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Meier Curves (meier + curve)
Selected AbstractsInfluence of cardiac-specific overexpression of insulin-like growth factor 1 on lifespan and aging-associated changes in cardiac intracellular Ca2+ homeostasis, protein damage and apoptotic protein expressionAGING CELL, Issue 6 2007Qun Li Summary A fall in circulating levels of cardiac survival factor insulin-like growth factor 1 (IGF-1) contributes to cardiac aging. To better understand the role of IGF-1 in cardiac aging, we examined the influence of cardiac IGF-1 overexpression on lifespan, cardiomyocyte intracellular Ca2+ homeostasis, protein damage, apoptosis and expression of pro- and anti-apoptotic proteins in young and old mice. Mouse survival rate was constructed by the Kaplan,Meier curve. Intracellular Ca2+ was evaluated by fura-2 fluorescence. Protein damage was determined by protein carbonyl formation. Apoptosis was assessed by caspase-8 expression, caspase-3 and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay. Pro- and anti-apoptotic proteins including Bax, p53, pp53, Bcl2, Omi/HtrA2, apoptosis repressor with caspase recruitment domain (ARC) and X-linked inhibitor of apoptosis protein (XIAP) were assessed by Western blot. Aging decreased plasma in IGF-1 levels, elevated myocyte resting intracellular Ca2+ levels, reduced electrically stimulated rise in intracellular Ca2+ and delayed intracellular Ca2+ decay associated with enhanced protein carbonyl formation, caspase-8 expression and caspase-3 activity in FVB mice, all of which with the exception of elevated resting intracellular Ca2+ were attenuated by IGF-1. Aging up-regulated expression of Bax, Bcl2 and ARC, down-regulated XIAP expression and did not affect p53, pp53 and Omi/HtrA2. The IGF-1 transgene attenuated or nullified aging-induced changes in Bax, Bcl2 and XIAP. Our data suggest a beneficial role for IGF-1 in aging-induced survival, cardiac intracellular Ca2+ homeostasis, protein damage and apoptosis possibly related to pro- and anti-apoptotic proteins. [source] Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in TaiwanJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009Emily Ya-Chi Hwang Background:, The epithelial cell adhesion molecule (Ep-CAM) is involved in cell signaling, migration, proliferation, cell-cycle regulation, and cancer metastasis. Methods:, This study used an immunohistochemical technique to examine the expression of Ep-CAM protein in 84 specimens of oral squamous cell carcinoma (OSCC), 98 specimens of oral epithelial dysplasia (OED, 31 mild, 41 moderate, and 26 severe OED cases), and 15 specimens of normal oral mucosa (NOM). Results:, We found that the mean Ep-CAM labeling indices (LIs) decreased significantly from NOM (80 ± 18%) and mild OED (76 ± 14%) through moderate OED (66 ± 22%) and severe OED (55 ± 20%) to OSCC samples (46 ± 16%, P < 0.001). A significant correlation was found between the lower mean Ep-CAM LI and OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.022), more advanced clinical stages (P < 0.001), cancer recurrence (P = 0.021), or extracapsular spread of lymph node (P = 0.015). However, only Ep-CAM LI < 50% (P < 0.0001) was identified as an independent unfavorable prognosis factor by multivariate analyses with Cox proportional hazard regression model. Kaplan,Meier curve showed that OSCC patients with an Ep-CAM LI < 50% had a significantly poorer cumulative survival than those with an Ep-CAM LI , 50% (P < 0.00001, log-rank test). Conclusions:, We conclude that the decreased expression of Ep-CAM protein is an early event in oral carcinogenesis. The Ep-CAM LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients. [source] Recurrence after a First Unprovoked Cryptogenic/Idiopathic Seizure in Children: A Prospective Study from São Paulo, BrazilEPILEPSIA, Issue 2 2004Anna E. Scotoni Summary: Purpose: To evaluate the recurrence risk after a first unprovoked seizure in a large population of children and adolescents of a developing country. Methods: This prospective study was conducted at two tertiary hospitals, between September 1989 and August 1998. Children were enrolled if they had a first unprovoked cryptogenic/idiopathic seizure and maximal interval to the enrollment ,90 days. EEG and computed tomography (CT) were performed in most patients. Potential predictors of recurrence were compared by using the Cox proportional hazards model in univariate and multivariate analyses. Survival analysis was performed by using the Kaplan,Meier curves. Results: Two hundred thirteen children were included. Recurrence occurred in 34% of the patients, and mean time for recurrence was 12 months. Statistical analysis showed significance for seizure recurrence only for patients with abnormal EEGs. CT was performed in 182 patients, and abnormalities were found in 9.5%. Small calcifications were the most frequent finding, and this was not a predictor for recurrence. Conclusions: The risk of recurrence after a first unprovoked seizure in children from a developing country is similar to that found in developed countries. An abnormal EEG is a risk factor for seizure recurrence in children with a cryptogenic/idiopathic