Burroughs Wellcome Fund

About: Burroughs Wellcome Fund is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Zidovudine & Trimethoprim. The organization has 89 authors who have published 58 publications receiving 8563 citations.

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.

Abstract: Background and Methods Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over a one-hour period, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. Results From April 1991 through Decemb...

Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women

Abstract: Background Most epidemiologic studies of cardiovascular disease in postmenopausal women suggest that estrogen-replacement therapy has a protective effect. The effects of the use of estrogen combined with progestin are less well studied. Methods To examine the associations of hormone-replacement therapy with concentrations of plasma lipids and hemostatic factors, fasting serum concentrations of glucose and insulin, and blood pressure, we studied 4958 postmenopausal women participating in a population-based investigation. Using cross-sectional data, we classified the women into four groups according to their use of hormone-replacement therapy: current users of estrogen alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, and nonusers who had never used them. Results Current users had higher mean levels of high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 and high-density lipoprotein3, and apolipoprotein A-I than nonusers, and lower me...

Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death.

Abstract: Nitric oxide produced by cytokine-inducible nitric oxide synthase (iNOS) is thought to be important in the pathogenesis of septic shock. To further our understanding of the role of iNOS in normal biology and in a variety of inflammatory disorders, including septic shock, we have used gene targeting to generate a mouse strain that lacks iNOS. Mice lacking iNOS were indistinguishable from wild-type mice in appearance and histology. Upon treatment with lipopolysaccharide and interferon gamma, peritoneal macrophages from the mutant mice did not produce nitric oxide measured as nitrite in the culture medium. In addition, lysates of these cells did not contain iNOS protein by immunoblot analysis or iNOS enzyme activity. In a Northern analysis of total RNA, no iNOS transcript of the correct size was detected. No increases in serum nitrite plus nitrate levels were observed in homozygous mutant mice treated with a lethal dose of lipopolysaccharide, but the mutant mice exhibited no significant survival advantage over wild-type mice. These results show that lack of iNOS activity does not prevent mortality in this murine model for septic shock.

Acyclovir for Prevention of Cytomegalovirus Infection and Disease after Allogeneic Marrow Transplantation

Abstract: Patients undergoing allogeneic bone marrow transplantation who are seropositive for cytomegalovirus are vulnerable to serious cytomegalovirus infection, presumably because of reactivation of latent endogenous virus and severe immunosuppression. We administered intravenous acyclovir from 5 days before to 30 days after allogeneic marrow transplantation for hematologic neoplasms in an effort to prevent cytomegalovirus infection and disease in patients seropositive for cytomegalovirus before transplantation. Eighty-six patients seropositive for both cytomegalovirus and herpes simplex virus before transplantation received acyclovir, whereas 65 patients seropositive only for cytomegalovirus served as controls (acyclovir is the standard prophylactic agent against herpes simplex virus in this setting). The probability that cytomegalovirus infection would develop within the first 100 days after transplantation was 0.70 among acyclovir recipients and 0.87 among control patients at medians of 62 and 40 days after transplantation, respectively (P = 0.0001 by log-rank test). Invasive cytomegalovirus disease developed in 19 acyclovir recipients (22 percent) and 25 control patients (38 percent) (P = 0.008). Survival within the first 100 days after transplantation was better among acyclovir recipients (P = 0.002). Acyclovir prophylaxis was associated with a relative risk of 0.5 or less for the development of cytomegalovirus infection or disease or for death within the first 100 days after transplantation (P less than or equal to 0.04), in proportional-hazards regression analysis. We conclude that prophylaxis with intravenous acyclovir significantly reduced the risk of both cytomegalovirus infection and cytomegalovirus disease in seropositive patients after allogeneic bone marrow transplantation and that it was also associated with significantly improved survival.

Progressive Disease Due to Ganciclovir-Resistant Cytomegalovirus in Immunocompromised Patients

Abstract: CYTOMEGALOVIRUS (CMV) infections are a major cause of morbidity and mortality among immunocompromised patients, especially recipients of bone marrow and solid-organ transplants and those with the a...