Effect of Ca2+-entry blockade and serotonergic antagonism on contractions of hypoxic isolated canine coronary arteries

Lidoflazine, flunarizine, and R 51 469 antagonized contractions of isolated canine coronary arteries caused by depolarizing solution or 5-hydroxytryptamine, and the further increase in tension caused by hypoxia during such contractions. The 5-HT2-antagonist ketanserin, but not methysergide, antagonized contractions induced by 5-hydroxytryptamine, but not those by high K+; it reduced further increases in tension caused by hypoxia only during contractions caused by 5-hydroxytryptamine. Augmentation by hypoxia of coronary vasoconstriction appears to be a Ca2+-dependent phenomenon.link_to_subscribed_fulltex

Medians for second‐trimester maternal serum markers: geographical differences and variation caused by median multiples‐of‐median equations

OBJECTIVES: To establish gestational age‐specific mid‐trimester normal medians for the prenatal serum markers α fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using the Beckman Coulter Access chemiluminiscent immunoassays; to compare these data with data obtained from other geographical regions; to propose regression coefficients for regressed medians and analyse variation induced by different regression equations; to evaluate the effect of formulas used for gestation correction on estimating risk in Down's syndrome. DESIGN: Data derived from 862 fresh serum samples from women being screened for Down's syndrome pregnancy, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Regressed medians were calculated by using a first‐degree logarithmic–linear fit of the raw data. Multiples‐of‐median (MoM) values estimated by using a simple logarithmic–linear equation were compared with those calculated with higher‐degree polynomials chosen with a goodness‐of‐fit analysis. Model‐specific variation was estimated and the effect on risk for Down's syndrome was evaluated. RESULTS: Regressed medians (Y) for Access serum markers AFP (IU/ml), HCG (IU/ml) and uE3 (nmol/l) for a Belgian population can be estimated with the equation Y = 10((A+BX)) with X = decimal weeks. The best fit was obtained with a third‐degree and a second‐degree polynomial for AFP and uE3, respectively. Differences between the medians and among the slopes of the geographical populations were found to be significant (analysis of covariance, p<0.001). CONCLUSIONS: Belgian marker medians versus gestational time are found to show a pattern that is similar to that in the literature. The log–linear equation is observed to give a good fit and can be suggested as a tool for calculating median MoM values for Belgian laboratories that use Access biochemical prenatal markers

Weight correction of MoM values: which method?

BACKGROUND: Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down's syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated. METHOD: The relationship between the maternal serum markers αfetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down's syndrome. Two different models (the log–linear equation and the linear–reciprocal equation) were used to determine the relationship between the serum markers and maternal weight. RESULTS: A significant relationship between log(10) multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log–linear model had higher coefficients of determination (r(2)) when compared with the linear–reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight‐corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight‐corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% ( 4.4%) for HCG and 5.9% ( 3.2%) for uE3. This resulted in a difference in risk estimate of 1.66–5.34% for Down's syndrome owing to weight correction algorithm differences in women of median weight. CONCLUSION: The log–linear weight correction approach was shown to be marginally more effective by a goodness‐of‐fit analysis. Differences in weight‐corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon's paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1

Antihypertensive properties of ketanserin (R 41 468)

The serotonergic receptor antagonist 3-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl}-2,4-[1H,3H] quinazolinedione (ketanserin) causes dose-dependent inhibition of the effects of 5-hydroxytryptamine (5-HT) on 5-HT2-serotonergic receptors. These receptors mediate facilitation of platelet aggregation, direct vasoconstriction in several arteries and veins, and direct amplification of vasoconstrictor responses to other neurohumoral mediators. Ketanserin does not inhibit vasodilator effects of 5-HT. At higher concentrations, ketanserin has α1-adrenergic blocking properties. The compound causes dose-related reductions in arterial blood pressure in hypertensive animals and humans that are larger and occur at lower doses than in normotensive controls. In humans, the antihypertensive properties of ketanserin do not appear to involve α1-adrenergic inhibition, because the compounds given i.v. (10 mg) do not affect the pressor dose-response curve to phenylephrine.link_to_subscribed_fulltex