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Worldwide, there are large inequalities in genetic service delivery. In 2011, we established a bi‐annual joint pediatric‐genetics clinic with a visiting clinical geneticist in the Dutch Caribbean. This retrospective study evaluates the yield of diagnostic testing and the clinical utility of a diagnosis for patients with rare diseases on these relatively isolated, resource‐limited islands. A total of 331 patients that were referred to the clinical geneticist between November 2011 and November 2019 and had genetic testing were included in this study. A total of 508 genetic tests were performed on these patients. Microarray, next‐generation sequencing gene panels, and single‐gene analyses were the most frequently performed genetic tests. A molecularly confirmed diagnosis was established in 33% of patients (n = 108). Most diagnosed patients had single nucleotide variants or small insertions and/or deletions (48%) or copy number variants (34%). Molecular diagnostic yield was highest in patients referred for seizures and developmental delay/intellectual disability. The genetic diagnosis had an impact on clinical management in 52% of patients. Referrals to other health professionals and changes in therapy were the most frequently reported clinical consequences. In conclusion, despite limited financial resources, our genetics service resulted in a reasonably high molecular diagnostic yield. Even in this resource‐limited setting, a genetic diagnosis had an impact on clinical management for the majority of patients. Our approach with a visiting clinical geneticist may be an example for others who are developing genetic services in similar settings. [ABSTRACT FROM AUTHOR]

Enhanced systolic function of the right ventricle during respiratory distress syndrome in newborn lambs. Am J Physiol Heart Circ Physiol 280: H392-H400, 2001.--Respiratory distress syndrome (RDS) causes pulmonary hypertension. It is often suggested that this increased afterload for the right ventricle (RV) might lead to cardiac dysfunction. To examine this, we studied biventricular function in an experimental model. RDS was induced by lung lavages in seven newborn lambs. Five additional lambs served as controls. Cardiac function was quantified by indexes derived from end-systolic pressure-volume relations obtained by pressure-conductance catheters. After lung lavages, a twofold increase of mean pulmonary arterial pressure (from 15 to 34 mmHg) was obtained and lasted for the full 4-h study period. Stroke volume was maintained (5.2 [+ or -] 0.6 ml at baseline and 6.1 [+ or -] 1.4 ml at 4 h of RDS), while, RV end-diastolic volume showed only a slight increase (from 6.5 [+ or -] 2.3 ml at baseline to 7.7 [+ or -] 1.3 ml at 4 h RDS). RV systolic function improved significantly, as indicated by a leftward shift and increased slope of the end-systolic pressure-volume relation. Left ventricular systolic function showed no changes. In control animals, pulmonary arterial pressure did not increase and right and left ventricular systolic function remained unaffected. In the face of increased RV afterload, the newborn heart is able to maintain cardiac output, primarily by improving systolic RV function through homeometric autoregulation. biventricular function; end-systolic pressure-volume relation; homeometric autoregulation; pulmonary hypertension

Takahashi, Yasushi, Maartje de Vroomen, Christine Roman, and Michael A. Heymann. Mechanisms of calcitonin gene-related peptide-induced increases of pulmonary blood flow in fetal sheep. Am J Physiol Heart Circ Physiol 279: H1654-H1660, 2000.--Fetal pulmonary blood flow is regulated by various vasoactive substances. One, calcitonin gene-related peptide (CGRP), increases pulmonary blood flow. We examined four key physiological mechanisms underlying this response using the blocker drugs CGRP receptor blocker ([CGRP.sub.8-37]), nitric oxide synthase inhibitor [[N.sup.[Omega]]-nitro-L-arginine (L-NNA)], adenosine triphosphate-dependent potassium ([K.sub.ATP]) channel blocker (glibenclamide), and cyclooxygenase inhibitor (indomethacin) in 17 near-term fetal sheep. Catheters were placed in the left (LPA) and main pulmonary arteries, and an ultrasonic flow transducer was placed around the LPA to measure flow continuously. CGRP was injected directly into the LPA (mean 1.02 [micro]g/kg) before and after blockade, and responses to CGRP were statistically compared. Before blockade, CGRP increased LPA blood flow from 23 [+ or-] 25 to 145 [+ or -] 77 ml/min (means [+ or ] SD), and these increases were significantly attenuated by [CGRP.sub.8-37] (n = 6; 91% inhibition), L-NNA (n = 6; 86% inhibition), and glibenclamide (n = 6; 69% inhibition). No significant changes were found with indomethacin (n = 6; 4% inhibition). Thus, in the fetal pulmonary circulation, CGRP increases pulmonary blood flow not only through its specific receptor but also, in part, through nitric oxide release and [K.sub.ATP] channel activation. pulmonary vascular resistance; fetus; nitric oxide; adenosine triphosphate-dependent potassium channel; indomethacin

De Vroomen, Maartje, Robbert H. Lopes Cardozo, Paul Steendijk, Frank Van Bel, and Jan Baan. Improved contractile performance of right ventricle in response to increased RV afterload in newborn lamb. Am. J. Physiol. Heart Circ. Physiol. 278: H100-H105, 2000.--Pulmonary hypertension results in an increased afterload for the right ventricle (RV). To determine the effects of this increased afterload on RV contractile performance, we examined RV performance before and during 4 h of partial balloon occlusion of the pulmonary artery and again after releasing the occlusion in nine newborn lambs. RV contractile performance was quantified by indexes derived from systolic RV pressure-volume relations obtained by a combined pressure-conductance catheter during inflow reduction. An almost twofold increase of end-systolic RV pressure (from 22 to 38 mmHg) was maintained during 4 h. Cardiac output (CO) (0.74 [+ or -] 0.08 1/min) and stroke volume (4.3 [+ or -] 0.4 ml) were maintained, whereas end-diastolic volume (7.9 [+ or -] 1.3 ml) did not change significantly during this period. RV systolic function improved substantially; the end-systolic pressure-volume relation shifted leftward indicated by a significantly decreased volume intercept (up to 70%), together with a slightly increased slope. In this newborn lamb model, maintenance of CO during increased RV afterload is not obtained by an increased end-diastolic volume (Frank-Starling mechanism). Instead, the RV maintains its output by improving contractile performance through homeometric autoregulation. conductance catheter; end-systolic pressure-volume relation; homeometric autoregulation; pulmonary hypertension; right ventricular function.