Gatekeeper for coronary angiography: reply

We thank Geluk and Zijlstra for their kind words as well astheir considerations and proposals. The latter hits right intothe heart of the issue: should one stick to the ‘anatomic’paradigm urging us to detect and treat coronary stenoses andcalcifications rather than follow     

Fixation of displaced femoral neck fractures: A comparison between sliding screw plate and four cancellous bone screws

In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.     

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

Do patient characteristics,disease, or treatment explain social inequality in survival from colorectal cancer?

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient.     

Anion channels in a leaky epithelium

We have used the patch-clamp technique to characterize three anion channels in the ventricular membrane of the choroid plexus epithelium from Necturus. The most frequently occurring channel had a nonlinear IV-curve. The conductance in excised patches with 112 mM chloride at both sides was 28 pS at 0 mV, increasing towards positive membrane potentials. The selectivity ratios were P _NaP _Cl 0.1 and . SITS and furosemide (1 mM) on the inside reduces chloride flux to 0.15 and 0.37 times the control value. In attached patches, the most commonly observed channel had a conductance of 7.5 pS. The single-channel current for this channel reversed direction at 15 mV hyperpolarization, indicating accumulation of chloride to a factor of 1.8 above equilibrium. External stimulation of the tissue by theophylline, IBMX and dbcAMP, or by hypotonic shock did not increase the activity of this channel. In very few excised patches, we have observed a chloride channel with a conductance of 7 pS with 112 mM chloride at both sides. The 7 pS channel appears to be identical to a 2 pS channel found in attached patches. The 2 pS channel was not normally active in attached patches but was activated in 28% of the patches by external stimulation. Finally, in few excised patches we have found a 375 pS channel which inactivates within seconds when membrane potential is stepped from 0 mV to a value that differs more than 10–20 mV from zero. The channel did not conduct gluconate but and P _NaP _Cl 0.1. Internal SITS and furosemide (1 mM) reduced chloride flux to 0.3 and 0.5 times the control value. The channel was never seen in attached patches. The current carried through these channels can not account for the transepithelial steady state Cl^–-flux measured by microelectrodes. KCl exit from the cell is suggested to be carried by KCl-cotransport or by channels that are too small to be seen in patch-clamp experiments.     

Differential vasomotor action of noradrenaline, serotonin, and histamine in isolated basilar artery from rat and guinea-pig

Vasomotor effects of the amines, serotonin (5-hydroxytryptamine; 5-HT), noradrenaline (NA) and histamine, were studied in isolated basilar arteries (BA) of the rat and guinea-pig in vitro. 5-HT produced marked contraction in rat BA, about 70% of that induced by high (124 mM) K+ solution. This response was inhibited by the specific 5-HT2 receptor antagonist, ketanserin, with a pA2 value of 9.35. In the guinea-pig, 5-HT caused only moderate contraction amounting to 30% of that produced by K+. Ketanserin at concentrations up to 10(-6) M showed a comparatively small, non-surmountable inhibition of the contraction. EC50 values for 5-HT in the guinea-pig and rat were 5.65 x 10(-8) M and 3.70 x 10(-7) M, respectively. NA had no effect on rat BA, but moderately contracted guinea-pig BA. The contraction was not altered by yohimbine but was inhibited by prazosin. Histamine contracted guinea-pig BA with a maximum that was 110% of the K+-induced contraction. It was not changed by the H2 antagonist, cimetidine. The H1 antagonist, pyrilamine, caused competitive inhibition with a pA2 of 9.20 at a slope of 0.94. In preconstricted rat BA, histamine induced vasodilatation in a concentration-dependent manner. The H1 agonist, pyridylethylamine (PEA), and the H2 agonist, impromidine, dilated less effectively than histamine. The vasodilatation induced by histamine was inhibited by the H2 antagonist, cimetidine, and to a smaller extent by the H1-receptor antagonist, pyrilamine. Removal of the endothelium abolished the vasodilator effect of PEA but not that of impromidine. In vessels with intact endothelium, the vasodilatation caused by histamine was slightly reversed by pyrilamine, which did not affect the dilatation in endothelium denuded vessels. Cimetidine markedly reversed this vasodilator effect in both intact and endothelium denuded preparations; in the latter the counteraction was almost complete. In precontracted guinea-pig vessels, histamine failed to induce dilatation even in the presence of the H1 antagonist, pyrilamine. Thus, 5-HT-induced contraction is mediated by 5-HT2 receptors in the rat and probably by 5-HT1 receptors in the guinea pig. NA failed to contract rat BA but contracted guinea-pig BA through alpha 1 receptors. Histamine was a potent dilator agent in rat BA through a combination of both H1 and H2 receptors. The dilatation mediated by the H1 receptors, but not that mediated by H2 receptors, was endothelium-dependent. Histamine caused strong vasoconstriction in the guinea-pig BA through H1 receptors.