Incidence of Chest Tube Malposition in the Critically Ill: A Prospective Computed Tomography Study

Background: Malposition of percutaneously inserted chest tubes is considered as a rare complication in critically ill patients. Its incidence, however, remains uncertain. The aims of the study were to assess the true incidence of chest tube malposition in critically ill patients and to identify predicting factors.

Methods: The authors prospectively studied 122 chest tubes percutaneously inserted in 75 consecutive critically ill patients. For clinical reasons independent of the study, thoracic computed tomography scanning was performed in 63 patients, allowing direct visualization of 106 chest tubes. Based on these findings, chest tube position was classified as intrapleural, intrafissural, or intraparenchymal. Factors predicting chest tube malposition were analyzed by univariate and multivariate analysis.

Results: The mean delay between chest tube placement and thoracic scan was 3.5 +/- 2.9 days. Twenty-two chest tubes were diagnosed as being intrafissural (21%), and 10 were diagnosed as being intraparenchymal (9%). The only predicting factor associated with the risk of malposition was the use of a trocar for the percutaneous insertion of the chest tube (P = 0.032).     

Postnatal development of the chemosensitivity of rat cerebellar Purkinje cells to excitatory amino acids. An in vitro study

In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PCs) to L-aspartate (L-Asp), L-glutamate (L-Glu) and related derivatives. As early as postnatal day 0 all PCs already displayed clear excitatory responses to short iontophoretic applications of L-Asp, L-Glu and quisqualate while in the same conditions no effect of N-methyl-D,L-aspartate (NMDLA) was detected. By postnatal day 5, i.e. after the onset of the synaptogenesis, the sensitivity of PCs to L-Asp, L-Glu and quisqualate significantly increased up to values similar to those recorded in adult rat cerebellum and surprisingly nearly all (87%) the recorded cells now also displayed excitatory responses to NMDLA. Although this sensitivity of PCs to NMDLA was significantly lower than that observed with the other drugs, it persisted until the end of the first postnatal month when the adult type of connectivity is already well established but at this stage only 30 per cent of the tested cells were still sensitive to the agonist. During this period, excitatory responses elicited by NMDLA were selectively antagonized by 2-amino-5-phosphonovalerate (2-APV), suggesting that during postnatal development, NMDA receptor types are transiently expressed on PCs membranes since in the adult, NMDLA no longer had an excitatory effect. Instead, this drug now exerted a preferential antagonistic action on the excitatory response elicited by L-Asp. Also in the adult, no major changes occurred in the sensitivity of PCs to L-Asp, L-Glu and quisqualate when these drugs were ejected at a dendritic site whereas, when ejected at the somatic level, the sensitivity of the cell appeared 2-3 times lower.     

Scientific and regulatory issues relevant to assessing risk for developmental neurotoxicity: an overview

The effects of chemical exposure on the developing nervous system have been documented in both humans and animals for a variety of agents. However, the comparability of these effects has not been carefully evaluated to determine the predictability of animal models to adverse effects in humans. A workshop sponsored by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse was held on April 11-13, 1989, to address the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity. Invited experts were asked to review the human and animal data on several agents that are known to cause developmental neurotoxicity in humans, including lead, methylmercury, selected abused agents, anticonvulsants, polychlorinated biphenyls (PCBs), ethanol and X-irradiation, and to make quantitative comparisons on a specific end point basis as well as on a functional category basis. In addition, they were asked to make quantitative comparisons when adequate dose-effect data were available. The data also were evaluated in the context of the proposed EPA developmental neurotoxicity testing battery to determine whether or not the battery would adequately detect the effects of each agent. Finally, four work groups were asked to reach consensus on issues relating to: 1) comparability of end points across species for developmental neurotoxicity; 2) testing methods in developmental neurotoxicity for use in human risk assessment; 3) weight-of-evidence and quantitative evaluation of data from developmental neurotoxicity studies; and 4) triggers for developmental neurotoxicity testing.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.