Prevalence and Characteristics of Exercise-Induced Bronchoconstriction in High School and College Athletes at 2,240 m Altitude.

BACKGROUND: Athletes practicing strenuous physical activities may develop exercise-induced bronchoconstriction (EIB). We aimed to determine the prevalence and features of this condition in Mexico City (altitude, 2,240 m). METHODS: In the present study, 208 high school and college athletes performed a standardized EIB test on a treadmill. RESULTS: Responses to exercise had large between-subject variability in all physiological parameters (forced expiratory volume in one second [FEV1], heart rate, blood oxygen saturation level [SpO2], blood pressure), with nearly similar proportions of subjects in whom FEV1 increased or decreased. According to the recommended cut-off value of 10% FEV1 decrease, only 15 (7.2%) athletes had a positive EIB test. Weight lifters were more prone to develop EIB (three out of seven athletes; p = 0.01). Subjects with a positive EIB test already had a lower baseline forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio (96.4 vs. 103.2% of predicted, respectively; p = 0.047), and developed more respiratory symptoms after exercise than subjects with a negative test. There were no differences with respect to age, gender, body mass index, history of asthma or atopic diseases, smoking habit, and exposure to potential indoor allergens. CONCLUSIONS: The relatively low prevalence of EIB in athletes from Mexico City raises the possibility that high altitude constitutes a protective factor for EIB. In contrast, weight lifters were especially prone to develop EIB, which suggests that repetitive Valsalva maneuvers could be a novel risk factor for EIB. There was a large between-subject variability of all physiological responses to exercise.

Goal-directed therapy in intraoperative fluid and hemodynamic management.

Intraoperative fluid management is pivotal to the outcome and success of surgery, especially in high-risk procedures. Empirical formula and invasive static monitoring have been traditionally used to guide intraoperative fluid management and assess volume status. With the awareness of the potential complications of invasive procedures and the poor reliability of these methods as indicators of volume status, we present a case scenario of a patient who underwent major abdominal surgery as an example to discuss how the use of minimally invasive dynamic monitoring may guide intraoperative fluid therapy.

Evolution of smooth tubercle Bacilli PE and PE_PGRS genes: evidence for a prominent role of recombination and imprint of positive selection.

BACKGROUND: PE and PE_PGRS are two mycobateria-restricted multigene families encoding membrane associated and secreted proteins that have expanded mainly in the pathogenic species, notably the Mycobacterium tuberculosis complex (MTBC). Several lines of evidence attribute to PE and PE_PGRS genes critical roles in mycobacterial pathogenicity. To get more insight into the nature of these genes, we sought to address their evolutionary trajectories in the group of smooth tubercle bacilli (STB), the putative ancestor of the clonal MTBC. METHODOLOGY/PRINCIPAL FINDINGS: By focussing on six polymorphic STB PE/PE_PGRS genes, we demonstrate significant incongruence among single gene genealogies and detect strong signals of recombination using various approaches. Coalescent-based estimation of population recombination and mutation rates (ρ and θ, respectively) indicates that the two mechanisms are of roughly equal importance in generating diversity (ρ/θ = 1.457), a finding in a marked contrast to house keeping genes (HKG) whose evolution is chiefly brought about by mutation (ρ/θ = 0.012). In comparison to HKG, we found 15 times higher mean rate of nonsynonymous substitutions, with strong evidence of positive selection acting on PE_PGRS62 (dN/dS = 1.42), a gene that has previously been shown to be essential for mycobacterial survival in macrophages and granulomas. Imprint of positive selection operating on specific amino acid residues or along branches of PE_PGRS62 phylogenetic tree was further demonstrated using maximum likelihood- and covarion-based approaches, respectively. Strikingly, PE_PGR62 proved highly conserved in present-day MTBC strains. CONCLUSIONS/SIGNIFICANCE: Overall the data indicate that, in STB, PE/PE_PGRS genes have undergone a strong diversification process that is speeded up by recombination, with evidence of positive selection. The finding that positive selection involved an essential PE_PGRS gene whose sequence appears to be driven to fixation in present-day MTBC strains lends further support to the critical role of PE/PE_PGRS genes in the evolution of mycobacterial pathogenicity.

Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis.

Global spread and limited genetic variation are hallmarks of M. tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology are restricted to East Africa. Here, we sequenced and analyzed the whole genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5× coverage), 454/Roche (13-18× coverage) and/or Illumina DNA sequencing (45-105× coverage). We show that STB isolates are highly recombinogenic and evolutionarily early branching, with larger genome sizes, higher rates of genetic variation, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse infection experiments showed that STB strains are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral STB-like pool of mycobacteria by gain of persistence and virulence mechanisms, and we provide insights into the molecular events involved.

Neuraxial morphine and respiratory depression: finding the right balance.

