Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease.

Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by high-performance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. The total body clearance (3.79 +/- 0.71 versus 3.94 +/- 1.05 ml/min), the steady-state volume of distribution (0.19 +/- 0.04 versus 0.18 +/- 0.03 liter/kg), and the terminal elimination half-life (47.91 +/- 7.20 versus 45.08 +/- 10.34 h) were not significantly altered in the presence of piperacillin. In contrast, the terminal elimination half-life (47.68 +/- 20.58 versus 35.67 +/- 11.18 h) of gentamicin was significantly reduced when gentamicin was given with piperacillin. The total body clearance (4.26 +/- 3.07 versus 4.89 +/- 1.94 ml/min) and the steady-state volume of distribution (0.19 +/- 0.04 versus 0.20 +/- 0.04 liter/kg) of gentamicin were not significantly altered during combination therapy; however, the nonrenal clearance of gentamicin administered in combination with piperacillin (3.56 +/- 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 +/- 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients.

Quantitative analysis of the active tablet ingredient by powder X-ray diffractometry.

A powder X-ray diffraction technique has been developed for the quantitative analysis of the active ingredient in intact tablets. Two model drugs were used: lithium carbonate (LC) and carbamazepine (CBZ). Mixtures containing various weight fractions of each drug and microcrystalline cellulose were compressed into tablets and the integrated intensities of several diffraction lines of each were used for quantitative purposes. The ratio of the integrated intensity of these lines in tablets, made from mixtures of drug and microcrystalline cellulose, to the intensity of the same lines in tablets made from only drug was calculated as a function of the weight fraction of the drug in the mixture. These ratios were also experimentally determined and the relative error in the determination of LC was less than 12%. CBZ tablets containing starch were also prepared. In the CBZ tablets containing microcrystalline cellulose or starch, the relative error in the determination of CBZ was less than 10% only when the weight fraction of CBZ in the tablets was greater than or equal to 0.4.

Infant size at 8 months of age: relationship to maternal use of alcohol, nicotine, and caffeine during pregnancy.

To examine the relationship of maternal alcohol consumption, caffeine use, and smoking to infant size at 8 months of age, a follow-up cohort of 453 infants was examined at birth and again at their 8-month birthday. Even after adjustment for other relevant variables, maternal alcohol use during early pregnancy (average ounces of absolute alcohol by self-report) was significantly related to infant weight and length at 8 months of age but not as strongly related to head circumference. Maternal smoking and caffeine use during pregnancy were not significantly related to infant size at 8 months, although nicotine use had been highly related to the birth size in this sample. Maternal use of marijuana was significantly and negatively related to infant length at 8 months of age, but not to weight or head circumference. The magnitude of the growth retardation is smaller at 8 months than at birth in this sample of infants whose mothers are primarily white, married, and well-educated, and who report a variety of alcohol use patterns. Significance was tested using multiple regression analyses that adjusted for the effects of nicotine use, caffeine use, birth order, maternal height, and gestational age as well as sex and age of infant at examination.

Decreased birth weight in infants of alcoholic women who abstained during pregnancy.

Fifty infants born to women who reported total abstinence during pregnancy, but who had a history of alcoholism prior to conception, were compared to 50 infants born to alcoholic women who reported drinking heavily during pregnancy, and to 50 infants of nonalcoholic controls. Mean birth weight of infants born to the abstinent alcoholics was 258 gm less than mean birth weight of the control infants. Infants of drinking alcoholics weighed 493 gm less than the control infants. These differences in offspring birth weight were statistically significant after adjusting for maternal smoking, height, age, and parity, as well as gestational age and sex of child. This finding suggests that a history of maternal alcoholism may pose a risk to fetal growth independent of alcohol use during the pregnancy.

Vigilance paradigm for preschool children used to relate vigilance behavior to IQ and prenatal exposure to alcohol.

A methodology for investigating vigilance behavior in preschool children was developed. The administration of the task was adapted to young children and a scoring system was devised to adjust for the higher level of random responding found in this sample of preschoolers. 28 3- and 4-yr.-olds were given the Stanford-Biner Intelligence Test and a 12-min. vigilance task. The children, drawn from a sample used in a larger study, were the offspring of three groups of mothers: recovered alcoholics who drank during pregnancy, recovered alcoholics who did not drink during pregnancy, and nonalcoholics who drank litt or nothing during pregnancy. A significant correlation was found between the number of correct responses on the vigilance task and IQ (r26 = . 53, p less than .01). The conclusions that can be drawn regarding the relationship of vigilance to maternal alcohol use (chi 2 = 4.82, p less than .09) are limited by small sample size.

Effects of maternal alcohol, nicotine, and caffeine use during pregnancy on infant mental and motor development at eight months.

Infant mental and motor development at 8 mo of age is significantly related to maternal alcohol use during early pregnancy. Data on 462 infants were analyzed with multiple regression techniques, adjusting for effects of nicotine, caffeine, gestational age, parity, and maternal education. Other possible intervening variables were evaluated and not found to explain the results. This study presents further evidence that maternal alcohol use during pregnancy at levels of about four drinks per day and above has an adverse effect on offspring, even in a sample that is basically low risk.

Stability of intelligence in the fetal alcohol syndrome: a preliminary report.

A clinical sample of 17 patients with fetal alcohol syndrome was given follow-up IQ testing 1-4 yr after an initial evaluation. Although 77% of the patients had a retest IQ that was within 1 SD of their initial IQ, some individual children did manifest considerable change in scores on retest. Repeated psychologic evaluation at regular intervals is recommended for children with fetal alcohol syndrome so that appropriate educational programming can be maintained in order to promote maximum development in each child.

Intelligence, behavior, and dysmorphogenesis in the fetal alcohol syndrome: a report on 20 patients.

In a sample of 20 patients with the fetal alcohol syndrome, ages 9 months to 21 years, the average IQ was 65, with a range of 16 to 105; 60% of the patients had IQ's more than two standard deviations below the mean. The sample included patients who ranged in severity of dysmorphogenesis from mild to severe. The severity of the dysmorphic features was related to degree of mental deficiency; children with the most severe manifestations of FAS had an average IQ of 55, whereas children with lesser manifestations had an average IQ of 82. All children were growth deficient for height and/or head circumference, but in this study only height was significantly correlated with IQ. Environmental and behavioral characteristics of the sample are discussed, and two adults with the fetal alcohol syndrome are presented.