169 research outputs found
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Risk Model Development and Validation for Prediction of Coronary Artery Aneurysms in Kawasaki Disease in a North American Population.
Background Accurate prediction of coronary artery aneurysms ( CAAs ) in patients with Kawasaki disease remains challenging in North American cohorts. We sought to develop and validate a risk model for CAA prediction. Methods and Results A binary outcome of CAA was defined as left anterior descending or right coronary artery Z score â„2.5 at 2 to 8 weeks after fever onset in a development cohort (n=903) and a validation cohort (n=185) of patients with Kawasaki disease. Associations of baseline clinical, laboratory, and echocardiographic variables with later CAA were assessed in the development cohort using logistic regression. Discrimination (c statistic) and calibration (Hosmer-Lemeshow) of the final model were evaluated. A practical risk score assigning points to each variable in the final model was created based on model coefficients from the development cohort. Predictors of CAAs at 2 to 8 weeks were baseline Z score of left anterior descending or right coronary artery â„2.0, age <6 months, Asian race, and C-reactive protein â„13 mg/ dL (c=0.82 in the development cohort, c=0.93 in the validation cohort). The CAA risk score assigned 2 points for baseline Z score of left anterior descending or right coronary artery â„2.0 and 1 point for each of the other variables, with creation of low- (0-1), moderate- (2), and high- (3-5) risk groups. The odds of CAA s were 16-fold greater in the high- versus the low-risk groups in the development cohort (odds ratio, 16.4; 95% CI , 9.71-27.7 [ P<0.001]), and >40-fold greater in the validation cohort (odds ratio, 44.0; 95% CI, 10.8-180 [ P<0.001]). Conclusions Our risk model for CAA in Kawasaki disease consisting of baseline demographic, laboratory, and echocardiographic variables had excellent predictive utility and should undergo prospective testing
Concordancia entre la técnica de hemaglutinación indirecta e inmunoabsorción ligado a enzimas en el diagnóstico de toxoplasmosis porcina
El documento digital no refiere un asesorDetermina la concordancia entre las pruebas de HAI y ELISA, para detectar IgG anti-Toxoplasma gondii en el diagnĂłstico de toxoplasmosis porcina. El trabajo se desarrolla en 407 animales provenientes de crianzas porcinas ubicadas en la franja costera del departamento de Lima. Se colectan las muestras de sangre de cerdos en la fase de acabado, posteriormente las muestras de suero son conservadas en congelaciĂłn (-70ÂșC) hasta su procesamiento en el Laboratorio de ParasitologĂa de la Facultad de Medicina Veterinaria de la UNMSM. La concordancia de las tĂ©cnicas diagnĂłsticas y la seroprevalencia correspondiente se evalĂșan mediante dos diferentes modelos estadĂsticos: Indice de Kappa y la prueba de McNemar. En los resultados se halla que la concordancia entre las pruebas de HAI-ELISA a travĂ©s del Ăndice de Kapa es igual a 26% considerĂĄndose de tipo regular, con valores de 18.7 ± 3.8% por el mĂ©todo de HAI, y 14.7 ± 3.4%, por el mĂ©todo de ELISA; sin embargo, mediante la prueba de McNemar no se encuentra diferencias significativas y sugerirĂan que ambas tĂ©cnicas son mutuamente reemplazables. Concluyendo que, como la correlaciĂłn es regular, no se recomienda.Tesi
Henoch-Schönlein nephritis associated with streptococcal infection and persistent hypocomplementemia: a case report
<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a systemic disease with frequent renal involvement, characterized by IgA mesangial deposits. Streptococcal infection can induce an abnormal IgA immune response like Henoch-Schönlein purpura, quite similar to typical acute post-infectious glomerulonephritis. Indeed, hypocomplementemia that is typical of acute glomerulonephritis has also been described in Henoch-Schönlein purpura.</p> <p>Case presentation</p> <p>We describe a 14-year-old Caucasian Spanish girl who developed urinary abnormalities and cutaneous purpura after streptococcal infection. Renal biopsy showed typical findings from Henoch-Schönlein purpura nephritis. In addition, she had low serum levels of complement (C4 fraction) that persisted during follow-up, in spite of her clinical evolution. She responded to treatment with enalapril and steroids.</p> <p>Conclusion</p> <p>The case described has, at least, three points of interest in Henoch-Schönlein purpura: 1) Initial presentation was preceded by streptococcal infection; 2) There was a persistence of low serum levels of complement; and 3) There was response to steroids and angiotensin-converting enzyme inhibitor in the presence of nephrotic syndrome. There are not many cases described in the literature with these characteristics. We conclude that Henoch-Schönlein purpura could appear after streptococcal infection in patients with abnormal complement levels, and that steroids and angiotensin-converting enzyme inhibitor could be successful treatment for the disease.</p
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Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores
Background: Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area (z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. Methods and Results: We explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) â„2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax â„2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax â„2.0 versus <2.0 (12 [16%] versus 3 [2%], respectively, P<0.001). Baseline zMax â„2.0 had a C statistic of 0.77, good sensitivity (80%), and excellent negative predictive value (98%). None of the risk scores alone had adequate discrimination. When highârisk status per the Japanese risk scores was added to models containing baseline zMax â„2.0, none were significantly better than baseline zMax â„2.0 alone. Conclusions: In a North American center, baseline zMax â„2.0 in children with Kawasaki disease demonstrated high predictive utility for later development of CAA. Future studies should validate the utility of our findings
Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain
The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here
The HSP70 Molecular Chaperone Is Not Beneficial in a Mouse Model of α-synucleinopathy
BACKGROUND: Aggregation and misfolded alpha-synuclein is thought to be central in the pathogenesis of Parkinson's disease (PD). Heat-shock proteins (HSPs) that are involved in refolding and degradation processes could lower the aggregate load of alpha-synuclein and thus be beneficial in alpha-synucleinopathies. METHODOLOGY/PRINCIPAL FINDINGS: We co-overexpressed human A53T point-mutated alpha-synuclein and human HSP70 in mice, both under the control of Thy1 regulatory sequences. Behavior read-outs showed no beneficial effect of HSP70 expression in mice. In contrast, motor coordination, grip strength and weight were even worse in the alpha-synucleinopathy model in the presence of HSP70 overexpression. Biochemical analyses revealed no differences in alpha-synuclein oligomers/aggregates, truncations and phosphorylation levels and alpha-synuclein localization was unchanged in immunostainings. CONCLUSION/SIGNIFICANCE: Overexpressing HSP70 in a mouse model of alpha-synucleinopathy did not lower the toxic load of alpha-synuclein species and had no beneficial effect on alpha-synuclein-related motor deficits
In silico validation of the autoinflammatory disease damage index
Introduction Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. Methods The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an Ăą observer-nested-within-subject\u27 design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach\u27s alpha. Results The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. Conclusion The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies
The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study
BACKGROUND: Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. METHODS: This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. RESULTS: At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 ± 3.0 years and females for 1.0 ± 1.8 years (p < 0.05). Of the 93 medical students who were not smokers at the time of registration, 30 (32.3%) were smokers at the end of the 6 years of the course. CONCLUSION: The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty
Development of the autoinflammatory disease damage index (ADDI)
OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency. METHODS: We developed the ADDI by consensus building. The top 40 enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions, which were then formally weighted in a scoring system derived using decision-making software, known as 1000minds. RESULTS: More than 80% of the experts and patients completed the online surveys. The preliminary ADDI contains 18 items, categorised in the following eight organ systems: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example, chronic musculoskeletal pain. CONCLUSIONS: An instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building. Patients fulfilled a significant role in this process
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