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101.
BACKGROUND: Drug-induced temporary amnesia is one of the principal goals of general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N) impairs hippocampus-dependent learning at relative, i.e., lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal theta oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a cellular model of memory) in vitro and are thought to represent a circuit level phenomenon that supports memory encoding. Therefore, the authors investigated the effects of F6 and isoflurane on theta oscillations (4-12 Hz). METHODS: Thirteen adult rats were implanted with multichannel depth electrodes to measure the microelectroencephalogram and were exposed to a range of concentrations of isoflurane and F6 spanning the concentrations that produce amnesia. Five of these animals also underwent control experiments without drug injection. The authors recorded the behavioral state and hippocampal field potentials. They confirmed the electrode location postmortem by histology. RESULTS: The tested concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to 3.6%, respectively. Isoflurane increased the fraction of time that the animals remained immobile, consistent with sedation, whereas F6 had the opposite effect. Electroencephalographic power in the theta band was less when the animals were immobile than when they explored their environment. F6 suppressed the power of oscillations in the theta band. Isoflurane slowed theta oscillations without reducing total power in the theta band. CONCLUSIONS: Drug-induced changes in theta oscillations may be a common basis for amnesia produced by F6 and isoflurane. The different patterns suggest that these drugs alter network activity by acting on different molecular and/or cellular targets. 相似文献
102.
Lehman DM Hunt KJ Leach RJ Hamlington J Arya R Abboud HE Duggirala R Blangero J Göring HH Stern MP 《Diabetes》2007,56(2):389-393
TCF7L2 acts as both a repressor and transactivator of genes, as directed by the Wnt signaling pathway. Recently, several highly correlated sequence variants located within a haplotype block of the TCF7L2 gene were observed to associate with type 2 diabetes in three Caucasian cohorts. We previously reported linkage of type 2 diabetes in the San Antonio Family Diabetes Study (SAFADS) cohort consisting of extended pedigrees of Mexican Americans to the region of chromosome 10q harboring TCF7L2. We therefore genotyped 11 single nucleotide polymorphisms (SNPs) from nine haplotype blocks across the gene in 545 SAFADS subjects (178 diabetic) to investigate their role in diabetes pathogenesis. We observed nominal association between four SNPs (rs10885390, rs7903146, rs12255372, and rs3814573) in three haplotype blocks and type 2 diabetes, age at diagnosis, and 2-h glucose levels (P = 0.001-0.055). Furthermore, we identified a common protective haplotype defined by these four SNPs that was significantly associated with type 2 diabetes and age at diagnosis (P = 4.2 x 10(-5), relative risk [RR] 0.69; P = 6.7 x 10(-6), respectively) and a haplotype that confers diabetes risk that contains the rare alleles at SNPs rs10885390 and rs12255372 (P = 0.02, RR 1.64). These data provide evidence that variation in the TCF7L2 genomic region may affect risk for type 2 diabetes in Mexican Americans, but the attributable risk may be lower than in Caucasian populations. 相似文献
103.
Weninger P Mauritz W Fridrich P Spitaler R Figl M Kern B Hertz H 《The Journal of trauma》2007,62(3):584-591
BACKGROUND: The early clinical management of patients with major trauma still represents a challenge. To clinically evaluate the full extent of a patient's injuries is difficult, especially when the patient is unconscious. Before December 2002, trauma patients admitted to our emergency room (ER) underwent a diagnostic protocol including physical examination, conventional radiography (CR), sonography and further procedures if necessary. After the installation of a MSCT scanner, all trauma patients underwent the "MSCT protocol" immediately after admission. The aim of the study was to compare the "MSCT-protocol" as it is performed at our institution, with the "Pre-MSCT-protocol". METHODS: We compared 185 patients undergoing the "Pre MSCT-protocol" with 185 patients undergoing "MSCT protocol". We evaluated the efficacy, speed and accuracy of the "MSCT protocol" using several variables. Time periods from admission to the ER to admission to the intensive care unit were compared as well as outcome parameters such as length of ICU stay, ventilation period and rates of organ. Dichotomous data were analyzed by Chi-square analysis; continuous data were analyzed by Student's t test. Any values of p < 0.05 were considered significant for any test. RESULTS: No significant differences were found regarding demographic data. The full extent of injuries was definitively diagnosed after 12 +/- 9 minutes in 92.4% of the "MSCT protocol" cohort. In only 76.2% of "Pre-MSCT protocol" cohort definitive diagnosis was possible after 41 +/- 27 minutes. Total ER time was 104 +/- 21 minutes with the "Pre-MSCT protocol" and 70 +/- 17 minutes with "MSCT protocol" (p < 0.05). "Pre-MSCT protocol" patients had a significantly longer ICU stay than "MSCT protocol" patients (p < 0.05). "MSCT protocol" patients had significantly fewer ventilation days (14.3 vs. 10.9 days). Furthermore, rates of organ failure were lower in patients undergoing the "MSCT protocol". CONCLUSION: We could demonstrate that immediate MSCT in patients with blunt major trauma leads to more accurate and faster diagnosis, and reduction of early clinical time intervals. We also observed a reduction in ventilation, ICU, and hospital days, and in organ failure rates, though this might have been partly due to small differences in case mix. The "MSCT protocol" algorithm seems to be safe and effective. 相似文献
104.
