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171.
Michael Nagler Lucas M. Bachmann Pirmin Schmid Pascale Raddatz Müller Walter A. Wuillemin 《PloS one》2014,9(4)
Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2–12.8 years). Median age at the time of training was 54.2 years (range 18.2–85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1–1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6–3.7; p<0.001), patients>50 years of age (2.0; 1.6–2.6; p<0.001), and men (1.6; 1.2–2.1; p = 0.036). The rate of thromboembolic events was 0.4 (0.2–0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9–1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted. 相似文献
172.
The effect of changes in arterial pCO2 on isogravimetric capillary pressure and vascular resistances
173.
A 4-week, province-wide nurses'' strike in Alberta in 1982 caused the closure of 57% of the acute care beds, including 47% of the intensive care beds, in Calgary. The effects of the strike on patient care at Foothills Provincial General Hospital, where nurses did not strike, were assessed. The number of emergency admissions, severity of illness and rate of death in the intensive care unit increased. On the other hand, the rate of death, length of stay and number of unexpected deaths on the medical wards were similar to those in the control periods before and after the strike. A subjective perception by hospital personnel of deteriorating patient care caused much anxiety; however, the results of analysis of measurable aspects of care suggested that the patients admitted to hospital received care during the strike that was comparable to care given before or after the strike. The inconvenience and potential harm to the patients not admitted because they had less severe illness were not measured. 相似文献
174.
Malik IA Triebel J Posselt J Khan S Ramadori P Raddatz D Ramadori G 《Histochemistry and cell biology》2012,137(3):279-291
MCRs are known to be expressed predominantly in the brain where they mediate metabolic and anti-inflammatory functions. Leptin
plays an important role in appetite and energy regulation via signaling through melanocortin receptors (MCRs) in the brain.
As serum levels of MCR ligands are elevated in a clinical situation [acute-phase response (APR)] to tissue damage, where the
liver is responsible for the metabolic changes, we studied hepatic gene expression of MCRs in a model of muscle tissue damage
induced by turpentine oil (TO) injection in rats. A significant increase in gene expression of all five MCRs (MC4R was the
highest) in liver at the RNA and protein level was detected after TO injection. A similar pattern of increase was also found
in the brain. Immunohistology showed MC4R in the cytoplasm, but also in the nucleus of parenchymal and non-parenchymal liver
cells, whereas MC3R-positivity was mainly cytoplasmic. A time-dependent migration of MC4R protein from the cytoplasm into
the nucleus was observed during APR, in parallel with an increase in α-MSH and leptin serum levels. An increase of MC4R was
detected at the protein level in wild-type mice, while such an increase was not observed in IL-6ko mice during APR. Moreover,
treatment of isolated liver cells with melanocortin agonists (α-MSH and THIQ) inhibited the endotoxin-induced upregulation
of the acute-phase cytokine (IL-6, IL1β and TNF-α) gene expression in Kupffer cells and of chemokine gene expression in hepatocytes.
MCRs are expressed not only in the brain, but also in liver cells and their gene expression in liver and brain tissue is upregulated
during APR. Due to the presence of specific ligands in the serum, they may mediate metabolic changes and exert a protective
effect on liver cells. 相似文献
175.
Dandu RR Lyons JA Raddatz R Huang Z Aimone LD Hudkins RL 《Bioorganic & medicinal chemistry letters》2012,22(6):2151-2153
A novel class of 1'-cyclobutyl-6-(4-piperidyloxy)spiro[benzopyran-2,4'-piperidine] derivatives with low nanomolar affinity for the human and rat histamine-3 receptors (H(3)Rs) are described. The spirobenzopyran piperidine ether analogs demonstrated excellent H(3)R affinity and selectivity against histamine receptor subtypes (H(1)R, H(2)R, and H(4)R), were stable in liver microsomes, and had selectivity against CYP P450 enzymes. Compounds 10, 13, 15, and 16 demonstrated high H(3)R affinity, in vitro liver microsomal stability, selectivity against CYP isoforms, moreover, these ether analogs exhibited acceptable iv pharmacokinetic (PK) properties but had poor oral exposure in rat. 相似文献
176.
