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Biomedical subjects

L R Brettman

Publications and source records attributed to L R Brettman.

11 recordsLinked to original sources
PubMed1996

Pharmacokinetics and safety of single oral doses of VX-366 (isobutyramide) in healthy volunteers.

VX-366 (isobutyramide) is an orally available branched chain amide that may offer an alternative to current treatments for beta-hemoglobinopathy. A phase I, double-blind, randomized, placebo-controlled study was conducted to investigate four single oral doses of VX-366 (1, 7, 14 or 28 grams or approximately 14, 100, 200 or 400 mg/kg) administered to four male volunteers each, with two other subjects in each group receiving a matching placebo. The total number of volunteers enrolled in this study was 24, with a mean age of 27 +/- 6.4 years. VX-366 was well tolerated at all dose levels studied, and peak plasma concentrations (Cmax) of 18.88 +/- 1.02 micrograms/mL (0.2 mmol/L), 171.13 +/- 32.13 micrograms/mL (2 mmol/L), 331.58 +/- 35.48 micrograms/mL (3.8 mmol/L), and 538.83 +/- 54.19 micrograms/mL (6 mmol/L) were achieved after the four respective doses. The half-life (t1/2) of VX-366 was more than 7 hours, and there was evidence of nonlinear pharmacokinetics. It is likely that nonrenal (metabolic) clearance plays a predominant role in elimination. Based on these data, VX-366 given as a single daily dose of 100 to 150 mg/kg should be well tolerated and can be expected to result in peak plasma levels in excess of 170 micrograms/mL (2 mmol/L) and in trough plasma levels in excess of 40 micrograms/mL (0.5 mmol/L). These plasma levels exceed the concentrations previously shown to stimulate gamma globin synthesis both in vitro and in baboons.

Administration, Oral↗
PubMed1988

Hemorrhagic cystitis due to herpes simplex virus as a marker of disseminated herpes infection.

Herpetic cystitis has rarely been reported. Herein are described two immunocompromised female patients with genital or buttock herpetic lesions in whom hemorrhagic cystitis due to herpes simplex virus type 2 developed in the setting of disseminated herpetic infection. Both patients had indwelling Foley catheters. Urinary tract instrumentation may cause local or widespread dissemination of genital herpes in immunocompromised patients.

Aged↗
PubMed1983

Crystallocryoglobulinemia resulting from human monoclonal antibodies to albumin.

Two patients had a previously unrecognized form of crystallocryoglobulinemia. Their clinical presentations were similar, consisting of necrotizing vasculitis and purpura involving the legs. Analysis of each cryoglobulin complex showed that two components, albumin and a monoclonal IgG-lambda, were present, and both components were needed in a fixed ratio for precipitation. In addition, cryoprecipitation occurred in serum, but not plasma, due to citrate inhibition of complex formation. Our findings suggest that the monoclonal IgGs have the properties of antibodies directed specifically against a calcium-dependent antigenic site on human albumin, and that the resultant IgG-lambda-albumin immune complexes crystallized in the cold.

Adult↗
PubMed1981

Rickettsialpox: report of an outbreak and a contemporary review.

Rickettsialpox is a mild illness characterized by the appearance of a primary eschar at the site of a mite bite followed by fever, headache, and a papulovesicular rash. It can be confused with a variety of illnesses including several other rickettsial diseases and chickenpox. R. akari, the etiologic agent, is a rickettsia belonging to the spotted fever group (SFG) of rickettsial illnesses. In spite of significant serologic cross-reactivity with other SFG agents, there is no convincing evidence of cross-immunity to these agents after recovery from rickettsialpox. Tetracyclinie is the drug of choice in the treatment of this disease.

Adult↗
PubMed1981

Infections in hypothermic patients.

Of 59 adults admitted to Bellevue Hospital, New York, between 1968 and 1979 because of hypothermia due to exposure, 24 (41%) had 32 serious infections. Nine infections were not diagnosed at the time of admission. Infected patients warmed to higher peak temperatures were more likely to be comatose and had lower lymphocyte counts. At admission, physicians gave antibiotics to only one of nine patients with occult infection but to ten of 35 uninfected patients, thus failing to identify which patients required prompt antibiotic therapy. Delay in therapy contributed to the death of two patients. Since infection is frequently masked in hypothermic patients, careful repeated evaluations should be carried out to identify early infections. Although the proper use of antibiotics in patients with hypothermia is unresolved, we believe that prompt empiric antibiotic therapy is appropriate.

Adult↗
PubMedDate not supplied

Actinobacillus actinomycetemcomitans prosthetic valve endocarditis.

Actinobacillus actinomycetemcomitans, a fastidious gram-negative bacillus, has been reported as the cause of prosthetic valve endocarditis in 11 patients. Two additional patients are reported and the literature is reviewed. All cases occurred greater than 1 year after implantation of the prosthesis. Six of the 13 patients had had recent dental work or had poor dentition. Three patients had received endocarditis prophylaxis. Ten of 13 were cured with antibiotics alone. Only one patient suffered from congestive heart failure, and only one had documented evidence of major systemic emboli during antimicrobial therapy. Valve replacement was necessary in only two during antimicrobial therapy. A actinomycetemcomitans should be considered as a possible etiologic agent in late prosthetic valve endocarditis, particularly when blood cultures are initially negative. A regimen of a beta-lactam antibiotic in combination with an aminoglycoside is recommended for 4-6 weeks. The excellent in vitro activity of the third-generation cephalosporins and rifampin promise new therapeutic options.

Actinobacillus Infections↗