The return of increased blood pressure after discontinuation of antihypertensive treatment is associated with an impaired post-ischemic skin blood flow response.

OBJECTIVE: To assess the post-ischemic skin blood flow response after withdrawal of antihypertensive therapy in hypertensive patients with normal blood pressure during treatment. DESIGN AND METHODS: Twenty hypertensive patients (group A) with a normal clinic blood pressure (<140/ 90 mmHg) receiving antihypertensive treatment (any monotherapy; one pill per day for at least 6 months) had their treatment discontinued. Before medication withdrawal and 2, 4, 12 and 24 weeks thereafter, the following measurements were made: clinic blood pressure, home blood pressure (three times per week, morning and evening) and skin blood flow response to a 5 min forearm arterial occlusion (using laser Doppler flowmetry). The patients were asked to perform an ambulatory blood pressure recording at any time if home blood pressure was > or =160/95 mmHg on two consecutive days, and treatment was initiated again, after determination of the skin hyperemic response, if daytime ambulatory blood pressure was > or =140/90 mmHg. The same studies were performed in 20 additional hypertensive individuals in whom antihypertensive treatment was not withdrawn (group B). The allocation of patients to groups A and B was random. RESULTS: The data fom 18 patients in group A who adhered strictly to the procedure were available for analysis. Seven of them had to start treatment again within the first 4 weeks of follow-up; four additional patients started treatment again during the next 8 weeks (group A1). The seven other patients remained untreated (group A2). The skin hyperemic response decreased significantly in patients in group A1 and returned to baseline values at the end of the study, when there were again receiving antihypertensive treatment. In patients in group A2 a significant attenuation of the hyperemic response was also observed. This impaired response was present even at the end of the 6 month follow-up, at which time the patients were still untreated but exhibited a significantly greater blood pressure than before drug discontinuation. The hyperemic response of patients who did not stop treatment (group B) did not change during the course of the study. CONCLUSIONS: Our findings show a decrease in the postischemic skin blood flow response after withdrawal of antihypertensive treatment in hypertensive patients. This impaired response may be due to the development of endothelial dysfunction, vascular remodeling, or both, and might contribute to the return of blood pressure to hypertensive values after withdrawal of antihypertensive therapy.

Effects of a whey protein supplementation on intrahepatocellular lipids in obese female patients.

Background & aims: High protein diets have been shown to improve hepatic steatosis in rodent models and in high-fat fed humans. We therefore evaluated the effects of a protein supplementation on intrahepatocellular lipids (IHCL), and fasting plasma triglycerides in obese non diabetic women.Methods: Eleven obese women received a 60 g/day whey protein supplement (WPS) for 4-weeks, while otherwise nourished on a spontaneous diet, IHCL concentrations, visceral body fat, total liver volume (MR), fasting total-triglyceride and cholesterol concentrations, glucose tolerance (standard 75 g OGTT), insulin sensitivity (HOMA IS index), creatinine clearance, blood pressure and body composition (bio-impedance analysis) were assessed before and after 4-week WPS.Results: IHCL were positively correlated with visceral fat and total liver volume at inclusion. WPS decreased significantly IHCL by 20.8 +/- 7.7%, fasting total TG by 15 +/- 6.9%, and total cholesterol by 7.3 +/- 2.7%. WPS slightly increased fat free mass from 54.8 +/- 2.2 kg to 56.7 +/- 2.5 kg, p = 0.005). Visceral fat, total liver volume, glucose tolerance, creatinine clearance and insulin sensitivity were not changed.Conclusions: WPS improves hepatic steatosis and plasma lipid profiles in obese non diabetic patients, without adverse effects on glucose tolerance or creatinine clearance. Trial Number: NCT00870077, ClinicalTrials.gov (C) 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries.

