Investigation of brain function in neuropsychiatric disorder using multimodal imaging analysis

Otto-von-Guericke-Universität Magdeburg, Fakultät für Naturwissenschaften, Dissertation, 2016

Untersuchung des Einflusses der point spread function (PSF)- und time-of-flight (TOF)-Bilddatenrekonstruktion auf die F18-FDG-PET/CT-basierte Zielvolumendefinition kolorektaler Lebermetastasen

Universität Magdeburg, Dissertation, 2016

Das natürliche System der chemischen Elemente. Abhandlungen von Lothar Meyer 1864-1869 und D. Mendelejeff 1869-1871.

The "Anhang" to the first treatise is here first printed from the original manuscript, the last treatise is reprinted from the translation by F. Wreden.

Chemistry, meteorology, and the function of digestion : considered with reference to natural theology /

Binder's title: Bridgewater treatises.

The Federal role in the federal system : the dynamics of growth.

"A-77 - A-87."

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation, Retrieval, Classification and Interpretation

Thesis (Ph.D.)--University of Washington, 2016-06

Function and Regulation of Cytochrome P450 4V2 and the Implications in Bietti’s Crystalline Dystrophy

Thesis (Ph.D.)--University of Washington, 2016-06

Cardiac function in fetuses of poorly-controlled pre-gestational diabetic pregnancies - a pilot study

Objective: Cardiac impairment is frequently found in babies of diabetic mothers. It is still controversial whether this is due to poor glucose control. The aim of this study is to compare the cardiac function in fetuses of well- and poorly-controlled pre-gestational diabetic pregnancy in third trimester. Methods:Women with type 1 pre-gestational diabetes were enrolled at 30-32 weeks. Cardiac size and interventricular septal wall thickness were measured by M-mode at end-diastolic phase. The right and left ventricular ejection fractions were calculated. At the mitral and tricuspid valves inflow, the ratio between early ventricular filling and active atrial filling (E/A) at both atrioventricular valves were measured by Doppler echocardiography. Peak velocities of ascending aorta and pulmonary artery were assessed. The angle of isonation was kept at 6.5%) were compared with those with satisfactorily controlled diabetes (HbA1c less than or equal to 6.5%). Results: A total of 21 women with pre-gestational diabetes were recruited for this study. Eight women with well-controlled diabetes were compared with 9 women who had poorly-controlled diabetes. HbA1c in the poorly-controlled group was 7.3% and in the well-controlled group it was 5.4% (p < 0.001). There was no difference between the two groups in cardiac size, interventricular septal wall thickness, ejection fraction, aorta and pulmonary artery peak flow velocities. The right atrioventricular E/A ratio was significantly lower among the poorly-controlled diabetic pregnancies (0.71 vs. 0.54; p < 0.05). Conclusion: Fetuses of poorly-controlled diabetic mothers had a lower right atrioventricular E/A ratio. This may be due to metabolic acidosis, non-hypertrophic cardiac dysfunction or fetal polycythemia. Copyright (C) 2003 S. Karger AG, Basel.

A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse

The c-fms gene encodes the receptor for macrophage colony-stimulating factor (CSF-1). The gene is expressed selectively in the macrophage and trophoblast cell lineages. Previous studies have indicated that sequences in intron 2 control transcript elongation in tissue-specific and regulated expression of c-fms. In humans, an alternative promoter was implicated in expression of the gene in trophoblasts. We show that in mice, c-fms transcripts in trophoblasts initiate from multiple points within the 2-kilobase (kb) region flanking the first coding exon. A reporter gene construct containing 3.5 kb of 5' flanking sequence and the down-stream intron 2 directed expression of enhanced green fluorescent protein (EGFP) to both trophoblasts and macrophages. EGFP was detected in trophoblasts from the earliest stage of implantation examined at embryonic day 7.5. During embryonic development, EGFP highlighted the large numbers of c-fms-positive macrophages, including those that originate from the yolk sac. In adult mice, EGFP location Was consistent with known F4/80-positive macrophage populations, including Langerhans cells of the skin, and permitted convenient sorting of isolated tissue macrophages from disaggregated tissue. Expression of EGFP in transgenic mice was dependent on intron 2 as no lines with detectable EGFP expression were obtained where either all of intron 2 or a conserved enhancer element FIRE (the Fms intronic regulatory element) was removed. We have therefore defined the elements required to generate myeloid- and trophoblast-specific transgenes as well as a model system for the study of mononuclear phagocyte development and function. (C) 2003 by The American Society of Hematology.

