Cholestérol, pression artérielle et fumée de cigarette dans la population en Suisse: le projet MONICA. [Cholesterol, blood-pressure and cigarette-smoking in switzerland - the MONICA-project].

Elevated plasma cholesterol, high blood pressure and cigarette smoking are three major risk factors for coronary heart disease. Within the framework of Switzerland's participation in the multicenter study MONICA (MONItoring of trends and determinants in CArdiovascular disease), proposed by the WHO, a first risk factor survey was conducted in a representative sample of the population (25-74 years) of two reporting units (cantons of Vaud and Fribourg, canton of Tessin). A high blood cholesterol level (>6,7 mmol/l) is the most common risk factor for coronary heart disease among the studied population. Among men, about 13% have elevated blood pressure, the proportion being about one in ten among women; these proportions increase with age and are slightly above these values in Tessin. Cigarette smoking is still a common behavior; between 25 and 45 years one third of the population (male and female) regularly smoke cigarettes.

Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients.

ABSTRACT: BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg.h/L, range for the 7 patients: 40-118 mg.h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg.h/L, range: 44-118 mg.h/L). CONCLUSIONS: Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

Adiposity indicators and blood pressure in children: nothing beyond body mass index?

Obesity is a major risk factor for elevated blood pressure in children. For instance, in a school-based study of 5207 children aged 10-12 years, the prevalence of hypertension, which is sustained elevated blood pressure over several visits, was 1.5%, 3.9% and 17.5% in normal weight, overweight and obese children, respectively. High body mass index (BMI) is commonly used to define overweight and obesity. However, because BMI is merely a proxy for adiposity, there is a longstanding debate about its performance to predict elevated blood pressure (or any other health conditions associated with adiposity) and whether other adiposity indicators, such as waist circumference, waist-to-hip ratio or hip circumference, should not be preferred... In this study, 7.4% of boys and 6.4% of girls had elevated blood pressure. The adiposity indicators were highly correlated to each other, apart from weight, waist-to-hip ratio and skinfold thickness z-scores. All indicators were associated with blood pressure. The ability to identify children with elevated blood pressure, assessed by the area under the receiver operating curve (AUC) statistic, was superior for BMI, body adiposity index and waist-to-height ratio z-scores compared with other indicators. BMI z-scores had a slightly higher AUC than other indicators. The authors concluded that BMIz-scores could be a better predictor of elevated blood pressure in children than other adiposity indicators.

Online estimation of respiratory mechanics in non-invasive pressure support ventilation: a bench model study.

An online algorithm for determining respiratory mechanics in patients using non-invasive ventilation (NIV) in pressure support mode was developed and embedded in a ventilator system. Based on multiple linear regression (MLR) of respiratory data, the algorithm was tested on a patient bench model under conditions with and without leak and simulating a variety of mechanics. Bland-Altman analysis indicates reliable measures of compliance across the clinical range of interest (± 11-18% limits of agreement). Resistance measures showed large quantitative errors (30-50%), however, it was still possible to qualitatively distinguish between normal and obstructive resistances. This outcome provides clinically significant information for ventilator titration and patient management.

Estimation of dynamic latent variable models using simulated nonparametric moments

Abstract. Given a model that can be simulated, conditional moments at a trial parameter value can be calculated with high accuracy by applying kernel smoothing methods to a long simulation. With such conditional moments in hand, standard method of moments techniques can be used to estimate the parameter. Because conditional moments are calculated using kernel smoothing rather than simple averaging, it is not necessary that the model be simulable subject to the conditioning information that is used to define the moment conditions. For this reason, the proposed estimator is applicable to general dynamic latent variable models. It is shown that as the number of simulations diverges, the estimator is consistent and a higher-order expansion reveals the stochastic difference between the infeasible GMM estimator based on the same moment conditions and the simulated version. In particular, we show how to adjust standard errors to account for the simulations. Monte Carlo results show how the estimator may be applied to a range of dynamic latent variable (DLV) models, and that it performs well in comparison to several other estimators that have been proposed for DLV models.

Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring

OBJECTIVE: To reach a consensus on the clinical use of ambulatory blood pressure monitoring (ABPM). METHODS: A task force on the clinical use of ABPM wrote this overview in preparation for the Seventh International Consensus Conference (23-25 September 1999, Leuven, Belgium). This article was amended to account for opinions aired at the conference and to reflect the common ground reached in the discussions. POINTS OF CONSENSUS: The Riva Rocci/Korotkoff technique, although it is prone to error, is easy and cheap to perform and remains worldwide the standard procedure for measuring blood pressure. ABPM should be performed only with properly validated devices as an accessory to conventional measurement of blood pressure. Ambulatory recording of blood pressure requires considerable investment in equipment and training and its use for screening purposes cannot be recommended. ABPM is most useful for identifying patients with white-coat hypertension (WCH), also known as isolated clinic hypertension, which is arbitrarily defined as a clinic blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic. Some experts consider a daytime blood pressure below 130 mmHg systolic and 80 mmHg diastolic optimal. Whether WCH predisposes subjects to sustained hypertension remains debated. However, outcome is better correlated to the ambulatory blood pressure than it is to the conventional blood pressure. Antihypertensive drugs lower the clinic blood pressure in patients with WCH but not the ambulatory blood pressure, and also do not improve prognosis. Nevertheless, WCH should not be left unattended. If no previous cardiovascular complications are present, treatment could be limited to follow-up and hygienic measures, which should also account for risk factors other than hypertension. ABPM is superior to conventional measurement of blood pressure not only for selecting patients for antihypertensive drug treatment but also for assessing the effects both of non-pharmacological and of pharmacological therapy. The ambulatory blood pressure should be reduced by treatment to below the thresholds applied for diagnosing sustained hypertension. ABPM makes the diagnosis and treatment of nocturnal hypertension possible and is especially indicated for patients with borderline hypertension, the elderly, pregnant women, patients with treatment-resistant hypertension and patients with symptoms suggestive of hypotension. In centres with sufficient financial resources, ABPM could become part of the routine assessment of patients with clinic hypertension. For patients with WCH, it should be repeated at annual or 6-monthly intervals. Variation of blood pressure throughout the day can be monitored only by ABPM, but several advantages of the latter technique can also be obtained by self-measurement of blood pressure, a less expensive method that is probably better suited to primary practice and use in developing countries. CONCLUSIONS: ABPM or equivalent methods for tracing the white-coat effect should become part of the routine diagnostic and therapeutic procedures applied to treated and untreated patients with elevated clinic blood pressures. Results of long-term outcome trials should better establish the advantage of further integrating ABPM as an accessory to conventional sphygmomanometry into the routine care of hypertensive patients and should provide more definite information on the long-term cost-effectiveness. Because such trials are not likely to be funded by the pharmaceutical industry, governments and health insurance companies should take responsibility in this regard.

The imidazoline receptors and the central regulation of the arterial blood pressure: a minireview

Recently, we proposed the hypothesis according to wich the central hypotensive effect of clonidine and related substances could be related to an action upon specific receptors, requiring the imidazoline or imidazoline-like structures, rather than alpha2-adrenoceptors. Since then, direct evidences have been accumulated to confirm the existence of a population of imidazoline specific binding sites in the brainstem of animals and man, more precisely in the Nucleus Reticularis Lateralis (NRL) region of the ventrolateral medulla (VLM), site of the antihypertensive action of clonidine. The purification of the putative endogenous ligand of the imidazoline receptors - named endazoline - is currently being attempted from human brain extracts. This new concept might at last lead to the expected dissociation of the pharmacological mechanisms involved, on the one hand, in the therapeutic antihypertensive effect, and on the other, in their major side-effect, which is sedation. In fact, it has been recently confirmed that hypotension is mediated by the activation of imidazoline preferring receptors (IPR) within the NRL region, while sedation is attributed to the inhibition of alpha2-adrenergic mechanisms in the locus coeruleus, which is involved in the control of the sleep-waking cycle. The IPRmay constitute on interesting target for new drugs in the treatment of arterial hypertension. Finally, dysfunctions of this modulatory system which could be involved in the pathophysiologyof some forms of the hypertensive disease are under investigation.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to mutation T494m in the Prpf3 gene

