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1.
2.
W. Nörenberg Ernst Schöffel Bela Szabo Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):159-165
The aim of the study was to subclassify the soma-dendritic α2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action
potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average
rate of 1 Hz. The selective α2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential
discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the
right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K
d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K
d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed
the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored
firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates –
against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the
presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even
at a concentration of 1 μM. These findings identify the soma-dendritic α2-autoreceptors of the LC as the rat variant of the α2A/D-adrenoceptor, i.e. α2D. Not only presynaptic but also soma-dendritic α2-autoreceptors may at least predominantly be α2A/D throughout the nervous system.
Received: 3 March 1997 / Accepted: 21 April 1997 相似文献
3.
Prof. Dr. Wolfgang Dörr Sabine Köst Klaus Keinert Felix-Herbert Glaser Gerd Endert Thomas Herrmann 《Strahlentherapie und Onkologie》2006,182(1):1-8
PURPOSE: To compare tests for intestinal function with clinical scores after abdominal irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy, Erfurt, Germany, intestinal changes were studied in 91 patients receiving abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2 Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly intervals during radiotherapy, the clinical response was scored according to RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests for vitamin B(12) and D-xylose were performed before the onset and immediately after treatment. RESULTS: The clinical response displayed a well-defined dose-effect relationship with grade 1 effects in 5% and 50% of the patients at about 10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly correlated. Changes in body weight did not show a correlation with other clinical symptoms. Changes in resorption also displayed a significant dose effect. However, no correlation was found with the clinical symptoms in the individual patient. CONCLUSION: In the present study, the clinical manifestation of intestinal side effects according to RTOG/EORTC criteria was reflected by neither the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot be regarded as useful for objective quantitation of intestinal radiation injury. 相似文献
4.
Introduction
Planning human resources for health (HRH) is a complex process for policy-makers and, as a result, many countries worldwide swing from surplus to shortage. In-depth case studies can help appraising the challenges encountered and the solutions implemented. This paper has two objectives: to identify the key challenges in HRH planning in Belgium and to formulate recommendations for an effective HRH planning, on the basis of the Belgian case study and lessons drawn from an international benchmarking. 相似文献5.
Saskia L.M.A. Beeres MD Katja Zeppenfeld MD Jeroen J. Bax MD Petra Dibbets-Schneider Marcel P.M. Stokkel MD Willem E. Fibbe MD Ernst E. van der Wall MD Douwe E. Atsma MD Martin J. Schalij MD 《Heart rhythm》2007,4(3):257-265
BACKGROUND: Bone marrow cell injection has been introduced to treat patients with ischemic heart disease. However, focal application of bone marrow cells may generate an arrhythmogenic substrate. OBJECTIVES: To assess the electrophysiological and arrhythmogenic effects of intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia. METHODS: Bone marrow was aspirated in 20 patients (65+/-11 years, 19 male) with drug-refractory angina and myocardial ischemia. Electroanatomical mapping (NOGA, Biosense-Webster, Waterloo, Belgium) was performed during mononuclear cell isolation. Areas for cell injection were selected based on the localization of ischemia on SPECT. These areas were mapped in detail to evaluate local bipolar electrogram duration, amplitude and fragmentation. Mononuclear cells were injected in the ischemic area with the NOGA system. SPECT and electroanatomical mapping were repeated at 3 months. Holter monitoring was repeated at 3 and 6 months. RESULTS: SPECT revealed a decrease in the number of segments with ischemia (3.5+/-2.5 vs. 1.1+/-1.0 at 3 months; P<0.01) and an increased left ventricular ejection fraction (44+/-13% vs. 49+/-17% at 3 months; P=0.02). The number of ventricular premature beats remained unchanged (10+/-24x10(2)/24h vs. 8+/-23x10(2)/24h at 3 months (P=NS) and 12+/-30x10(2)/24h at 6 months (P=NS)). At 3 months follow-up, bone marrow cell injection did not prolong electrogram duration (15.9+/-4.6 ms vs. 15.6+/-4.0 ms; P=NS), decrease electrogram amplitude (3.8+/-1.5 mV vs. 3.8+/-1.5 mV; P=NS), or increase fragmentation (2.0+/-0.5 vs. 1.9+/-0.4; P=NS). CONCLUSION: Intramyocardial bone marrow cell injection does not increase the incidence of ventricular arrhythmias and does not alter the electrophysiological properties of the injected myocardium. 相似文献
6.
