Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.     

Use of censored data to monitor surgical-site infections.

OBJECTIVE: To take into account the proportion of patients lost to follow-up when calculating surgical-site infection (SSI) rates. DESIGN: A multicenter SSI monitoring network in Basse-Normandie, France, using the definitions for SSI of the National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention. PATIENTS: Between January 1, 1998, and December 31, 1999, 3,705 patients were operated on in 25 units of 10 institutions. RESULTS: Of the patients, 41.2% (range, 5.1% to 95.5%) were seen 30 days or more after their operation. The global SSI attack rate was 2.19% (95% confidence interval, 1.72% to 2.66%). With the use of the Kaplan-Meier method, the incidence rate was 3.11% (95% confidence interval, 3.06% to 3.16%). The difference between the attack rate and the Kaplan-Meier incidence rate for each unit varied according to the percentage of patients seen on or after day 30 postoperatively and the number of SSIs diagnosed in patients seen on or after day 30. CONCLUSIONS: Practice guidelines are needed for the international monitoring for postdischarge SSIs and the calculation of SSI rates. The proportion of patients seen 30 days after their operation is a major quality criterion for SSI monitoring and should be routinely given in monitoring reports, oral communications, and publications to compare results obtained by different teams     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.