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Biomedical subjects

J Leslie

Publications and source records attributed to J Leslie.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy.

The effects of ascorbic acid on the excretion of homogentisic acid and its derivative benzoquinone acetic acid were studied in two adults and three infants. The administration of relatively large amounts of ascorbic acid to the adults was followed by a disappearance of benzoquinone acetic acid from the urine, whereas the level of excretion of homogentisic acid did not change. This could have relevance to the pathogenesis of ochronotic arthritis. In the 4-mo-old infant and the 5-mo-old infant ascorbic acid in the urine may have doubled the amount of homogentisic acid, presumably through an effect on the immature p-hydroxyphenylpyruvic acid oxidase. Dietary reduction of the intake of tyrosine and phenylalanine substantially reduced the excretion of homogentisic acid.

Aged↗
PubMed1988

Relationships between renal function and disposition of oral ciprofloxacin.

The relationships between creatinine clearance (CLCR) and the pharmacokinetics of oral ciprofloxacin were characterized. On the basis of these data, a dosage adjustment strategy, which incorporates the severity of infection and the size and renal function of the patient, was developed. An adaptive (feedback) control algorithm is proposed. A total of 32 subjects (8 normal, 8 anuric, and 16 with CLCR between 0.53 and 4.3 liters/h per 1.73 m2) were given a single 750-mg tablet of ciprofloxacin by mouth. Serial serum and urine samples were collected, assayed by high-pressure liquid chromatography, and comodeled. The population relationship between total apparent ciprofloxacin clearance (CL/f) and CLCR, both measured in liters per hour per 1.73 m2, was CL/f = 2.83 x CLCR + 21.8 (r = 0.69; P less than 0.001). The mean terminal half-life was not significantly related to CLCR but was much more variable in subjects with CLCR less than 3 liters/h per 1.73 m2 (F = 4.8; P less than 0.005). We conclude that patients with CLCR less than 1.2 liters/h per 1.73 m2 should receive two-thirds of the normal daily dose and that the dose interval should not be lengthened.

Administration, Oral↗
PubMed1986

Imipenem coadministered with cilastatin compared with moxalactam: integration of serum pharmacokinetics and microbiologic activity following single-dose administration to normal volunteers.

We administered 1 g of imipenem along with equal amounts of cilastatin (a dehydropeptidase I inhibitor) or 2 g of moxalactam intravenously over a period of 30 min to six volunteers in a crossover manner 1 week apart. The antibiotic concentrations and pharmacokinetics for each drug were determined and integrated with the microbiologic activity by measuring the duration of time that the free drug concentrations remained above the MICs for 90% of 581 clinical isolates and by measuring serum bactericidal activities against organisms which commonly infect granulocytopenic cancer patients. Moxalactam produced serum levels at 1 h after infusion of 99.9 micrograms/ml; these levels were four times greater than the plasma levels of imipenem (22.8 micrograms/ml). The trough (5.5-h) moxalactam serum levels were 10 times greater than those of imipenem (18.5 and 1.7 micrograms/ml, respectively). Essentially all of the imipenem was unbound to protein, whereas 36 to 42% of the moxalactam was unbound. Moxalactam produced free antibiotic concentrations that were above the MIC for 90% of the strains tested for more than 6 h against all of the species tested except Staphylococcus aureus (5.3 h), Enterobacter hafnia (1.6 h), and Pseudomonas aeruginosa (0 h). The imipenem concentrations were above the MIC for 90% of the strains tested for 5.6 h or more against all of the bacteria tested except Proteus spp. and Pseudomonas aeruginosa (4.5 h). The geometric mean peak bactericidal titers from volunteers receiving imipenem were more than 1:8 against all bacteria and were significantly higher than the titers from volunteers receiving moxalactam against S. aureus (1:7.3) and Pseudomonas aeruginosa (1:4.5). These data, in addition to information obtained from animal models, indicate that imipenem is a promising new candidate for carefully controlled clinical trials as a single agent for therapy of serious infections, including empiric therapy for fever in granulocytopenic cancer patients.

Adolescent↗
PubMed1986

Absolute oral bioavailability of ciprofloxacin.

