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Ohne Zusammenfassung     

The metabolism of the anti-tumour agent 1(1-aziridinyl)- 2,4-dinitrobenzene (CB 1837).

1-(1-Aziridinyl)-2,4-dinitrobenzene (CB 1837) is the parent member of a series of nitrophenyla-ziridines having a highly specific action against the Walker tumour in the rat. CB 1837 was much less cytotoxic in vitro than was predicted on the basis of its antitumour activity in vivo, but its activity was enhanced in the presence of liver 9000-g supernatant and cofactors, which also converted it into a metabolite, 2-amino-1-(1-aziridinyl)-4-nitrobenzene. This metabolite was more active in the in vitro test than was CB 1837.CB 1837 is extensively metabolised in vivo by the rat, and the following urinary metabolites have been identified by mass spectrometry and quantitatively determined after administration of the tritium-labelled drug: 1-(2-chloroethyl)amino-2,4-dinitrobenzene and its 2-hydroxyethylamino analogue; 2,4-dinitroaniline: 2-amino-1-(1 -aziridinyl)-4-nitrobenzene,2-amino-1-(2-chloroethyl)amino-4-nitrobenzene and their respective N(2)-acetyl derivatives; and S-[N-(2,4-dinitrophenyl)-2-aminoethyl] mercapturic acid.     

The treatment of primary central nervous system lymphoma in 122 immunocompetent patients: a population-based study of successively treated cohorts from the British Colombia Cancer Agency

BACKGROUND: The objective of this study was to evaluate the clinical outcome of a population-based cohort of immunocompetent patients with primary central nervous system lymphoma (PCNSL) treated with 3 different strategies over 13 years. METHODS: One hundred twenty-two consecutive patients (median age, 66 years) with PCNSL were identified. Three treatment strategies were employed: 1) whole-brain irradiation with (from January, 1990, to June, 1991) or without (from April, 1995, to December, 1999) cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-type chemotherapy (n=50 patients); 2) combined-modality therapy, including 1 g/m2 methotrexate plus whole-brain irradiation (from July, 1991, to March, 1995; n=34 patients); and 3) 8 g/m2 methotrexate alone (from January, 2000, to March, 2003) with whole-brain irradiation reserved for those with progressive disease (n=38 patients). Treatment failure was defined as progressive disease, disease recurrence, death from toxicity or lymphoma, or toxicity that necessitated a change in primary treatment. RESULTS: The median failure-free survival was 7 months, and the median overall survival (OS) was 17 months. The median OS was similar in all 3 eras. In this population-based analysis, one-third of patients did not receive the treatment strategy of the era. Therefore, the data also were analyzed by treatment received. On multivariate analysis (including era of treatment), 3 factors-age > 60 years, lactate dehydrogenase > normal, and omission of methotrexate-were associated significantly with poorer OS (hazard ratio: 2.3, 2.2, and 2.3, respectively). CONCLUSIONS: Outcomes for a general population with PCNSL remained constant despite different treatment strategies over three eras. For the two-thirds of patients who could receive potentially curative treatment, age, lactate dehydrogenase level, and receipt of > or = 1 g/m2 methotrexate appeared to be important determinants of OS.     

Developing and evaluating a residents' curriculum

This study examines the impact of a Bright Futures-based curriculum designed to teach pediatric residents how to integrate health education principles into everyday clinical practice. A two-phase study was conducted to evaluate the curriculum using both quantitative and qualitative methods. To measure the curriculum's impact on residents' clinical performance, a pre- and post-objective structured clinical examination (OSCE) design was administered to 14 residents in two groups: a control group (n=8) and an intervention group (n=6). Performance scores improved in the intervention group from pre- to post-testing in three core curriculum concepts (there was no change in the control group); performance in a fourth concept improved in both groups; and for the remaining two concepts, there was no change among the intervention group but an improvement in scores among those in the control group. Residents in the intervention group reported the curriculum to be of high quality and low difficulty. This study demonstrated that the curriculum had a positive impact on a resident's perceptions of his or her practice one year after participating in the intervention. The data suggest that each of the modules can be taught, the content learned and the principles applied to one's clinical practice.     

Variation in outcomes in Veterans Affairs intensive care units with a computerized severity measure

OBJECTIVE: To quantify the variability in risk-adjusted mortality and length of stay of Veterans Affairs intensive care units using a computer-based severity of illness measure. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of 34 intensive care units in 17 Veterans Affairs hospitals. PARTICIPANTS: A consecutive sample of 29,377 first intensive care unit admissions from February 1996 through July 1997. INTERVENTIONS: Standardized mortality ratio (observed/expected deaths) and observed minus expected length of stay (OMELOS) with 95% confidence intervals were estimated for each unit using a hierarchical logistic (standardized mortality ratio) or linear (OMELOS) regression model with Markov Chain Monte Carlo simulation. We adjusted for patient characteristics including age, admission diagnosis, comorbid disease, physiology at admission (from laboratory data), and transfer status. MEASUREMENTS AND MAIN RESULTS: Mortality across the intensive care units for the 12,088 surgical and 17,289 medical cases averaged 11% (range, 2-30%). Length of stay in the intensive care units averaged 4.0 days (range, mean unit length of stay 3.0-5.9). Standardized mortality ratio of the intensive care units varied from 0.62 to 1.27; the standardized mortality ratio and 95% confidence interval were <1 for four intensive care units and >1.0 for seven intensive care units. OMELOS of the intensive care units ranged from -0.89 to 1.34 days. In a random slope hierarchical model, variation in standardized mortality ratio among intensive care units was similar across the range of severity, whereas variation in length of stay increased with severity. Standardized mortality ratio was not associated with OMELOS (Pearson's r = .13). CONCLUSIONS: We identified intensive care units whose indicators for mortality and length of stay differ substantially using a conservative statistical approach with a severity adjustment model based on data available in computerized clinical databases. Computerized risk adjustment employing routinely available data may facilitate research on the utility of intensive care unit profiling and analysis of natural experiments to understand process and outcome links and quality efforts.     

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.