Morphine is a drug commonly administered via the epidural or intrathecal route, and is regarded by many as the 'gold-standard' single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action. However, respiratory depression is a recognized side effect of neuraxial morphine administered in the perioperative setting. We conducted an extensive review of articles published since 1945 that examine respiratory depression or failure associated with perioperative intrathecal or epidural morphine use. Respiratory depression was previously thought to result from the interaction of opioid in the cerebrospinal fluid with ventral medullary opioid receptors. More recently, the preBötzinger complex located in the medulla has been identified as the site responsible for the decrease in respiratory rate following systemic administration of opioids. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are selectively inhibited by opioids, and therefore are the mediators of opioid-induced respiratory depression. Epidural, intrathecal and plasma pharmacokinetics of opioids are complex, vary between neuraxial compartments, and can even differ within the epidural space itself depending upon level of insertion. Caution should be exercised when prescribing systemic opioids (intravenous or oral) in addition to neuraxial morphine as this can compound the potential for early or delayed respiratory depression. There is a wide range of incidences for respiratory depression following neuraxial morphine in a perioperative setting. Disparity of definitions used for the diagnosis of respiratory depression in the literature precludes identification of the exact incidence of this rare event. The optimal neuraxial opioid dose is a balance between the conflicting demands of providing optimal analgesia while minimizing dose-related adverse effects. Dose-response studies show that neuraxial morphine appears to have an analgesic efficacy 'ceiling'. The optimal 'single-shot' intrathecal dose appears to be 0.075-0.15 mg and the ideal 'single-shot' epidural morphine dose is 2.5-3.75 mg. Analgesic efficacy studies have not been adequately powered to show differences in the incidence of clinically significant respiratory depression. Opioid antagonists such as naloxone to prevent or treat opioid-induced respiratory depression have a number of limitations. Researchers have recently focused on non-opioid drugs such as serotonin receptor agonists. Early evidence suggests that ampakine (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA]) receptor modulators may be effective at reducing opioid-induced respiratory depression while maintaining analgesia. Sodium/proton exchanger type 3 (NHE3) inhibitors, which act centrally on respiratory pathways, also warrant further study.

Mycobacterium genavense infections: a retrospective multicenter study in France, 1996-2007.

Mycobacterium genavense, a nontuberculous mycobacterium, led to devastating infections in patients with acquired immunodeficiency syndrome (AIDS) before highly active antiretroviral therapy (HAART) was available, as well as in other immunocompromised patients. We conducted the current study to describe the features of this infection in patients infected with human immunodeficiency virus (HIV) in the HAART era and in non HIV-infected patients.We conducted a retrospective cohort survey in France. All patients with M. genavense infection diagnosed from 1996 to 2007 at the National Reference Center, Institut Pasteur, Paris, were identified and their clinical, laboratory, and microbiologic data were centralized in a single database. Twenty-five cases of M. genavense infection originating from 19 centers were identified. Twenty patients had AIDS, 3 had solid organ transplantation, and 2 had sarcoidosis. Sixty-four percent (n = 16) were male, mean age was 42 years, and median CD4 count was 13/mm (range, 0-148/mm) in patients with AIDS. Twenty-four patients had disseminated infection with fever (75%, n = 18), weight loss (79%, n = 19), abdominal pain (71%, n = 17), diarrhea (62.5%, n = 15), splenomegaly (71%, n = 17), hepatomegaly (62.5%, n = 15), or abdominal adenopathy (62.5%, n = 15). M. genavense was isolated from the lymph node (n = 13), intestinal biopsy (n = 9), blood (n = 6), sputum (n = 3), stool (n = 3), and bone marrow (n = 5). Eleven patients (44%) died, 8 (32%) were considered cured with no residual symptoms, and 6 (24%) had chronic symptoms. The 1-year survival rate was 72%.The prognosis of M. genavense infection in HIV-infected patients has dramatically improved with HAART. Clinical presentations in HIV and non-HIV immunocompromised patients were similar.

The forest behind the tree: phylogenetic exploration of a dominant Mycobacterium tuberculosis strain lineage from a high tuberculosis burden country.

