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Biomedical subjects

R E Keeney

Publications and source records attributed to R E Keeney.

11 recordsLinked to original sources
PubMed1979

Acyclovir kinetics after intravenous infusion.

The disposition and safety of the antiviral drug acyclovir were studied in 14 subjects with advanced malignancies. Acyclovir was administered by a 1-hr intravenous infusion at doses of 0.5, 1.0, 2.5, and 5.0 mg/kg. At the end of infusion, mean peak plasma levels (+/- SEM), determined by radioimmunoassay, were 6.4 +/- 0.7, 12.1 +/- 2.3, 14.9 +/- 2.7, and 33.7 +/- 7.1 microM. The plasma concentration-time profiles could be described by a biexponential equation. The half-life of acyclovir in the slow disposition phase ranged from 2.2 to 5 hr and the drug was detected in the plasma for at least 18 hr after infusion. The total body clearance ranged from 117 to 396 ml/min/1.73 m2. A proportionality between area under the curve and dose suggests that acyclovir exhibits dose-independent kinetics in the dose range studied. There was wide variation in cumulative urinary excretion of unchanged drug, ranging from 30 to 69% of the dose. From renal clearances of acyclovir, which were higher than creatinine clearances, it appears that both glomerular filtration and tubular secretion contribute to its renal excretion. Analysis of the urine by reverse-phase high-performance liquid chromatography revealed the presence of the metabolite 9-carboxymethoxymethylguanine. There was no indication of toxicity either clinically or from laboratory findings in any of the study subjects. This study demonstrates that in addition to selectivity and low toxicity, the kinetic profile and metabolic disposition of acyclovir make it an attractive candidate for therapy in a variety of herpes infections.

Aged↗
PubMed1979

The comparative efficacy of minocycline and penicillin-V in Staphylococcus aureus skin and soft tissue infections.

The antistaphylococcal properties of orally administered minocycline and penicillin-V were compared for one hundred and fifteen patients receiving minocycline and one hundred and twenty-eight receiving penicillin-V for various types of cutaneous infections. The majority of bacterial isolates were staphylococcal organisms. Of these 82 percent showed initial in vitro sensitivity to minocycline while only 20 percent did to penicillin-V. The percentage of clinical cures was higher with minocycline (74 percent) than with penicillin-V (54 percent), however, most patients, in both groups, showed clinical improvement. The rate of clinical improvement appeared to be significantly faster with minocycline. There was a higher percentage of adverse, chiefly vestibular, effects in the minocycline group (16 percent vs 7 percent). The study clearly demonstrates the superior antistaphylococcal properties of minocycline as compared with penicillin-V.

Adolescent↗
PubMed1977

Cellular immune responses to herpesviruses during treatment with adenine arabinoside.

Thirteen patients severely infected with herpesvirus were treated with intravenous adenine arabinoside (ara-A), and two patients received placebo therapy. Blastogenic and cytotoxic responses specific for the virus infecting each patient were determined before, during, and after treatment. Blastogenic responses to three mitogens (phytohemagglutinin, pokeweed, and concanavalin-A) were examined, as were titers of viral antibody. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared with values before treatment. Newborn infants, presumably infected at or shortly before birth, did not demonstrate cellular immune reactivity to the infecting virus until after four days of life. In this series of patients, prognosis appeared to be in part determined by the cellular immune competence of the host at the time of infection.

Adolescent↗
PubMed1975

Effects of adenine arabinoside on cellular immune mechanisms in humans.

In vitro lymphocyte blastogenic responses to the commonly employed mitogens, phytohemagglutinin, pokeweed, and concanavalin A, were evaluated when adenine arabinoside (ara-A) in a concentration of 3 mug/ml was added to the culture materials. Similarly, blastogenic and cytotoxic responses to cell cultures persistently infected with herpes simplex virus 1, herpes simplex virus 2, and varicella-zoster virus were determined in the presence of ara-A. No depression of these cellular immune responses by ara-A was demonstrated. This was in contrast to the effect of cytosine arabinoside, which at a concentration of 3 mug/ml severely inhibited these immune responses. Further studies examined lymphocyte blastogenic responses to the mitogens and blastogenic and cytotoxic responses specific for the herpes group virus infecting patients who were subsequently treated with ara-A; determinations were made before, during, and after treatment. In vitro responses during and after treatment with ara-A were unchanged or often enhanced as compared to pretreatment values. Therefore, the antiviral chemotherapeutic agent, ara-A, does not appear to depress the host's cellular immune responses, which are vital to successful elimination of invading herpes group viruses.

Humans↗
PubMed1975

Clindamycin treatment of osteomyelitis and septic arthritis in children.

Forty-eight children, 1 month to 14 years of age, including 11 patients with untreated acute osteomyelitis, 8 with pretreated acute osteomyelitis, 12 with septic arthritis, and 11 with cellulitis or soft tissue abscess, were treated with clindamycin. Staphylococcus aureus was isolated from the blood, synovial fluid, bone, or soft tissues of 27 of these individuals while group A, beta-hemolytic streptococci or Clostridia were isolated from 9 patients. Clindamycin was provided intravenously until patients were afebrile for three days followed by orally administered clindamycin for one week in patients with cellulitis to as long as six months in patients with chronic osteomyelitis. Clinical and bacteriologic responses to treatment generally were excellent, most likely reflecting the excellent serum and tissue concentrations of clindamycin which were achieved. Serum concentrations of clindamycin following intravenous infusion at 20 to 30 mg/kg/day in three divided doses were 8- to 32-fold in excess of the minimal inhibitory concentrations of all organisms isolated in this study. Bone and synovial fluid concentrations of clindamycin were 60% to 85% of the serum concentrations measured concomitantly. Clindamycin provides an effective alternative treatment of osteomyelitis and septic arthritis in children who are sensitive to penicillin.

Abscess↗