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Biomedical subjects

W C Buhles

Publications and source records attributed to W C Buhles.

32 records · Page 2Linked to original sources
PubMed1975

Evaluation ofprimary blood monocyte and bone marrow cell culture for the isolation of Rickettsia rickettsii.

Rickettsia rickettsii was isolated from experimentally infected guinea pigs by culture of blood monocytes and bone marrow cells, and from experimentally infected rhesus monkeys by blood monocyte culture. Rickettsiae were identified in monocyte-macrophage monolayers stained by Giménez or flourescent antibody techniques. A total of 78 culture attempts were made from 20 guinea pigs and 16 monkeys. The success of isolation of R. rickettsii in culture was positively correlated with the numbers of rickettsiae present in the blood and bone marrow. in cultures derived from infected guinea pigs, rickettsiae were usually observed after 5 to 7 days of culture, and in monkeys monocyte cultures they were usually observed within 3 to 5 days. Positive cultures were derived from guinea pigs and monkeys as early as the first day of fever and 1 to 3 days before the appearance of other clinical signs. Monocyte cultures became negative with the resolution of rickettsemia and concomitantly with the appearance of serum antibody. Monocyte culture isolation of R. rickettsii may be as sensitive for the detection of rickettsiae in blood and marrow as the intraperitoneal inoculation of guinea pigs or the plaque assay technique. Because of the simplicity of the method and because rickettsiae were often identified within 3 to 5 days after initiation, the monocyte culture technique may be useful in the early diagnois of human rickettsial disease.

Animals↗
PubMed1972

Murine resistance to inhaled Neisseria meningitidis after infection with an encephalomyocarditis virus.

A reduction in pulmonary anti-bacterial activity due to a preceding viral illness has been suggested as the mechanism responsible for some meningococcal infections of the lung. We investigated this proposed pathogenesis by infecting mice with airborne encephalomyocarditis virus (EMC) and then challenging them 1, 4, and 7 days later with aerosols of Neisseria meningitidis. Meningococcal clearance was assessed by comparing the numbers of bacteria present immediately after inhaling the aerosols with the numbers present 3 hr later. To insure that EMC virus adequately depressed murine defense mechanisms, we also determined staphylococcal killing rates at 4 hr by using radiophosphorus-labeled staphylococcal aerosols. Viral infection depressed murine pulmonary antimeningococcal activity at 1 and 4 days (P < 0.01) but not at 7 days. Intrapulmonary staphylococcal killing was impaired on day 4 (P < 0.01) but not on days 1 or 7. Pulmonary viral titers decreased rapidly from 10(7) to 10(3) plaque-forming units/ml of lung during the experimental period. According to these data viral disease transiently depresses resistance to meningococcal infection. This impairment in host resistance is present while the viral titer is decreasing and follows a relatively similar pattern to the transient decrease noted for staphylococci.

Aerosols↗
PubMedDate not supplied

Ganciclovir treatment of life- or sight-threatening cytomegalovirus infection: experience in 314 immunocompromised patients.

A total of 314 immunocompromised patients with serious cytomegalovirus (CMV) infection treated with ganciclovir administered intravenously were studied. Rates of favorable clinical response among evaluatable patients were 91 (84%) of 108 for CMV retinitis, 35 (83%) of 42 for gastrointestinal CMV infection, and 26 (72%) of 36 for CMV pneumonia. Of 167 treated patients who had AIDS, improvement or stabilization of CMV disease occurred in 83% as compared with 13% of 39 untreated, historical control patients with AIDS and similar CMV disease (P less than or equal to .004). Virologic response was noted in 111 (92%) of 121 patients who had sequential cultures of blood, urine, or throat washings for CMV. In an attempt to prevent relapse of CMV disease after discontinuation of ganciclovir, maintenance treatment was evaluated in a group of 61 patients with AIDS and CMV retinitis who had received an initial dosage of greater than or equal to 7.5 mg/(kg.d) for greater than or equal to 10 days. Median time to relapse of retinitis was 47 days in patients not receiving maintenance treatment as compared with 105 days in patients treated with 25-35 mg/(kg.w) (P = .0002). Adverse effects of treatment included neutropenia (42%), thrombocytopenia (19%), central nervous system effects (18%), nausea (6%), fever (6%), rash (6%), vomiting, diarrhea, infusion site reactions, and anemia (4% each). It was concluded that ganciclovir has clinical efficacy against CMV disease, as well as an in vivo antiviral effect, and that this agent reduces morbidity of serious CMV infections in immunocompromised patients.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Clinical pharmacokinetics of ganciclovir in patients with normal and impaired renal function.

The pharmacokinetics of ganciclovir was evaluated in 21 patients with life- or sight-threatening cytomegalovirus infections. Thirteen patients had normal renal function and eight patients had various degrees of renal insufficiency. Most patients received 5 mg of ganciclovir/kg as a 1-hour intravenous infusion twice daily for periods of up to 2 weeks. Quantification of ganciclovir was assessed by high-performance liquid chromatography and radioimmunoassay. In patients with normal renal function, a biexponential decay of ganciclovir from plasma was observed, with an initial distribution half-life (t1/2) of 0.76 +/- 0.67 hour and a terminal elimination t1/2 of 3.60 +/- 1.40 hours. A large fraction of the administered dose was excreted in urine, and total clearance of ganciclovir correlated well with creatinine clearance. In patients with renal insufficiency who were receiving 5 mg of ganciclovir/kg, the terminal elimination t1/2 of ganciclovir was markedly increased (11.50 +/- 3.90 hours), as compared with values obtained in patients with normal renal function. Hemodialysis efficiently reduced levels of ganciclovir in plasma by approximately 53.0% +/- 11.5%, a finding that indicates this drug should be administered after dialysis.

Acyclovir↗
PubMedDate not supplied

Ganciclovir treatment of serious cytomegalovirus infection in heart and heart-lung transplant recipients.

Experience with ganciclovir treatment of life- or sight-threatening cytomegalovirus (CMV) infections in 22 heart and heart-lung transplant recipients at six medical centers was reviewed. All six heart-lung recipients and six of 16 heart recipients had CMV pneumonitis; five heart recipients had CMV gastrointestinal disease, three had retinitis, and two had infections in more than one organ system. Of the 18 patients (82%) surviving initial ganciclovir therapy, 16 improved, one stabilized, and one showed no change in clinical status. All cultures positive for CMV before treatment became negative during therapy. Six patients (33% of survivors) had recurrent episodes and received additional therapy. Four patients (18%) died during initial therapy; death was believed to be related to CMV infection in only two cases and to ganciclovir treatment in no case. Adverse reactions possibly attributable to ganciclovir included neutropenia (four patients), impaired renal function (one), thrombocytopenia (one), decreased blood pressure (one), and seizure (one). Ganciclovir appears to be well tolerated and to alter favorably the outcome of serious CMV infection in this patient population.

Acyclovir↗