Performance of parental history for the targeted screening of hypertension in children.

OBJECTIVES: Several guidelines recommend universal screening for hypertension in childhood and adolescence. Targeted screening to children with parental history of hypertension could be a more efficient strategy than universal screening. Therefore, we assessed the association between parental history of hypertension and hypertension in children, and estimated the sensitivity, specificity, negative, and positive predictive values of parental history of hypertension for hypertension in children. METHODS: The present study was a school-based cross-sectional study including 5207 children aged 10-14 years from all public 6th grade classes in the Canton of Vaud, Switzerland. Children had hypertension if they had sustained elevated blood pressure over three separate visits. RESULTS: In children, the prevalence of hypertension was 2.2%. Some 8.5% of mothers and 12.9% of fathers reported to be hypertensive. Maternal history of hypertension (odds ratio 2.0, 95% confidence interval 1.2-3.3) and paternal history of hypertension (odds ratio 2.2, 95% confidence interval 1.4-3.6) were independent risk factors for hypertension in children. Nevertheless, the sensitivity of parental history of hypertension for the identification of hypertension in children was low (from 4% for both parents' positive history up to 41% for at least one parent's positive history). Positive predictive values were also low (between 4 and 5%). CONCLUSION: Children with hypertensive parents were at higher risk of hypertension. Nevertheless, parental history of hypertension helped only marginally to identify hypertension in offspring. Targeting screening only toward children with a parental history of hypertension may not be a substantially better strategy to identify hypertension in children compared with universal screening.

Interplay between connexin40 and nitric oxide signaling during hypertension.

Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.

Essential surgery: the way forward.

INTRODUCTION: Very little surgical care is performed in low- and middle-income countries (LMICs). An estimated two billion people in the world have no access to essential surgical care, and non-surgeons perform much of the surgery in remote and rural areas. Surgical care is as yet not recognized as an integral aspect of primary health care despite its self-demonstrated cost-effectiveness. We aimed to define the parameters of a public health approach to provide surgical care to areas in most need. METHODS: Consensus meetings were held, field experience was collected via targeted interviews, and a literature review on the current state of essential surgical care provision in Sub-Saharan Africa (SSA) was conducted. Comparisons were made across international recommendations for essential surgical interventions and a consensus-driven list was drawn up according to their relative simplicity, resource requirement, and capacity to provide the highest impact in terms of averted mortality or disability. RESULTS: Essential Surgery consists of basic, low-cost surgical interventions, which save lives and prevent life-long disability or life-threatening complications and may be offered in any district hospital. Fifteen essential surgical interventions were deduced from various recommendations from international surgical bodies. Training in the realm of Essential Surgery is narrow and strict enough to be possible for non-physician clinicians (NPCs). This cadre is already active in many SSA countries in providing the bulk of surgical care. CONCLUSION: A basic package of essential surgical care interventions is imperative to provide structure for scaling up training and building essential health services in remote and rural areas of LMICs. NPCs, a health cadre predominant in SSA, require training, mentoring, and monitoring. The cost of such training is vastly more efficient than the expensive training of a few polyvalent or specialist surgeons, who will not be sufficient in numbers within the next few generations. Moreover, these practitioners are used to working in the districts and are much less prone to gravitate elsewhere. The use of these NPCs performing "Essential Surgery" is a feasible route to deal with the almost total lack of primary surgical care in LMICs.

No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.

Urate is the metabolic end point of purines in humans. Although supra-physiological plasma urate levels are associated with obesity, insulin resistance, dyslipidemia, and hypertension, a causative role is debated. We previously established a mouse model of hyperuricemia by liver-specific deletion of Glut9, a urate transporter that provides urate to the hepatocyte enzyme uricase. These LG9 knockout mice show mild hyperuricemia (120 μmol/l), which can be further increased by the urate precursor inosine. Here, we explored the role of progressive hyperuricemia on the cardiovascular function. Arterial blood pressure and heart rate were periodically measured by telemetry over 6 months in LG9 knockout mice supplemented with incremental amounts of inosine in a normal chow diet. This long-term inosine treatment elicited a progressive increase in uricemia up to 300 μmol/l; however, it did not modify heart rate or mean arterial blood pressure in LG9 knockout compared with control mice. Inosine treatment did not alter cardiac morphology or function measured by ultrasound echocardiography. However, it did induce mild renal dysfunction as revealed by higher plasma creatinine levels, lower glomerular filtration rate, and histological signs of chronic inflammation and fibrosis. Thus, in LG9 knockout mice, inosine-induced hyperuricemia was not associated with hypertension despite partial renal deficiency. This does not support a direct role of urate in the control of blood pressure.

Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism.

OBJECTIVES: Prorenin can be detected in plasma of hypertensive patients. If detected in patients with primary aldosteronism could implicate prorenin in the development of primary aldosteronism. To address this issue, we measured the plasma prorenin levels in primary aldosteronism patients, the expression of the prorenin receptor (PRR) in the normal human adrenocortical zona glomerulosa and aldosterone-producing adenoma (APA), and we investigated the functional effects of PRR activation in human adrenocortical cells. METHOD: Plasma renin activity, aldosterone, and active and total trypsin-activated renin were measured in primary aldosteronism patients, essential hypertensive patients, and healthy individuals, and then prorenin levels were calculated. Localization and functional role of PRR were investigated in human and rat tissues, and aldosterone-producing cells. RESULTS: Primary aldosteronism patients had detectable plasma levels of prorenin. Using digital-droplet real-time PCR, we found a high PRR-to-porphobilinogen deaminase ratio in both the normal adrenal cortex and APAs. Marked expression of the PRR gene and protein was also found in HAC15 cells. Immunoblotting, confocal, and immunogold electron microscopy demonstrated PRR at the cell membrane and intracellularly. Renin and prorenin significantly triggered both CYP11B2 expression (aldosterone synthase) and ERK1/2 phosphorylation, but only CYP11B2 transcription was prevented by aliskiren. CONCLUSION: The presence of detectable plasma prorenin in primary aldosteronism patients, and the high expression of PRR in the normal human adrenal cortex, APA tissue, CD56+ aldosterone-producing cells, along with activation of CYP11B2 synthesis and ERK1/2 phosphorylation, suggest that the circulating and locally produced prorenin may contribute to the development or maintenance of human primary aldosteronism.

Why Mathematics is essential in Biomedical Sciences degree?

Improvement of mathematical education and motivation of students in the mathematics" area is needed. What can be done? We introduce some ideas to generate the student"s interest for mathematics, because they often present difficulties in appreciating the relevance of mathematics and its role in the health sciences. We consider that a cornerstone in the strategy to attract the students" interest is linking the mathematics with real biomedical situations. We proceed in the following manner: We first present a real biomedical situation to produce interest and to generate curiosity. Second, we ask thought-provoking questions to students as: Which is the biomedical problem presented? Which is my knowledge on this situation? What could I do to solve this biomedical situation? Do I need some new mathematical concepts and procedures? Thereupon, the teacher explains the mathematical concepts necessary to solve the case presented, providing definitions, properties and tools for graphical display and/or mathematical calculations. In this learning methodology, ICTs were cornerstones for reaching the proposed competences. Furthermore, ICTs can also be used in the evaluative task in its two possible aspects: formative and for obtaining a qualification. Comments from students about this new mathematics teaching method indicate that the use of real biomedical case studies kept the lessons in mathematics interesting.

Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.