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.

Resistance to oxidative stress is associated with metastasis in mucocutaneous leishmaniasis.

Mucocutaneous leishmaniasis (MCL) in South and Central America is characterized by the dissemination (metastasis) of Leishmania Viannia subgenus parasites from a cutaneous lesion to nasopharyngeal tissues. Little is known about the pathogenesis of MCL, especially with regard to the virulence of the parasites and the process of metastatic dissemination. We previously examined the functional relationship between cytoplasmic peroxiredoxin and metastatic phenotype using highly, infrequently, and nonmetastatic clones isolated from an L. (V.) guyanensis strain previously shown to be highly metastatic in golden hamsters. Distinct forms of cytoplasmic peroxiredoxin were identified and found to be associated with the metastatic phenotype. We report here that peroxidase activity in the presence of hydrogen peroxide and infectivity differs between metastatic and nonmetastatic L. (V.) guyanensis clones. After hydrogen peroxide treatment or heat shock, peroxiredoxin was detected preferentially as dimers in metastatic L. (V.) guyanensis clones and in L. (V.) panamensis strains from patients with MCL, compared with nonmetastatic parasites. These data provide evidence that resistance to the first microbicidal response of the host cell by Leishmania promastigotes is linked to peroxiredoxin conformation and may be relevant to intracellular survival and persistence, which are prerequisites for the development of metastatic disease.

Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Estudi de la configuració magnètica de l'experiment LTP (LISA Technology Package)

La Teoria de la Relativitat General preveu que quan un objecte massiu és sotmès a una certa acceleració en certes condicions ha d’emetre ones gravitacionals. Es tracta d’un tipus d’on altament energètica però que interacciona amb la matèria de manera molt feble i el seu punt d’emissió és força llunyà. Per la qual cosa la seva detecció és una tasca extraordinàriament complicada. Conseqüentment, la detecció d’aquestes ones es creu molt més factible utilitzant instruments situats a l’espai. Amb aquest objectiu, neis la missió LISA (Laser Interferometer Space Antenna). Es tracta aquesta d’una missió conjunta entre la NASA i l’ESA amb llançament previst per 2020-2025. Per reduir els riscs que comporta una primera utilització de tecnologia no testejada, unit a l’alt cost econòmic de la missió LISA. Aquesta missió contindrà instruments molt avançats: el LTP (LISA Technoplogy Package), desenvolupat per la Unió Europea, que provarà la tecnologia de LISA i el Drag Free flying system, que s’encarregarà de provar una sèrie de propulsors (thrusters) utilitzats per al control d’actitud i posició de satèl•lit amb precisió de nanòmetres. Particularment, el LTP, està composat per dues masses de prova separades per 35 centímetres, i d’un interferòmetre làser que mesura la variació de la distància relativa entre elles. D’aquesta manera, el LTP mesurarà les prestacions dels equips i les possibles interferències que afecten a la mesura. Entre les fonts de soroll es troben, entre d’altres, el vent i pressió de radiació solar, les càrregues electrostàtiques, el gradient tèrmic, les fluctuacions de voltatge o les forces internes. Una de les possibles causes de soroll és aquella que serà l’objecte d’estudi en aquest projecte de tesi doctoral: la presència dintre del LTP de camps magnètics, que exerceixen una força sobre les masses de prova, la seva estimació i el seu control, prenent en compte les caracterírstiques magnètiques de l’experiment i la dinàmica del satèl•lit.

PPARβ/δ prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism.

AIM/HYPOTHESIS: Endoplasmic reticulum (ER) stress, which is involved in the link between inflammation and insulin resistance, contributes to the development of type 2 diabetes mellitus. In this study, we assessed whether peroxisome proliferator-activated receptor (PPAR)β/δ prevented ER stress-associated inflammation and insulin resistance in skeletal muscle cells. METHODS: Studies were conducted in mouse C2C12 myotubes, in the human myogenic cell line LHCN-M2 and in skeletal muscle from wild-type and PPARβ/δ-deficient mice and mice exposed to a high-fat diet. RESULTS: The PPARβ/δ agonist GW501516 prevented lipid-induced ER stress in mouse and human myotubes and in skeletal muscle of mice fed a high-fat diet. PPARβ/δ activation also prevented thapsigargin- and tunicamycin-induced ER stress in human and murine skeletal muscle cells. In agreement with this, PPARβ/δ activation prevented ER stress-associated inflammation and insulin resistance, and glucose-intolerant PPARβ/δ-deficient mice showed increased phosphorylated levels of inositol-requiring 1 transmembrane kinase/endonuclease-1α in skeletal muscle. Our findings demonstrate that PPARβ/δ activation prevents ER stress through the activation of AMP-activated protein kinase (AMPK), and the subsequent inhibition of extracellular-signal-regulated kinase (ERK)1/2 due to the inhibitory crosstalk between AMPK and ERK1/2, since overexpression of a dominant negative AMPK construct (K45R) reversed the effects attained by PPARβ/δ activation. CONCLUSIONS/INTERPRETATION: Overall, these findings indicate that PPARβ/δ prevents ER stress, inflammation and insulin resistance in skeletal muscle cells by activating AMPK.

