Objectives: This study sought to investigate the influence of time, dose, and inversion time(TI) and their interactions on myocardial infarct size measurements to establish the foundation for a standardized protocol f...Objectives: This study sought to investigate the influence of time, dose, and inversion time(TI) and their interactions on myocardial infarct size measurements to establish the foundation for a standardized protocol for multicenter trials. Background: There is growing interest in using magnetic resonance imaging(MRI) infarct size measurements as an end point in clinical trials. However, no standardized protocol exists, and there are limited data concerning the effects of time, contrast agent dose, and TI. Methods: First, we determined the influence of postcontrast imaging time(5 to 40 min), contrast agent dose(0.1 vs. 0.2 mmol/kg), TI, and their interactions in an animal model(n=14). Second, we tested whether the findings of the animal study apply to patients and are generalizable. Therefore, we retested the diagnostic window in a multicenter study. A total of 48 patients with first acute myocardial infarction(AMI) from three centers were imaged twice(5 and 30 min) after injection of 0.15 mmol/kg gadolinium diethylenetriamine-pentaacetate using an adjusted TI. Results: The animal study showed that the infarct size is independent of time and dose(p=0.9 and p=0.16, respectively) using an adjusted TI. Using a fixed TI, however, infarct size is a function of time and dose(p=0.0001 and p=0.01, respectively). The multicenter study showed that MRI 1(16.9±12%of left ventricle) was not statistically different from MRI 2(16.4±12%of left ventricle, p=NS)with no difference between sites(p=NS). Conclusions: The AMI size can be measured with MRI using a contrast dose between 0.1 and 0.2 mmol/kg and a time window of 5 to 30 min after contrast administration, provided that the TI is adjusted.展开更多
Background & Aims: Hereditary nonpolyposis colorectal carcinoma(HNPCC) is caused by a mutated mismatch repair(MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large se...Background & Aims: Hereditary nonpolyposis colorectal carcinoma(HNPCC) is caused by a mutated mismatch repair(MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. Methods: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry(IHC) were performed in the available tumors.Results: A total of 146 MSH6 mutation carriers were identified.In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH 6 mutation carriers, the risk for colorectal cancer was significantly lower(P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P =0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. Conclusions:We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis.展开更多
文摘Objectives: This study sought to investigate the influence of time, dose, and inversion time(TI) and their interactions on myocardial infarct size measurements to establish the foundation for a standardized protocol for multicenter trials. Background: There is growing interest in using magnetic resonance imaging(MRI) infarct size measurements as an end point in clinical trials. However, no standardized protocol exists, and there are limited data concerning the effects of time, contrast agent dose, and TI. Methods: First, we determined the influence of postcontrast imaging time(5 to 40 min), contrast agent dose(0.1 vs. 0.2 mmol/kg), TI, and their interactions in an animal model(n=14). Second, we tested whether the findings of the animal study apply to patients and are generalizable. Therefore, we retested the diagnostic window in a multicenter study. A total of 48 patients with first acute myocardial infarction(AMI) from three centers were imaged twice(5 and 30 min) after injection of 0.15 mmol/kg gadolinium diethylenetriamine-pentaacetate using an adjusted TI. Results: The animal study showed that the infarct size is independent of time and dose(p=0.9 and p=0.16, respectively) using an adjusted TI. Using a fixed TI, however, infarct size is a function of time and dose(p=0.0001 and p=0.01, respectively). The multicenter study showed that MRI 1(16.9±12%of left ventricle) was not statistically different from MRI 2(16.4±12%of left ventricle, p=NS)with no difference between sites(p=NS). Conclusions: The AMI size can be measured with MRI using a contrast dose between 0.1 and 0.2 mmol/kg and a time window of 5 to 30 min after contrast administration, provided that the TI is adjusted.
文摘Background & Aims: Hereditary nonpolyposis colorectal carcinoma(HNPCC) is caused by a mutated mismatch repair(MMR) gene. The aim of our study was to determine the cumulative risk of developing cancer in a large series of MSH6 mutation carriers. Methods: Mutation analysis was performed in 20 families with a germline mutation in MSH6. We compared the cancer risks between MSH6 and MLH1/MSH2 mutation carriers. Microsatellite instability (MSI) analysis and immunohistochemistry(IHC) were performed in the available tumors.Results: A total of 146 MSH6 mutation carriers were identified.In these carriers, the cumulative risk for colorectal carcinoma was 69% for men, 30% for women, and 71% for endometrial carcinoma at 70 years of age. The risk for all HNPCC-related tumors was significantly lower in MSH6 than in MLH1 or MSH2 mutation carriers (P = 0.002). In female MSH 6 mutation carriers, the risk for colorectal cancer was significantly lower(P = 0.0049) and the risk for endometrial cancer significantly higher (P = 0.02) than in MLH1 and MSH2 mutation carriers. In male carriers, the risk for colorectal cancer was lower in MSH6 mutation carriers, but the difference was not significant (P =0.0854). MSI analysis in colorectal tumors had a sensitivity of 86% in predicting a MMR defect. IHC in all tumors had a sensitivity of 90% in predicting a mutation in MSH6. Conclusions:We recommend starting colonoscopic surveillance in female MSH6 mutation carriers from age 30 years. Prophylactic hysterectomy might be considered in carriers older than 50 years. MSI and IHC analysis are sensitive tools to identify families eligible for MSH6 mutation analysis.
