Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.     

Women physicians during residency years: workload, work satisfaction and self concept

Fifteen women pediatric residents, 15 non-medical women academicians similar in age and marital status and 15 women pediatricians at least 10 years past residency were surveyed. Subjects were asked to estimate the amount of time they devote to their professional work, domestic work and the degree to which they feel overworked. Subjects were also questioned regarding their perceptions of the advantages and disadvantages of their life-style and their self-concept as a women and as a professional. The results of this study show that residents, who work significantly more hours per week, have a significantly lower level of work satisfaction than do women in the other two groups. It also suggests the fact that the stress of the residency years affects not only the residents' work satisfaction but their entire self-concept as well. The paper offers possible suggestions the medical profession can take in order to help physicians better cope with their professional stress.     

Variant colony surface antigenic phenotypes within mycoplasma strain populations: implications for species identification and strain standardization.

Immunobinding assays with mycoplasma colonies on agar plates (immunofluorescence and immunoperoxidase techniques) or with imprints of colonies transferred to solid supports (colony immunoblotting) are widely used as standard diagnostic tests for serological species identification of mycoplasma isolates. However, in light of the high rate of variability of surface antigens in many mycoplasmas, diagnostic data obtained with these techniques require a more critical evaluation. In this report, we demonstrate with some examples that mycoplasma surface variability based on alterations in expression, in size, and in surface presentation of integral and peripheral membrane proteins may lead to misinterpretation of colony immunostaining reactions obtained by using specific monoclonal antibodies as well as conventional diagnostic hyperimmune sera. To more easily identify phenotypically mixed isolates or samples which contain more than one species, we have introduced some minor modifications of the colony immunoblot technique which provide sharp signals of positive as well as negative reactions and enable identification of cryptic epitopes. It is further demonstrated that because of the variability in colony surface antigenic phenotype, mycoplasma strains, including well-established reference and other prototype strains which are used under the same designation in many laboratories, can differ markedly in their antigen profiles and their potentially virulence-related surface properties, since they are usually purified by filter cloning and often propagated by subcultivation of randomly selected agar-grown subpopulations. We conclude from this study that because of this surface variability, the establishment of criteria for standardization of mycoplasma strains and diagnostic antisera is urgently required in order to obtain reproducible results in different laboratories.     

Failure of rat placenta to inhibit prolactin secretion by ectopic pituitary gland

At mid-pregnancy in the rat, episodic secretion of pituitary prolactin ceases when the placenta is sufficiently developed. At this time, sufficient placental lactogen is secreted by the placenta to inhibit prolactin secretion. The present study tested whether the fully developed placenta at mid-pregnancy can inhibit prolactin secreted by a donor pituitary gland implanted under the kidney capsule. Three pituitary glands were implanted in rats on day 7 of pregnancy; muscle fragments were implanted in controls. Blood was collected during the first and second halves of pregnancy. It was found that prolactin concentrations in the animals with the pituitary implants were high on days 9 and 10 of pregnancy and remained raised during the second half of pregnancy while in control animals nocturnal surges were absent in the second half of pregnancy, the last one occurring on day 10. This observation indicates that the placental hormone cannot act directly on the pituitary gland to inhibit prolactin secretion, but presumably exerts its suppressive effect on prolactin secretion through the hypothalamus.     

Distinction of species and strains of mycoplasmas (mollicutes) by genomic DNA fingerprints with an rRNA gene probe.

Genomic fingerprints of Acholeplasma laidlawii, Mycoplasma hominis, and Mycoplasma pneumoniae strains were obtained by Southern blot hybridization of the digested mycoplasmal DNAs with an rRNA gene probe. The hybridization patterns revealed genotypic heterogeneity among A. laidlawii and M. hominis strains and a remarkable degree of homogeneity among M. pneumoniae strains isolated from pneumonia patients during a 10-year period. Genomic fingerprints with the rRNA gene probe can thus serve as indicators of intraspecies genetic homogeneity or heterogeneity and can provide a new, sensitive tool for strain identification with a potential for application in epidemiology.     

