Gentamicin dosage in children with extensive burns

During the treatment of Gram-negative bacillary infections in severely burned children, it was noted that administration of standard dosages of gentamicin commonly produced inadequately low serum concentrations of the antibiotic. Pharmakokinetic studies demonstrated that mean peak serum gentamicin levels were significantly lower in 18 burned children as compared with peak serum levels in five unburned children. Furthermore, inadequately low peak serum levels (less than 3.0 mug/ml) were observed in 15 of 18 burned children and in only one unburned child. Clearance studies in two children suggested that the increased requirement for gentamicin can result from either loss of the antibiotic across burn wounds or increased urinary excretion. These studies indicate that the therapy of severe infections in children with major burns often requires administration of gentamicin at higher doses and more frequent intervals than usually employed.     

Gentamicin therapy in preterms: a comparison of two dosage regimens

OBJECTIVE: To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates. DESIGN: Randomized double blind study. SETTING: Tertiary level Neonatal Intensive Care Unit. SUBJECTS: Eighteen preterms admitted during the period January 1994 to May 1994. METHODS: The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required. MAIN OUTCOME MEASURES: Initial peak levels and steady state trough and peak levels in both groups. RESULTS: Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity. CONCLUSION: Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage.     

Influence of dosage form on the gastroenteropathy of flurbiprofen in the rat: evidence of shift in the toxicity site

PURPOSE: Gastroduodenal and intestinal permeability were compared after single doses of sustained release and regular release flurbiprofen in the rat to assess possible site-specific formulation-dependent toxicity. METHODS: Pharmacokinetics was assessed and gastrointestinal permeability was evaluated using sucrose and 51Cr-EDTA as gastroduodenal and intestinal permeability probes, respectively. RESULTS: The two formulations demonstrated equal areas under the flurbiprofen concentration-time curve. The sustained release formulation peaked 2-3 h slower with 57-74% lower concentrations than regular release formulation. In comparison, the regular release powder induced greater gastroduodenal permeability while sustained release granules induced greater intestinal permeability. When S-flurbiprofen concentrations were plotted versus intestinal permeability, a linear relationship and an anti-clockwise hysteresis were obtained for regular and sustained release formulations, respectively. CONCLUSIONS: Sustained release formulations of flurbiprofen demonstrate reduced gastroduodenal permeability but shift the site of this side-effect to the more distal intestine.     

Fresh Freud: No longer lost in translation.

The new translations of Freud into English highlight the question as to the nature of Freud's quest and achievement. They show a livelier Freud than the Strachey translations (Freud, 1953-1974), who used everyday language in his work instead of trying to establish a new technical vocabulary for an esoteric new discipline. However, with the new Penguin editions thus far, fresh Freud is no longer lost in translation. The Standard Edition was created importantly to create an authoritative international trademark and was made more natural "scientific" in appearance. The fresh translations show a Freud in tune with Karl Popper's (1976) approach in his later work that viewed science as essentially problem solving. The example of "Mourning and Melancholia" (Freud, 1917/ 1964, 1917/1981, 1917/2005) is discussed as an exercise in exploration, conjectures, criticism, construct formation, and problem solving. Translation issues are discussed. Instead of being a particular trade mark, the very fact of there being new and different translations opens Freud's works to further questioning about their meanings and intents in the marketplace of ideas and practices. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sudden swimming deaths: No longer hopelessness in rats?

Reiterates C. W. Hughes and J. J. Lynch's (see record 1979-12747-001) position that the psychological state of nonverbal animals cannot be assessed, in response to comments by Y. Binik and M. E. Seligman (1979) on Hughes and Lynch's review of studies of sudden swimming death as a measure of learned helplessness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parenting and survival in anthropoid primates: caretakers live longer

Most anthropoid primates are slow to develop, their offspring are mostly single births, and the interbirth intervals are long. To maintain a stable population, parents must live long enough to sustain the serial production of a sufficient number of young to replace themselves while allowing for the death of offspring before they can reproduce. However, in many species there is a large differential between the sexes in the care provided to offspring. Therefore, we hypothesize that in slowly developing species with single births, the sex that bears the greater burden in the care of offspring will tend to survive longer. Males are incapable of gestating infants and lactating, but in several species fathers carry their offspring for long periods. We predict that females tend to live longer than males in the species where the mother does most or all of the care of offspring, that there is no difference in survival between the sexes in species in which both parents participate about equally in infant care, and that in the species where the father does a greater amount of care than the mother, males tend to live longer. The hypothesis is supported by survival data for males and females in anthropoid primate species.     

