Nitric ocide mediates the blood pressure response to mental stress in humans

Objectif : Le monoxyde d'azote (NO) régule la pression artérielle en modulant le tonus vasculaire périphérique et l'activité sympathique vasoconstrictrice. La synthèse du NO est altérée dans plusieurs maladies cardiovasculaires importantes. La perte de l'effet vasodilatateur du NO et de son effet freinateur sur la décharge sympathique pourrait entraîner une réponse vasopressive exagérée au stress mental. Méthodes : Nous avons donc comparé les réponses sympathique (activité nerveuse musculaire sympathique) et hémodynamique au stress mental pendant une perfusion isotonique de NaCI et lors de l'administration d'un inhibiteur systémique de la NO- synthase (NG-monomethyl-L-arginine, L-NMMA). Résultats : Le résultat principal est que le stress mental qui pendant la perfusion saline augmente l'activité nerveuse sympathique d'environ 50% et la pression artérielle moyenne d'environ 15%, n'a eu aucun effet sympathoexcitateur et vasopresseur détectable lors de la perfusion de L-NMMA. Ces observations ne sont pas liées à une atteinte généralisée de la réponse hémodynamique et/ou sympathique lors de la perfusion de L-NMMA, car ces réponses étaient conservées lors de l'immersion de la main dans de l'eau glacée. Conclusions : Le stress mental induit des effets vasopresseurs et sympathoexcitateurs chez l'homme qui sont médiés par le NO. Ces résultats laissent penser que, contrairement à ce qui a été généralement supposé, le NO peut dans certaines circonstances augmenter la pression artérielle in vivo

Missed Opportunities: Evolution of Patients Leaving without Being Seen or against Medical Advice during a Six-Year Period in a Swiss Tertiary Hospital Emergency Department.

Aim. The study aimed at describing the evolution over a 6-year period of patients leaving the emergency department (ED) before being seen ("left without being seen" or LWBS) or against medical advice ("left against medical advice" or LAMA) and at describing their characteristics. Methods. A retrospective database analysis of all adult patients who are admitted to the ED, between 2005 and 2010, and who left before being evaluated or against medical advice, in a tertiary university hospital. Results. During the study period, among the 307,716 patients who were registered in the ED, 1,157 LWBS (0.4%) and 1,853 LAMA (0.9%) patients were identified. These proportions remained stable over the period. The patients had an average age of 38.5 ± 15.9 years for LWBS and 41.9 ± 17.4 years for LAMA. The median time spent in the ED before leaving was 102.4 minutes for the LWBS patients and 226 minutes for LAMA patients. The most frequent reason for LAMA was related to the excessive length of stay. Conclusion. The rates of LWBS and LAMA patients were low and remained stable. The patients shared similar characteristics and reasons for leaving were largely related to the length of stay or waiting time

Emergency department management of body packers and body stuffers.

Trafficking and sale of narcotics frequently involves the intra-abdominal transport of large quantities of drugs, usually cocaine or heroin ("body packing"), or, when there is a risk of being arrested, the oral ingestion of minor quantities of narcotics dedicated for immediate resale ("body stuffing"). This study aimed to describe the characteristics, complications and medical follow through of 132 cases of body packing (n = 36), cases of body stuffing (n = 83) or mixed cases (n = 13), referred by the authorities to our emergency department over the course of 12 years. Analysis of these 132 cases did not reveal any intra-abdominal rupture or leak of the packaging, or any case of acute intoxication. Nevertheless, a surgical intervention was required in three of the body packers (2.3%) owing to stasis of the packages inside the stomach. The mean length of stay was longer when the packets were located in the stomach at time of diagnosis than when they were lower in the gastrointestinal tract (61.9 vs 43.8 hours, respectively), but this was not statistically significant (p = 0.13). Length of stay was not associated with the presence of (nonspecific) symptoms or the total number of packs ingested. In conclusion, the study of this cohort of 132 body packers and body stuffers permits us to state that the medical management of these patients is rarely associated with serious complications, and that their length of stay is generally long, averaging 2 days before complete elimination of the drug packages

Emergency department use by oldest-old patients from 2005 to 2010 in a Swiss university hospital.

