Effect on blood pressure and the renin-angiotensin system of repeated doses of the converting enzyme inhibitor CGS 14824A.

A new, orally active angiotensin converting enzyme (ACE) inhibitor, CGS 14824A, was evaluated in 12 healthy male volunteers. Two groups each of 6 volunteers were given 5 or 10 mg once daily p.o. for 8 days. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone and plasma converting enzyme activity had fallen, while blood angiotensin I and plasma renin activity had risen. Throughout the study, more than 90% inhibition of ACE was found immediately before giving either the 5 or 10 mg dose and 50% blockade was still present 72 h following the last dose. Based on the determination of ACE, there was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed during the course of the study. CGS 14824A was an effective, orally active, long-lasting and well tolerated converting enzyme inhibitor.

Changes in spring-mass model characteristics during repeated running sprints.

This study investigated fatigue-induced changes in spring-mass model characteristics during repeated running sprints. Sixteen active subjects performed 12 × 40 m sprints interspersed with 30 s of passive recovery. Vertical and anterior-posterior ground reaction forces were measured at 5-10 m and 30-35 m and used to determine spring-mass model characteristics. Contact (P < 0.001), flight (P < 0.05) and swing times (P < 0.001) together with braking, push-off and total stride durations (P < 0.001) lengthened across repetitions. Stride frequency (P < 0.001) and push-off forces (P < 0.05) decreased with fatigue, whereas stride length (P = 0.06), braking (P = 0.08) and peak vertical forces (P = 0.17) changes approached significance. Center of mass vertical displacement (P < 0.001) but not leg compression (P > 0.05) increased with time. As a result, vertical stiffness decreased (P < 0.001) from the first to the last repetition, whereas leg stiffness changes across sprint trials were not significant (P > 0.05). Changes in vertical stiffness were correlated (r > 0.7; P < 0.001) with changes in stride frequency. When compared to 5-10 m, most of ground reaction force-related parameters were higher (P < 0.05) at 30-35 m, whereas contact time, stride frequency, vertical and leg stiffness were lower (P < 0.05). Vertical stiffness deteriorates when 40 m run-based sprints are repeated, which alters impact parameters. Maintaining faster stride frequencies through retaining higher vertical stiffness is a prerequisite to improve performance during repeated sprinting.

Percutaneous central venous catheterization in premature infants: a method for facilitating insertion of silastic catheters via peripheral veins.

Peripheral venous cannulation is the preferred method of inserting central venous silastic catheters in premature infants. The standard techniques are placement of the catheter using a breakaway introducer needle or introduction of the catheter through a cannula. In extremely low birth weight infants (<1000 g) successful cannulation is impeded by the small size of the vessels. After repeated attempts, both procedures can be time-consuming and stressful to the infant. We present a modified insertion technique of the standard 2-French silastic catheter with an increased success rate, thus reducing insertion time, stress to the infant, and costs. The method uses the tip of a 20-gauge cannula as dilator/introducer for the 2-French catheter. This tip is inserted into the vessel with a standard 24-gauge cannula. After successful insertion of the dilator/introducer cannula, the standard 2-French catheter can then be advanced easily.

Estimating the probability of leaving unemployment using uncompleted spells from repeated cross-section data

We propose a new econometric estimation method for analyzing the probabilityof leaving unemployment using uncompleted spells from repeated cross-sectiondata, which can be especially useful when panel data are not available. Theproposed method-of-moments-based estimator has two important features:(1) it estimates the exit probability at the individual level and(2) it does not rely on the stationarity assumption of the inflowcomposition. We illustrate and gauge the performance of the proposedestimator using the Spanish Labor Force Survey data, and analyze the changesin distribution of unemployment between the 1980s and 1990s during a periodof labor market reform. We find that the relative probability of leavingunemployment of the short-term unemployed versus the long-term unemployedbecomes significantly higher in the 1990s.