seizure. Calcifications on CT do not increase the risk of recurrence. [source] Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancerGENES, CHROMOSOMES AND CANCER, Issue 7 2006Ling-Ming Tseng Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various tumors, including breast cancer. However, it still remains unclear whether the alterations in mtDNA are related to the clinicopathological features and/or the prognosis in the breast cancer. We analyzed somatic mutations in the D-loop region, the common 4,977-bp deletion, and the copy number of mtDNA in breast cancer and paired nontumorous breast tissues from 60 Taiwanese patients. We found that 18 of the 60 (30%) breast cancers displayed somatic mutations in mtDNA D-loop region. The incidence of the 4,977-bp deletion in nontumorous breast tissues (47%) was much higher than that in breast cancers (5%). The copy number of mtDNA was significantly decreased in 38 of the 60 (63%) breast cancers as compared to their corresponding nontumorous breast tissues (P = 0.0008). The occurrence of D-loop mutations was associated with an older onset age (,50 years old, P = 0.042), and tumors that lacked expressions of estrogen receptor and progesterone receptor (P = 0.024). Patients with mtDNA D-loop mutation and breast cancer had significantly poorer disease-free survival than those without mutation, when assessed by Kaplan,Meier curves and log-rank test (P = 0.005). Multivariate Cox regression analysis indicated that a D-loop mutation is a significant marker that is independent of other clinical variables and that it can be used to assess the prognosis of patients. Our findings suggest that somatic mutations in mtDNA D-loop can be used as a new molecular prognostic indicator in breast cancer. © 2006 Wiley-Liss, Inc. [source] Elective neck dissection in early-stage oral squamous cell carcinoma,does it influence recurrence and survival?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2007Ana Capote MD Abstract Background. This study investigates the influence on survival and regional control rates of neck dissection therapy at the time of surgery of the primary tumor in early stages of squamous cell carcinoma (SCC) of the oral cavity. Methods. A series of 154 patients with pT1N0M0 and pT2N0M0 intraoral carcinomas was analyzed retrospectively. Neck dissection was associated with tumor ablation in 87 patients (56.5%), although 67 patients (43.5%) were treated with local resection exclusively. Survival and relapse rates were studied with the Kaplan,Meier curves and the log-rank test for univariate analysis and Cox proportional model for multivariate analysis (p < .05). Results. Regional recurrences occurred in 25 cases (16.2%), 7 cases (8%) with primary neck dissection and 18 cases (26.8%) with local excision alone. Neck dissection therapy was a significant prognostic factor for recurrences and survival (p < .05). The 5-year regional control rate was of 92.5% for patients with elective lymph node ablation versus 71.2% for patients without primary neck dissection. Neck dissection was also significant for recurrences in stage I and for survival and recurrences in stage II. Neck dissection therapy also showed independent prognostic value in the Cox analysis. Conclusions. In patients with intraoral carcinomas, elective neck treatment should be considered even in cases with a small primary tumor and negative clinical examination because of the high incidence of occult nodal metastases and the tendency to regional recurrences. © 2006 Wiley Periodicals, Inc. Head Neck 2007 [source] The impact of HIV-1 co-infection on long-term mortality in patients with hepatitis C: a population-based cohort studyHIV MEDICINE, Issue 2 2009LH Omland Objective To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV). Methods From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient, four control HCV patients without HIV were matched on age, gender and year of HCV diagnosis. Data on comorbidity, drug abuse, alcoholism and date of death were extracted from two healthcare databases. We constructed Kaplan,Meier curves and used Cox regression analyses to estimate mortality rate ratios (MRRs), controlling for comorbidity. Results We identified 483 HCV,HIV co-infected and 1932 HCV mono-infected patients, yielding 2192 and 9894 person-years of observation with 129 and 271 deaths, respectively. The 5-year probability of survival was 0.74 [95% confidence interval (CI) 0.69,0.80] for HCV,HIV co-infected patients and 0.87 (95% CI 0.85,0.89) for HCV mono-infected patients. Co-infection was associated with substantially increased mortality (MRR 2.1, 95% CI 1.7,2.6). However, prior to the first observed decrease in CD4 counts to below 300 cells/,L, HIV infection did not increase mortality in HCV-infected patients (MRR 0.9, 95% CI 0.5,1.50). Conclusions HIV infection has a substantial impact on mortality among HCV-infected individuals, mainly because of HIV-induced immunodeficiency. [source] Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2007G Weinlich Abstract Background, Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. Immunohistochemical MT overexpression in paraffin-embedded tissues of patients