Search

Rationale and objectives Vocational trainees in general practice are often confronted with new and unusual situations. The application of the principles and techniques of evidence-based medicine (EBM) could often be appropriate in these situations. We aimed to investigate attitudes towards EBM among doctors undergoing postgraduate training in general practice in Germany. In particular, we were interested in which aspects the answers of doctors with an overall negative attitude towards EBM differed from those with a positive attitude. Methods A total of 153 doctors participating in courses for postgraduate medical training in general practice were asked to fill in a questionnaire on attitudes towards EBM and relevance of clinical research. Answers of doctors with a negative attitude towards EBM (negative sum in the questions asking personal judgment on EBM) were compared with those of the remaining doctors. Results A total of 142 (93%) doctors returned the questionnaire and 121 responded to the questions on EBM (21 responded that they had not heard about EBM). On average, attitudes towards EBM were positive; however, nine doctors gave negative ratings. EBM-sceptics were similar regarding age, years working as doctors and working hours per week, but were more often male (P = 0.03). EBM-sceptics considered keeping up to date as important as non-sceptics but were significantly (P

The alkylated maleic imide adducts of type 3 have been shown to undergo highly regioselective selectride reductions. As with these compounds regioselectivity in further transformations including a thermal retro process translates directly into enantioselectivity, various cyclisation techniques were applied. The advanced cycloadducts obtained led to the enantiopure alkaloid precursors 9, 17, 20 and 25 in very high yield.

Objective: Evidence based on controlled studies is still limited for treatment strategies that prevent recurrence of suicide attempts. Findings from observational as well as meta-analytic studies strongly suggest that lithium may have suicide-protective properties. Method: Patients with a recent suicide attempt in the context of an affective spectrum disorder (n = 167) were treated with either lithium or placebo during a 12-month period. Results: Survival analysis showed no significant difference of suicidal acts between lithium and placebo-treated individuals (adjusted hazard ratio 0.517; 95% CI 0.18–1.43). However, post hoc analysis revealed that all completed suicides had occurred in the placebo group accounting for a significant difference in incidence rates (P = 0.049). Conclusion: Results indicate that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with affective disorders. Our findings contribute to the growing body of evidence suggesting a specific antisuicidal effect of lithium.

Subjective quality of life (QOL) is predominantly measured as satisfaction in various life domains. However, this approach has often been criticized for not taking individual preferences into account. A combination of importance and satisfaction ratings allows for the different weights that different life domains have in a person's QOL. The present study aimed to investigate empirically the usefulness of combined satisfaction and importance ratings in the assessment of schizophrenic patients. In a cross-sectional study, 149 schizophrenic patients and 106 healthy controls rated their satisfaction with and the importance of 19 different life domains. Results of multidimensional scaling suggested that satisfaction and importance ratings tap different concepts in mentally healthy controls and schizophrenic patients. However, as compared with satisfaction ratings, importance ratings were even more shifted towards the positive pole of the scale and showed less variance. Very high correlations were found between the pure and the weighted satisfaction scores. No additional variance could be accounted for with regard to psychopathology, age or sex. Although a combination of satisfaction and importance ratings fits better with the subjective concept of QOL on a theoretical level, the results of this study do not support the application of this model in QOL assessment in schizophrenic patients. Copyright © 1999 Whurr Publishers Ltd.

A general synthetic route to the enantiopure bicyclic cyclopentadienes (S)-3 and (R)-3 of the hydrindane series, starting from the Hajos-Wiechert ketone 4 or its enantiomer is described. Reasons for the excellent face and endo selectivity of cycloadditions and the resulting consequences for chiral recognition are discussed.

A general synthetic route to the enantiopure bicyclic cyclopentadienes (S)-3 and (R)-3 of the hydrindane series, starting from the Hajos-Wiechert ketone 4 or its enantiomer is described. Reasons for the excellent face and endo selectivity of cycloadditions and the resulting consequences for chiral recognition are discussed.

The alkylated maleic imide adducts of type 3 have been shown to undergo highly regioselective selectride reductions. As with these compounds regioselectivity in further transformations including a thermal retro process translates directly into enantioselectivity, various cyclisation techniques were applied. The advanced cycloadducts obtained led to the enantiopure alkaloid precursors 9, 17, 20 and 25 in very high yield.

The total syntheses of eight members of the palmarumycin family have been achieved, with identification of the absolute stereochemistry for three of these natural products. In addition, the ras-farnesyl transferase inhibitor (-)-preussomerin G has been synthesized, achieving the first enantioselective route for accessing this family of natural products. Highlights of the synthetic work include an asymmetric epoxidation of a cyclic enone in excellent yield and enantiomeric excess and a potentially biomimetic oxidative spirocyclization for the introduction of the bis-spiroketal array unique to the preussomerin natural products.

1. Satraplatin is an investigational orally administered platinum-based antitumour drug. The present study compared the plasma protein binding, stability and degradation of satraplatin with that of its active metabolite JM118 and cisplatin. 2. The platinum complexes were incubated in human plasma for up to 2 h at 37 degrees C and quantified in plasma fractions by inductively coupled plasma-mass spectrometry on- or off-line to high-performance liquid chromatography. 3. All three platinum drugs became irreversibly bound to plasma proteins and showed negligible reversible protein binding. They were also unstable in plasma and generated one or more platinum-containing degradation products during their incubation. However, the three platinum complexes differed in the kinetics of their instability and protein binding, as well as in the number of degradation products formed during their incubation. 4. In conclusion, the plasma protein binding, instability and degradation of satraplatin and its active metabolite JM118 are qualitatively similar to that of cisplatin and other clinically approved platinum-based drugs. Quantitative differences in their irreversible protein binding and degradation were related to their respective physiochemical properties and bioactivation mechanisms.