CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A guanilina e a uroguanilina foram recentemente descobertas, respectivamente, no intestino e na urina, (Currie et al., 1992; Hamra et al., 1993). Fazem parte da famÃlia de peptÃdeos que ativam a guanilato ciclase de membrana (GC-C), aumentando os nÃveis intracelulares de cGMP (Schulz et al., 1990). EstÃo presentes em diversos tecidos, como respiratÃrio, linfonodos, testÃculos, cÃrebro e medula adrenal (Field et a.l., 1978; Forte et al., 1988, 1989; Hamra et al., 1993; Schulz et al., 1992). Foi comprovado que adicionando uma lisina na porÃÃo N-terminal, obtÃm-se um anÃlogo mais estÃvel e potente que a guanilina. O objetivo desse estudo à pesquisar os efeitos renais de um novo anÃlogo, ser-thr-lys-guanilina em sistema de perfusÃo. Os rins foram perfundidos com a soluÃÃo de Krebs-Henseleit modificada com 6g% de albumina bovina. Os dados foram comparados atravÃs de teste t de Student e ANOVA, com significÃncia p<0,05. Na dose de 0,1 Âg/mL, esse peptÃdeo apresentou efeitos similares aos da uroguanilina, na dose de 0,5 Âg/mL, em todos os parÃmetros testados. Ambas causaram aumento na pressÃo de perfusÃo (PP: de 101,5Â3,7 para 111Â2,9mmHg; de 101,2Â2,6 para 113,4Â2,5mmHg), no fluxo urinÃrio (FU: de 0,158Â0,016 para 0,223Â0,01 mL.g-1.min-1; de 0,16Â0,016 para 0,226Â0,2mL.g-1.min-1) e diminuiÃÃo no transporte tubular total e proximal de sÃdio (%TNa+: de 0,774Â0,06 para 0,724Â0,035; de 0,735Â0,065 para 0,773Â0,084), potÃssio (%TK+: de 66,89Â2,77 para 47,29Â3,34; de 63,54Â3,82 para 42,54Â8,14) e cloreto (%TCl-: de 85,69Â1,19 para 73,59Â2,63). Esses resultados foram similares aos previamente descritos apÃs a administraÃÃo da toxina termo-estÃvel da Escherichia coli (STa), guanilina, uroguanilina e lys-guanilina no mesmo sistema (Lima et al., 1992; Fonteles et al., 1996 e 1998). A dose maior (1 Âg/mL) causou aÃÃo antidiurÃtica (FU: de 0,165Â0,004 para 0,111Â0,009mL.g-1.min-1) e nenhum efeito sobre o transporte de sÃdio, embora a diminuiÃÃo na reabsorÃÃo tubular de potÃssio (%TK+: de 72,29Â1,2 para 49,73Â6,75) e cloreto (%TCl-: de 85,96Â0,79 para 81,9Â1,47) continuassem presentes. Nesta dose, nÃo apenas bloqueou o efeito diurÃtico da uroguanilina, como continuou causando um efeito antidiurÃtico significativo (FU: de 0,168Â0,004 para 0,116Â0,006). No entanto, nÃo foi capaz de bloquear os efeitos natriurÃticos da uroguanilina (%TNa+: de 85,35Â2,55 para 79,92Â1,05). O mecanismo de aÃÃo renal preciso dos peptÃdeos da famÃlia das guanilinas ainda nÃo foi completamente esclarecido. Sabe-se que esses peptÃdeos se ligam aos receptores GC-C (Schulz et al., 1990), porÃm hà indÃcios de que existam outras vias de aÃÃo renal, independentes desse receptor. Hà ainda a possibilidade de que haja duas entidades agindo de modo antagÃnico no sistema. Talvez haja a necessidade de isolÃ-los. A descoberta dos peptÃdeos da famÃlia das guanilinas promoveu avanÃos significativos na compreensÃo da regulaÃÃo endÃgena dos transportes de Ãgua e eletrÃlitos. O completo esclarecimento do seu mecanismo de aÃÃo renal oferece perspectivas reais para o tratamento de doenÃas como a hipertensÃo arterial. / Guanylin and uroguanylin are members of a family of peptides that stimulates cGMP