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61.
BACKGROUND: Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS: New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS: Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION: These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.  相似文献   
62.
We report herein the rare case of a 79-year-old man who suffered permanent paraplegia after undergoing an otherwise successful total arch replacement for a ruptured aortic arch aneurysm. During cardiopulmonary bypass, perfusion to the distal aorta was maintained from the femoral artery, and postoperative aortography showed intact tributaries from the aorta including the intercostal arteries. Postoperative paraplegia is an extremely rare complication of operations on the aortic arch; however, we speculate that the paraplegia in this patient could be attributed either to a steal phenomenon involving the radicular artery, or to the anatomical particularity of the spinal cord artery described by Cole and Gutelius as the segmental system.  相似文献   
63.
We have developed a new in vitro method of quantitatively analyzing ciliary movement in the ependymal wall of the aqueduct in rats. An axial slice of the midbrain containing ependymal wall was placed in a culture dish filled with a culture medium containing latex beads 1 m in diameter at a concentration of 107 beads/ml. The movement of the beads caused by flow of culture medium generated by the to-and-fro ciliary movement was recorded by a high speed video system attached to an inverted phase-contrast microscope. Ciliary movement was expressed by the speed of the latex beads (m/s). Aqueductal ciliary movement in congenitally hydrocephalic HTX rats, congenitally hydrocephalic WIC-Hyd rats, and other normal rats was evaluated. The results suggest that in congenitally hydrocephalic WIC-Hyd rats the degree of hydrocephalus related strongly to the degree of ciliary dyskinesia, but in congenitally hydrocephalic HTX rats it did not. Considering this discrepancy, we attempted to see whether or not hydrocephalus was caused by artificial disturbance of ependymal ciliary movement in vivo. We found that continuous infusion of metavana date, an inhibitor of ciliary movement, into the III ventricle of normal Sprague-Dawley rats for 7 days induced dilatation of the ventricular system. Although the question whether or not disturbance of aqueductal ependymal ciliary movement is related to the development of human congenital hydrocephalus is debatable, the results of the present in vitro and in vivo experimental investigations appear to suggest that the disturbance of ciliary movement in the aqueduct could at least be one of the factors contributing to the inducement of hydrocephalus in experimental conditions.  相似文献   
64.
The ability of lidocaine to suppress activity of single vagal afferent fiber and that of phrenic nerve was studied in 20 cats anesthetized with pentobarbital. Slowly adapting stretch receptors (SAR, n = 16) and rapidly adapting stretch receptors (RAR, n = 7) were identified by their discharge pattern to pulmonary inflation. Intravenous lidocaine (1mg·kg–1 or 2mg·kg–1) produced a suppression of SAR activity but not of RAR activity. Suppression of phrenic nerve activity lasted much longer than that of SAR. These findings indicate that iv lidocaine acts more dominantly on CNS than on peripherals. We conclude that iv lidocaine prevents cough and hemodynamic changes caused by airway manipulation mainly through its action on CNS and not on peripherals (peripheral nerves or their receptor).(Aoki M, Harada Y, Namiki A, et al.: Effects of intravenously administered lidocaine of pulmonary vagal afferents and phrenic nerve activity in cats. J Anesth 6: 395–400, 1992)  相似文献   
65.
It has been known that the serum concentration of antipsychotics is varied according to individual case. There are several factors that may affect the plasma levels of antipsychotics; e.g., antipsychotic dose, body weight, interaction with other drugs, enzyme activity in the human liver, age and smoking. The enzyme cytochrome P450 2D6 (CYP2D6) is an important factor affecting the plasma levels of antipsychotics, because CYP2D6 is involved in the metabolism of these drugs. In this paper, we review the effect of several factors on plasma haloperidol concentration.  相似文献   
66.
PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.  相似文献   
67.
PURPOSE: The purpose is to evaluate whether inhibition of epidermal growth factor receptor (EGFR) activation by PKI166, an EGFR-tyrosine kinase inhibitor, affects growth of human lung cancer implanted orthotopically into the lungs of nude mice. EXPERIMENTAL DESIGN: Lungs of mice were injected with NCI-H358 human bronchioloalveolar cancer cells. In three experiments, groups of mice (n = 10 per group) were randomized 7 days after tumor implantation to receive one of the following treatments: i.p. paclitaxel 100 or 200 microg (4 or 8 mg/kg) once per week, oral PKI166 100 or 200 mg/kg three times per week, paclitaxel plus PKI166, or i.p. saline and oral PKI166-vehicle (control) for 5 weeks. Mice were killed 6.5 to 8 weeks after tumor implantation. The experiments were repeated with PC14PE6 human lung adenocarcinoma cells to assess effect on survival. RESULTS: Immunohistochemical analyses revealed the expression and phosphorylation of EGFR in the growing tumors. Treatment with PKI166 alone or in combination with paclitaxel diminished activation of EGFR on tumor cells, yet maximal therapeutic effect was observed in mice treated with paclitaxel alone. Activated mitogen-activated protein kinase and basic fibroblast growth factor expression were similar in all treatment groups. Survival in mice treated with the combination of paclitaxel and PKI166 was shorter than in those treated with paclitaxel alone. CONCLUSIONS: Our results suggest that concurrent administration of EGFR-tyrosine kinase inhibitor and chemotherapy is equivalent and may indeed be inferior to chemotherapy alone, even if EGFR is functional and its phosphorylation effectively inhibited. Our data show that the interaction of EGFR-TKIs and chemotherapy is complex and suggest that other growth factors may activate the downstream signaling events.  相似文献   
68.
