Corticosteroid treatment exacerbates nephrotic syndrome in a zebrafish model of magi2a knockout

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Numerische Strömungssimulation

The current options for objective assessment of nasal breathing are limited. The maximum they can determine is the total nasal resistance. Possibilities to analyze the endonasal airstream are lacking. In contrast, numerical flow simulation is able to provide detailed information of the flow field within the nasal cavity. Thus, it has the potential to analyze the nasal airstream of an individual patient in a comprehensive manner and only a computed tomography (CT) scan of the paranasal sinuses is required. The clinical application is still limited due to the necessary technical and personnel resources. In particular, a statistically based referential characterization of normal nasal breathing does not yet exist in order to be able to compare and classify the simulation results.     

A WINNING COMBINATION: WOMEN,LITERACY, AND PARTICIPATION IN HEALTH CARE

Health information materials written at the appropriate reading level help individuals manage their own health care. In this study, we assessed the reading ability of clients and readability of the patient information materials at a rural women's health clinic. We administered a reading comprehension test to 50 subjects and tested the patient education materials using a readability formula. More than one in six women could not read all of the patient information, which could limit their understanding, and achievement of good health care. Commercially available materials can be checked readily for reading level using software installed in most computers. This software also allows clinicians who prepare their own materials for their patients to generate versions that are appropriate for different reading levels.     

Prevalence of diastolic dysfunction as a possible cause of dyspnea in the elderly

PURPOSE: Symptoms in patients with heart failure and preserved left ventricular ejection fraction may be caused by isolated diastolic dysfunction. The purpose of this study was to assess the prevalence of diastolic dysfunction as a potential cause of dyspnea in a sample of elderly subjects, as well as of isolated diastolic dysfunction as a potential cause of dyspnea in a subgroup with a preserved left ventricular ejection fraction and normal lung function. METHODS: A total of 152 subjects with dyspnea underwent echocardiography, electrocardiography, and lung function testing. Subjects with normal lung function test results (n = 60) underwent cardiac magnetic resonance imaging, chest radiography, bicycle exercise tests, and blood tests. Left ventricular diastolic function was assessed by a variety of echocardiographic/Doppler techniques. RESULTS: Of 129 subjects with dyspnea, 81 (63%) had signs of lung disease or 'obvious' cardiac disease. In the remaining 48 subjects, 32 (67%) had a potential cardiac/noncardiac cause of dyspnea. In all subjects with dyspnea, 1% to 11% had diastolic dysfunction, and in the 48 remaining subjects, 0% to 10% had isolated diastolic dysfunction, depending on the definition used. CONCLUSION: The frequency of diastolic dysfunction was low in the sample of elderly subjects with dyspnea as well as in the subgroup of persons with no signs of lung disease, left ventricular systolic dysfunction, atrial fibrillation, or valvular heart disease. Diastolic dysfunction was infrequent as a possible cause of dyspnea, and coexisting potential causes of dyspnea were often present.     

Prolonged cardiac arrest and resuscitation in dogs: brain mitochondrial function with different artificial perfusion methods

Clinical techniques for artificial perfusion have not previously been examined directly for their effects on brain high-energy metabolism. Our study involved 24 large mongrel dogs that were anesthetized, instrumented for central venous intravenous access, and subjected to craniotomy to expose the dura and underlying parietal cortex. The animals were divided into the following six experimental groups of four animals each: nonischemic controls; 15-minute cardiac arrest without resuscitation; 45-minute cardiac arrest without resuscitation; 15-minute cardiac arrest plus 30 minutes resuscitation with conventional cardiopulmonary resuscitation (CPR); 15-minute cardiac arrest plus 30 minutes resuscitation with interposed abdominal compression (IAC) CPR; and 15-minute cardiac arrest plus 30 minutes resuscitation with internal cardiac massage. Cardiac arrest was induced by central venous injection of KCl 0.6 mEq/kg, and it was confirmed by continuous ECG monitoring. The three active resuscitation models included administration of NaHCO3 and epinephrine, but no attempt was made to restart the heart by defibrillation during resuscitation. At the indicated time in each group, a 4- to 5-g sample of brain was removed through the craniotomy, immediately cooled to 0 C and processed for isolation of mitochondria. The mitochondria were studied for their content of superoxide dismutase and for quantitative oxygen consumption with glutamate/malate substrate during resting and ADP-stimulated respiration. Our results show a significant drop in brain mitochondrial superoxide dismutase activity during the first 15 minutes of cardiac arrest. There is minimal injury to brain mitochondrial oxygen consumption during both 15 and 45 minutes of complete ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease‐associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL‐like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease‐causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL.     

Gravitational effects on volume distribution in a model of partial and total liquid ventilation

To estimate regional lung volume during ventilation with liquids (e. g. perfluorochemicals, PFC) we developed a multi-compartment mathematical model of a lung and thorax. The height of the fluid column and the fluid's density determine alveolar pressure (PA). The weight of thoracic contents above any given gravitational plane influences pleural pressure (PPL). Transpulmonary pressure (PTP=PA−PPL) and compliance of the lung and chest wall permit estimation of volumes. The results indicate the lung inflates almost uniformly during total liquid ventilation despite a substantial vertical PA gradient. Inflation uniformity is due to the offsetting vertical PPL gradient created by the added weight of the PFC and sustained by the relative rigidity of the chest wall. During partial liquid ventilation our model indicates that the combination of uniform PA with a large vertical gradient in PPL leads to a vertical PTP gradient and therefore relative over-inflation of the top of the lung. This effect increases with increasing PFC dose and with lung height.     

Plasma N-terminal pro-brain natriuretic peptide as a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria

Aims/hypothesis We examined whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) predicts cardiovascular outcome in patients with type 2 diabetes.Methods A total of 160 microalbuminuric type 2 diabetic patients (mean age 55.1 years [SD 7.2], 119 men) were enrolled in the Steno-2 Study examining the effect of multifactorial treatment, and were divided into two groups according to baseline levels of plasma NT-proBNP below or above the median for the cohort, which was followed for an average of 7.8 years. Cardiovascular outcome was a composite of cardiovascular mortality, myocardial infarction, stroke, revascularisation procedures in the heart or legs, and amputations.Results In the whole group, plasma NT-proBNP being above the median was associated with an increased risk of cardiovascular disease during follow-up, with an unadjusted hazard ratio of 4.4 (95% CI 2.3–8.4; p<0.0001). A decrease in plasma NT-proBNP of 10 pg/ml during the first 2 years of intervention was associated with a 1% relative reduction in the primary endpoint (p<0.001). Despite polypharmacological treatment targeting cardiovascular disease, the mean plasma NT-proBNP level increased during follow-up.Conclusions/interpretation We conclude that high plasma NT-proBNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.