Purpose:to describe the clinical features in a five generations family segregating autosomal dominant retinitis pigmentosa and to identify the causative gene Patient and Methods:Twenty five individuals of a large five-generation family originating from Western Switzerland were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldman perimetry and digital fundus photography. Some patients had autofluorescence (AF) imaging, ocular coherence tomography (OCT) and ISCEV-standard full-field electroretinography (ERG). Blood samples were collected from 10 affected (4 to 70 years of age) and 15 unaffected members after informed consent. DNA was isolated and exons and intron-exons junctions of known adRP genes were sequenced using a Big Dye sequencing kit 1.1. Results:Age of onset of nightblindness and severity of progression of the disease was variable between members of the family. Some patients had early onset of nightblindess aged 3, others at mid-twenties. Most patients had visual acuity above 0.6 for the first 4 decades. Two older patients still had good vision (0.4) in their seventies. Myopia (range: -2 to -5) was noticed in most affected subjects. Fundus findings showed areas of atrophy along the arcades. The AF imaging showed a large high density ring bilaterally. A T494M change was found in exon 11 of PRPF3 gene. The change segregates with the disease in the family. Conclusion: A mutation in the PRPF3 gene is rare compared with other genes causing ADRP. Although a T494M change has been reported, our family is the first one with a variable expressivity. Mutations in PRPF3 gene can cause a variable phenotype of ADRP unlike the previously described Danish and English families. Our report gives a better understanding as to the phenotype/genotype description of ADRP due to PRPF3 mutation.

Genetic architecture of ambulatory blood pressure in the general population: insights from cardiovascular gene-centric array.

Genetic determinants of blood pressure are poorly defined. We undertook a large-scale, gene-centric analysis to identify loci and pathways associated with ambulatory systolic and diastolic blood pressure. We measured 24-hour ambulatory blood pressure in 2020 individuals from 520 white European nuclear families (the Genetic Regulation of Arterial Pressure of Humans in the Community Study) and genotyped their DNA using the Illumina HumanCVD BeadChip array, which contains ≈50 000 single nucleotide polymorphisms in >2000 cardiovascular candidate loci. We found a strong association between rs13306560 polymorphism in the promoter region of MTHFR and CLCN6 and mean 24-hour diastolic blood pressure; each minor allele copy of rs13306560 was associated with 2.6 mm Hg lower mean 24-hour diastolic blood pressure (P=1.2×10(-8)). rs13306560 was also associated with clinic diastolic blood pressure in a combined analysis of 8129 subjects from the Genetic Regulation of Arterial Pressure of Humans in the Community Study, the CoLaus Study, and the Silesian Cardiovascular Study (P=5.4×10(-6)). Additional analysis of associations between variants in gene ontology-defined pathways and mean 24-hour blood pressure in the Genetic Regulation of Arterial Pressure of Humans in the Community Study showed that cell survival control signaling cascades could play a role in blood pressure regulation. There was also a significant overrepresentation of rare variants (minor allele frequency: <0.05) among polymorphisms showing at least nominal association with mean 24-hour blood pressure indicating that a considerable proportion of its heritability may be explained by uncommon alleles. Through a large-scale gene-centric analysis of ambulatory blood pressure, we identified an association of a novel variant at the MTHFR/CLNC6 locus with diastolic blood pressure and provided new insights into the genetic architecture of blood pressure.