BACKGROUND: Genotyping of Mycobacterium tuberculosis isolates is a powerful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. Standardized PCR-based typing, based on 15 to 24 mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) loci combined with spoligotyping, has been shown to have adequate resolution power for tracing TB transmission and to be useful for predicting diverse strain lineages in European settings. Its informative value needs to be tested in high TB-burden countries, where the use of genotyping is often complicated by dominance of geographically specific, genetically homogeneous strain lineages. METHODOLOGY/PRINCIPAL FINDINGS: We tested this genotyping system for molecular epidemiological analysis of 369 M. tuberculosis isolates from 3 regions of Brazil, a high TB-burden country. Deligotyping, targeting 43 large sequence polymorphisms (LSPs), and the MIRU-VNTRplus identification database were used to assess phylogenetic predictions. High congruence between the different typing results consistently revealed the countrywide supremacy of the Latin-American-Mediterranean (LAM) lineage, comprised of three main branches. In addition to an already known RDRio branch, at least one other branch characterized by a phylogenetically informative LAM3 spoligo-signature seems to be globally distributed beyond Brazil. Nevertheless, by distinguishing 321 genotypes in this strain population, combined MIRU-VNTR typing and spoligotyping demonstrated the presence of multiple distinct clones. The use of 15 to 24 loci discriminated 21 to 25% more strains within the LAM lineage, compared to a restricted lineage-specific locus set suggested to be used after SNP analysis. Noteworthy, 23 of the 28 molecular clusters identified were exclusively composed of patient isolates from a same region, consistent with expected patterns of mostly local TB transmission. CONCLUSIONS/SIGNIFICANCE: Standard MIRU-VNTR typing combined with spoligotyping can reveal epidemiologically meaningful clonal diversity behind a dominant M. tuberculosis strain lineage in a high TB-burden country and is useful to explore international phylogenetical ramifications.

Aspecto psicológico en los padres de recién nacidos y lactantes menores con labio fisurado y/o paladar endido / Psychological aspect in parents of newborns and infants with cleft lip and / or palate

El labio fisurado y/o paladar hendido es una de las malformaciones congénitas más comunes en el ser humano, constituyendo uno de los problemas de salud pública más importantes en la consulta odontopediátrica. Los padres de niños y niñas con esta patología pueden presentar alteraciones desde el punto de vista físico y psicológico. Por lo tanto, la presente investigación tuvo como finalidad describir el aspecto psicológico en los padres de recién nacidos y lactantes menores con labio fisurado y/o paladar hendido que acudieron al servicio de Odontopediatría y Cirugía Pediátrica en el Instituto Autónomo Hospital Universitario de Los Andes (IAHULA), durante el período Enero - Diciembre 2007. La investigación fue de tipo descriptiva, transeccional, que utilizó como método de estudio el suministro de encuestas para la identificación de la situación socioeconómica, los niveles de bienestar psicológico, el estado - rasgo de ansiedad y la presencia de síntomas depresivos. Los resultados permitieron concluir que las variables dependientes estudiadas se vieron modificadas en la conducta de los padres ante esta patología

A cleft lip and/or palate is one of the most common congenital malformations in human beings, effectively making it one of the most important public health issues in odontopediatrics. It is worth noting that parents with kids who present this pathology can suffer from physical and psychological anguish caused by the condition; and that is why this study had as its main purpose the description of the level of the psychological wellbeing of the parents whose kids suffered from the pathology at hand examined at the Odondopediatrics and Pediatric Surgery inside the Autonomous University Hospital of Los Andes (IAHULA) between January - December 2007. This investigation was descriptive and trans-sectional in nature and utilized surveys to identify the socioeconomic situation, stress level, psychological wellbeing, the existence of anxiety, and the presence of symptoms of depression amongst parents. The conclusion offered by this research study was one in which, amongst all dependent variables, changes in stress levels had no bearing on the subjects while all the other variables affected the behavior of parents of cleft palate/lip children

A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery.

OBJECTIVE(S): The authors have developed an alternative dosing schedule for tranexamic acid that incorporates the effects of renal function on tranexamic acid concentrations. The objectives of this study were to determine if this new dosing schedule can achieve the desired plasma concentration of tranexamic acid and reduce intra- and interpatient variability in tranexamic acid plasma concentrations relative to the current dosing schedule. DESIGN: A prospective randomized trial. SETTING: A tertiary referral medical center hospital. PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: Cardiac surgery patients were randomly assigned to receive the authors' standard tranexamic acid loading dosage of 10 mg/kg given over 20 minutes, followed by an infusion of 1 mg/kg/h (9 patients), or the new drug dosage schedule described later (11 patients). MEASUREMENTS AND MAIN RESULTS: Perioperative plasma tranexamic acid concentrations were measured using high-performance liquid chromatography. From repeated-measures analysis of variance, a significant (p < 0.001) time-by-treatment interaction effect was detected indicating that differences in mean tranexamic acid concentration between treatment groups were dependent on time period. Among patients receiving the standard dosing regimen, those with renal insufficiency had lower tranexamic acid concentration at 5 minutes on cardiopulmonary bypass (p = 0.003). For patients receiving the experimental regimen, the mean tranexamic acid concentration did not differ significantly at any time point between patients with and without renal insufficiency (p > 0.20 at all time points). CONCLUSIONS: The new dosing protocol for tranexamic acid resulted in more consistent blood concentrations of tranexamic acid, but not stable tranexamic acid levels >20 microg/mL on cardiopulmonary bypass.