BACKGROUND: Aging of the population in all western countries will challenge Emergency Departments (ED) as old patients visit these health services more frequently and present with special needs. The aim of this study is to describe the trend in ED visits by patients aged 85 years and over between 2005 and 2010, and to compare their service use to that of patients aged 65-84 years during this period and to investigate the evolution of these comparisons over time. METHODS: Data considered were all ED visits to the University of Lausanne Medical Center (CHUV), a tertiary Swiss teaching hospital, between 2005 and 2010 by patients aged 65 years and over (65+ years). ED visit characteristics were described according to age group and year. Incidence rates of ED visits and length of ED stay were calculated. RESULTS: Between 2005 and 2010, ED visits by patients aged 65 years and over increased by 26% overall, and by 46% among those aged 85 years and over (85+ years). Estimated ED visit incidence rate for persons aged 85+ years old was twice as high as for persons aged 65-84 years. Compared to patients aged 65-84 years, those aged 85+ years were more likely to be hospitalized and have a longer ED stay. This latter difference increased over time between 2005 and 2010. CONCLUSIONS: Oldest-old patients are increasingly using ED services. These services need to adapt their care delivery processes to meet the needs of a rising number of these complex, multimorbid and vulnerable patients

Safety and Tolerability of Adoptive Cell Therapy in Cancer.

Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection. In recent years, some ACTs have produced unprecedented breakthrough responses: TIL therapy has moved from melanoma to solid tumor applications, TCR-engineered cells are developed for hematologic and solid tumors, and CAR-engineered T cells have received Food and Drug Administration (FDA) approval for the treatment of patients with certain B-cell malignancies. Although results are encouraging, to date, only a small percentage of patients with advanced malignancies can benefit from ACT. Besides ACT availability and accessibility, treatment-related toxicities represent a major hurdle in the widespread implementation of this therapeutic modality. The large variety of observed toxicities is caused by the infused cell product or as side effects of accompanying medication and chemotherapy. Toxicities can occur immediately or can be delayed. In order to render those highly promising therapeutic approaches safe enough for a wider pool of patients outside of clinical trials, an international consensus for toxicity management needs to be established

Postmetamorphic ontogenetic allometry and the evolution of skull shape in Nest-building frogs Leptodactylus (Anura: Leptodactylidae)

Allometry constitutes an important source of morphological variation. However, its influence in head development in anurans has been poorly explored. By using geometric morphometrics followed by statistical and comparative methods we analyzed patterns of allometric change during cranial postmetamorphic ontogeny in species of Nest-building frogs Leptodactylus (Leptodactylidae). We found that the anuran skull is not a static structure, and allometry plays an important role in defining its shape in this group. Similar to other groups with biphasic life-cycle, and following a general trend in vertebrates, ontogenetic changes mostly involve rearrangement in rostral, otoccipital, and suspensorium regions. Ontogenetic transformations are paralleled by shape changes associated with evolutionary change in size, such that the skulls of species of different intrageneric groups are scaled to each other, and small and large species show patterns of paedomorphic/peramorphic features, respectively. Allometric trajectories producing those phenotypes are highly evolvable though, with shape change direction and magnitude varying widely among clades, and irrespective of changes in absolute body size. These results reinforce the importance of large-scale comparisons of growth patterns to understand the plasticity, evolution, and polarity of morphological changes in different clades.Fil: Duport Bru, Ana Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Ponssa, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Vera Candioti, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; Argentin

Skull diversity and evolution in miniaturized amphibians, genus Brachycephalus (Anura: Brachycephalidae)