with primary melanoma is associated with poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical technique for high-risk melanoma patients with predictive value for progression, the benefit of this procedure for the individual patient's overall survival remains unclear. Aim and methods, We examined the role of MT overexpression in comparison with SLN biopsy in melanoma patients as a prognostic marker for progression and survival. One hundred and fifty-eight (158) patients underwent SLN biopsy due to high-risk melanoma. Primary melanoma specimens were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. The patients were followed up (median 37 months); the data of disease free survival and overall survival were calculated with a broad panel of statistical analyses. Results, Twenty-eight (18%) out of 158 recruited melanoma patients developed metastases, 17 (11%) patients died due to widespread disease. Kaplan,Meier curves gave significant disadvantages for the MT-positive as well as the SLN-positive group for progression and survival. In the Fisher's exact test and Pearson's ,2 -test MT overexpression was highly significant for progression, whereas SLN biopsy failed significance. In univariate as well as multivariate Cox regression analysis MT overexpression proved an excellent marker for progression (P = 0.007 and P = 0.009), although the P -values for survival were not significant. In contrast, while in the univariate analysis SLN biopsy did not show significant results for progression it did for survival, and in the multivariate analysis reached a P -value < 0.05 for both measured endpoints. Conclusion, Results corroborate the validity of MT overexpression in primary melanoma as a useful prognostic marker in melanoma patients. Accuracy is comparable and to some degree supplementary to the results of SLN biopsy. [source] Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomasNMR IN BIOMEDICINE, Issue 1 2004Xiaojuan Li Abstract Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton (1H) MRSI. Thirty-nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N -acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan,Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho-to-Cr, higher Cho-to-NAA, higher LL and lower Cr-to-NAA abnormalities. The survival functions were significantly different between the sub-groups of patients obtained from the survival tree for both pre-surgery and post-surgery data. The results of this study suggest that pre-treatment MRI and three-dimensional 1H-MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques. Copyright © 2004 John Wiley & Sons, Ltd. [source] Low donor-to-recipient weight ratio does not negatively impact survival of pediatric heart transplant patientsPEDIATRIC TRANSPLANTATION, Issue 6 2010Liwen Tang Tang L, Du W, Delius RE, L'Ecuyer TJ, Zilberman MV. Low donor-to-recipient weight ratio does not negatively impact survival of pediatric heart transplant patients. Pediatr Transplantation 2010: 14:741,745. © 2010 John Wiley & Sons A/S. Abstract:, A major limitation to success in pediatric heart transplantation is donor organ shortage. While the use of allografts from donors larger than the recipient is accepted, the use of undersized donor grafts is generally discouraged. Using the UNOS database, we wanted to evaluate whether using smaller donor hearts affects the short- and long-term survival of pediatric heart transplant patients. A retrospective analysis of data entered into the UNOS database from April 1994 to May 2008 was performed. Pediatric heart transplant recipients (ages 0,18 yr) with DRWR <2.0 were identified and divided into two groups: Low-DRWR (<0.8) and Ideal-DRWR (0.8,2.0). Patients' demographics, pretransplant diagnoses, age at transplantation, severity of pretransplant condition, and rate of complications prior to hospital discharge after transplantation were noted. Fisher's exact, chi-square, and Wilcoxon rank sum tests were used to compare patients' baseline characteristics. Kaplan,Meier curves and Cox proportional hazard regression were used to compare patients' survival and to identify independent risk factors for outcomes. There were 3048 patients (204 with Low- and 2844 with Ideal-DRWR). The Low-ratio group patients were older (8.3 vs. 6.9 yr; p = 0.001), there was a slight male predominance in the Low-DRWR group (p = 0.055). The Low-DRWR group had longer transplant wait time than the Ideal-DRWR group (97 vs. 85 days; p = 0.04). The groups did not differ in race, primary diagnoses, severity of pretransplant condition (medical urgency status, need for ventilation, inotropic support, ECMO, nitric oxide, or dialysis, the PVR for those with bi-ventricular anatomy), or post-transplant complications (length of stay, need for inotropic support, dialysis, and rate of infections). The Low-DRWR patients had less episodes of acute rejection during the first-post-transplant month. Infants with DRWR 0.5,0.59 had lower 30-day survival rate (p = 0.045). There was no difference in short- and long-term survival between the patients with DRWR 0.6,0.79 and DRWR 0.8,2.0. Use of smaller allografts (DRWR 0.6,0.8) has no negative impact on the short- and long-term survival