Biomedical subjects
Publications and source records attributed to R E Thieme.
We describe a biopsy-confirmed case of acute interstitial nephritis associated with the use of loracarbef in an 18-month-old boy, which resulted in end-stage renal failure. This complication has been documented with the use of beta-lactam antibiotics, and it seems likely the loracarbef was responsible for acute interstitial nephritis in this patient.
An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P < .05). Concomitant exposure to 0.125 mM HWA-448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P < .05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.
In our hospital pharmacy an injectable solution of haloperidol decanoate 141 mg/ml (equivalent to haloperidol 100 mg/ml) in sesame oil was prepared. The aim of this study was to prove bioequivalence of this formulation with the reference product, Haldol Decanoas. 15 schizophrenic patients, already stabilized with Haldol Decanoas, were enrolled. Intramuscular injections were given every three weeks in the following doses: 100 mg (1 x), 200 mg (7 x) and 300 mg (7 x). In this open, randomized, cross-over study all patients received four injections of the reference product, and four injections of the test product. Only after the fourth injection of each product (when steady-state levels were reached) a concentration-time profile of haloperidol was established during the dose interval of 21 days. The pharmacokinetic parameters AUC0-21 and Cmax were statistically evaluated. Based on these parameters the conclusion was drawn that both products were bioequivalent. The preparation of this injectable haloperidol decanoate solution in our hospital pharmacy amounts to an annual saving of approximately $39,000.
Predicting immediate neonatal morbidity after perinatal asphyxia has been difficult. A review of asphyxiated neonates greater than or equal to 36 weeks' gestation admitted to The Children's Hospital Newborn Intensive Care Unit in 1983 was conducted to devise a scoring system that would rapidly predict organ dysfunction observed in the immediate neonatal period. Comparison of potential score components to morbidity by multiple regression analysis yielded significant association with abnormalities in fetal heart rate monitoring, the 5-minute Apgar score, and neonatal base deficit. A scoring system was devised whose sensitivity (93.8%) and specificity (81.3%) were more predictive than any of its individual components. Prospective analysis in a similar population in 1984 validated its ability to distinguish severe from moderate morbidity after asphyxia. Positive predictive value for the score in the combined study groups (n = 98) was 79% and the negative predictive value was 83%. The scoring system may offer a rapid and accurate prediction of organ dysfunction in the immediate neonatal period after asphyxia.
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The effects of anesthetics on intracranial pressure (ICP) may be different in preterm neonates than in adults because the neonate's cranial sutures are not yet fused. The authors monitored changes in anterior fontanel pressure (AFP), a noninvasive indicator of ICP, during anesthesia in 44 preterm neonates without neurologic disease. Atropine, 0.02 mg/kg, and pancuronium, 0.1 mg/kg, were given intravenously to all patients, who were ventilated with oxygen and air. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic blood pressure (SAP) and mean blood pressure (MAP) were recorded at 1-min intervals. After a 5-min control period of stable AFP, each of the four groups of 11 patients then received either 0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine. Anterior fontanel pressure decreased 11% during isoflurane administration, 9% during halothane administration, 10% after fentanyl, and 10% after ketamine. These changes were statistically significant, but clinically mild, and AFP remained within the normal range. Statistically significant decreases in SAP and MAP occurred during isoflurane and halothane administration, but not after fentanyl or ketamine. The authors conclude that indirectly measured ICP decreases slightly in preterm neonates without neurologic disease after administration of the anesthetics studied. The difference between these results and those of studies of ICP in adults is presumably due to the compliance of the neonate's open-sutured cranium.
Anterior fontanel pressure (AFP), a noninvasive indicator of intracranial pressure (ICP), was monitored during tracheal intubation in two groups of preterm neonates without neurologic disease. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic and mean blood pressures were recorded at 1-min intervals. In group 1 (n = 6) patients, 0.02 mg/kg intravenous atropine was administered and awake intubation was performed. Group 2 (n = 6) patients received 0.02 mg/kg intravenous atropine and 0.1 mg/kg pancuronium and one of four anesthetics--0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine--with intubation after 10 min of mask ventilation. In group 1, AFP increased from 7.7 cm H2O to 23.8 cm H2O (P less than 0.05); the mean increase in AFP was 197%. Anterior fontanel pressure did not change significantly in group 2. Significant increases in AFP may increase the risk of intraventricular hemorrhage in preterm neonates. The present data indicate that indirectly measured ICP increases significantly during awake tracheal intubation in preterm neonates and that this increase can be prevented by prior administration of pancuronium and a general anesthetic.
Due to the high mortality associated with pulmonary interstitial emphysema in the low-birth-weight infant, a method was developed to predict the infants most at risk for death. This information will allow the discriminant selection of patients for future trials of an alternative method of mechanical ventilation, high-frequency ventilation. During a 3-year-period (July 1, 1979 through June 30, 1982), 70 infants were retrospectively analyzed to determine the clinical parameters important in predicting mortality. The infants at highest risk for death included those of younger gestational age, those with birth weight less than 1,500 g (95% of all mortalities), and those that developed pulmonary interstitial emphysema within the first 24 hours of life. Mortality sharply increased in the infants with birth weight less than 1,500 g whose ventilatory requirements exceeded a peak inspiratory pressure of 25 cm H2O on day 1. Morbidity was high in the survivors as evidenced by a 54% incidence of bronchopulmonary dysplasia. With multivariant analysis, it was possible to isolate the variables (birth weight and highest peak inspiratory pressure on day 1) most influential in predicting mortality and to construct a formula for predicting mortality in the infants with birth weight less than 1,500 g. With a subsequent prospective study of 30 infants, the predictive accuracy of the formula was established.
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Three main symptoms of minimal brain dysfunction (MBD), a common disorder in children, are hyperactivity, learning disabilities, and attention deficits. Drugs like amphetamine and methylphenidate have been demonstrated to produce a significant behavioral improvement in these children. The behavioral response of young rats (3--4 weeks), with selective lesioning of the central dopaminergic system, to a novel environment was analyzed. Both the frequencies and durations of eight mutually exclusive and complementary behavioral categories were scored. By analyzing the behavior in this way it appeared that considerable hyperactivity and learning disabilities could be demonstrated in these rats. Moreover, the bout length of some behavioral categories was somewhat shortened, which might be an indication of deficits in attention. However, treatment of the animals with amphetamine did not produce any "therapeutic" effect on the three symptoms. Since pharmacotherapeutic support is, in our opinion, a "conditio sine qua non" for the validity of the model, we do not believe that the young DA-lesioned rat is an appropriate animal model for MBD.
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