Evaluation of a Bayesian method of amikacin dosing in intensive care unit patients with normal or impaired renal function

Our study was designed to determine the population pharmacokinetic parameters of amikacin in intensive care unit patients and to develop a Bayesian method allowing individual estimation of pharmacokinetic parameters. A two-stage method was used for estimating the population characteristics of the pharmacokinetic parameters. Calculations of optimum doses and dosing intervals were based on individual parameters. Our results indicate that the Bayesian method is capable of estimating the individual pharmacokinetic parameters with no significant bias and good precision. Individualization of amikacin dosage was assessed 70 times in 52 patients. To determine the predictive performance of the method, observed peak and trough levels were compared with predicted values by computing precision, bias, and correlation. The amikacin dosing method was unbiased and showed a high correlation coefficient (r = 0.962) between measured and predicted drug serum concentrations. No significant differences were found between the predicted and observed peak (17.3 +/- 3.5 and 17.3 +/- 3.8 micrograms/ml, respectively) and trough (2.86 +/- 0.93 and 3.08 +/- 1.41 micrograms/ml, respectively) amikacin serum concentrations. Among the 52 patients, wide variations were observed in the pharmacokinetic parameters (Vd = 0.21-0.50 L/kg; t 1/2 = 1.1-22 h) and the daily doses (2.8-42 mg/kg/day).     

The influence of diet and dimethylhydrazine on the large intestine of vervet monkeys: scanning and transmission electron microscope studies

The study was designed to identify diet and carcinogen-dependent ultrastructural changes in the epithelium of macroscopically normal colonic mucosa in primates. Seventy adult female vervet monkeys were divided into seven equal treatment groups. Four received a Western high-fat low fibre diet (WD), two a prudent low-fat higher fibre diet (PD) and one a control low-fat high fibre diet (CD). Three groups (2 WD, 1 PD) received dimethylhydrazine intramuscularly at 14 day intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD (WD----PD) and 30 months later all were killed. Mucosae of caecum, colon transversum and rectum were examined by scanning and transmission electron microscopy and showed close similarity to that of humans. Rectal mucosae showed increased surface goblet cell secretory activity, mucin production and microvillar changes related to WD and WD----PD. The enhancing effect of a carcinogen on ultrastructural changes such as cellular pleomorphism, cytoplasmic interbridging, nuclear and nucleolar irregularities and appearance of argentaffin cells in the free surface epithelium were noted predominantly in high-fat treated animals. Such changes observed in the upper part of crypt, orifice and free surface epithelium can be characteristic for precancerous change and could be utilised practically in the detection of precursor lesions of the colon.     

Non-invasive detection of coronary artery disease by dobutamine-stress echocardiography in children after heart transplantation.

BACKGROUND: Coronary vasculopathy is the main cause of cardiac graft failure. Because yearly coronary angiography is invasive in children, a non-invasive method for detecting graft vasculopathy is needed. The aim of this study was to test dobutamine-stress echocardiography in a pediatric population to determine its feasibility, safety and reliability in the detection of graft coronary artery disease. METHODS: Eighteen patients, aged 2 days to 16.8 years at transplantation (mean 8.4 years), underwent 44 dobutamine-stress echocardiography (DSE) exams, at a follow-up of 1.1 to 11.8 years (mean 5.1 years). Selective coronary angiography was performed for comparison. Echocardiographic recordings were obtained in 4 standard views of the left ventricle and measurements carried out within the frames of a 16-segment model. Segmental scores of contractility were obtained for each segment and a total segmental contractility index was calculated at each stage. RESULTS: All patients reached the maximum dose stage. Maximum heart rate was 57% to 90% of predicted maximum. Maximum systolic blood pressure reached 190 mmHg. Segmental scores were normal in 37 and abnormal in 7 cases. Echographic results were concordant with angiography in 82% and discordant in 18% of the cases (4 negative DSEs with minor angiographic lesions, 2 positive DSEs with normal angiography), but there was no significant angiographic lesion with normal DSE. CONCLUSIONS: DSE is a safe and highly feasible non-invasive technique in transplanted children. A normal DSE study successfully predicts the absence of significant coronary artery disease in the post-transplant population.