Miniaturized amphibians of the genus Brachycephalus are phenotypically diverse. The species of Brachycephalus have bufoniform or leptodactyliform baupläne and any of three skeletal states: nonhyperossified, hyperossified without dorsal shield, and hyperossified with dorsal shield. We integrate high-resolution microcomputed tomography, geometric morphometrics, and an estimate of molecular phylogenetic relationships to investigate skull diversity in shape and size-shape space in selected species of Brachycephalus. Skull diversity amongst species of Brachycephalus can be partitioned into shape and size-shape space according to the four conditions of skeletal states-baupläne, namely, nonhyperossified leptodactyliform, nonhyperossified bufoniform, hyperossified bufoniform without dorsal shield, and hyperossified bufoniform with dorsal shield. Skull diversity in shape and size-shape space in nonhyperossified leptodactyliform species of Brachycephalus is markedly larger, when compared to skull diversity in species of the three other conditions of skeletal states-baupläne. Variation in skull shape scales with size across Brachycephalus and, therefore, can be explained by allometry. Skull diversity, baupläne, and skeletal states covary to a large extent with monophyletic lineages of Brachycephalus, as revealed by a mitochondrial DNA species tree. Nonhyperossified bufoniform species and hyperossified bufoniform species with or without dorsal shield are monophyletic lineages, as inferred from a mitochondrial DNA species tree. Nonhyperossified leptodactyliform species of Brachycephalus do not share, however, a most recent common ancestor. The nonhyperossified leptodactyliform species of Brachycephalus, due to their marked skull diversity and lack of monophyly, emerge as evolutionarily complex. Therefore, further sampling of the nonhyperossified leptodactyliform condition of skeletal states-baupläne will be necessary to further understand the evolutionary history of Brachycephalus.Fil: dos Reis, Sérgio F.. Universidade Estadual de Campinas. Instituto de Biología; BrasilFil: Clemente Carvalho, Rute B.G.. Queens University; CanadáFil: dos Santos, Caio M. S. F. F.. Universidade Federal do Rio de Janeiro; BrasilFil: Lopes, Ricardo T.. Universidade Federal do Rio de Janeiro; BrasilFil: Von Zuben, Fernando J.. Universidade Estadual de Campinas; BrasilFil: Laborda, Prianda R.. Universidade Estadual de Campinas. Instituto de Biología; BrasilFil: Perez, Sergio Ivan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Departamento Científico de Antropología; Argentin

Differences in triage category, priority level and hospitalization rate between young-old and old-old patients visiting the emergency department.

Emergency Department (ED) are challenged by the increasing number of visits made by the heterogeneous population of elderly persons. This study aims to 1) compare chief complaints (triage categories) and level of priority; 2) to investigate their association with hospitalization after an ED visit; 3) to explore factors explaining the difference in hospitalization rates among community-dwelling older adults aged 65-84 vs 85+ years. All ED visits of patients age 65 and over that occurred between 2005 and 2010 to the University of Lausanne Medical Center were analyzed. Associations of hospitalization with triage categories and level of priority using regressions were compared between the two age groups. Blinder-Oaxaca decomposition was performed to explore how much age-related differences in prevalence of priority level and triage categories contributed to predicted difference in hospitalization rates across the two age groups. Among 39'178 ED visits, 8'812 (22.5%) occurred in 85+ patients. This group had fewer high priority and more low priority conditions than the younger group. Older patients were more frequently triaged in "Trauma" (20.9 vs 15.0%) and "Home care impossible" (10.1% vs 4.2%) categories, and were more frequently hospitalized after their ED visit (69.1% vs 58.5%). Differences in prevalence of triage categories between the two age groups explained a quarter (26%) of the total age-related difference in hospitalization rates, whereas priority level did not play a role. Prevalence of priority level and in triage categories differed across the two age groups but only triage categories contributed moderately to explaining the age-related difference in hospitalization rates after the ED visit. Indeed, most of this difference remained unexplained, suggesting that age itself, besides other unmeasured factors, may play a role in explaining the higher hospitalization rate in patients aged 85+ years

Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron