve during this decade, but they can also be anticipated to alter the spectrum of clinical manifestations that health care providers are going to see during this epidemic's second decade.

HIV Infections↗
PubMed1990

Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas.

The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Recent advances in the diagnosis, treatment, and prevention of Pneumocystis carinii pneumonia.

In summary, recent advances in our ability to diagnose, treat, and prevent recurrences of pneumocystis pneumonia have significantly improved the clinical management of this infection, especially in HIV-1-infected individuals. As current investigations allow our therapeutic armamentarium in this disease to be strengthened even further, it is likely that pneumocystis pneumonia will pose a diminishing threat to those patients currently most susceptible to this infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Thin-walled cavities, cysts, and pneumothorax in Pneumocystis carinii pneumonia: further observations with histopathologic correlation.

Thin-walled pulmonary cystic lesions were found in five immunocompromised patients, four with acquired immunodeficiency syndrome (AIDS). Four patients had Pneumocystis carinii pneumonia (PCP), and one had pulmonary lesions and disseminated P carinii infection. Two patients demonstrated P carinii within necrotizing, thin-walled, smaller intraparenchymal cavities lined by organisms, exudate, and chronic inflammation. Larger, typically apical and subpleural cysts, lined by fibrosis and/or alveolar parenchyma with little inflammation, were also found during acute episodes. The larger subpleural cysts can arise via rupture of intraparenchymal necrotizing cavities into the subpleural area. Pneumothorax in the four patients with AIDS could not be cured by close thoracostomy drainage; all required pleurodesis. The cysts persisted in cases that were followed up. All cysts were more obvious and numerous with computed tomography (CT), especially with 1.5-mm collimation. CT may be indicated in immunocompromised patients with unexplained pneumothorax or when tube thoracostomy has failed and surgery is being considered, as it can positively influence the operative approach.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Interaction of sulfonamide and sulfone compounds with Toxoplasma gondii dihydropteroate synthase.

Toxoplasma gondii is a common protozoan disease that often causes life-threatening disease, particularly among patients with the acquired immunodeficiency syndrome. This study demonstrates that the dihydropteroate synthase in T. gondii is kinetically distinct from the enzyme characterized from other sources and can be highly purified with a high yield using sequential dye-affinity chromatography. Conditions have been identified that allow for stabilization of the purified enzyme, and its physical characteristics have been elucidated. The molecular weight of the native protein was 125,000 and the protein appeared to contain both dihydropteroate synthase and 6-hydroxymethyl-dihydropterin pyrophosphokinase activities. The sulfonamide class of compounds vary in inhibitory potency by more than three orders of magnitude. Sulfathiazole, sulfamethoxazole, and sulfamethazine, with 50% inhibitory concentrations (IC50's) of 1.7, 2.7, and 5.7 microM, respectively, represent the most potent of this class of inhibitors. Several sulfone analogues, including dapsone, were identified as highly potent inhibitors with IC50's less than 1 microM. The results of these cell-free experiments were corroborated by investigating the metabolic inhibition produced by the various inhibitors in intact organisms. The qualitative and quantitative relations among the inhibitors were preserved in both the cell-free and intact cell assay systems. These studies suggest that the sulfones may be important therapeutic agents for the treatment of toxoplasmosis.

4-Aminobenzoic Acid↗
PubMed1990

Respiratory cryptosporidiosis in a patient with malignant lymphoma. Report of a case and review of the literature.

Respiratory cryptosporidiosis is a rare complication of intestinal infection by cryptosporidia, with only six cases reported (to our knowledge) since its first description in 1983. We report the first case of respiratory cryptosporidiosis recognized at the National Institutes of Health, Bethesda, Md. An antemortem diagnosis was made based on recognition of acid-fast cryptosporidia in an induced sputum specimen obtained from a 64-year-old woman with malignant lymphoma and an associated profound immunodeficiency. Autopsy confirmed the presence of cryptosporidia along the apical aspect of the respiratory epithelium lining the trachea, bronchi, and bronchioles. Cryptosporidia were also identified in the duodenum and gallbladder. Immunohistochemical staining of the paraffin-embedded autopsy lung sections using a monoclonal antibody verified the diagnosis of cryptosporidiosis. Review of our case and the literature suggests that respiratory cryptosporidiosis is characterized by a chronic tracheitis, bronchitis, and bronchiolitis but generally does not cause severe pulmonary dysfunction.

Animals↗
PubMed1989

NIH conference. Pneumocystis pneumonia: from bench to clinic.

Pneumocystis carinii is an intriguing organism found almost exclusively in the lungs. Very little is known about this organism's biologic or epidemiologic character. Over the past two decades, P. carinii has been recognized with increasing frequency as a cause of pneumonia in cancer patients, transplant recipients, and patients infected with the human immunodeficiency virus (HIV). With the increased number of cases of P. carinii pneumonia and a greater emphasis on studying this organism, sophisticated immunologic, metabolic, and molecular biologic tools have ben applied to enhance diagnosis, therapy, and prevention. Immunologic studies have identified specific antigens of human P. carinii, resulting in the development of new diagnostic tests and more specific serologic data. Metabolic studies have allowed screening and identification of new therapeutic and preventive drugs. The development of nucleic acid libraries has allowed enzymes and other proteins to be elaborated in large quantities, facilitating a wide range of studies. These new techniques have changed and will continue to change the ways that pneumocystis pneumonia is diagnosed, treated, prevented, and understood.