production in several organic tissues, as intestine, kidney, airway, linfonodes, testis, brain and adrenal medulla (Field et a.l., 1978; Forte et al., 1988, 1989; Hamra et al., 1993; Schulz et al., 1992). Their 15 amino acid structures have been identified from rat intestine and opossum urine, respectively (Currie et al., 1992; Hamra et al., 1993), and they seem to be the link between intestine and kidney functions in controling blood pressure, as the âintestinal natriuretic hormoneâ suggested by some authors (Carey, 1978; Lennane et al., 1975). It was demonstrated that a Lysine-1 analog of guanylin is a more potent natriuretic and kaliuretic peptide. The aim of this study was to evaluate the renal effects of a novel analog of guanylin: ser-thr-lys-guanylin. Its effects were examined using isolated perfused kidneys from Wistar rats. All experiments were preceded by a 30 minutes internal control period and an external control group (C), in which the kidneys were perfused only with Krebs-Henseleit solution containing 6g% of a previously dialysed bovine albumine serum. The data was analyzed by Student t-test and ANOVA. The level of significance was set at p<0,05. Ser-thr-lys-guanylin, at the lowest dose (0.1 Âg/mL) and uroguanylin (0.5Âg/mL) caused similar effects. Both groups were able to increase perfusion presure (PP: 101.5Â3.7 to 111Â2.9mmHg; 101.2Â2.6 to 113.4Â2.5 mmHg), urinary flow (UF: 0.158Â0.016 to 0.223Â0.019 mL.g-1.min-1; 0.16Â0.016 to 0.226Â0.2mL.g-1.min-1) and to decrease sodium (%TNa+: 0.774Â0.06 to 0.724Â0.035; 0.735Â0.065 to 0.773Â0.084), potassium (%TK+: 66.89Â2.77 to 47.29Â3.34; 63.54Â3.82 to 42.54Â8.14) and cloride (%TCl-: 85.69Â1.19 to 73.59Â2.63) tubular reabsorption. Similar effects were also found in response to the Escherichia coli heat-stable enterotoxin (STa), guanylin, uroguanylin and lys-guanylin in the same system (Lima et al., 1992; Fonteles et al., 1996 e 1998). However, a greater dose (1Âg/mL), not only caused signifcantly decrease in the urinary flow (UF: 0.165Â0.004 to 0.111Â0.009 mL.g-1.min-1), but was also able to block the diuretic effects of uroguanylin (UF: 0.168Â0.004 to 0.116Â0.006 mL.g-1.min-1), although it still decreased potassium (%TK+: 72.29Â1.2 to 49.73Â6.75) and cloride(%TCl-: 85.96Â0.79 to 81.9Â1.47) tubular reabsorption. The precise renal mecanism of action of this family of peptides has not yet been fully elucidated. Deletion of GC-C genes in transgenic mice reveals that intestinal fluid secretion responses to STa are completely lost (Schulz et al., 1997 & Mann et al., 1997), but the natriuretic responses to STa and uroguanylin are retained (Carrithers et al., 1999), suggesting that other receptors are envolved. There is a possibility that there are to peptides causing antagonic effects. Further isolation may be necessary. Further studies are required to elucidate the specific renal mechanism of action of this new peptide. The discovery of guanylin and its family has promoted significant advances in the understanding of endogenous control of salt, water and eletrolites. The study of its analogs in perfused rat kidneys could help in elucidating their specific renal mecanism of action and bring great perspectives in the control of blood pressure.