BACKGROUND: Obesity is increasing worldwide because developing countries are adopting Western high-fat foods and sedentary lifestyles. In parallel, in many of them, hypertension is rising more rapidly, particularly with age, than in Western countries. OBJECTIVE: To assess the relationship between adiposity and blood pressure (BP) in a developing country with high average BP (The Seychelles, Indian Ocean, population mainly of African origin) in comparison to a developed country with low average BP (Switzerland, population mainly of Caucasian origin). DESIGN: Cross-sectional health examination surveys based on population random samples. SETTING: The main Seychelles island (Mahé) and two Swiss regions (Vaud-Fribourg and Ticino). SUBJECTS: Three thousand one hundred and sixteen adults (age range 35-64) untreated for hypertension. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP, mean of two measures). METHODS: Scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: On average, SBP and DBP were found to increase linearly over the whole variation range of BMI, WHR and WC. A modest, but statistically significant linear association was found between each indicator of adiposity and BP levels in separate regression models controlling for age. The regression coefficients were not significantly different between the Seychelles and the two Swiss regions, but were generally higher in women than in men. For the latter, a gain of 1.7 kg/m(2) in BMI, of 4.5 cm in WC or of 3.4% in WHR corresponded to an elevation of 1 mmHg in SBP. For women, corresponding figures were 1.25 kg/m(2), 2.5 cm and 1.8% respectively. Regression coefficients for age reflected a higher effect of this variable on both SBP and DBP in the Seychelles than in Switzerland. CONCLUSION: These findings suggest a stable linear relation of adiposity with BP, independent of age and body fat distribution, across developed and developing countries. The more rapid increase of BP with age observed in the latter countries are likely to reflect higher genetic susceptibility and/or higher cumulative exposure to another risk factor than adiposity.

Reactive rise in blood pressure upon cuff inflation : cuff inflation at the arm causes a greater rise in pressure than at the wrist in hypertensive patients

Résumé en français: Il est admis que l'inflation d'une manchette à pression au niveau du bras engendre une augmentation réactionnelle de la tension artérielle qui peut être le résultat d'une gêne lors de l'inflation et peut diminuer la précision de la mesure. Dans cette étude, nous comparons séquentiellement l'augmentation de la tension artérielle lorsque la manchette à pression est positionnée au niveau du bras et au niveau du poignet. Nous avons étudié un collectif de 34 participants normotendus et 34 patients hypertendus. Chacun d'eux était équipé de deux manchettes à pression, l'une au niveau du bras et l'autre au niveau du poignet. Nous avons randomisé l'ordre d'inflation des manchettes ainsi que la pression d'inflation maximale (180mmHg versus 240mmHg). Trois mesures étaient effectuées pour chaque pression d'inflation maximale, ceci au bras comme poignet, et leur séquence était également randomisée. En parallèle, un enregistrement continu de la tension artérielle avait lieu au niveau du majeur de la main opposée à l'aide d'un photoplethysmographe. Cette valeur était considérée comme la valeur de tension artérielle au repos. Pour les participants normotendus, aucune différence statistiquement significative n'a pu être mise en évidence en lien avec la position de la manchette à pression, ceci indépendamment de la pression d'inflation maximale. Variation de la pression systolique à 180 mmHg: 4.3+/-3.0 mmHg au bras et 3.7+/-2.9 mmHg au poignet (p=ns), à 240 mmHg: 5.5+/-3.9 au bras et 4.2+/-2.7 mmHg au poignet (p=0.052). En revanche, concernant les patients hypertendus, une augmentation significative de la tension artérielle a été mise en évidence entre le bras et le poignet. Ceci pour les valeurs de tension artérielle systolique et diastolique et quelle que soit la pression d'inflation maximale utilisée. Augmentation de la pression artérielle systolique 6.513.5 mmHg au bras et 3.812.1mmHg au poignet pour une pression d'inflation maximale de 180 mmHg (p<0.01) et respectivement 6.413.5 mmHg et 4.713.0 mmHg pour 240 mmHg (p=0.01). L'augmentation des valeurs de tension artérielle était indépendante de la valeur tensionnelle de base. Ces résultats montrent que les patients hypertendus réagissent significativement moins à l'inflation d'une manchette ä pression lorsque celle-ci est positionnée au niveau du poignet par rapport au bras, ceci indépendamment des valeurs de tension artérielle de base des patients. Nous pouvons donc suggérer que l'inflation d'une manchette à pression cause moins de désagrément lorsqu'elle est placée au niveau du poignet, notamment chez les patients hypertendus et qu'elle peut être une alternative à la mesure standard au niveau du bras.

