Photodynamic therapy (PDT) is a relatively new form of cancer therapy utilizing a photosensitizer such as hematoporphyrin derivative. We conducted a pilot study to determine the efficacy of its use in palliating advanced rectal cancer, to determine toxicity, and to establish objective outcome criteria. Six patients with very advanced, usually recurrent rectal cancer were treated with PDT after being photosensitized with Photofrin II®. A protocol was established to measure clinical and radiologic response to therapy. A new intraluminal delivery system was incorporated. Five patients had both clinical and radiologic responses to therapy. In two patients we observed such significant responses that they cannot be accounted for on a photobiologic basis alone. One patient developed a significant sunburn after discharge. There was no major toxicity of bleeding or sepsis even at maximum doses (200 J/cm2). We are confident that PDT has a role to play in rectal cancer and speculate as to future applications. 相似文献
Right bundle branch block and complete atrioventricular (AV) block are conduction disorders (CDs) that have been observed in 14% of patients admitted with ST-elevation acute myocardial infarction. CDs carry a poor prognosis, with a threefold increase in the mortality rate, mainly due to cardiogenic shock and recurrent fatal myocardial infarction at 1-year follow-up. According to multivariable analysis, CD was the second strongest predictor of death, after high Killip class. Compared with patients without CD, the 1-year outcome of patients with CD was identically worse, irrespective of whether CD appeared during admission, disappeared, or remained constant. Similar adverse outcomes were seen in patients with complete AV block and right bundle branch block. 相似文献
Ovarian carcinoma patients are initially responsive to platinum-based therapy, but eventually become refractory to treatment due to the development of platinum chemoresistance. Elevated levels of interleukin-6 (IL-6) in the sera and ascites of these patients predict poor clinical outcome. Our goal was to analyze the interaction between cisplatin and cisplatin-resistant ovarian cancer cells, and to identify means of circumventing platinum resistance. We studied ovarian carcinoma cell lines and cells drawn from ovarian carcinoma patients. Gene array analyses were performed on ovarian carcinoma cells upon treatment with cisplatin, and the results were validated by ELISA and Western blotting (WB). Cytotoxicity assays were performed on anti-IL-6 Ab-, IL-6-, and cellular inhibitor of apoptosis 2 (cIAP-2) siRNA-treated cells, following cisplatin addition. Our results revealed a highly significant increase in IL-6 and cIAP-2 mRNA and protein levels upon treatment with cisplatin. WB analysis of cisplatin-treated cells exhibited decreased cIAP-2 expression level following anti-IL-6 Ab addition. Furthermore, IL-6 by itself, significantly increased cIAP-2 levels in ovarian carcinoma cells. Finally, cytotoxicity assays showed sensitization to cisplatin following the addition of IL-6 and cIAP-2 inhibitors. In conclusion, cisplatin treatment of ovarian carcinoma cells upregulates IL-6 and cIAP-2 levels while their inhibition significantly sensitizes them to cisplatin. Here, we present cIAP-2 as a novel inducer of platinum resistance in ovarian carcinoma cells, and suggest an axis beginning with an encounter between cisplatin and these cells, mediated sequentially by IL-6 and cIAP-2, resulting in cisplatin resistance. Consequently, we propose that combining IL-6/cIAP-2 inhibitors with cisplatin will provide new hope for ovarian carcinoma patients by improving the current treatment. 相似文献
Prior studies have yielded conflicting data on the advantage of primary angioplasty compared with thrombolysis in elderly patients with acute myocardial infarction (AMI). These studies, however, were performed before the contemporary widespread use of intracoronary stents and glycoprotien IIb/IIIa antagonists.
Methods
We prospectively compared the outcome of 130 consecutive elderly patients (aged ≥70 years) with ST-elevation AMI who were admitted to 2 similar neighboring medical centers. Patients were assigned to receive either thrombolytic therapy with accelerated tissue-type plasminogen activator (center I) or primary angioplasty with routine stenting (center II).
Results
Of the patients assigned to receive primary angioplasty, 91% underwent stenting. At 6 months, patients treated with primary angioplasty, compared with those treated with thrombolytic therapy, had a lower incidence of reinfarction (2% vs 14%, P = .053) and revascularization for recurrent ischemia (9% vs 61%, P < .001) and a significant reduction in the prespecified combined end point of death, reinfarction, or revascularization for recurrent ischemia (29% vs 93%, P < .01). Primary angioplasty remained an independent predictor of the triple combined end point after controlling for potential covariables (relative risk 0.63, 95% CI 0.38-0.84). Major bleeding complications were also significantly reduced in the primary angioplasty group (0% vs 17%, P = .03).