Undar A Eichstaedt HC Clubb FJ Fung M Lu M Bigley JE Vaughn WK Fraser CD 《The Annals of thoracic surgery》2002,74(2):355-62; discussion 362
BACKGROUND: Adverse outcomes after cardiopulmonary bypass (CPB) are often related to systemic inflammation triggered by complement and leukocyte activation. To determine how inhibition of the alternative complement pathway affects systemic inflammation and tissue injury, we studied a novel monoclonal antibody (Mab), anti-human factor D murine Mab 166-32, in baboons. METHODS: Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. The treatment group (n = 7) received a single injection of anti-factor D Mab 166-32 (5 mg/kg), and the control group (n = 7) was given saline solution. After initiation of CPB, all animals were subjected to 20 minutes of core cooling (rectal temperature, 27 degrees C), followed by 60 minutes of aortic cross-clamping, 25 minutes of rewarming, and 30 minutes of normothermic CPB. Blood samples were collected before CPB, during CPB, and 1, 2, 3, 6, and 18 hours after CPB. To measure neutrophil and monocyte activation, we performed flow cytometry for CD11b expression, ELISA for complement activation (Bb, C3a, C4d, and sC5b-9) and interleukin-6 (IL-6) production, and tissue injury studies for creatine kinase MB isoenzymes (CK-MB), creatine kinase (CK), and lactic dehydrogenase (LDH) levels. RESULTS: Anti-factor D Mab almost completely inhibited plasma Bb, C3a, and sC5b-9 production during CPB (P < .001). CD11b expression on neutrophils (129 +/- 5% vs. 210 +/- 42%; P = .0006) and on monocytes (139 +/- 14% vs. 245 +/- 43%; P = .0002) was also lower in the treatment group during CPB. The treated animals had a significantly smaller increase in plasma IL-6 concentrations than did the control animals (71 +/- 27 pg/mL vs. 104 +/- 54 pg/mL; P = .0002). CK-MB levels were also lower in the treatment group 6 hours after the end of CPB (204 +/- 30 vs. 335 +/- 59 IU/L; P = .003) and 18 hours after the end of CPB (P < .05). Creatine kinase levels (6 and 18 hours after the end of CPB) and LDH levels (3 and 6 hours after the end of CPB) showed patterns similar to those of CK-MB (P < .05). CONCLUSIONS: The alternative complement pathway plays a major role in systemic inflammation during CPB. Inhibition of complement activation via the alternative pathway by anti-factor D Mab 166-32 significantly reduces leukocyte activation and tissue injury in our baboon model. 相似文献
105.
Bartsch DK Sina-Frey M Lang S Wild A Gerdes B Barth P Kress R Grützmann R Colombo-Benkmann M Ziegler A Hahn SA Rothmund M Rieder H 《Annals of surgery》2002,236(6):730-737
OBJECTIVE: To evaluate the prevalence of mutations in the CDKN2A gene encoding p16 and p14 in familial pancreatic cancer (FPC). SUMMARY BACKGROUND DATA: The genetic basis of FPC is still widely unknown. Recently, it has been shown that germline mutations in the p16 tumor suppressor gene can predispose to pancreatic cancer. The presence of p14 germline mutations has yet not been determined in this setting. METHODS: Eighteen families with at least two first-degree relatives with histologically confirmed pancreatic cancer and five families with at least one patient with pancreatic cancer and another first-degree relative with malignant melanoma of the German National Case Collection for Familial Pancreatic Cancer were analyzed for CDKN2A germline mutations including p16 and p14 by direct DNA sequencing. All participating family members were genetically counseled and evaluated by a three-generation pedigree. RESULTS: None of 18 FPC families without malignant melanoma revealed p16 mutations, compared to 2 of 5 families with pancreatic cancer and melanoma. Truncating p16 germline mutations Q50X and E119X were identified in the affected patients of pancreatic cancer plus melanoma families. None of the 23 families revealed p14 germline mutations. CONCLUSIONS: CDKN2A germline mutations are rare in FPC families. However, these data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16. Thus, all members of families with combined occurrence of pancreatic cancer and melanoma should be counseled and offered screening for p16 mutations to identify high-risk family members who should be enrolled in a clinical screening program. 相似文献
106.
Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart 总被引:3,自引:0,他引:3
Pruefer D Buerke U Khalil M Dahm M Darius H Oelert H Buerke M 《The Journal of thoracic and cardiovascular surgery》2002,124(5):942-949
OBJECTIVE: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. METHODS: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. RESULTS: Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 +/- 25 vs 585 +/- 98 creatine kinase difference in units per 100 mg, P <.01). Administration of 5000 U/kg of the protease inhibitor resulted in partial inhibition of myocardial reperfusion injury. Moreover, cardiac myeloperoxidase activity in the ischemic myocardium, a marker of neutrophil accumulation, was significantly reduced after aprotinin treatment. Histologic analysis of the reperfused myocardium demonstrated reduced polymorphonuclear leukocyte infiltration and reduced tissue injury. Furthermore, aprotinin treatment resulted in decreased induction of cardiac myocyte apoptosis compared with that seen in vehicle-treated rats. CONCLUSIONS: Inhibition of serine proteases with aprotinin appears to be an effective means of preserving ischemic myocardium from reperfusion injury, even after 24 hours of reperfusion. Aprotinin might exert cardioprotection through inhibition of polymorphonuclear leukocyte-induced myocardial injury and inhibition of reperfusion-induced apoptosis of cardiac myocytes. 相似文献
107.
