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141.
Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation. 相似文献
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In brain injury, concentrations of extracellular excitatory amino acids are increased and stimulate glutamate receptors in general and the N-methyl-D-aspartate (NMDA)-preferring subtype in particular. That stimulation causes substantial calcium influx, which appears to initiate a cascade of events leading to neuronal death. Blockage of NMDA receptors with specific antagonists or noncompetitive ion channel blockers provides protection against excitatory amino acid-induced neurotoxicity. We previously reported that the NMDA receptor antagonist dizocilpine maleate improved the neurological severity score (NSS) after head trauma in rats. The present study was designed to determine whether ketamine, a NMDA receptor antagonist like dizocilpine maleate, improves neurological outcome following head trauma in rats. Thirty-two male Sprague-Dawley rats (235-250 g) were divided into four groups. Groups A and B were surgically prepared only. Groups C and D were surgically prepared and then a nonpenetrating impact was delivered to the cranium over the left hemisphere. Groups A and C received no treatment. Groups B and D were treated with ketamine, 180 mg/kg i.p., 1 h after head trauma. The NSS was determined at 1, 2, 4, 10, 24, and 48 h following head trauma. After killing at 48 h, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites on the nontraumatized hemisphere to measure the tissue specific gravity and water content. Brains were then placed in 4% formaldehyde and the volume of hemorrhagic necrosis measured 4 days later. Head trauma increased the NSS and, in the traumatized hemisphere, decreased the specific gravity, increased the water content, and caused cerebral infarction. With ketamine, the NSS at 24 and 48 h following head trauma was 7.4 +/- 2.6 and 6.7 +/- 2.6 (mean +/- SEM), respectively, significantly improved compared to the NSS in the untreated group of 12.6 +/- 2.6 and 11.3 +/- 2.6, respectively (p <0.02, Mann-Whitney U test). With ketamine, the volume of hemorrhagic necrosis was 88.0 +/- 23.1 mm, significantly less than that in the untreated group (147.4 +/- 22.4 mm; p <0.05, unpaired t test). The brain tissue specific gravity and water content at 48 h and the rectal temperature at 4 and 48 h after head trauma were not significantly different between treated and untreated groups. It is concluded that in this model of closed cranial impact, ketamine improves neurological outcome and decreases the volume of hemorrhagic necrosis without altering brain edema. 相似文献
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The pathogenesis of duodenal ulcer disease is multifactorial and the contribution ofHelicobacter pylori in relation to the other factors to the release of duodenal ulcer is unknown. To investigate this, we studied 147 patients with endoscopically proven healed ulcers. These patients were randomized to receive either placebo, misoprostol 200 g or misoprostol 300 g four times daily, and clinical, personal, physiological and endoscopic characteristics were obtained prospectively. Endoscopy was performed at the active phase of the ulcer and when the ulcer healed. Biopsies were taken from the antrum to assess histologically for: (1) the activity of gastritis as assessed by the degree of polymorph infiltration, (2) the degree of chronic inflammation by the degree of chronic inflammatory cells infiltration and degree of mucosal degeneration, and (3) bacteriologically for the presence ofH. pylori. The severity of the gastritis and the bacterial density were graded independently by two pathologists. The patients were assessed at two-month intervals for 12 months or until the ulcer relapsed. The results demonstrated that the relapse rates of duodenal ulcer were similar in the three treatment groups. The relapse rate was higher in the group with higher density of the bacteria (P<0.05). The degree of gastritis did not affect the relapse rate of duodenal ulcer in either the placebo or misoprostol group or in all patients combined. Stepwise logistic regression analysis identified that increased duodenal inflammation, male sex, early-onset disease, andH. pylori adversely affected relapse of the ulcer. We conclude that multiple factors affect the relapse of duodenal ulcer andH. pylori is one of them. 相似文献
146.
双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化 总被引:1,自引:0,他引:1
目的 在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5~ 17岁 ) ,引起短肢的病因不同。术后 7~ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果 不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%~ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%~ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论 DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。 相似文献
147.
Correlation of cytochrome P450 (CYP) 1A2 activity using caffeine phenotyping and olanzapine disposition in healthy volunteers. 总被引:1,自引:0,他引:1
Kara Lee Shirley Yuen Y Hon Scott R Penzak Y W Francis Lam Vicky Spratlin Michael W Jann 《Neuropsychopharmacology》2003,28(5):961-966
Olanzapine has previously been shown to have predominant metabolism by cytochrome (CYP) P450 1A2. Caffeine has been shown to provide an accurate phenotypic probe for measuring CYP1A2 activity. The purpose of this study is to determine if a significant correlation exists between olanzapine disposition and caffeine metabolic ratios. Subjects were phenotyped for CYP1A2 activity with caffeine probe methodology. After 200-mg caffeine administration, blood (4 h), saliva (6 and 10 h), and urine (8 h total) were collected for high-performance liquid chromatography (HPLC) analysis of caffeine and its metabolites.CYP1A2 activity was measured as plasma (PMR(4 h)), saliva (SMR(6 h) and SMR(10 h)), and three urinary metabolic (UMR1(8 h), UMR2(8 h), and UMR3(8 h)) ratios. Each of the 14 healthy nonsmokers (13 male) received a single 10 mg olanzapine dose after which blood was collected for HPLC determination of olanzapine concentrations at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 h postdose. Olanzapine pharmacokinetic parameters in this study were similar to those previously published. All caffeine metabolic ratios (PMR(4 h), SMR(6 h), SMR(10 h), UMR1(8 h), and UMR2(8 h)) significantly correlated with each other (p <0.001) except for UMR3(8 h), which did not correlate. A significant correlation (p <0.05) was also found between olanzapine clearance and PMR(4 h) (r=0.701), SMR(6 h) (r=0.644), SMR(10 h) (r=0.701), UMR1(8 h) (r=0.745), and UMR2(8 h) (r=0.710). A negative correlation was observed between olanzapine clearance and UMR3(8 h) (r=-0.029, p=NS). A significant correlation was found between olanzapine clearance and various caffeine metabolic ratios. Interpatient variability in CYP1A2 activity may explain the wide interpatient variability in olanzapine disposition. Compounds that modulate CYP1A2 activity may be expected to alter olanzapine pharmacokinetics accordingly. 相似文献
148.
Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy. 总被引:13,自引:0,他引:13
Winnie Yeo Paul K S Chan Wing M Ho Benny Zee Kwok C Lam Kenny I K Lei Anthony T C Chan Tony S K Mok Jam J Lee Thomas W T Leung Sheng Zhong Philip J Johnson 《Journal of clinical oncology》2004,22(5):927-934
PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy. 相似文献
149.
150.