We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion. Half-lives (mean +/- standard deviation) for the intravenous and oral administration arms were 4.2 +/- 0.77 and 4.11 +/- 0.74 h, respectively. The serum clearance rate averaged 28.5 +/- 4.7 liters/h per 1.73 m2 for the intravenous administration arm. The renal clearance rate accounted for approximately 60% of the corresponding serum clearance rate and was 16.9 +/- 3.0 liters/h per 1.73 m2 for the intravenous arm and 17.0 +/- 2.86 liters/h per 1.73 m2 for the oral administration arm. Absorption was rapid, with peak concentrations in serum occurring at 0.71 +/- 0.15 h. Bioavailability, defined as the ratio of the area under the curve from 0 h to infinity for the oral to the intravenous dose, was 69 +/- 7%. We conclude that ciprofloxacin is rapidly absorbed and reliably bioavailable in these healthy volunteers. Further studies with ciprofloxacin should be undertaken in target patient populations under actual clinical circumstances.

Adult↗
PubMed1985

Safety and tolerability of multiple doses of imipenem/cilastatin.

The safety and tolerability of 1 gm imipenem and cilastatin given together every 6 hours for 10 days was evaluated in a randomized, double-blind, placebo-controlled trial in normal subjects. Nausea was more common in the drug-treated group (five of six subjects) than in the control group (two of six subjects). No consistent changes in hepatic function indices were noted. Although beta 2-microglobulin excretion showed a significant trend of rising over time in the drug group, there were no differences between groups with regard to 24-hour urinary excretion of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin. Urinalysis did not reveal any casts and serial creatinine clearance determinations showed no change in renal function in either the drug- or placebo-treated groups. Pure tone audiograms were performed before and after dosing in 11 of 12 subjects; no changes were noted. We conclude that the combination of imipenem and cilastatin was well tolerated and safe.

Acetylglucosaminidase↗
PubMed1985

Forensic aspects of fraternity hazing.

Although the news media has occasionally reported deaths and injuries related to fraternity hazing in the past, little, if any, attention has been given to the subject in the medical literature. In light of the medicolegal implications surrounding many of these incidents, it is important that medical examiners be aware of the problem. One hundred sixty-eight (168) cases of injuries and deaths related to fraternity hazing activities occurring in the past 60 years in the United States have been collected from secondary sources. A descriptive statistical analysis of the data is presented.

Adolescent↗
PubMed1985

Pharmacokinetics of ceftazidime, alone or in combination with piperacillin or tobramycin, in the sera of cancer patients.

We administered 2 g of ceftazidime intravenously every 8 h to cancer patients for the empiric therapy of febrile episodes. Ceftazidime was administered as monotherapy for patients with granulocyte counts in excess of 1,000/microliter. Febrile, neutropenic patients were randomized to also receive either piperacillin or tobramycin. The pharmacokinetic profile of ceftazidime during a steady-state dosing interval was ascertained in 21 patients. No differences were seen between groups for any of the pharmacokinetic parameters examined. As expected, the observed half-life was longer, the serum clearance was smaller, and the volumes of distribution were larger than in previously reported studies of volunteers. Serum concentrations remained above the MIC for inhibition of 90% of strains of the most common bacteremic pathogens seen in our cancer center for the entire 8-h dosing interval.

Adolescent↗
PubMed1984

Characteristics and determinants of child nutritional status in Nepal.

Herein, we examine characteristics and determinants of child malnutrition in the districts of Bara and Rautahat of the Terai region of Nepal. The sample studied consists of 510 rural children ranging in age from 3 to 10 yr. The Nepali children were found to have one of the highest reported prevalences of stunting (65% were less than 90% National study for Health Statistics median height for age). The study children were also 1 to 1.5 kg lighter when compared to US children of the same height. Fat deposits, as measured by anthropometric variables and Hb levels were also very low. Multiple regression analysis showed that age, district of residence, household income, breast-feeding, and several specific food items were significant predictors of nutritional status. Association with other factors such as caste and parental schooling, were not evident in multiple regressions. Boys were as likely to be malnourished as girls. Prolonged breast-feeding was associated with greater fat stores, but with reduced stature and low Hb values. Both landholdings and household income were found to be positively and significantly associated with almost all measures of nutritional status.