of pediatric heart transplant patients. [source] An Early Regional Experience with Expansion of Milan Criteria for Liver Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010J. J. Guiteau The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ,3 lesions, none >5 cm and total diameter <9 cm,[R4 T3]) to receive the same exception points as MC lesions. Kaplan,Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann,Whitney U tests were used to compare patient data. A p - value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging. [source] Extent of mesorectal invasion is a prognostic indicator in T3 rectal carcinomaANZ JOURNAL OF SURGERY, Issue 7 2002Malcolm C. A. Steel Background: The aim of this study was to determine if local recurrence (LR) rates in patients with minimally invasive and advanced T3 rectal cancer are different. This may influence the use of adjuvant therapy. Methods: Consecutive patients with T3 rectal cancer undergoing curative surgery were classified into minimally invasive or advanced groups. Minimally invasive T3 was defined as a tumour that had invaded beyond the muscularis propria on microscopic examination only, whereas advanced T3 tumours had invasion beyond the muscularis propria that was obvious on macroscopic examination and confirmed histologically. Local recurrence rates of the two groups were compared by construction of Kaplan,Meier curves. The log-rank test was used to determine equivalence, and Cox regression to estimate the hazard ratio. The Grambsch, Therneau test and graphical comparison of predicted and observed Kaplan,Meier curves was used to test the proportional hazards assumption. Results: There were 222 patients in total, 74 in the minimally invasive group and 148 in the advanced. The overall LR rate was 11.2%. The LR rates in the minimally invasive and advanced groups were 5.4% and 14.2%, respectively. The log-rank test gives a P value of 0.042 for equivalence, with the minimally invasive patients doing significantly better. The hazard ratio estimated by Cox regression was 0.35 (early relative to advanced), 95% confidence intervals (0.12, 1.0). There was no evidence of confounding by age at surgery, pathology type, gender or postoperative adjuvant therapy. Conclusions: The extent of invasion into the mesorectum appears to be an independent prognostic variable. If oncologically sound surgical techniques are employed, the LR rate of patients with minimal invasion is low. Adjuvant therapy may not confer additional benefit in this group. [source] The effect of screening for cardio-renal risk factors on drug use in the general populationBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2007Jarir Atthobari What is already know about this subject ,,Screening of the population may result in medicalization. ,,There is no report about the effect of a health screening programme on drug prescribing. What this study adds ,,Screening of the general population for cardiovascular risk factors does not lead to more drug prescribing, for either screening-related or screening-unrelated drugs. ,,The incidence of drug use increases in screened subjects with high risk, but only for drugs related to the purpose of screening. ,,For screening to be successful, i.e. increased drug use in the detected diseased subjects, it has to be performed in a population expected to be at increased risk. Aim To evaluate the effect of a cardio-renal screening programme on desired and undue drug use. Methods Data from the PREVEND cohort (Prevention of REnal and Vascular ENd-stage Disease) were used. The drug use of screened (randomly) selected subjects (n = 2650) was compared with unscreened subjects, matched for age and sex (n = 10 434). Drug use in the overall PREVEND cohort, enriched for albuminuria (n = 6751), was also studied. Screening-related drugs (antihypertensive, antilipidaemic, antidiabetic and antithrombotic) were selected, as well as screening-unrelated drugs (benzodiazepines, drugs for acid-related disorders and painkillers). Time to first prescription after screening is presented as Kaplan,Meier curves. Results After 6.5 years of follow-up, the incidence of drug use was not significantly different between the screened, randomly selected and unscreened cohorts. Antihypertensives were used by 21.5 and 20.8%, respectively; antilipidaemic 12.8 and 10.2%, antidiabetics 4.0 and 3.9%, and antithrombotic 11.4 and 12.0%. Screening-unrelated drugs were used at comparable frequencies. Compared with the unscreened cohort, screening-related drugs were prescribed more frequently for subjects in the enriched cohort (25.8, 15.5, 5.5 and 13.5% for antihypertensive, antilipidaemic, antidiabetic and antithrombotic, respectively), whereas screening-unrelated drugs were used at comparable frequencies. Conclusions The incidence of drug use did not differ between the screened, randomly selected and unscreened cohorts. Screening does not lead to more drug prescription, thus arguing against the fear of undue medicalization after screening. The data also show that, for screening to be successful, it should be performed in a targeted population, such as one enriched for albuminuria. [source] | |||||||||||||||||||