Moxalactam in the treatment of pediatric infections

The clinical efficacy and safety of the new oxacephalosporin moxalactam disodium were evaluated in 54 children with a variety of pediatric infections. Except for a terminally ill neutropenic leukemic patient with pneumonia and sepsis due to Pseudomonas aeruginosa who died shortly after initiation of therapy, moxalactam treatment was effective in all patients. No recurrent infections were observed. The rate of clinical response to moxalactam appeared to be at least comparable to that of patients treated with traditional antibiotics. In vitro sensitivity testing demonstrated that all bacteria isolated except P aeruginosa were sensitive to moxalactam while Haemophilus influenzae was exquisitely sensitive. Side effects included thrombocytosis (five patients), transient SGPT elevations and eosinophilia (three each), fever with rash (one), and neutropenia (one). In one patient, superinfection with Streptococcus faecalis developed. We conclude that moxalactam may be a useful antibiotic in pediatrics, particularly for the treatment of infections due to H. influenzae and Enterobacteriaceae. Its role in infections caused by group B streptococcus and Pseudomonas awaits further studies.     

Measurements of optic disk size with HRT II, Stratus OCT, and funduscopy are not interchangeable

PURPOSE: To assess the interchangeability of optic disk size measurements using slit-lamp funduscopy, optical coherence tomography (OCT-3), and confocal scanning laser ophthalmoscopy (HRT-II) in clinical practice. DESIGN: Prospective nonrandomized clinical study. METHODS: Measurements of vertical disk diameter (VDD) were obtained with the three methods. Disk area was obtained from OCT and HRT printouts. True agreement between methods in measuring VDD was assessed using Bland-Altman graphs and 95% limits of agreement (LoA). Disks were classified as small, average, or large, and agreement between methods in this classification was assessed using kappa statistics. RESULTS: Forty-eight patients were enrolled (mean age 53.4 +/- 14.3 years). VDD (mean +/- SD) was 1.58 +/- 0.15, 1.70 +/- 0.22, and 1.90 +/- 0.24 mm with funduscopy, HRT, and OCT, respectively. Very large LoA were observed: -0.29 to 0.70 mm for OCT and HRT, -0.07 to 0.71 mm for OCT and funduscopy, and -0.29 to 0.53 mm for HRT and funduscopy. There was poor agreement (kappa < 0.4) in classification of disk size as small, average, or large whether disk diameter or area was compared and using two definitions of disk size. CONCLUSIONS: We observed a large range of differences in estimating disk size with HRT, OCT, and funduscopy. This precludes interchangeable use of these measurements in clinical practice, and does not allow simple conversion formulas to be proposed. In addition, there is poor agreement between these methods in classifying disk size as small, average, or large. At present, estimation of both absolute and relative disk size can only be defined separately for each measurement modality.     

Central corneal thickness measurement with the Pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry

PURPOSE: To assess the intraoperator repeatability and interoperator reproducibility of central corneal thickness measurements by the Pentacam Scheimpflug imaging system (Oculus) and the optical low-coherence reflectometer (OLCR) pachymeter (Haag-Streit) and to compare them with those of ultrasound (US) pachymetry. SETTING: Assaf Harofe Medical Center Ophthalmology Outpatient Clinic, Zerifin, Israel. METHODS: Repeatability was determined from 10 successive measurements in each of 4 healthy patients. Reproducibility for the Pentacam Scheimpflug system was determined from measurements by 2 operators in each of 24 patients; in these 24 patients, central corneal thickness measurements were compared between the Pentacam and US pachymetry. For the OLCR pachymeter, reproducibility was determined from measurements by 2 operators in each of 16 patients, in whom central corneal thickness was also measured with the Pentacam. RESULTS: Mean coefficient of repeatability was 0.84% for the Pentacam Scheimpflug system and 0.33% for the OLCR pachymeter. For the Pentacam, the coefficient of interoperator reproducibility was 1.10% and the 95% limits of agreement were -10.2 microm to +11.9 microm. Mean difference between Pentacam and US was 6.09 microm. For the OLCR pachymeter, the coefficient of interoperator reproducibility was 0.59% and the 95% limits of agreement were -5.4 microm to +7.0 microm. Mean difference between central corneal thickness values obtained with the OLCR pachymeter and Pentacam Scheimpflug system was 1.7 microm. CONCLUSIONS: Objective, noncontact measurement of central corneal thickness with the Pentacam Scheimpflug system and OLCR pachymeter was convenient and yielded excellent intraoperator repeatability and interoperator reproducibility. Central corneal thickness values obtained with the Pentacam were similar to those obtained with both the OLCR pachymeter and an US pachymeter. Further research is needed to corroborate whether central corneal thickness measurements by the Pentacam and OLCR devices can be used interchangeably and are more clinically useful than US pachymetry.