Codeine and breastfeeding: cases and STIS position

Codeine is commonly used in North America in the postpartum period for pain associated with episotomyand caesarean section. Analgesic properties of codeine are mainly due to its metabolisation intomorphine (5-10%) via CYP2D6. This enzyme is subject to genetic variability, which can alter theamount of active narcotic excreted into breastmilk. A recent case report highlighted this issue, reportingfatal consequences in a newborn whose mother was taking codeine for episiotomy-related pain (1-2). New-born's blood (post-mortem) and mother's milk showed high morphine concentrations. Genotypeanalysis classified the mother as a CYP2D6 ultrarapid metabolizer, a genotype associated withenhanced formation of morphine from codeine. The authors concluded "clinical and laboratory picturewas consistent with opioid toxicity leading to neonatal death". Subsequent comments expressed reasonnabledoubts on this conclusion, though (3-4). Since, anxiety increased about the safety of codeineduring breastfeeding and genetic screening was proposed as a prevention strategy.STIS position:? Codeine with paracetamol is not a usual pain prescription in the postpartum period in Switzerland.This markedly reduces codeine use during lactation in our country, and may partly explain why webarely collected 3 codeine exposures through breastmilk in 15 years at the STIS (all reported afterabove case's publication and without side effects).? Other centrally acting analgesics are not considered safer (5) than codeine during lactation andrequire close observation for somnolence in both the mother and the infant in case of repeated maternaldosage. A lack of monitoring was salient in the case reported above (1).? If the incidence of CYP2D6 polymorphism (1-10% of individuals in Western Europe) (6) can beconsidered of clinical significance, it is not the exclusive predisposing factor to toxic effects. Healthynewborns can be particularly sensitive to even usual doses of narcotic analgesics because of immaturedrug disposition (7). Conditions leading to impaired clearance or increased susceptibility inthe infant (e.g. preterm birth, metabolic diseases) represent further risk factors for opioid toxicity,regardless of the molecule.In conclusion, when prescribed on a large scale, codein can be rarely associated with adverse drugreactions in breastfed infants (8-9). However, other central acting analgesics cannot be considered asinvariably safer. Therefore, paracetamol and well documented NSAID should be used in 1st choiceduring lactation. In case of severe pain, codeine (with paracetamol) remains an acceptable choice butrequires close monitoring, and breastfeeding mothers should be educated regarding risks related toaccumulation in the newborn. Finally, it is doubtful whether CYP2D6 genetic screening would preventall toxic effects, as other risk factors exist for opioids toxicity

Total hemoglobin mass--a new parameter to detect blood doping?

PURPOSE: All kinds of blood manipulations aim to increase the total hemoglobin mass (tHb-mass). To establish tHb-mass as an effective screening parameter for detecting blood doping, the knowledge of its normal variation over time is necessary. The aim of the present study, therefore, was to determine the intraindividual variance of tHb-mass in elite athletes during a training year emphasizing off, training, and race seasons at sea level. METHODS: tHb-mass and hemoglobin concentration ([Hb]) were determined in 24 endurance athletes five times during a year and were compared with a control group (n = 6). An analysis of covariance was used to test the effects of training phases, age, gender, competition level, body mass, and training volume. Three error models, based on 1) a total percentage error of measurement, 2) the combination of a typical percentage error (TE) of analytical origin with an absolute SD of biological origin, and 3) between-subject and within-subject variance components as obtained by an analysis of variance, were tested. RESULTS: In addition to the expected influence of performance status, the main results were that the effects of training volume (P = 0.20) and training phases (P = 0.81) on tHb-mass were not significant. We found that within-subject variations mainly have an analytical origin (TE approximately 1.4%) and a very small SD (7.5 g) of biological origin. CONCLUSION: tHb-mass shows very low individual oscillations during a training year (<6%), and these oscillations are below the expected changes in tHb-mass due to Herythropoetin (EPO) application or blood infusion (approximately 10%). The high stability of tHb-mass over a period of 1 year suggests that it should be included in an athlete's biological passport and analyzed by recently developed probabilistic inference techniques that define subject-based reference ranges.