Isotretinoin: which dosage?

Milia are small subepidermal keratin cysts. They may arise either spontaneously or in the course of bullous diseases or trauma. We describe an unusual case of multiple eruptive milia on the posterior neck and back and review the classification of milia.     

Confusion of confidence intervals and credibility intervals in meta-analysis.

A review of 30 meta-analyses that have been conducted in organizational behavior and human resource management using procedures described by J. E. Hunter et al (1982) suggests that there is confusion regarding the use and interpretation of confidence intervals and credibility intervals. This confusion can lead to conflicting conclusions about the relationships between variables. The most frequent mistake has been the attempt to address the accuracy of the estimate of the mean effect size using "confidence intervals" based on the corrected standard deviation instead of on the standard error of the mean r or d. The corrected standard deviation should be used to generate a "credibility interval" to assess the extent to which moderators might account for the unexplained variance in effect sizes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gentamicin intravenous infusion rate: effect on interstitial fluid concentration

To assess the possible role of intravenous (i.v.) infusion rate as a determinant of degree and rate of interstitial fluid penetration, six rabbits, each with four intraperitoneal implanted capsules, were studied by crossover design after a single dose of 1.7 mg of gentamicin per kg by either slow 2.5-min i.v. bolus or 30 min i.v. infusion. The mean serum peak antibiotic level after slow bolus was 17.4 mug/ml. After 30 min of infusion, mean serum peak was 8.3 mug/ml (P < 0.025). Mean capsule fluid antibiotic levels at 30 min, 1, and 2 h were 0.9 mug/ml, 1.6 mug/ml, and 1.8 mug/ml, respectively, after slow bolus and 0.6 mug/ml, 0.9 mug/ml, and 1.3 mug/ml after 30-min infusion (P < 0.05 at 30 min, P < 0.001 at 1 h, and P < 0.05 at 2 h). Comparison of capsule levels beyond 2 h revealed no significant differences, and peak capsular concentrations achieved by the two methods were similar. Slow 2.5-min i.v. bolus administration of gentamicin established higher interstitial fluid levels during the first 2 h of therapy and may be the preferred mode of delivery when rapid extravascular penetration is desired.     

Sex chromosomes: evolving dosage compensation

Dosage compensation of some X-linked genes varies among mammals. Inactivation of an X-linked copy of a gene in females appears to correlate with lack of an active homologue on the Y chromosome, implying that dosage compensation evolves in response to the loss of function of genes on the Y.     

Gentamicin and tobramycin pharmacokinetics in pediatric bone marrow transplant patients

OBJECTIVE: To describe the pharmacokinetic parameters of gentamicin and tobramycin in pediatric bone marrow transplant patients. DESIGN: Retrospective medical record review. SETTING: Pediatric bone marrow transplant unit in a university teaching hospital. MAIN OUTCOME MEASURES: Pharmacokinetic parameters (apparent volume of distribution [Vd] in L/kg, half-life [t1/2] in h, elimination rate constant [ke] in h-1, clearance [Cl] in mL/min/1.73 m2 and mL/min/kg) calculated from serum concentrations. PATIENTS: Thirty-three patients aged 15 years or less who underwent bone marrow transplant and received gentamicin or tobramycin. RESULTS: Mean pharmacokinetic parameters were Vd 0.32 +/- 0.07 L/kg, t1/2 2.32 +/- 0.65 h, Cl 1.71 +/- 0.53 mL/min/kg, and Cl 86.2 +/- 24.5 mL/min/1.73 m2. Factors such as disease state, type of marrow graft, gender, or exposure to cyclosporine had no significant effect on pharmacokinetic parameters. Linear regression indicated a weak relationship between serum creatinine (SCr) and Cl in mL/min/kg (r = 0.59), but no relationship was found between SCr and Cl in mL/min/1.73 m2, between age and apparent Vd, or between SCr and apparent Vd. Models for estimating Cl and Ke developed by multiple regression were somewhat predictive (r = 0.7). Required calculated maintenance dosages to obtain therapeutic concentrations were 8, 7, and 6 mg/kg/d in children 6 or younger, 7-12, and 13-15 years, respectively. CONCLUSIONS: The mean Cl and apparent Vd for all ages are similar to those reported in pediatric oncology patients who had not undergone marrow transplantation. Children 6 years or younger had lower than expected Cls and larger apparent Vds than did the older children. Dosages estimated to be necessary to achieve therapeutic concentrations were 6-8 mg/kg/d.