Neurally-mediated increase in calcineurin activity regulates cardiac contractile function in absence of hypertrophy

Objective: The calcineurin pathway has been involved in the development of cardiac hypertrophy, yet it remains unknown whether calcineurin activity can be regulated in myocardium independently from hypertrophy and cardiac load. Methods: To test that hypothesis, we measured calcineurin activity in a rat model of infrarenal aortic constriction (IR), which affects neurohormonal pathways without increasing cardiac afterload. Results: In this model, there was no change in arterial pressure over the 4-week experimental period, and the left ventricle/body weight ratio did not increase. At 2 weeks after IR, calcineurin activity was increased 1.8-fold (P

Alpha-lipoic acid does not acutely affect resistance and conduit artery function or oxidative stress in healthy men

Aims Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively. Methods In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography. Results There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress. Conclusions Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.

Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function

Objective: We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. Methods: We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. Results: There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. Conclusion: Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Noninvasive tests for arterial structure, function, and compliance: Do they identify risk or diagnose disease?

Background: Brachial artery reactivity (BAR), carotid intima-media thickness (IMT), and applanation tonometry for evaluation of total arterial compliance may provide information about preclinical vascular disease. We sought to determine whether these tests could be used to identify patients with coronary artery disease (CAD) without being influenced by their ability to identify those at risk ford CAD developing. Methods: We studied 100 patients and compared 3 groups: 35 patients with known CAD; 34 patients with symptoms and risk factors but no CAD identified by stress echocardiography (risk group); and 31 control subjects. BAR and IMT were measured using standard methods, and total arterial compliance was calculated by the pulse-pressure method from simultaneous radial applanation tonometry and pulsed wave Doppler of the left ventricular outflow. Ischemia was identified as a new or worsening wall-motion abnormality induced by stress. Results: In a comparison between the control subjects and patients either at risk for developing CAD or with CAD, the predictors of risk for CAD were: age (P = .01); smoking history (P = .002); hypercholesterolemia (P = .002); and hypertension (P = .004) (model R = 0.82; P = .0001). The independent predictors of CAD were: IMT (P = .001); BAR (P = .04); sex (P = .005); and hypertension (P = .005) (model R = 0.80; P = .0001). Conclusion: IMT, BAR, and traditional cardiovascular risk factors appear to identify patients at risk for CAD developing. However, only IMT was significantly different between patients at risk for developing CAD and those with overt CAD.

Patients with a hypertensive response to exercise have impaired systolic function without diastolic dysfunction or left ventricular hypertrophy

OBJECTIVES We sought to determine if a hypertensive response to exercise (HRE) is associated with myocardial changes consistent with early hypertensive heart disease. BACKGROUND An HRE predicts the development of chronic hypertension (HT) and may reflect a preclinical stage of HT. METHODS Patients with a normal left ventricular (LV) ejection fraction and a negative stress test were recruited into three matched groups: 41 patients (age 56 +/- 10 years) with HRE (210/105 mm Hg in men; > 190/105 in women), comprising 22 patients with (HT+) and 19 without resting hypertension (HT-); and 17 matched control subjects without HRE. Long-axis function was determined by measurement of the strain rate (SR), peak systolic strain, and cyclic variation (CV) of integrated backscatter in three apical views. RESULTS An HRE was not associated with significant differences in LV mass index. Exercise performance and diastolic function were reduced in HRE(HT+) patients, but similar in HRE(HT-) patients and controls. Systolic dysfunction (peak systolic strain, SR, and CV) was significantly reduced in HRE patients (p < 0.001 for all). These reductions were equally apparent in patients with and without a history of resting HT (p = NS) and were independent of LV mass index and blood pressure (p < 0.01). CONCLUSIONS An HRE is associated with subtle systolic dysfunction, even in the absence of resting HT. These changes occur before the development of LV hypertrophy or detectable diastolic dysfunction and likely represent early hypertensive heart disease. (C) 2004 by the American College of Cardiology Foundation.

Response of B-type natriuretic pepticle to exercise in hypertensive patients with suspected diastolic heart failure: Correlation with cardiac function, hemodynamics, and workload

Background Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Methods Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (So) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Results Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 57 to 74 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise So, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Conclusions Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.