Dispersion of natural arsenic in the Malcantone watershed, Southern Switzerland: field evidence for repeated sorption-desorption and oxidation-reduction processes

In recent years, elevated arsenic concentrations have been found in waters and soils of many, countries, often resulting in a health threat for the local population. Switzerland is not an exception and this paper deals with the release and subsequent fate of arsenic in a 200-km(2) mountainous watershed, characterized by crystalline silicate rocks (gneisses, schists, amphibolites) that contain abundant As-bearing sulfide ore deposits, some of which have been mined for iron and gold in the past. Using analytical methods common for mineralogical, ground water and soil studies (XRD, XRF, XAS-XANES and -EXAFS, electron microprobe, extraction, ICP, AAS with hydride generator, ion chromatography), seven different field situations and related dispersion processes of natural arsenic have been studied: (1) release by rock weathering, (2) transport and deposition by water and ice; (3) release of As to the ground and surface water due to increasing pH; (4) accumulation in humic soil horizons; (5) remobilization by reduction in water-saturated soils and stagnant ground waters; (6) remobilization by using P-rich fertilizers or dung and (7) oxidation, precipitation and dilution in surface waters. Comparison of the results with experimental adsorption studies and speciation diagrams from the literature allows us to reconstruct and identify the typical behavior of arsenic in a natural environment under temperate climatic conditions. The main parameters identified are: (a) once liberated from the primary minerals, sorption processes on Fe-oxy-hydroxides dominate over Al-phases, such as Al-hydroxides or clay minerals and limit the As concentrations in the spring and well waters between 20 and 300 mug/l. (b) Precipitation as secondary minerals is limited to the weathering domain, where the As concentrations are still high and not yet too diluted by rain and soils waters. (c) Although neutral and alkaline pH conditions clearly increase the mobility of As, the main factor to mobilize As is a low redox potential (Eh close or below 0 mV), which favors the dissolution of the Fe-oxy-hydroxides on which the As is sorbed. (d) X-ray absorption spectroscopy (XAS) of As in water-logged humic forest soils indicates that the reduction to As III only occurs at the solid-water interface and that the solid contains As as As V (e) A and Bh horizons of humic cambisols can effectively capture As when As-rich waters flow through them. Complex spatial and temporal variation of the various parameters in a watershed results in repeated mobilization and immobilization of As, which continuously transports As from the upper to the lower part of a watershed and ultimately to the ocean. (C) 2004 Elsevier B.V. All rights reserved.

Weak and strong altruism in traitgGroups: Reproductive suicide, personal fitness and expected value

A simple variant of trait group selection, employing predators as themechanism underlying group selection, supports contingent reproductivesuicide as altruism (i.e., behavior lowering personal fitness whileaugmenting that of another) without kin assortment. The contingentsuicidal type may either saturate the population or be polymorphicwith a type avoiding suicide, depending on parameters. In addition tocontingent suicide, this randomly assorting morph may also exhibitcontinuously expressed strong altruism (sensu Wilson 1979) usuallythought restricted to kin selection. The model will not, however,support a sterile worker caste as such, where sterility occurs beforelife history events associated with effective altruism; reproductivesuicide must remain fundamentally contingent (facultative sensu WestEberhard 1987; Myles 1988) under random assortment. The continuouslyexpressed strong altruism supported by the model may be reinterpretedas probability of arbitrarily committing reproductive suicide, withoutbenefit for another; such arbitrary suicide (a "load" on "adaptive"suicide) is viable only under a more restricted parameter spacerelative to the necessarily concomitant adaptive contingent suicide.

Effects of prior repeated-sprints with different recovery duration on oxygen uptake kinetics during subsequent heavy-exercise

