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Reduced Survival (reduced + survival)
Terms modified by Reduced Survival Selected AbstractsAlcohol inhibition of neurogenesis: A mechanism of hippocampal neurodegeneration in an adolescent alcohol abuse modelHIPPOCAMPUS, Issue 5 2010Stephanie A. Morris Abstract Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder. Immunohistochemistry of various markers along with Bromo-deoxy-Uridine (BrdU) injections were used to examine different aspects of neurogenesis. After 4 days of binge alcohol exposure, neurogenesis was decreased by 33 and 28% at 0 and 2 days after the last dose according to doublecortin expression. To determine whether this decrease in neurogenesis was due to effects on neural stem cell proliferation, quantification of BrdU-labeled cells revealed a 21% decrease in the dentate gyrus of alcohol-exposed brains. Cell survival and phenotype of BrdU-labeled cells were assessed 28 days after alcohol exposure and revealed a significant, 50% decrease in the number of surviving cells in the alcohol-exposed group. Reduced survival was supported by significant increases in the number of pyknotic-, FluoroJade B positive-, and TUNEL-positive cells. However, so few cells were TUNEL-positive that cell death is likely necrotic in this model. Although alcohol decreased the number of newborn cells, it did not affect the percentage of cells that matured into neurons (differentiation). Thus, our data support that in a model of an adolescent alcohol use disorder, neurogenesis is impaired by two mechanisms: alcohol-inhibition of neural stem cell proliferation and alcohol effects on new cell survival. Remarkably, alcohol inhibition of neurogenesis may outweigh the few dying cells per section, which implies that alcohol inhibition of neurogenesis contributes to hippocampal neurodegeneration in alcohol use disorders. © 2009 Wiley-Liss, Inc. [source] Using artificial streams to assess the effects of metal-mining effluent on the life cycle of the freshwater midge (Chironomus tentans) in situENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2004Kimberly A. Hruska Abstract In 2002, we developed an in situ life-cycle bioassay with Chironomus tentans in artificial streams to evaluate the effects of a complex metal mine effluent under ambient environmental conditions. The bioassay was tested in the field using effluent from the Copper Cliff Waste Water Treatment Plant at INCO (Sudbury, ON, Canada). Chironomus tentans were exposed throughout the life cycle to 45% Copper Cliff effluent, which is the average effluent concentration measured in Junction Creek (ON, Canada), the natural receiving environment. Chironomus tentans in the effluent treatment exhibited reduced survival (p = 0.001), reduced total emergence (p = 0.001), increased time-to-emergence (p = 0.001), and reduced hatching success (p = 0.001) relative to animals in the reference water treatment. Chironomus tentans in the effluent treatment were not significantly different from the reference in terms of growth, sex ratio, number of egg cases/female, and number of eggs/egg case. This research showed how a life-cycle bioassay could be used in situ to assess metal mine effluent effects on a benthic invertebrate. [source] REPRODUCTIVE ISOLATION CAUSED BY NATURAL SELECTION AGAINST IMMIGRANTS FROM DIVERGENT HABITATSEVOLUTION, Issue 4 2005Patrik Nosil Abstract The classification of reproductive isolating barriers laid out by Dobzhansky and Mayr has motivated and structured decades of research on speciation. We argue, however, that this classification is incomplete and that the unique contributions of a major source of reproductive isolation have often been overlooked. Here, we describe reproductive barriers that derive from the reduced survival of immigrants upon reaching foreign habitats that are ecologically divergent from their native habitat. This selection against immigrants reduces encounters and thus mating opportunities between individuals from divergently adapted populations. It also reduces the likelihood that successfully mated immigrant females will survive long enough to produce their hybrid offspring. Thus, natural selection against immigrants results in distinctive elements of premating and postmating reproductive isolation that we hereby dub "immigrant inviability". We quantify the contributions of immigrant inviability to total reproductive isolation by examining study systems where multiple components of reproductive isolation have been measured and demonstrate that these contributions are frequently greater than those of traditionally recognized reproductive barriers. The relevance of immigrant inviability is further illustrated by a consideration of population-genetic theory, a review of selection against immigrant alleles in hybrid zone studies, and an examination of its participation in feedback loops that influence the evolution of additional reproductive barriers. Because some degree of immigrant inviability will commonly exist between populations that exhibit adaptive ecological divergence, we emphasize that these barriers play critical roles in ecological modes of speciation. We hope that the formal recognition of immigrant inviability and our demonstration of its evolutionary importance will stimulate more explicit empirical studies of its contributions to speciation. [source] INBREEDING IN THE SEYCHELLES WARBLER: ENVIRONMENT-DEPENDENT MATERNAL EFFECTSEVOLUTION, Issue 