Contribution of horizontally acquired genomic islands to the evolution of the tubercle bacilli.

The contribution of horizontal gene transfer (HGT) to the evolution of Mycobacterium tuberculosis -- the main causal agent of tuberculosis in humans -- and closely related members of the M. tuberculosis complex remains poorly understood. Using a combination of genome-wide parametric analyses, we have identified 48 M. tuberculosis chromosomal regions with atypical characteristics, potentially due to HGT. These specific regions account for 4.5% of the genome (199 kb) and include 256 genes. Many display features typical of the genomic islands found in other bacteria, including residual material from mobile genetic elements, flanking direct repeats, insertion in the vicinity of tRNA sequences, and genes with putative or documented virulence functions. Southern blotting analysis of nine of these 48 regions confirmed their presence in "Mycobacterium prototuberculosis," the ancestral species of the M. tuberculosis complex. Finally, our results strongly suggest that the ancestor of the tubercle bacilli was an environmental bacillus that exchanged genetic material with other bacterial species, including Proteobacteria in particular, present in its surroundings. This study describes a rational approach to searching for mycobacterial virulence genes, and highlights the importance of dissecting gene transfer networks to improve our understanding of mycobacterial pathogenicity and evolution.

New variable-number tandem-repeat markers for typing Mycobacterium avium subsp. paratuberculosis and M. avium strains: comparison with IS900 and IS1245 restriction fragment length polymorphism typing.

Mycobacterium avium subsp. paratuberculosis, the etiological agent of paratuberculosis, affects a wide range of domestic ruminants and has been suggested to be involved in Crohn's disease in humans. Most available methods for identifying and differentiating strains of this difficult species are technically demanding and have limited discriminatory power. Here, we report the identification of novel PCR-based typing markers consisting of variable-number tandem repeats (VNTRs) of genetic elements called mycobacterial interspersed repetitive units (MIRUs). Eight markers were applied to 183 M. avium subsp. paratuberculosis isolates from bovine, caprine, ovine, cervine, leporine, and human origins from 10 different countries and to 82 human isolates of the closely related species M. avium from France. Among the M. avium subsp. paratuberculosis isolates, 21 patterns were found by MIRU-VNTR typing, with a discriminatory index of 0.751. The predominant R01 IS900 restriction fragment length polymorphism type, comprising 131 isolates, was divided into 15 MIRU-VNTR types. Among the 82 M. avium isolates, the eight MIRU-VNTR loci distinguished 30 types, none of which was shared by M. avium subsp. paratuberculosis isolates, resulting in a discriminatory index of 0.889. Our results suggest that MIRU-VNTR typing is a fast typing method that, in combination with other methods, might prove to be optimal for PCR-based molecular epidemiological studies of M. avium/M. avium subsp. paratuberculosis pathogens. In addition, presumably identical M. avium subsp. paratuberculosis 316F vaccine strains originating from the Weybridge laboratory and from different commercial batches from Mérial actually differed by one or both typing methods. These results indicate a substantial degree of genetic drift among different vaccine preparations, which has important implications for prophylactic approaches.

Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis.

Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%--and by 23% in combination with spoligotyping--among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold--by threefold in combination with spoligotyping--under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies.

Against all odds: molecular confirmation of an implausible case of bone tuberculosis.

We report the use of typing based on a variable number of tandem repeats of genetic elements called "mycobacterial interspersed repetitive units" to clarify a puzzling situation involving a patient with an exceptional case of spondylodiskitis that initially led to the suspicion of a possible event of laboratory cross-contamination with Mycobacterium tuberculosis.

Calidad de atención de enfermería del Hospital Neurosiquíatrico en los pabellones I-II de mujeres agudas de la ciudad de Asunción del año 1999

Estudio descriptivo realizado con el personal de enfermería de los pabellones I-II de mayores del Hospital Neuropsiquiátrico. Busca determinar el nivel de calidad de Atención de Enfermería, para los casos agudos registrados en ese hospital. Presenta los servicios de la Institución, evolución como Centro de Atención de personas con transtornos mentales, la atención de las enfermeras y categorías profesionales en el Departamento de Enfermería

Gangliosidosis GM1 Tipo I: forma infantil / Gangliosidosis GM1 Type I: infantile form

Se presenta un caso de Gangliosidosis GM1, tipo I, de diagnóstico tardío para llamar la atención sobre una enfermedad hereditaria. Se trata de una lactante de sexo femenino que a pesar de presentar los signos principales de la enfermedad no fue reconocida tempranamente. El diagnóstico se confirmó a los 6 meses por dosificación de la enzima beta-galactosidasa lisosomal en leucocitos. Se destaca la falla de la atención primaria y la necesidad de un diagnóstico seguro para poder realizar un adecuado consejo genético