Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-ß-lactamase-producing Escherichia coli.

Urinary tract infections (UTIs) due to extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P < 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation.

A study of the effect of benzylpenicillin on isolated human gallbladder.

The contractile effect of benzylpenicillin on isolated rings of human gallbladder was studied using preparations taken from surgical specimens after gallbladderectomy. The gallbladder was cut into two pieces and one ring was cut from each piece; one ring was mounted in a 100 ml organ bath containing Krebs solution and the isotonic changes of the preparation were recorded for each experiment. Benzylpenicillin (1 x 10(4) to 1 x 10(8) IU/l) was shown to exert a dose-dependent contractile effect on isolated human gallbladder rings which was blocked by atropine (1 x 10(-8) M). The benzylpenicillin-induced contractile effect was analogous to contraction observed with acetylcholine (1 x 10(-7) to 1 x 10(-2) M). The effect of benzylpenicillin on isolated human gallbladder may reflect a possible decrease in gallbladder emptying time in vivo, suggesting a beneficial effect of benzylpenicillin in antimicrobial treatment of gallbladder infections.

A phase I clinical trial of dextromethorphan in intractable partial epilepsy.

We conducted an open-label pilot study of dextromethorphan (DM) in intractable partial epilepsy with the following objectives: a preliminary evaluation of the drug's safety and efficacy in the epileptic patient and a definition of a concentration range which can be safely achieved in future studies. Sixteen patients with drug-resistant, localization-related epilepsies entered the trial. After an 8-week baseline period, DM was added to the existing antiepileptic drugs at a dose of 40 and 50 mg every 6 h (160 and 200 mg/day). Each treatment period lasted 8 weeks. Seizure control improved after administration of DM, especially in the group of intermediate and slow metabolizers. Two patients, however, experienced increased seizure frequency and withdrew from the study. Adverse effects during DM administration were mild and transient. DM was well tolerated even in patients with high plasma levels of the drug (up to 15020 ng/dl). Our results indicate that DM is safe and effective in the treatment of comedicated patients with intractable partial epilepsies.

A study of the mechanism of action of aminoglycoside antibiotics on the guinea pig vas deferens.

Aminoglycoside antibiotics inhibit contractility of the isolated guinea pig vas deferens in a dose-related manner. However, total inhibition of the contractility cannot be attained, a phenomenon most probably attributed to the partial inhibition of the function of Ca channels by the antibiotics. The inhibitory potency of aminoglycoside antibiotics was found to be: sisomicin greater than gentamicin greater than netilmicin greater than streptomycin greater than dactimicin greater than amikacin greater than kanamycin greater than kanendomycin greater than dibekacin greater than tobramycin. Ca2+ antagonize the action of aminoglycoside antibiotics on the vas deferens competitively. This observation indicates that the untoward effect of aminoglycoside antibiotics on contractility of the vas deferens can be attributed to their ability to interfere with Ca2+ entry through cell membranes of the tissue, a prerequisite for subsequent contraction. Above a specific threshold (7.5 mM) Ca2+ have a prophylactic effect on vas deferens and prevent the inhibitory action of ICmax doses of the antibiotics. Thus, Ca could be used as a prophylactic medium or as an antidote in restoring contractility of the vas deferens if it is inhibited by aminoglycoside antibiotics.

The effects of endogenous and exogenous sex hormones and of maturation on cGMP phosphodiesterase activity in the brain.

Kinetic analysis of cGMP phosphodiesterase activity in the rat brain indicated that Km values did not differ significantly with sex, age (1 to 270 days old), or brain area (amygdala, cerebellum, cerebral cortex, hypothalamus, thalamus, reticular formation). There was no dimorphism in enzyme activity between normal or artificially mimicked gender, nor was there any significant variation in activity following short or long term alterations of endogenous levels of gonadal hormones in any of the brain regions investigated. Highest activity was observed in cerebral cortex and amygdala. Maturation caused a significant increase in enzyme activity, the adult levels being reached by the 38th to 40th day of life.

Maturational aspects of the dopaminergic system: ontogenesis of high affinity dopamine binding to neural membrane fragments of the rat brain.

High affinity binding of [3H]-dopamine was measured in membrane fractions prepared from cerebral cortex, amygdala, hypothalamus, thalamus and reticular formation of female rats aged 1 to 260 days old. [3H]-dopamine bound with approximately 30 x 10(-9) M affinity to neural membrane fractions of female brains of any age. [3H]-dopamine binding increased with age either in a sigmoid fashion, as was the case in the amygdala, hypothalamus and reticular formation, or in a parabolic fashion, as was the case in the cerebral cortex and thalamus, the adult levels being reached on the 30th and 70th day of life respectively.