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1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR.

This paper presents an application of a linear model with correlated errors to the assessment of the precision of acoustic rhinometry in clinical medicine. The design of the reproducibility study involved 20 healthy subjects measured by five investigators with three replicate measurements of four variates taken from the right and left nasal cavities, altogether 2400 measurements. The parametric model may be structured to account for random variation between subjects, serial correlation within subjects and measurement error. The model-based reproducibility correlation coefficient was estimated to be fair both for the nasal volume measurements and for the nasal minimal cross-sectional area measurements with an overall average of 0.65. An alternative measure, the within-subject coefficient of variation, averaged 15 per cent. The choice between the measures of reproducibility depends on the degree of heterogeneity of the studied populations, the presence of time trend and the scale of measurement of the rhinometric variates. In clinical practice, repeated measurements should always be made to attain a reasonable level of reproducibility in acoustic rhinometry., (Copyright 2000 John Wiley & Sons, Ltd.)

1. The effects of nitric oxide (NO) releasing substances, sodium nitroprusside, 3-morpholino sydnonimine (SIN-1) and a novel oxatriazole derivative, GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wistar rats. 2. Given as cumulative intravenous injections, both nitroprusside and GEA 3162 (24-188 nmol kg-1) induced short-lasting and dose-dependent decreases in mean arterial pressure, while SIN-1 decreased blood pressure only slightly even after larger doses (94-3000 nmol kg-1). Heart rate increased concomitantly with the hypotensive effect of the NO-releasing substances. 3. Cumulative intracerebroventricular administration of GEA 3162 (24-188 nmol kg-1) induced a dose-dependent hypotension with slight but insignificant increases in heart rate. In contrast, intracerebroventricular nitroprusside induced little change in blood pressure, while a large dose of SIN-1 (3000 nmol kg-1, i.c.v.) slightly increased mean arterial pressure. However, intracerebroventricular nitroprusside and SIN-1 increased heart rate at doses that did not significantly affect blood pressure. 4. To determine whether the cardiovascular effects of GEA 3162 were attributable to an elevation of cyclic GMP levels, pretreatments with methylene blue, a putative guanylate cyclase inhibitor, were performed. This substance failed to attenuate the cardiovascular effects of peripherally or centrally administered GEA 3162, suggesting that the effects were independent of guanylate cyclase. 5. In conclusion, the centrally administered NO-donor, GEA 3162, induced a dose-dependent. hypotensive response without significant changes in heart rate. Furthermore, intracerebroventricular injections of nitroprusside and SIN-1 increased heart rate without affecting blood pressure. These results suggest that NO released by these drugs may affect central mechanisms involved in cardiovascular regulation independently of cyclic GMP.

In this paper, we examine comparative analysis of rates with a view to each of the usual comparative parameters-rate difference (RD), rate ratio (RR) and odds ratio (OR)-and with particular reference to first principles. For RD and RR we show the prevailing statistical practices to be rather poor. We stress the need for restricted estimation of variance in the chi-square function underlying interval estimation (and also point estimation and hypothesis testing). For RR analysis we propose a chi-square formulation analogous to that for RD and, thus, one which obviates the present practice of log transformation and its associated use of Taylor series approximation of the variance. As for OR analysis, we emphasize that the chi-square function, introduced by Cornfield for unstratified data, and extended by Gart to the case of stratified analysis, is based on the efficient score and thus embodies its optimality properties. We provide simulation results to evince the better performance of the proposed (parameter-constrained) procedures over the traditional ones.

Recent developments in statistical methods for epidemiology have revived the application of sampling techniques in the design and analysis of cohort studies. The 'case-base' design involves sampling of both the cases and the cohort base of the study. This paper reviews some data-analytic imperfections of the approaches to risk ratio estimation, and modifies and advances a consistent likelihood-based procedure-analogous to Miettinen and Nurminen's proposal for a full cohort design--for interval estimation (and also point estimation and significance testing) in the context of binary case-base data. First, the procedure avoids the use of Taylor-series approximations to derive variance estimators for non-linear functions of parameters. Second, the asymptotic condition effects a simple computational expression for the chi-square function of risk ratios that is universally applicable to small samples. The statistical modelling underlying the method allows inferences about risk ratios without the assumption of rare disease either for the general population or for a particular base. The paper also extends the analysis to encompass stratified data. Finally, a numerical evaluation evinced the accurate small-sample properties of the proposed method.