Obrowsky S Chandak PG Patankar JV Pfeifer T Povoden S Schreiber R Haemmerle G Levak-Frank S Kratky D 《Biochimica et biophysica acta》2012,1821(11):1406-1414
Hormone sensitive lipase (HSL) regulates the hydrolysis of acylglycerols and cholesteryl esters (CE) in various cells and organs, including enterocytes of the small intestine. The physiological role of this enzyme in enterocytes, however, stayed elusive. In the present study we generated mice lacking HSL exclusively in the small intestine (HSLiKO) to investigate the impact of HSL deficiency on intestinal lipid metabolism and the consequences on whole body lipid homeostasis. Chow diet-fed HSLiKO mice showed unchanged plasma lipid concentrations. In addition, feeding with high fat/high cholesterol (HF/HC) diet led to unaltered triglyceride but increased plasma cholesterol concentrations and CE accumulation in the small intestine. The same effect was observed after an acute cholesterol load. Gavaging of radioactively labeled cholesterol resulted in increased abundance of radioactivity in plasma, liver and small intestine of HSLiKO mice 4h post-gavaging. However, cholesterol absorption determined by the fecal dual-isotope ratio method revealed no significant difference, suggesting that HSLiKO mice take up the same amount of cholesterol but in an accelerated manner. mRNA expression levels of genes involved in intestinal cholesterol transport and esterification were unchanged but we observed downregulation of HMG-CoA reductase and synthase and consequently less intestinal cholesterol biosynthesis. Taken together our study demonstrates that the lack of intestinal HSL leads to CE accumulation in the small intestine, accelerated cholesterol absorption and decreased cholesterol biosynthesis, indicating that HSL plays an important role in intestinal cholesterol homeostasis. 相似文献
177.
Stephan Seiler Helena Schmidt Anita Lechner Thomas Benke Guenter Sanin Gerhard Ransmayr Riccarda Lehner Peter Dal-Bianco Peter Santer Patricia Linortner Christian Eggers Bernhard Haider Margarete Uranues Josef Marksteiner Friedrich Leblhuber Peter Kapeller Christian Bancher Reinhold Schmidt PRODEM Study Group 《PloS one》2012,7(12)
Objective
To assess the influence of cognitive, functional and behavioral factors, co-morbidities as well as caregiver characteristics on driving cessation in dementia patients.Methods
The study cohort consists of those 240 dementia cases of the ongoing prospective registry on dementia in Austria (PRODEM) who were former or current car-drivers (mean age 74.2 (±8.8) years, 39.6% females, 80.8% Alzheimer’s disease). Reasons for driving cessation were assessed with the patients’ caregivers. Standardized questionnaires were used to evaluate patient- and caregiver characteristics. Cognitive functioning was determined by Mini-Mental State Examination (MMSE), the CERAD neuropsychological test battery and Clinical Dementia Rating (CDR), activities of daily living (ADL) by the Disability Assessment for Dementia, behavior by the Neuropsychiatric Inventory (NPI) and caregiver burden by the Zarit burden scale.Results
Among subjects who had ceased driving, 136 (93.8%) did so because of “Unacceptable risk” according to caregiver’s judgment. Car accidents and revocation of the driving license were responsible in 8 (5.5%) and 1(0.7%) participant, respectively. Female gender (OR 5.057; 95%CI 1.803–14.180; p = 0.002), constructional abilities (OR 0.611; 95%CI 0.445–0.839; p = 0.002) and impairment in Activities of Daily Living (OR 0.941; 95%CI 0.911–0.973; p<0.001) were the only significant and independent associates of driving cessation. In multivariate analysis none of the currently proposed screening tools for assessment of fitness to drive in elderly subjects including the MMSE and CDR were significantly associated with driving cessation.Conclusion
The risk-estimate of caregivers, but not car accidents or revocation of the driving license determines if dementia patients cease driving. Female gender and increasing impairment in constructional abilities and ADL raise the probability for driving cessation. If any of these factors also relates to undesired traffic situations needs to be determined before recommendations for their inclusion into practice parameters for the assessment of driving abilities in the elderly can be derived from our data. 相似文献178.
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180.