Regulation of free corticosterone and CBG capacity under different environmental conditions in altricial nestlings.

The concentration of circulating glucocorticoids is regulated in response to environmental and endogenous conditions. Total circulating corticosterone, the main glucocorticoid in birds, consists of a fraction which is bound to corticosterone-binding globulins (CBG) and a free fraction. There is increasing evidence that the environment modulates free corticosterone levels through varying the concentration of CBG, but experimental evidence is lacking. To test the hypothesis that the regulation of chronic stress in response to endogenous and environmental conditions involves variation in both corticosterone release and CBG capacity, we performed an experiment with barn owl (Tyto alba) nestlings in two different years with pronounced differences in environmental conditions and in nestlings experimentally fed ad libitum. In half of the individuals we implanted a corticosterone-releasing pellet to artificially increase corticosterone levels and in the other half we implanted a placebo pellet. We then repeatedly collected blood samples to measure the change in total and free corticosterone levels as well as CBG capacity. The increase in circulating total corticosterone after artificial corticosterone administration varied with environmental conditions and with the food regime of the nestlings. The highest total corticosterone levels were found in nestlings growing up in poor environmental conditions and the lowest in ad libitum fed nestlings. CBG was highest in the year with poor environmental conditions, so that, contrary to total corticosterone, free corticosterone levels were low under poor environmental conditions. When nestlings were fed ad libitum total corticosterone, CBG and free corticosterone did not increase when administering corticosterone. These results suggest that depending on the individual history an animal experienced during development the HPA-axis is regulated differently.

Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication.

The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Bi-ventricular axial micropump: impact on blood cell integrity.

BACKGROUND AND OBJECTIVE: Off-pump coronary artery bypass grafting has stimulated the development of micro-pumps designed to prevent the hemodynamic instability induced by heart luxation for the exposure of target vessels of the posterior wall. Impella (Aachen, Germany) developed micro-pumps with a miniaturized propeller system for both sides of the heart. The aim of this study was to analyze the impact of both pumps working together on blood cell integrity. MATERIALS AND METHODS: Both right and left-sided micro-pumps were implanted in 5 calves (body weight, 72_4 Kg) during 3 h. Blood samples for hematology and hemolysis parameters were drawn hourly. RESULTS: Both pumps performed well with a flow of 3.6 L +/- 0.3 L during the 3 h of the experiment with stable hemodynamic conditions. Mixed venous oxygen saturation was 63.4 +/- 15.2% at baseline and 63.8 +/- 16.3% at the end of the experiment (P = ns). Red cell count, LDH and free plasma hemoglobin were 6.7 +/- 2.1 x 10(12)/L, 1807 +/- 437 IU/L, and 32 +/- 9 mg/L at baseline vs. 6.1 +/- 2.1 x 10(12)/L, 1871 +/- 410 IU/L, and 52 +/- 9 mg/L at the end of the experiment (P = ns for all comparisons). Platelet count exhibited a non-significant drop (872 +/- 126 vs. 715 +/- 22 x 10(9)/L). CONCLUSIONS: This double pump system based on the Archimed screw principle is hematologically well tolerated under conditions of prolonged cardiac assist.

Direct analysis of dried blood spots coupled with mass spectrometry: concepts and biomedical applications.

Because of the emergence of dried blood spots (DBS) as an attractive alternative to conventional venous plasma sampling in many pharmaceutical companies and clinical laboratories, different analytical approaches have been developed to enable automated handling of DBS samples without any pretreatment. Associated with selective and sensitive MS-MS detection, these procedures give good results in the rapid identification and quantification of drugs (generally less than 3 min total run time), which is desirable because of the high throughput requirements of analytical laboratories. The objective of this review is to describe the analytical concepts of current direct DBS techniques and to present their advantages and disadvantages, with particular focus on automation capacity and commercial availability. Finally, an overview of the different biomedical applications in which these concepts could be of major interest will be presented.