Abstract In Oulu University Hospital Haematological Ward during the years 1990–1991, a manual blood culture system was able to detect bloodstream infection (BSI) in 23% of febrile episodes of patients with acute myeloid leukaemia (AML), whereas during the years 1992–1993 an automated continuous-monitoring blood culture system (CMBCS) BacT/Alert® detected BSI in 40% of febrile episodes (p = 0.043). During the years 1997–2003, regimens containing high-dose cytarabine predisposed patients to laboratory-confirmed BSI (LCBI) with an odds ratio (OR) of 2.3 (with 95% confidence interval (CI) from 1.2 to 4.2). The LCBI risk was lowest after thioguanine-containing regimens (OR 0.26, 95% CI; 0.12–0.58). In the register data (years 1992–2006) from the prospective multi-centre AML -92 trial, when compared to cycle I, the OR for LCBI was significantly higher (from 4.8 to 5.8) in subsequent cycles (p &lt; 0.001). In all, 67% of mortality due to BSI occurred in patients with active leukaemia. An inoculum of microorganisms to produce 10 colony-forming units (cfu)/ml of 10 gram-positive coccal strains, 10 gram-negative bacillar strains and 8 Candida yeast strains was cultured in BacT/Alert® blood culture bottles in the presence of several chemotherapeutic drugs. Of the chemotherapeutic drugs tested, the anthracyclines exhibited inhibitory effects on the growth of microorganisms in concentrations corresponding to the therapeutic levels. In the standard bottles, doxorubicin increased the incubation time of gram-positive cocci and idarubicin increased the incubation time of Candida glabrata. However, no increase in the incubation time of any microbes was detected in the antimicrobial-neutralizing FAN bottles. In conclusion, the use of CMBCSs has resulted in an increased LCBI rate in neutropenic AML patients. In general, chemotherapeutic agents have no significant inhibitory effects on the growth of common microbial pathogens in blood culture. The detection of some difficult-to-culture microbial strains – C. glabrata for example – in blood cultures may be impaired by the presence of chemotherapeutics in blood. The chemotherapeutics may also affect the LCBI rate in other ways. As a predictor of adverse outcome of infection, the presence of active leukaemia is more important than the type of chemotherapy being administered.

Over 4 million avoidable hospital admissions result from medication errors (IMS Insitute for Healthcare Informatics, 2013). Human error accounts for 80% of all medical errors (Palmieri, DeLucia, Peterson, Ott, & Green, 2008). Medication administration is a complex process. It is important to understand the cognitive load (CL) of Registered Nurses (RNs) working in an electronic health record environment to identify the risk factors of medication errors. The purpose of this study is to investigate the factors that influence the CL of RNs during medication administration who are working in an electronic health record environment. Simulated medication administration scenarios with varying degrees of multi-tasking were completed with 30 participants. When RNs multi-task during medication administration their CL increases. Furthermore, RNs who have poor sleep quality cannot process high-level tasks as well as those RNs who report a good sleep quality. Future work can limit EEG lead placement to the frontal channels of the EEG. Furthermore, replication of this study with a larger sample and a broader range of competing tasks is indicated.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.

Masters of Science / The Coronaviridae family consists of RNA viruses within the order Nidovirales. The family is classified into two genera, namely the corona- and toroviruses. Coronaviruses are enveloped, single stranded, positive sense RNA viruses with genomes ranging between 27-32kb in size. The 5’ two-thirds of the genome encodes for the 1a/b polyprotein, while the 3’ one-third of the genome encodes for the structural proteins that mediate viral entry into the host cell. These structural proteins include the spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins. The nucleocapsid protein is expressed at high levels within an infected cell. Studies have shown that this protein plays a key regulatory role in different cellular pathways, including the inhibition of interferon production and the up-regulation of the AP1 signal transduction pathway, amongst others. Also, the N protein is vital in the formation of the ribonucleocapsid core by binding to the viral RNA during virion assembly. The focus of this study is the immune response in whole blood cultures to the presence of human coronavirus (HCoV) NL63 N protein. To characterise the stimulation of the immune activity against HCoV-NL63 N in blood cultures, the HCoV-NL63 N gene was expressed in a bacterial system. In this pilot study, GSTtagged N constructs were then purified and used to treat whole blood cultures from three volunteers. ELISAs were used to measure the cytokine response in these treated whole blood cultures. Results showed that the nucleocapsid protein has an inflammatory response on whole blood cultures. These results have generated vital information in the potential function of the HCoV-NL63 N protein on the immune system. It is suffice to say that the HCoV-NL63 N protein is able to elicit an effective inflammatory response within the host cell. Future studies into the cellular pathways affected by the HCoV-NL63 N protein will clarify its exact role in stimulating the host immune system.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / CT abdomen and pelvis is a widely-used imaging modality used in the evaluation of appendicitis but it carries risks of radiation. A recent retrospective review localizes all appendices (both normal and abnormal) below the level of the L1 vertebral body, obviating the need to scan superior to that level. This study is a retrospective review of prospectively-collected data from 171 consecutive pediatric patients presenting with clinical suspicion of acute appendicitis and undergoing “low FOV CT.” The low FOV CT uses the L1 vertebral body as the superior aspect of the exam instead of the of the dome of the diaphragm as in standard CT.