Introduction: Prior repeated-sprints (6) has become an interesting method to resolve the debate surrounding the principal factors that limits the oxygen uptake (V'O2) kinetics at the onset of exercise [i.e., muscle O2 delivery (5) or metabolic inertia (3)]. The aim of this study was to compare the effects of two repeated-sprints sets of 6x6s separated by different recovery duration between the sprints on V'O2 and muscular de-oxygenation [HHb] kinetics during a subsequent heavy-intensity exercise. Methods: 10 male subjects performed a 6-min constant-load cycling test (T50) at intensity corresponding to half of the difference between V'O2max and the ventilatory threshold. Then, they performed two repeated-sprints sets of 6x6s all-out separated by different recovery duration between the sprints (S1:30s and S2:3min) followed, after 7-min-recovery, by the T50 (S1T50 and S2T50, respectively). V'O2, [HHb] of the vastus lateralis (VL) and surface electromyography activity [i.e., root-mean-square (RMS) and the median frequency of the power density spectrum (MDF)] from VL and vastus medialis (VM) were recorded throughout T50. Models using a bi-exponential function for the overall T50 and a mono-exponential for the first 90s of T50 were used to define V'O2 and [HHb] kinetics respectively. Results: V'O2 mean value was higher in S1 (2.9±0.3l.min-1) than in S2 (1.2±0.3l.min-1); (p<0.001). The peripheral blood flow was increased after sprints as attested by a higher basal heart rate (HRbaseline) (S1T50: +22%; S2T50: +17%; p≤0.008). Time delay [HHb] was shorter for S1T50 and S2T50 than for T50 (-22% for both; p≤0.007) whereas the mean response time of V'O2 was accelerated only after S1 (S1T50: 32.3±2.5s; S2T50: 34.4±2.6s; T50: 35.7±5.4s; p=0.031). There were no significant differences in RMS between the three conditions (p>0.05). MDF of VM was higher during the first 3-min in S1T50 than in T50 (+6%; p≤0.05). Conclusion: The study show that V'O2 kinetics was speeded by prior repeated-sprints with a short (30s) but not a long (3min) inter-sprints-recovery even though the [HHb] kinetics was accelerated and the peripheral blood flow was enhanced after both sprints. S1, inducing a greater PCr depletion (1) and change in the pattern of the fibres recruitment (increase in MDF) compared with S2, may decrease metabolic inertia (2), stimulate the oxidative phosphorylation activation (4) and accelerate V'O2 kinetics at the beginning of the subsequent high-intensity exercise.

Fatal tolperisone poisoning: autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10 g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0 mg/l, 14 mg/l and 19 mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.

The response of a Swiss university hospital's palliative care consult team to assisted suicide within the institution.

In January 2006 the Centre Hospitalier Universitaire Vaudois (CHUV), a large university hospital in Lausanne, Switzerland, became the first hospital in Switzerland to allow assisted suicide (AS) in exceptional cases within its walls. However, euthanasia is illegal. This decision has posed several ethical and practical dilemmas for the hospital's palliative care consult service. To address these, the team embarked on a formal process of open dialogue amongst its members with the goal of identifying a collective response and position. This process involved meetings every 4 to 6 weeks over the course of 10 months. An iterative process unfolded. One of the principal dilemmas relates to finding a balance between the team's position against AS and the patient's autonomy and the institution's directive. Although all team members expressed opposition to AS, there were mixed opinions as to whether or not the team members should be present during the act if requested so by patients. Some thought this could be misinterpreted as complicity in the act and could send out mixed messages to the public and other health professionals about palliative care. Others felt that the team's commitment to nonabandonment obliged them to be present even if they did not provide the drug or give any advice or assistance. The implications of nonabandonment are explored, as are several other questions such as whether or not the teams are obliged to provide detailed information on AS when requested by patients.

Ultrasound assessment of ocular vascular effects of repeated intravitreal injections of ranibizumab for wet age-related macular degeneration.

PURPOSE: Determine the effect of repeated intravitreal injections of ranibizumab (0.5 mg; 0.05 ml) on retrobulbar blood flow velocities (BFVs) using ultrasound imaging quantification in twenty patients with exudative age-related macular degeneration treated for 6 months. METHODS: Visual acuity (ETDRS), central macular thickness (OCT), peak-systolic, end-diastolic and mean-BFVs in central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries were measured before, 2 days, 3 weeks and 6 months after the first injection. Patients were examined monthly and received 1-5 additional injections depending on ophthalmologic examination results. RESULTS: Six months after the first injection, a significant increase in visual acuity 50.9 ± 25.9 versus 44.4 ± 21.7 (p < 0.01) and decrease in mean central macular thickness 267 ± 74 versus 377 ± 115 μm (p < 0.001) were observed compared to baseline. Although mean-BFVs decreased by 16%±3% in CRA and 20%±5% in TPCA (p < 0.001) 2 days after the first injection, no significant change was seen thereafter. Mean-BFVs in OA decreased by 19%±5% at week 3 (p < 0.001). However, the smallest number of injections (two injections) was associated with the longest time interval between the last injection and month 6 (20 weeks) and with the best return to baseline levels for mean-BFVs in CRA, suggesting that ranibizumab had reversible effects on native retinal vascular supply after its discontinuation. Moreover, a significant correlation between the number of injections and percentage of changes in mean-BFVs in CRA was observed at month 6 (R = 0.74, p < 0.001) unlike TPCA or OA. CONCLUSION: Ranibizumab could impair the native choroidal and retinal vascular networks, but its effect seems reversible after its discontinuation.

