The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Patterns of femoral head migration in osteoarthritis of the hip: a reappraisal with CT and pathologic correlation

Although medial, superior, and axial patterns of migration of the femoral head in osteoarthritis of the hip have been well described, it is not clear what anatomic and biomechanical factors determine the direction of migration. The authors studied 22 patients with bilateral (11 patients) or unilateral (11 patients) osteoarthritis by means of conventional radiography and computed tomography (CT) to define any relationships between migration in the coronal plane and that in the transverse plane and to determine whether femoral anteversion, acetabular anteversion, femoral neck-shaft angle, or acetabular inclination were related to particular migration patterns. Anterior migration was evident in 14 of the 19 hips with a superior migration pattern, whereas posterior migration was present in five of the seven hips with a medial migration pattern. In the remainder of cases, no migration in the transverse plane was present. Femoral anteversion as determined with CT, femoral neck-shaft angle, angle of acetabular inclination, and acetabular anteversion angle in this relatively small sample were all found to be within normal limits and appeared to have no influence on the occurrence of a specific pattern of femoral head migration.     

Conditioned flavor aversion induced by inhaled p-xylene in rats

Xylenes have the potential for widespread public exposure, yet their neurotoxic properties are poorly understood. The conditioned flavor aversion (CFA) paradigm provides a sensitive behavioral assay for the aversiveness of many drugs and toxic chemicals. Male Long-Evans rats were placed on a restricted water schedule (30 min/day) 1 week after arrival in the laboratory at 40 days of age. Ten days later, all rats received 0.1% saccharin in place of water, and then were exposed immediately either to filtered air or to 50, 100, 200, 400, 800 or 1,600 ppm p-xylene for 4 hr, or to air or 400 ppm p-xylene for 0.5, 1, 2, 4 or 8 hr. The restricted water schedule remained in effect for the next 72 hr, at which time the rats were given a choice between saccharin and water. Inhalation of all concentrations of p-xylene reduced relative saccharin intake, with maximal aversion at 800 and 1,600 ppm. The aversion produced by 400 ppm p-xylene was maximal at exposures of 2 or more hr, with shorter exposures producing intermediate effects. Total fluid intake was unaffected by p-xylene exposure with the exception of a slight (nonsignificant) decrease in consumption following 1,600 ppm. Exposure to saccharin 24 hr prior to p-xylene produce no aversion, indicating that the reduction in saccharin intake required close temporal pairing of saccharin and p-xylene. Thus inhaled p-xylene at a concentration of 1/2 its TLV (= 100 ppm) caused a significant, learned change in rats' normal consumption of saccharin-flavored water, without disrupting total fluid consumption.     

Changes in Blood Catecholamine Levels and. Blood Coagulation and Fibrinolytic Activity in Response to Graded Exercise in Man

Measurements of catecholamines, fibrinogen, factor VIII, thrombelastography, euglobulin lysis time and platelet adhesiveness have been carried out on venous blood obtained from normal males exposed to exercise on a bicycle ergometer at various work loads. Significant increases in adrenaline, factor VIII and fibrinogen were found only after exercise to exhaustion at 1500 kpm min-1 whereas the euglobulin lysis time was inversely proportional to the excercise load. There was no change in platelet adhesiveness. These findings support the results of studies using adrenaline infusions or adrenergic blockade which suggest that stress-induced increases in factor VIII are mediated via adrenergic stimulation but that activation of fibrinolysis is not dependent on adrenaline.     

General practitioners' satisfaction with and attitudes to out-of-hours services

Background  

In recent years, Dutch general practitioner (GP) out-of-hours service has been reorganised into large-scale GP cooperatives. Until now little is known about GPs' experiences with working at these cooperatives for out-of-hours care. The purpose of this study is to gain insight into GPs' satisfaction with working at GP cooperatives for out-of-hours care in separated and integrated cooperatives.