Jan J. Kootstra Josette E. H. M. Hoekstra-Weebers Johan S. Rietman Jakob de Vries Peter C. Baas Jan H. B. Geertzen Harald J. Hoekstra 《Annals of surgical oncology》2010,17(9):2384-2394
Background
Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients. 相似文献108.
Acute Toxicity and Changes in Quality of Life during a Combined Radio-Chemotherapy of Glioblastomas with Topotecan (Hycamtin®) 总被引:2,自引:0,他引:2
Markus W. Groß Riglef Altscher Michael Brandtner Harald Häußer-Mischlich Ion C. Kiricuta Alessandra D. Siegmann Rita Engenhart-Cabillic 《Strahlentherapie und Onkologie》2001,177(12):656-661
BACKGROUND: Because of the pronounced radioresistance of glioblastoma multiforme the prognosis of this disease remains poor. Therefore, we investigated the impact of an additional simultaneous chemotherapy with the topoisomerase-I inhibitor topotecan (Hycamtin) on the quality of life and toxicity of radiotherapy. PATIENTS AND METHODS: In this multicenter trial patients with histologically proven glioblastoma multiforme underwent a simultaneous radio-chemotherapy. Including pilot phase 60 patients, 41 male and 19 female, were treated. Age ranged from 26 to 76 years, the mean was 57 years. Conventional fractionated conformal radiotherapy was performed with daily doses of 2.0 Gy to a total dose of 60 Gy. 1 hour prior to irradiation 0.5 mg (absolute dose) of topotecan were administered intravenously resulting in a cumulative dose of 15 mg. Besides hematologic and non-hematologic toxicity, quality of life was assessed by Karnofsky index and Spitzer index. Additionally local control and survival time were recorded. RESULTS: 57 patients completed the combined therapy. Median administered dose of radiation was 60 Gy (16-76 Gy). Median cumulative topotecan dose was 15 mg (7.5-18.5 mg). Grade-III toxicity was found in six cases (two hematologic, two motoric disorder, one infection, one nausea) and grade-IV toxicity in three cases (one esophagitis, one motoric disorder, one mental disorder). Two patients died of septic disease most likely caused by steroid induced immunosuppression. Mean Karnofsky index and Spitzer index initially, at the end of therapy and 6 weeks after therapy showed values of 87%, 81% and 80% and 19 points, 18 points and 19 points, respectively. Median survival time was 15 months. CONCLUSION: This multimodal approach for patients with glioblastoma multiforme is well tolerated. Quality of life remains preserved and outpatient treatment is possible. The relatively long median survival time even for patients bearing macroscopic tumors is promising. 相似文献
109.
Gerda L. Leinsinger Lilia Friedl Reinhold Tiling Michael K. Scherr Dirk T. Heiss Christoph Kandziora Birka Camerer Harald Sommer Thomas Pfluger Klaus Hahn 《European radiology》2001,11(10):2050-2057
The aim of this study was to compare Tc-99m sestamibi scintimammography and dynamic contrast-enhanced MR imaging for the evaluation of indeterminate mammographic lesions. Forty patients with questionable mammographic findings were included in a prospective study. Thirty lesions were non-palpable. Mean lesion size was 1.6+/-0.7 cm (range 0.5-3.5 cm). Scintigraphy was considered as malignant when focal tracer accumulation was present. In MR imaging, lesions were classified according to their signal intensity time course: no enhancement or steady enhancement with low signal intensity (M0); steady enhancement with high signal intensity (M1); or rapid enhancement with plateau (M2) or washout (M3). Lesions classified as M2 or M3 were considered as suspicious for malignancy. Histopathologic evaluation was performed in 24 lesions. In 16 cases lesions were classified as benign from follow-up examinations (mean 24 months). Malignancies were proven in 14 patients (9 invasive carcinomas, 5 ductal carcinoma in situ). Sensitivity of MR imaging was 12 of 14 (86%) and sensitivity of scintimammography was 8 of 14 (57%). One of 26 benign lesions was false positive at MR imaging. Scintigraphy showed no false-positive results. In conclusion, magnetic resonance imaging provided high accuracy in evaluation of indeterminate mammographic lesions. Sensitivity of scintimammography was too low in detecting small carcinomas. 相似文献
110.
Martin Heni Caroline Ketterer Claus Thamer Silke A. Herzberg-Sch?fer Martina Guthoff Norbert Stefan Fausto Machicao Harald Staiger Andreas Fritsche Hans-Ulrich H?ring 《Diabetes》2010,59(12):3247-3252