7.
Sabine J Presser Guido Schumacher Ruth Neuhaus Peter Thuss-Patience Jens Stieler Peter Neuhaus 《Liver transplantation》2007,13(3):443-450
The purpose of the study was to determine the incidence, risk factors, treatment, and influence on survival of patients with de novo esophageal cancer after liver transplantation (LT). From 1988 to 2006, 1,926 patients underwent LT in our institution. A total of 9 patients (0.5%) developed a de novo esophageal cancer and 1 patient a cancer of the cardia (0.05%). A retrospective analysis was performed to reveal underlying diseases, timeframes between LT and appearance of cancer, predisposing factors, cancer therapy, complications, immunosuppressive regimens, and survival. Of our 10 patients, 7 (70%) suffered from esophageal squamous cell carcinoma (SCC) and 3 patients (30%) developed an adenocarcinoma, including the patient with cancer of the cardia. A total of 9 patients were transplanted due to alcoholic cirrhosis; 1 patient suffered from hepatocellular carcinoma in nonA-nonB hepatitis-related cirrhosis. Median time to tumor diagnosis was 51 months after transplantation. A total of 5 patients were treated conservatively with combined radiochemotherapy and 5 underwent surgical resection. Patients with radiochemotherapy showed a mean survival of 14.8 months vs. 24.8 months for the patients of the surgery group. No major postoperative complication has been observed. A total of 2 patients of the surgery group are still alive after a follow-up of 15 and 89 months. In conclusion, de novo esophageal and cancer of the cardia after LT is a rare event. In spite of immunosuppression, no increased complication rate has been observed. Patients may have a survival benefit from surgical resection. 相似文献
8.
Edward J Boland Mary MacDougall David L Carnes Sabine H Dickens 《Dental materials》2006,22(4):338-345
Recently, a resin-based calcium phosphate cement (RCPC) has been reported as a remineralizing pulp-capping or lining cement. RCPC consists mainly of tetracalcium and dicalcium phosphates, ethoxylated bisphenol A dimethacrylate and pyromellitic glycerol dimethacrylate monomers and photo- and chemical initiators. OBJECTIVES: Here, the cytotoxic effects of RCPC were evaluated. The hypothesis was that RCPC induced only minor cytotoxic response in immortalized murine odontoblast and pulp cells, comparable to that produced by similar dimethacrylates due to unpolymerized dimethacrylate monomer present after curing. METHODS: Cytotoxicity was determined following the changes in cell succinate dehydrogenase activity after 24 h exposure to the cement components and after a 24 h recovery period. A fourfold range of concentrations was tested of the monomers, the eluate of cured RCPC leached in Dulbecco's modified Eagle's medium, and crushed cured cement in dimethyl sulfoxide. RESULTS: The monomers themselves had cytotoxicities similar to those reported for other dimethacrylates, although they are significantly less toxic than Bis-GMA. Differential cell sensitivity was demonstrated, with the pulp cells having greater sensitivity to the unpolymerized monomer than the odontoblast-like cells. The leached components have cytotoxicity similar to that of the free monomers. The crushed material demonstrated no apparent cytotoxicity at the dilutions tested. SIGNIFICANCE: These data demonstrate that RCPC has an in vitro cytotoxicity that is comparable to other materials containing dimethacrylate monomers and suggest that the material may be suitable for use in dental restorations. The data also indicate that the pulp cells appear more sensitive to dimethacrylates than the odontoblasts. 相似文献
9.
Herlinde Dumez Gunther Guetens Gert De Boeck Martin S Highley Robert A A Maes Allan T van Oosterom Ernst A de Bruijn 《Clinical chemistry and laboratory medicine》2004,42(11):1219-1227
Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only. 相似文献
10.
Holger F. Boehm Felix Eckstein Caecilia Wunderer Volker Kuhn Eva-Maria Lochmueller Karin Schreiber Dirk Mueller Ernst J. Rummeny Thomas M. Link 《Journal of clinical densitometry》2005,8(4):488-494
We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL. 相似文献