BACKGROUND: Bleeding isolated gastric varices with a spontaneous portosplenorenal shunt are difficult to control. The urgent use of transjugular retrograde obliteration (TJO) to prevent early rebleeding and to improve early mortality has not yet been demonstrated. We report our experience with this technique in patients with isolated gastric varices after treatment of acute bleeding. METHODS: We reviewed our experience of 6 patients with isolated gastric varices with a spontaneous portosplenoral shunt treated with TJO after treatment of acute bleeding. We basically applied endoscopic glue embolization using cyanoacrylate monomer for treatment of acute bleeding. TJO was a method using an occlusive balloon catheter to control a spontaneous portosplenorenal shunt flow while injecting sclerosant retrograde into the gastric varices. RESULTS: Treatment of acute bleeding was achieved immediately by endoscopic glue embolization, endoscopic variceal ligation, and ligating the varices with sutures following anterior gastrotomy in 4, 1 and 1 patients, respectively, and then TJO was performed. Permanent hemostasis and variceal eradication was achieved in these 6, and they all survived. They were alive for 6-66 months without gastric variceal recurrence. CONCLUSIONS: We conclude that urgent TJO is effective in the prophylaxis of early and late rebleeding from isolated gastric varices in patients with a spontaneous portosplenorenal shunt.  相似文献   
69.
BACKGROUND AND PURPOSE: The accuracy of factors for predicting lymph node metastasis in patients with early-stage (stage I and II) mobile tongue carcinoma and prognostic factors associated with the clinical and pathological findings of lymph node metastasis were examined. MATERIAL AND METHODS: Between 1971 and 1998, 616 patients with early stage mobile tongue carcinoma were treated by brachytherapy with or without external irradiation. Neck lymph node metastasis occurred in a total of 237 cases, and 191 of them were not associated with primary failure. Neck dissection was performed in 169 of these 191 cases, and 16 cases were treated by radiotherapy. A pathological analysis was possible in 159 of the 169 neck dissection cases. RESULTS: There were 88 tongue cancer recurrences, and the incidence of neck metastasis was 38% (191/528) in the cases of primary controlled early tongue carcinoma, and 25% (38/151) and 41% (153/377), in stage-I and -II carcinoma, respectively. Neck metastasis was diagnosed within 12 months in 80% of cases, and within 24 months in 95%. Macroscopic appearance, tumor thickness and tumor length were identified as significant risk factors by a univariate analysis, but macroscopic appearance was the only significant risk factor identified by a multivariate analysis (P<0.001). The incidence of cervical lymph node metastasis was 62% among the invasive/ulcerative type tongue carcinomas, and was lower among the superficial type and exophytic/nodular type (20 and 35%, respectively). Regional and/or distant failure occurred in 75 of the 169 neck dissection cases (44%). The incidence of regional/distant failure was extremely high (49/68=72%) in the extra-nodal invasion group, and extra-nodal invasion was found even in small metastatic node less than 1 cm in length (20%). CONCLUSIONS: The macroscopic appearance of the primary tongue carcinoma has a major impact on the incidence of lymph node metastasis in patients with early tongue cancer, and extra-nodal invasion was the dominant risk factor for regional and distant failure. Treatment policy for clinically negative neck metastasis in early tongue cancer patients should be determined after considering the possibility of neck metastases and the morbidity associated with elective neck dissection.  相似文献   
70.
The purpose was to compare three-dimensional (3D) constructive interference in steady state (CISS) and conventional spin-echo (SE) MR imaging in tumor volume measurements of acoustic neuromas. Twenty-two patients with acoustic neuromas were examined using high-resolution 3D-CISS and SE imaging at a 1.5-T system. Tumor volume determined by SE imaging with the ellipsoid formula was overestimated by 692 mm(3)(35%) on average as compared with that at 3D-CISS with the voxel-count method (the reference standard). Intra- and interobserver variations in SE imaging were poor as compared with 3D-CISS imaging. However, tumor volume results with SE imaging showed a high correlation with those using 3D-CISS imaging (P <. 0001). On the basis of diameters shown on SE images, the tumor volume could be assessed using the following equation (P <.0001): (Tumor volume) = -26.407 + 0.387 x (maximum diameter along the pyramid) x(maximum diameter perpendicular to the pyramid) x (maximum height). J. Magn. Reson. Imaging 2000;12:826-832.  相似文献   
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