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Objective: To obtain current data on practice patterns of the U.S. pediatric critical care medicine workforce., Data Sources: Membership of the American Academy of Pediatrics Section on Critical Care and individuals certified by the American Board of Pediatrics in pediatric critical care medicine., Study Selection: All active members of the American Academy of Pediatrics Section on Critical Care, and nonduplicative individuals certified by the American Board of Pediatrics in pediatric critical care medicine, were classified as eligible to participate in this electronically administered workforce survey., Data Extraction: Data were extracted by a doctorate-level research professional. Extracted data included demographic information, work environment, number of hours worked, training, clinical responsibilities, work satisfaction and burnout, and plans to leave the practice of pediatric critical care medicine., Data Synthesis: Of 1,857 individuals contacted, 923 completed the survey (49.7%). The majority of respondents were white, male, non-Hispanic, university-employed, and taught residents. Respondents who worked full time were on clinical intensive care service for a median of 15 wk/yr and responsible for a median of 13 ICU beds, working a median of 60 hr/wk. Total night call responsibility was a median of 60 nights/yr; about half of respondents indicated night call was in-hospital. Fewer than half were engaged in basic science or clinical research. Compared with earlier data, there was minimal change in work hours and proportion of time devoted to research, but there was an increase in the proportion of female pediatric critical care medicine physicians., Conclusions: These data provide a description of the typical intensivist and a snapshot of the current pediatric critical care medicine workforce, which may be experiencing a mild-to-moderate undersupply. The results are useful for assessing the current workforce and valuable for future planning.

The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory "safe harbor" for exploratory genome-based data, and to provide a forum for industry-regulatory agency dialogue on these important issues.

Mezlocillin is a new acyl-ureido-penicillin with a broad spectrum of action, particularly directed against Gram-negative bacteria, including Pseudomonas aeruginosa. The therapeutic efficacy of this new antibiotic was assayed in 20 patients affected by serious biliary tract infections. Complete recovery was reached in 80% of the patients. Such a recovery rate is very high, considering the type of infectious pathology. Furthermore, the pharmacokinetics of mezlocillin was followed in the bile, as well as in the wall of the gallbladder, in gall-stones and in serum after single or repeated administration of the drug; the results favored the therapeutic use of mezlocillin. It is concluded that mezlocillin is a first choice antibiotic in the treatment of biliary tract infections.

A method to efficiently screen antiepileptic drugs (AED) for their actions against complex partial and secondarily generalized seizures is presented. The procedure relies on rapidly recurring hippocampal seizures (RRHS) in rats which are first used to bring epileptic responses to a stable, fully kindled state and then to test 3 parameters--behavioral seizures, electrographic seizures, and afterdischarge thresholds--before and after drug administration. With the methods described, the effects of a given drug treatment can be thoroughly determined in a single study period. Quantitative determinations of dose-response, time-action and relative potency characteristics are readily ascertained. A battery of known AED, encompassing those in common clinical use, was studied with this system. Kindled motor seizures (classes 4 and 5) were more readily suppressed than limbic behavioral seizures (classes 1-3). Electrographic seizures were usually, but not always, shortened concurrently with suppression of behavioral seizures. Under the conditions of this study, afterdischarge thresholds were not elevated, indicating that a critical role of AED is to counteract seizure spread and prolongation. The overall behavior of the RRHS test system with AED was identical to that with traditional amygdala kindled seizures and results were in good agreement with the clinical responsiveness of the kinds of seizures that these experimental systems model. The features of RRHS make it a useful system for screening new agents for antiepileptic effects, even in circumstances where little or no information about the drug under study is available.

Previous work has shown that closely spaced stimuli can activate short-term and long-term inhibitory processes that suppress kindling and the expression of kindled responses. The present experiments employed stimulus trains of longer duration than traditionally used in kindling work. Hippocampal seizures were triggered in rats at rates considerably faster than those reported to activate these inhibitory processes. Such rapidly recurring hippocampal seizures (RRHS) promptly led to a persistent, fully kindled state in which consistent kindled motor responses, constant duration electrographic seizures and stable afterdischarge thresholds were present. These kindled responses could be elicited every 30 min for 6-8 h/day on an alternate day schedule, but the kindled responses depended on delivery of supramaximal stimuli. Extending the number of RRHS on a given test day led to the appearance of a slowly developing but enduring suppression of kindled responses and an elevation of afterdischarge thresholds. Restricting the study period to 6 h on a given day, but using a consecutive instead of alternate day schedule, also led to a long-duration suppression of kindled responses. These results show that the short-duration inhibitory processes associated with kindled seizures can be more easily overcome than long-duration processes. The latter seem to involve an elevation of afterdischarge thresholds. The experiments also establish procedures by which detailed investigations of the effects of experimental manipulations on kindled responses can be examined.

The Lowry method for quantitation of protein was adapted to automated flow injection analysis. The procedure was developed using two different pure proteins: bovine serum albumin and hepatitis B surface antigen. The system was optimized for reagent concentration, pH, gain, temperature, sample volume, and output. The response of each protein was affected differently by temperature. The reaction slopes and absorbance values of the proteins were similar at 90 degrees C to allow quantitation of hepatitis surface antigen against bovine serum albumin. Advantages of the automated flow injection analysis Lowry procedure include: rapid analyses (90 samples/h), small sample volume (30 microliters, 100 microliters), fast response (20 s), reproducibility (less than or equal to 2% CV within an assay and 3 to 6% CV among assays), sensitivity (5 micrograms), and high correlation (99.8%) with manual assay. After a 30-min set-up period, the analyzer was available to assay protein on demand throughout the day, making it suitable for process and quality control testing.