The Security Council and the Legitimacy of the Use of Force: Legal, Normative, and Social Aspects.

Tal i com estableix la Carta de les Nacions Unides, el Consell de Seguretat determina l’existència d’una amenaça a la pau, un trencament de la pau o un acte d’agressió i decideix les mesures que han de fer-se servir per restaurar la pau i seguretat internacionals, també l’ús de la força. L’objectiu d’aquest article és explorar la legitimitat d’aquest ús de la força. Amb aquest objectiu, el text parteix d’una definició centrada en les seves dimensions legal, normativa i social. En segon lloc, s’analitzarà com aquestes dimensions estan representades als debats del Consell de Seguretat de la guerra d’Irak de 2003, un dels usos de la força més controvertits i que més debat ha generat als darrers anys. Finalment, l’anàlisi proposat permet treure algunes conclusions sobre les bases canviants de la legitimitat de l’ús de la força.

Effects of corticosterone pellets on baseline and stress-induced corticosterone and corticosteroid-binding-globulin.

Exogenous administration of glucocorticoids is a widely used and efficient tool to investigate the effects of elevated concentrations of these hormones in field studies. Because the effects of corticosterone are dose and duration-dependent, the exact course of plasma corticosterone levels after exogenous administration needs to be known. We tested the performance of self-degradable corticosterone pellets (implanted under the skin) in elevating plasma corticosterone levels. We monitored baseline (sampled within 3min after capture) total corticosterone levels and investigated potential interactions with corticosteroid-binding-globulin (CBG) capacity and the endogenous corticosterone response to handling in Eurasian kestrel Falco tinnunculus and barn owl Tyto alba nestlings. Corticosterone pellets designed for a 7-day-release in rodents elevated circulating baseline total corticosterone during only 2-3 days compared to placebo-nestlings. Highest levels occurred 1-2days after implantation and levels decreased strongly thereafter. CBG capacity was also increased, resulting in a smaller, but still significant, increase in baseline free corticosterone levels. The release of endogenous corticosterone as a response to handling was strong in placebo-nestlings, but absent 2 and 8 days after corticosterone pellet implantation. This indicates a potential shut-down of the hypothalamo-pituitary-adrenal axis after the 2-3 days of elevated baseline corticosterone levels. 20 days after pellet implantation, the endogenous corticosterone response to handling of nestlings implanted with corticosterone pellets attained similar levels as in placebo-nestlings. Self-degradable pellets proved to be an efficient tool to artificially elevate circulating baseline corticosterone especially in field studies, requiring only one intervention. The resulting peak-like elevation of circulating corticosterone, the concomitant elevation of CBG capacity, and the absence of an endogenous corticosterone response to an acute stressor have to be taken into account.

Assaigs Stress Corrosion Cracking (SCC)

En aquest projecte es presenta la realització d’un sistema d’assaig de la corrosió sota tensió (stress corrosion cracking, SCC) i un estudi de l’efecte de l’SCC sobre dos acers d’eina per matrius d’estampació en calent. L’SCC és la formació i propagació d’esquerdes en un material degut a la interacció de tres factors: un medi corrosiu, un material susceptible i una tensió estàtica aplicada. Aquestes esquerdes són difícils de detectar i poden provocar fallades catastròfiques inesperades i, en concret, s’ha detectat aquest fenomen en matrius refrigerades d’estampació en calent. Es pretén dissenyar i construir un dispositiu d’assaig SCC per tal d’utilitzar-lo per l’estudi dels materials 1.2367 i 1.2343 en condicions d’aigua de xarxa, aigua destil·lada i inhibidor. Aquests assaigs es realitzen a les temperatures de 40 i 80ºC ja que un estudi previ ha simulat les condicions de temperatura als canals de refrigeració de les matrius d’estampació en calent i s’ha vist que aquestes són les temperatures assolides. La raó d’estudiar aquests materials és perquè són dos acers d’eina per treball en calent convencionals, usats en l’àmbit de les matrius refrigerades d’estampació en calent i en general en processos de conformat en calent (forja, moldeig). S’estudia el comportament a tracció d’aquests materials en aquestes condicions comparant-lo amb el mateix assaig però en condicions en aire, i s’avaluen les diferències en la tensió màxima, la ductilitat, el mecanisme de fractura o l’esquerdament sofert. Es fa un estudi fractogràfic de les mostres mitjançant microscòpia electrònica de rastreig (SEM) i un estudi de les superfícies laterals i del secondary cracking mitjançant microscòpia òptica. Es comparen els diferents resultats obtinguts i es determina en quines condicions s’ha desenvolupat SCC i en quines no, en quina intensitat i quines opcions hi ha per evitar-lo.