Anthropometry↗
PubMed1984

Self-inflicted ocular injuries. A rare form of self-mutilation.

Two unusual patients with chronic, undifferentiated schizophrenia committed acts of ocular self-mutilation. The types of patients who perform acts of self-inflicted ocular injuries are described, with particular emphasis on individuals suffering from post-traumatic stress disorder (PTSD). A discussion of these cases, as well as a review of the literature on the more common forms of self-mutilation, is presented.

Adult↗
PubMed1984

Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers.

We compared ceftazidime with moxalactam, a commonly utilized, currently available drug. The microbiological activities of ceftazidime and moxalactam were studied. In addition, single-dose pharmacokinetics and serum bactericidal activity 1 and 6 h after a 2.0-g, 30-min infusion of each drug were determined in a crossover study in human volunteers. In vitro, both drugs had MICs for 90% of the isolates of less than 1.0 microgram/ml against the common members of the family Enterobacteriaceae and of 8.0 micrograms/ml against Staphylococcus aureus. Against Pseudomonas aeruginosa ceftazidime was more active than moxalactam, the respective MICs for 90% of the isolates being 8 and 128 micrograms/ml. Mean half-lives were 1.75 (+/- 0.21) h for ceftazidime and 2.5 (+/- 0.38) h for moxalactam. The serum bactericidal titers for both compounds against Escherichia coli and Klebsiella pneumoniae were high. Titers against S. aureus 6 h after infusion were negative. The mean (geometric) serum bactericidal titer of ceftazidime against 31 strains of P. aeruginosa (1:44) was higher than that of moxalactam (1:3.4).

Adolescent↗
PubMed1984

Multiple-dose pharmacokinetics of imipenem-cilastatin.

We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma concentrations of imipenem and cilastatin 1 h after the end of a 30-min infusion were 18.7 (+/- 2.1) and 19.1 (+/- 4.6), 20.0 (+/- 3.2) and 17.8 (+/- 4.8), and 23.4 (+/- 2.3) and 19.1 (+/- 3.5) micrograms/ml in the 1st, 17th, and 37th dosing intervals, respectively. The central compartment volumes of distribution for imipenem and cilastatin were 0.16 (+/- 0.05) and 0.14 (+/- 0.03) liter/kg, respectively. Elimination half-lives were short: 0.93 (+/- 0.09) h for imipenem and 0.84 (+/- 0.11) h for cilastatin. Plasma clearances were 12.1 (+/- 0.06) liters/h per 1.73 m2 for imipenem and 12.4 (+/- 1.1) liters/h per 1.73 m2 for cilastatin. Renal clearance accounted for 54% of the plasma clearance of imipenem and 69% of the plasma clearance of cilastatin. The concentrations of imipenem in plasma and urine remained above the MICs of the vast majority of pathogens throughout the dosing interval.

Adult↗
PubMed1983

The human fetal heart in the second trimester of gestation: a gross morphometric study of normal fetuses.

One hundred fifty-three midtrimester fetuses obtained from normal pregnancies terminated for nonmedical reasons were studied to establish normal standard measurements. Mean, standard deviation, range, and percentiles of body weight, foot length, crown-rump length, biparietal diameter, cardiac weight, thickness of ventricles, and ventricular septum were derived by computer analysis. Statistical analysis showed no sex difference. Equations for predicting body weight, cardiac weight, and septal thickness were derived with the use of fetal age and biparietal diameter as variables. The mean ratio of septal to left ventricular wall thickness was 1.14 +/- 0.34; a ratio of 1.3 or greater was found in 25% and a ratio of 1.5 or greater in 10% of this cohort. The results are at variance with the reported high incidence of septal hypertrophy seen in normal developing fetal hearts. We suggest that septal hypertrophy, ratio of 1.5 or greater, may reflect disturbances in fetal or placental circulation and warrants careful monitoring of the pregnancy.

Anthropometry↗