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991.
B Alessandri E Schwandt Y Kamada M Nagata A Heimann O Kempski 《Journal of neurotrauma》2012,29(12):2181-2191
Abstract For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5?m/sec, 2.5?mm). To study the effects of lactate treatment on lesion volume, glutamate release, and CBF, animals were infused with either NaCl or 100?mM lactate for up to 3?h. The role of endogenous lactate was investigated by inhibiting transport with α-cyano-4-hydroxy-cinnamic acid (4-CIN; 90?mg/kg). Lactate treatment 15?min post-CCI reduced lesion volume from 21.1±2.8?mm(3) to 12.1±1.9?mm(3) at day 2 after CCI. Contusion produced a significant three- to fourfold increase of glutamate in microdialysates, but there was no significant difference between treatments that began 30?min before CCI. In this experiment lesion volume was significantly reduced by lactate at day 7 post-CCI (23.7±4 to 9.3±1-2?mm(3)). CBF increased immediately after CCI and dropped thereafter below baseline in all animals. Lactate infusion 15?min post-CCI elevated CBF for 20?min in 7 of 10 animals, whereas 7 of 8 NaCl-treated animals showed a further CBF decline. Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients. 相似文献
992.
993.
Harder A Wesemann M Hagel C Schittenhelm J Fischer S Tatagiba M Nagel C Jeibmann A Bohring A Mautner VF Paulus W 《The American journal of surgical pathology》2012,36(5):702-709
We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses. 相似文献
994.
995.
Ulmert D Kaboteh R Fox JJ Savage C Evans MJ Lilja H Abrahamsson PA Björk T Gerdtsson A Bjartell A Gjertsson P Höglund P Lomsky M Ohlsson M Richter J Sadik M Morris MJ Scher HI Sjöstrand K Yu A Suurküla M Edenbrandt L Larson SM 《European urology》2012,61(1):78-84
Background
Nocturia, a common complaint in aging men and women, is frequently cited as the cause of nocturnal awakenings leading to sleep loss, daytime fatigue, and reduced quality of life (QOL).Objective
Investigate the association of nocturia with QOL and depressive symptoms among men and women.Design, setting, and participants
A population-based epidemiologic survey of urologic symptoms among persons aged 30-79 yr. A multistage stratified cluster sample design was used to randomly sample 5503 residents of Boston, MA, USA.Measurements
Nocturia was defined as a self-report of two or more voiding episodes nightly or having to get up to urinate more than once nightly “fairly often,” “usually,” or “almost always.” QOL was assessed using the physical and mental health component scores of the 12-Item Short-Form Survey (SF-12). Depression was assessed using the Center for Epidemiological Studies Depression Scale. Multiple linear and logistic regression methods were used to model the nocturia and QOL association and to control for confounders.Results and limitations
Nocturia was associated with decreased SF-12 scores for both the physical and mental health components after multivariate adjustment. Nocturia was also associated with increased odds of depressive symptoms (men: adjusted odds ratio [OR]: 2.79; 95% confidence interval [CI], 1.81-4.31; women: adjusted OR: 1.80; 95% CI, 1.29-2.51). Among women who reported sleep interference due to urologic symptoms, nocturia was associated with a threefold increase in odds of depression. In this cross-sectional analysis, the temporal sequence of causality of the nocturia and depression association could not be assessed.Conclusions
Nocturia is associated with decreased QOL and with an increased prevalence of depressive symptoms in both men and women. 相似文献996.
Michael P. Müller Torsten Richter Norbert Papkalla Cynthia Poenicke Carsten Herkner Anne Osmers Sigrid Brenner Thea Koch Uta Schwanebeck Axel R. Heller 《Resuscitation》2014
Aim of the study
Many hospitals have basic life support (BLS) training programmes, but the effects on the quality of chest compressions are unclear. This study aimed to evaluate the no-flow fraction (NFF) during BLS provided by standard care nursing teams over a five-year observation period during which annual participation in the BLS training was mandatory.Methods
All healthcare professionals working at Dresden University Hospital were instructed in BLS and automated external defibrillator (AED) use according to the current European Resuscitation Council guidelines on an annual basis. After each cardiac arrest occurring on a standard care ward, AED data were analyzed. The time without chest compressions during the period without spontaneous circulation (i.e., the no-flow fraction) was calculated using thoracic impedance data.Results
For each year of the study period (2008–2012), a total of 1454, 1466, 1487, 1432, and 1388 health care professionals, respectively, participated in the training. The median no-flow fraction decreased significantly from 0.55 [0.42; 0.57] (median [25‰; 75‰]) in 2008 to 0.3 [0.28; 0.35] in 2012. Following revision of the BLS curriculum after publication of the 2010 guidelines, cardiac arrest was associated with a higher proportion of patients achieving ROSC (72% vs. 48%, P = 0.025) but not a higher survival rate to hospital discharge (35% vs. 19%, P = 0.073).Conclusion
The NFF during in-hospital cardiac resuscitation decreased after establishment of a mandatory annual BLS training for healthcare professionals. Following publication of the 2010 guidelines, more patients achieved ROSC after in-hospital cardiac arrest. 相似文献997.
998.
999.
Axel Dalhoff Andrej Weintraub Carl Erik Nord 《Antimicrobial agents and chemotherapy》2014,58(8):4257-4263
The proof that a new antibacterial agent is not only active in vitro but also effective in vivo under clinically relevant conditions is currently provided (i) by using appropriate nonclinical models of infection and pharmacokinetic-pharmacodynamic (PK-PD) analysis providing evidence of the likelihood of clinical efficacy and (ii) by examining the study drug in exploratory clinical trials, as well as dose and schedule finding during phase II of clinical development. This approach is both time-consuming and costly. Furthermore, PK-PD targets for any novel antibacterial agent cannot be derived from studies with experimental animals. Therefore, alternative strategies have to be identified to prove the principle that a novel antibacterial agent is active under clinically relevant conditions. This review summarizes evidence that the quantitative analysis of shifts in the viable counts of pathogens in infected patients or the evaluation of the PD effect of an investigational agent on indicator organisms of the human resident microflora or colonizers of healthy volunteers, if paralleled with PK monitoring of serum and the target site, provides an alternative to a classical proof-of-principle study in the course of a phase II study program. 相似文献
1000.
Sebastian Christoph Schmid Alexander Geith Alena Böker Robert Tauber Anna Katharina Seitz Markus Kuczyk Christoph von Klot Jürgen Erich Gschwend Axel Stuart Merseburger Margitta Retz 《Advances in therapy》2014,31(2):234-241