Conclusions
Compared with thrombolysis, primary angioplasty with routine stenting in elderly patients with AMI is associated with better clinical outcomes and a lower risk of bleeding complications. 相似文献
OBJECTIVE: Reducing time to reperfusion therapy is one of the goals in the management of acute myocardial infarction (AMI). We assessed the association between timing of aspirin administration and outcome of patients with AMI. PATIENTS: We studied 922 consecutive AMI patients with ST-segment elevation in Killip class I-III on admission. Patients were divided into two groups based upon the timing of emergency aspirin administration: before (early aspirin users) or after (late aspirin users) hospital admission. RESULTS: Early aspirin users (n = 338; 37%) were younger, less likely to be women, and more likely to smoke (p < 0.006) than late users (n = 584; 63%). Other baseline and clinical characteristics were similar. Early aspirin users were more likely to be treated with thrombolysis or primary percutaneous transluminal coronary angioplasty. Compared with late users, early aspirin users had significantly lower in-hospital complications and lower mortality rates at 7 (2.4 vs. 7.3%, p = 0.002) and 30 days (4.9 vs. 11.1%, p = 0.001). By multivariate adjustment, pre-hospital aspirin was an independent determinant of survival at 7 (odds ratio 0.43; 95% confidence interval 0.18-0.92) and at 30 days (odds ratio, 0.60; 95% confidence interval 0.32-1.08). Survival benefit associated with aspirin persisted for subgroups treated or not with reperfusion therapy. CONCLUSIONS: Outcome of AMI patients treated with aspirin is improved by pre-hospital administration. Our findings suggest that emergency pre-hospital aspirin might facilitate early reperfusion. 相似文献
PURPOSE: Photodynamic therapy (PDT) is a relatively new alternative modality for palliation of rectal cancer. Current source of light for PDT are laser systems that are expensive and not necessarily needed for PDT. We evaluated a new nonlaser light source for PDT, Versa-Light®.METHODS AND RESULTS:In vitroPDT—CT26 murine colon carcinoma cells were incubated with aluminum phthalocyanine (AlPcS4) for 48 hours and subjected to photoradiation using Versa-Light®,and viability was assessed. There was a significant decrease in viability of treated cells compared with controls.In vivoPDT—BALB/c mice were injected either subcutaneously or intrarectally with CT26 cancer cells. IP AlPcS4(2.5 mg/kg) was injected when tumors were visible. After 24 hours, mice were subjected to photoradiation. Massive tumor necrosis in response to PDT was observed. PDT also prolonged survival of treated mice. Patient treatment—A 70-year-old woman with recurrent local rectal carcinoma received intravenous Photofrin II®(2 mg/kg). After 48 and 96 hours, she was subjected to direct photoradiation. After the first light session, there was complete macroscopic disappearance of the tumor. Biopsies up to 10 weeks after the treatment showed no cancer cells in the treated area. Sixteen weeks later, a randomized biopsy from previous tumor site showed carcinoma cells. CONCLUSIONS: We believe that Versa-Light®,is a good light source for PDT. It was effective in bothin vitroand animal studies. It can also be safely used for clinical PDT.Supported by the Roni Udassin Memorial Fund of the Israel Cancer Society. 相似文献
Objectives. This study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients.
Background. We previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear.
Methods. Wall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).
Results. Multivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9).
Conclusions. There is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation. 相似文献
Aspirin failure, defined as occurrence of an acute coronary syndrome despite aspirin use, has been associated with a higher cardiovascular risk profile and worse prognosis. Whether this phenomenon is a manifestation of patient characteristics or failure of adequate platelet inhibition by aspirin has never been studied. We evaluated 174 consecutive patients with acute myocardial infarction. Of them, 118 (68%) were aspirin naive and 56 (32%) were regarded as having aspirin failure. Platelet function was analyzed after ≥72 hours of aspirin therapy in all patients. Platelet reactivity was studied by light-transmitted aggregometry and under flow conditions. Six-month incidence of major adverse coronary events (death, recurrent acute coronary syndrome, and/or stroke) was determined. Those with aspirin failure were older (p = 0.002), more hypertensive (p <0.001), more hyperlipidemic (p <0.001), and more likely to have had a previous cardiovascular event and/or procedure (p <0.001). Cumulative 6-month major adverse coronary events were higher in the aspirin-failure group (14.3% vs 2.5% p <0.01). Patients with aspirin failure had lower arachidonic acid-induced platelet aggregation (32 ± 24 vs 45 ± 30, p = 0.003) after aspirin therapy compared to their aspirin-naive counterparts. However, this was not significant after adjusting for differences in baseline characteristics (p = 0.82). Similarly, there were no significant differences in adenosine diphosphate-induced platelet aggregation and platelet deposition under flow conditions. In conclusion, our results suggest that aspirin failure is merely a marker of higher-risk patient profiles and not a manifestation of inadequate platelet response to aspirin therapy. 相似文献
STUDY OBJECTIVES: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI). PATIENTS: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission. INTERVENTIONS: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood. RESULTS: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events. CONCLUSION: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients. 相似文献
Shape-memory compression bowel anastomosis using a nickel and titanium alloy may reduce leak rates and eliminate foreign anastomotic
material. Its safety and efficacy had been demonstrated by animal studies. We conducted the first prospective multi-center
clinical evaluation of the safety and effectiveness of BioDynamix anastomosis with ColonRing™ for large-bowel end-to-end or
side-to-end anastomosis. 相似文献