Introduction: Patients with acute kidney injury (AKI) in developing countries are described in a profile of young age, with less comorbidities, with unifactorial, and with a lower mortality compared to patients in developed countries. Objective: To assess mortality in patients with acute kidney injury undergoing hemodialysis (HD) and its associated factors in a developing country setting. Methods: Retrospective study. Demographic, clinical, and mortality variables were collected from patients who presented AKI and underwent HD between January 2014 and December 2015 at a national reference hospital in Lima, Peru. Risk ratios (RR) and 95% confidence intervals (95%CI) were estimated through Poisson regressions. Results: Data from 72 patients with AKI that underwent HD were analyzed, 66.7% of them were < 64 years old, and 40.2% of all patients died undergoing HD. Crude analysis showed higher mortality among those who used vasopressors, but lower mortality among those with creatinine values > 8.9 mg/ dL. The adjusted analysis showed that having had a creatinine level of > 8.9 mg/ dL, compared to a creatinine level of < 5.2 mg/dL at the time of initiating HD, was associated with 74% less probability of death. Conclusion: Four out of every ten AKI patients undergoing HD die. Higher levels of creatinine were associated with lower probability of mortality.

Abstract Several studies have shown that altered cardiovascular autonomic regulation is associated with hypertension, diabetes, aging, angiographic severity of coronary artery disease (CAD), and increased mortality after acute myocardial infarction (AMI). The purpose of this study was to assess the temporal changes and prognostic significance of various measures of heart rate (HR) behaviour and their possible associations to coronary risk variables, and the progression of CAD in different populations. This study comprised five patient populations. The first consisted of 305 patients with recent coronary artery bypass graft surgery (CABG) and lipid abnormalities, the second of 109 male patients with recent CABG, the third of 53 type II diabetic patients with CAD, the fourth of 600 patients with recent AMI, and the fifth of 41 elderly subjects. HR variability and non-linear measures of HR dynamics were analysed. Among the patients with prior CABG, a significant correlation existed between the baseline HR variability (standard deviation of N-N intervals, SDNN) and the progression of CAD (r = 0.26, p &lt; 0.001)). In the longitudinal study of patients with prior CABG, only the fractal indexes of HR dynamics, such as the power law slope (β) and the short-term fractal exponent (α1), decreased significantly. In diabetic patients, SDNN decreased significantly (p &lt; 0.001) during the three-year period. The reduction of SDNN was related to cholesterol, triglyceride, and glucose levels, and also to progression of CAD (r = 0.36, p &lt; 0.01). In the longitudinal follow-up study of patients with recent AMI, reduced fractal indices (α1 and β), and reduced HR turbulence predicted cardiac death when measured at the convalescent phase after AMI. Reduced β and turbulence slope predicted cardiac death when measured at 12 months after AMI. In the elderly population, β (p &lt; 0.001) and α1 (p &lt; 0.01) reduced significantly. Low-frequency power spectra were the only traditional measure of HR variability that decreased significantly during the 16-year period. HR variability is associated with many risk factors of atherosclerosis and with progression of CAD among patients with ischemic heart disease. Fractal HR dynamics are more sensitively able to detect age-related changes in cardiovascular autonomic regulation. Altered fractal HR dynamics and HR turbulence are associated with increased mortality after AMI.

Abstract The development of commercially available assays from the measurement of enzyme activity to mass concentrations of proteins, especially the assays of cardiac troponin I and T, has been the most important innovation in the field of cardiovascular laboratory diagnostics over the decade. The availability of a simple, rapid test using whole blood to facilitate processing and to reduce the turnaround time could improve the management of patients presenting with chest pain. The aim of this study was to evaluate the analytical and clinical performance of a new time-resolved fluorometry-based immunology technology using the cardiac marker and high-sensitivity C-reactive protein assays. In addition, the use of high-sensitivity C-reactive protein assay for the investigation of patients with acute atrial fibrillation and the influence of heparin for cardiac marker assays were studied. The levels of precision attained with pooled serum and plasma samples and control materials were acceptable. The assays were found to be linear within the ranges tested. The correlation coefficient between the Innotrac Aio! 1st generation cTnI and Abbott AxSYM cTnI assays was 0.960, and the slope was 0.07. The correlations between the 2nd generation Innotrac Aio!, Access AccuTnI and Abbott AxSYM assays were good, but there were biases between the methods. The correlation coefficients between the Innotrac Aio! and Abbott AxSYM CK-MB and myoglobin assays were 0.995 and 0.971, respectively, but the Innotrac Aio! CK-MB assay yielded about 9% higher values than the Abbott assay. The correlations between Innotrac Aio! usCRP and Cobas Integra CRP latex and between Innotrac Aio! usCRP and Hitachi CRP (Latex ) HS were good. Furthermore, the sample material correlation studies showed no significant differences when the Innotrac Aio! System was used. However, the mean Abbott AxSYM CK-MB values and the cTnI values for heparin plasma samples were 17% higher and about 15% lower than for serum samples, respectively. In the investigation of CRP levels in patients with acute atrial fibrillation CRP tended to be higher in the patients with acute FA, and there was a positive correlation between the concentrations of CRP and IL-6. The results demonstrate the excellent analytical performance of the Innotrac Aio! 2nd generation cTnI, myoglobin, CK-MB and usCRP assays, and all the matrices, including serum, plasma and whole blood, are suitable sample matrices to be used with these methods without further standardization.

INTRODUCTION: The worldwide incidence of acute kidney injury is 18% and the overall hospital mortality can rise above 50%. In Peru, there are few series about mortality of acute kidney injury in hemodialysis patients. OBJECTIVES: To identify risk factors associated to hospital mortality of acute kidney injury in hemodialysis patients. METHODS: This is a retrospective cohort of patients with acute kidney injury in hemodialysis of Hospital Nacional Edgardo Rebagliati Martins gathered between January 2013 and December 2015. The sample size was 154 patients which allowed a power of 80% and a CI of 95%. ICD-10 codes were used to identify medical records of patients with acute kidney injury (N.17) and hemodialysis (Z.49). The independent variable was oliguria, and the primary outcome was hospital mortality. Poisson regression was used for multivariate analysis. RESULTS: We identified a total of 285 patients; 212 medical records were analyzed and 44 were excluded. Out of the 168 medical records, 129 belonged to living patients and 39 to deceased ones. The overall mortality incidence was 17.2%. The principal etiologies of acute kidney injury while in hemodialysis were sepsis (39.2%), and severe dehydration (10.8%). In the adjusted model, the risk factors associated to hospital mortality of acute kidney injury while in hemodialysis were elevated serum lactate (RR 1.09), elevated serum potassium (RR 0.93), and mean arterial pressure (RR 0.97). CONCLUSIONS: Lactate is an objective parameter that can predict prognosis and contributes to a better management of acute kidney injury in hemodialysis patients. INTRODUCCIÓN: La incidencia de insuficiencia renal aguda a nivel mundial es 18% y la mortalidad intrahospitalaria puede alcanzar más del 50%. En Perú, existen escasos estudios acerca de la mortalidad en pacientes con insuficiencia renal aguda en hemodiálisis. OBJETIVOS: Identificar los factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis. MÉTODOS: Es una cohorte retrospectiva, en la cual se estudió a los pacientes con insuficiencia renal aguda en hemodiálisis en el Hospital Nacional Edgardo Rebagliati Martins entre enero de 2013 y diciembre de 2015. Se halló un tamaño de muestra de 154 pacientes con una potencia de 80%, y un intervalo de confianza de 95%. Se utilizaron los códigos de la Clasificación Internacional de Enfermedades-10 para identificar las historias clínicas de pacientes con insuficiencia renal aguda (N.17) y hemodiálisis (Z.49). La variable independiente fue oliguria y la variable dependiente fue mortalidad intrahospitalaria. Para el análisis multivariado, se utilizó regresión de Poisson. RESULTADOS: El universo fue de 285 pacientes. Se revisaron 212 historias clínicas y se excluyeron 44. De las 168 historias clínicas estudiadas, 129 pertenecían a pacientes vivos y 39 a fallecidos. La incidencia de mortalidad fue de 17,2%. Las principales causas de insuficiencia renal aguda en hemodiálisis fueron sepsis (39,2%) y deshidratación severa (10,8%). En el modelo ajustado, los factores de riesgo asociados a mortalidad intrahospitalaria de insuficiencia renal aguda en hemodiálisis fueron lactato (riesgo relativo 1,09), potasio (riesgo relativo 0,93), y presión arterial media (riesgo relativo 0,97). CONCLUSIONES: El lactato es un parámetro objetivo que permite predecir el pronóstico y contribuye a un mejor manejo de los pacientes con insuficiencia renal aguda en hemodiálisis.