Acquired Immunodeficiency Syndrome↗
PubMed1989

CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection.

STUDY OBJECTIVE: To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. DESIGN: Retrospective, consecutive sample study. SETTING: Referral-based clinic and wards. PATIENTS: We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations. MEASUREMENTS AND MAIN RESULTS: Circulating CD4 counts were less than 0.200 X 10(9) cells/L (200 cells/mm3) before 46 of 49 episodes of pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively. In contrast, circulating CD4 counts before episodes of nonspecific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 10(9) cells/L. The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts. Serum p24 antigen levels had no predictive value. CONCLUSIONS: Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C. neoformans or M. avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 10(9) cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation. Patients infected with HIV who have a CD4 count below 0.200 X 10(9) cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.

Cryptococcosis↗
PubMed1989

Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A phase II randomized, placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the toxicity, effects on immune function, antitumor effects, antiretroviral effects, and pharmacokinetics of zidovudine therapy in patients with early human immunodeficiency virus (HIV) infection and Kaposi sarcoma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: National Institutes of Health, a referral-based research institution (single site). PATIENTS: Physician-referred volunteer patients with HIV infection, Kaposi sarcoma, CD4+ lymphocyte counts greater than 0.2 x 10(9)/L, and no systemic symptoms or history of opportunistic infection. Of 41 patients enrolled, 4 had not met all entry criteria and were therefore not evaluable. INTERVENTIONS: Patients were randomized to one of four treatment groups for an initial 12-week treatment period: oral placebo (9 patients); zidovudine, 250 mg orally every 4 hours (9 patients); zidovudine, 0.5 mg/kg body weight intravenously every 4 hours (9 patients); and zidovudine, 2.5 mg/kg intravenously every 4 hours (10 patients). After at least 12 weeks of therapy at their assigned dose, patients were treated with oral zidovudine, generally 250 mg every 4 hours, with a mean 42-week follow-up. MEASUREMENTS AND MAIN RESULTS: Anemia and granulocytopenia were the major toxicities. Significant increases in platelet counts and declines in serum HIV antigen and IgG and IgM levels occurred in treated patients. Treated patients were more likely than those on placebo to clear HIV from the cerebrospinal fluid. There were no differences in tumor progression or CD4+ or CD8+ lymphocyte counts among the groups. CONCLUSIONS: Zidovudine was well tolerated and had antiretroviral activity in patients with early HIV infection and Kaposi sarcoma but it had no significant effect on the extent of Kaposi sarcoma or on immune function.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS).

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Monoclonal antibodies to Pneumocystis carinii: identification of specific antigens and characterization of antigenic differences between rat and human isolates.

To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii reacted with human P. carinii, and none of four monoclonal antibodies to human P. carinii reacted with rat P. carinii. Two antibodies to human P. carinii reacted by immunofluorescence with only one human P. carinii isolate. Immunoblot studies identified major antigens of rat P. carinii with molecular masses of 40,000-100,000 daltons and of human P. carinii with molecular masses of 22,000-95,000 daltons. These studies document the existence of antigenic differences between rat and human P. carinii and are consistent with the suggestion that individual isolates of human P. carinii are also antigenically different. Further studies with these antibodies should increase understanding of the antigenic nature of P. carinii and of the interaction of P. carinii with its host.

Animals↗
PubMed1989

Characterization of de novo folate synthesis in Pneumocystis carinii and Toxoplasma gondii: potential for screening therapeutic agents.

Drug therapy studies imply that Pneumocystis carinii and Toxoplasma gondii possess the enzymes necessary for de novo folate synthesis. To verify this, incorporation of [3H]paraaminobenzoic acid [( 3H]PABA) into reduced folates by P. carinii and T. gondii was investigated. Both organisms synthesized tritiated reduced folates. In P. carinii, 10-formyltetrahydrofolate and tetrahydrofolate, and in T. gondii, 5-formyltetrahydrofolate were the major synthesized folates. P. carinii remained metabolically active in vitro for only a few days. Because current systems for screening antipneumocystis agents are cumbersome, the utility of this assay system for screening therapeutic agents was investigated. Sulfonamides and pentamidine efficiently inhibited de novo folate synthesis in P. carinii. Inhibitors of dihydrofolate reductase such as trimethoprim and trimetrexate were poor inhibitors for P. carinii but efficient inhibitors for T. gondii. This study demonstrates the first unambiguous evidence of metabolic activity in P. carinii, and provides a potential assay for efficiently screening antipneumocystis drugs in vitro.

4-Aminobenzoic Acid↗
PubMed1989

Prophylaxis of Pneumocystis carinii pneumonia: an update.

Note from Dr. Merle A. Sande--We have recently come to appreciate the fact that successful chemotherapy of opportunistic infections in patients with AIDS is akin to treatment of certain malignancies: In both instances, induction, followed by maintenance, therapy is required. Although control of initial infections is usually successful with current regimens, relapse is common if lifelong prophylactic or suppressive therapy is not used. This is true in human immunodeficiency virus (HIV)-infected individuals with Pneumocystis carinii pneumonia, cryptococcosis, histoplasmosis, toxoplasmosis, and cytomegaloviral infection. Because Drs. Joseph A. Kovacs and Henry Masur of the National Institutes of Health have been instrumental in developing strategies for the management of P. carinii pneumonia, they were asked to discuss their current approach to chemoprophylaxis of this infection in this AIDS Commentary.

Acquired Immunodeficiency Syndrome↗