Repeated surgical excision for an unusual variant of nephroblastoma: case report and review of the literature.

Bilateral fetal rhabdomyomatous nephroblastoma is a rare variant of Wilms' Tumor. The authors report the evolution over 48 months of a 10-month-old baby with bilateral nephroblastoma for which a left nephrectomy was initially performed. A right kidney tumor was enucleated preserving the kidney. The transformation of the primary tumor into a completely differentiated cystic nephroblastoma or nephromalike tumor and the appearance of a metachronous lesion was seen. This report emphasizes the role of nephron-sparing surgery in bilateral Wilms' Tumor when a benign transformation occurs under chemotherapy.

Neurobiology of suicide: do biomarkers exist?

Clinical risk factors have a low predictive value on suicide. This may explain the increasing interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. This review aims to present the current neurobiological findings that have been shown to be implicated in suicide completers and to discuss how postmortem studies may be useful in characterizing these individuals. Data on the role of the main neurobiological systems in suicidality, such as the neurotransmitter families, hypothalamic-pituitary-adrenal axis, neurotrophic factors, and polyamines, are exposed at the different biochemical, genetic, and epigenetic levels. Some neuroanatomic and neuropathological aspects as well as their in vivo morphological and functional neuroimaging correlates are also described. Except for the serotoninergic system, particularly with respect to the polymorphism of the gene coding for the serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor, data did not converge to produce a univocal consensus. The possible limitations of currently published studies are discussed, as well as the scope for long-term prospective studies.

Estimates of genetic parameters of trotting performance traits for repeated annual records

Selostus: Ravihevosten jalostettavia ominaisuuksia kuvaavien kilpailumittojen perinnölliset tunnusluvut

Treatment of suicide attempters prior to hospital admission

Résumé : De nombreux auteurs ont rapporté des sérieux problèmes dans le traitement des patients suicidaires. Cette étude a examiné le traitement que des patients, ayant commis une tentative de suicide avant leur admission à un hôpital psychiatrique en Suisse, ont eu avant leur tentamen. 31 patients ont été admis à l'hôpital pendant l'année 2000, ce qui représente 36 tentamen et cela correspond à 6,5 ci/0 du nombre annuel d'admissions. Trois de ces patients ont été admis deux fois, et un patient a été admis trois fois. Des entrevues personnelles ont permis de rassembler l'information sur le traitement précédent l'hospitalisation : la médication et son dosage, à un mois et à deux semaines avant la tentative de suicide, et si le patient avait bénéficié d'une psychothérapie. En outre, des détails sur l'aspect psychosocial du tentamen et les moyens utilisés pour la tentative de suicide ont été enregistrés. Des médicaments psychotropes avaient été prescrits dans 24 situations à 21 patients, mais seulement dans 17 événements qui concernent 15 patients, des antidépresseurs avaient été prescrits avant l'hospitalisation. Des antipsychotiques et des benzodiazépines ont été prescrits dans 6 et 21 situations (8 situations avec des hypnotiques). Aucun des patients n'avait été traité avec du lithium, pourtant connu pour diminuer la suicidalité chez des patients à risque. Dans 19 situations, 16 patients avaient reçu la psychothérapie avant l'admission. Dans 32 situations, des médicaments psychotropes ont été employés pour le tentamen. En conclusion, ces résultats confirment le sous-traitement de patients qui commettent une tentative de suicide, comme déjà rapporté par d'autres auteurs. Bien que la majorité de patients ait été soignée par un psychiatre, aucune pharmacothérapie adéquate n'avait été prescrite, en particulier pour des patients dépressifs.