Monetary policy rules and financial stress: does financial instability matter for monetary

We examine whether and how main central banks responded to episodes of financial stress over the last three decades. We employ a new methodology for monetary policy rules estimation, which allows for time-varying response coefficients as well as corrects for endogeneity. This flexible framework applied to the U.S., U.K., Australia, Canada and Sweden together with a new financial stress dataset developed by the International Monetary Fund allows not only testing whether the central banks responded to financial stress but also detects the periods and type of stress that were the most worrying for monetary authorities and to quantify the intensity of policy response. Our findings suggest that central banks often change policy

Primaries the unifying force

We present a formal model of intra-party politics to explain candidate selection within parties. We think of parties as heterogeneous groups of individuals who aim to implement a set of policies but who differ in their priorities. When party heterogeneity is too large, parties are in danger of splitting into smaller yet more homogeneous groups. In this context we argue that primaries can have a unifying role if the party elite cannot commit to policy concessions. Our model shows how alignment in the preferred policies of various factions within a party, the relative weight of each of these factions and the electoral system interact to create incentives for the adoption of primary elections. We discuss the existing empirical literature in the light of our theoretical predictions to provide a new, structured perspective on the adoption of primary elections.

Pelvic organ prolapse surgery with and without tension-free vaginal tape in women with occult or asymptomatic urodynamic stress incontinence: a randomised controlled trial.

INTRODUCTION: We set out to determine if insertion of a retropubic tension-free vaginal tape (TVT) sling at the time of pelvic organ prolapse surgery improves continence outcomes in women with pre-operative occult stress incontinence (OSI) or asymptomatic urodynamic stress incontinence (USI). METHODS: We conducted a randomised controlled study of prolapse surgery with or without a TVT midurethral sling. The pre- and post-operative assessment at 6 months included history, physical examination and urodynamic testing. Quality of life (QOL) and treatment success was assessed with the UDI-6 SF, IIQ-7 SF and a numerical success score. The primary outcome was symptomatic stress urinary incontinence (SUI) requiring continence surgery (TVT) at 6 months. Long-term follow-up continued to a minimum of 24 months. Secondary outcomes were quality of life parameters. RESULTS: Eighty women received prolapse surgery alone (n = 43) or prolapse surgery with concurrent TVT (n = 37). Six months following prolapse surgery 3 out of 43 (7 %) patients in the no TVT group requested sling surgery compared with 0 out of 37 (0 %) in the TVT group (ARR 7 % [95 %CI: 3 to 19 %], p = 0.11). After 24 months there was one further participant in the no TVT group who received a TVT for treatment of SUI compared with none in the TVT group (4 out of 43, 9.3 % versus 0 out of 37; ARR 9.3 % [95 %CI: -1 to 22 %], p = 0.06). Both groups showed improvement in QOL difference scores for within-group analysis, without difference between groups. CONCLUSION: These results support a policy that routine insertion of a sling in women with OSI at the time of prolapse repair is questionable and should be subject to shared decision-making between clinician and patient.

Stress Perception in Public Organizations: Expanding the Job Demands - Job Resources Model by Including Public Service Motivation

Although stress has been a longstanding issue in organizations and management studies, it has never been studied in relation to Public Service Motivation. This article therefore aims to integrate PSM into the job demands-job resources model of stress in order to determine whether PSM might contribute to stress in public organizations. Drawing upon original data from a questionnaire in a Swiss municipality, this study unsurprisingly shows that "red tape" is an antecedent of stress perception, whereas satisfaction with organizational support, positive feedback, and recognition significantly decrease the level of perceived stress. Astonishingly, the empirical results show that PSM is positively and significantly related to stress perception. By increasing individuals' expectations towards their jobs, PSM might thus contribute to increased pressure on public agents. Ultimately, this article investigates the "dark side" of PSM, which has been neglected by the literature thus far.