9 2004David S. Richardson Abstract The deleterious effects of inbreeding can be substantial in wild populations and mechanisms to avoid such matings have evolved in many organisms. In situations where social mate choice is restricted, extrapair paternity may be a strategy used by females to avoid inbreeding and increase offspring heterozygosity. In the cooperatively breeding Seychelles warbler, Acrocephalus sechellensis, neither social nor extrapair mate choice was used to avoid inbreeding facultatively, and close inbreeding occurred in approximately 5% of matings. However, a higher frequency of extra-group paternity may be selected for in female subordinates because this did reduce the frequency of mating between close relatives. Inbreeding resulted in reduced individual heterozygosity, which, against expectation, had an almost significant (P= 0.052), positive effect on survival. Conversely, low heterozygosity in the genetic mother was linked to reduced offspring survival, and the magnitude of this intergenerational inbreeding depression effect was environment-dependent. Because we controlled for genetic effects and most environmental effects (through the experimental cross-fostering of nestlings), we conclude that the reduced survival was a result of maternal effects. Our results show that inbreeding can have complicated effects even within a genetic bottlenecked population where the "purging" of recessive alleles is expected to reduce the effects of inbreeding depression. [source] Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomasHISTOPATHOLOGY, Issue 1 2010Michael G A Norwood Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology,57, 101,111 Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:, ,-Catenin is an important molecule in cancer biology. Membranous ,-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results:, Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess ,-catenin expression. Increasing ,-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of ,-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions:, This is one of the largest prognostic studies of ,-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic ,-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic ,-catenin could be used as a prognostic marker for less aggressive disease. [source] Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Tanya R. Newton Abstract The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9,29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining was associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. © 2006 Wiley-Liss, Inc. [source] Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancerINTERNATIONAL JOURNAL OF CANCER, Issue 3 2002Barbara Bachtiary Abstract To obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin-fixed, paraffin-embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal-amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression-free survival (PFS) and cervical cancer-specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety-six patients (90.6%) were HPV-positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment. © 2002 Wiley-Liss, Inc. [source] Comparative changes in adult vs. juvenile survival affecting population trends of African ungulatesJOURNAL OF ANIMAL ECOLOGY, Issue 4 2005NORMAN OWEN-SMITH Summary 1Among large mammalian herbivores, juvenile survival tends to vary widely and may thus have a greater influence on population dynamics than the relatively constant survival rates typical of adults. However, previous studies yielding stage-specific survival rates have been mostly on temperate zone ungulates and in environments lacking large predators. 2Annual censuses coupled with assessments of population structure enabled annual survival rates to be estimated for the juvenile, yearling and adult segments of nine ungulate species in South Africa's Kruger National Park. Four of these populations persisted at high abundance after initial increases (zebra, wildebeest, impala and giraffe), while five showed progressive declines during the latter part of the study period (kudu, waterbuck, warthog, sable antelope and tsessebe). 3The magnitude of the reduction in adult survival between periods showing contrasting population trends was similar to or greater than the corresponding change in juvenile survival for five of the nine species. Accordingly alterations in population phase, from increasing to stable or stable to declining, were brought about mostly through reduced survival within the adult segment. Elevated predation risk may have been responsible. 4Estimates were derived of the relative survival rates of juveniles, yearlings and adult segments associated with zero population growth, and the survival differential between adult males and females, for all nine species. Stage-specific survival rates appeared dependent on body mass, but with some anomalies. The sex difference in adult survival showed no obvious relation with sexual size dimorphism. 5For large mammalian herbivores, assessments of relative elasticities of stage-specific survival rates on population growth are problematic for several reasons. Sensitivity to corresponding increments in either survival or mortality rates provides a better basis for ecological or adaptive interpretation. Survival rates of adults seem to vary more over multiyear periods compared with mainly annual fluctuations in juvenile survival. More studies are needed on tropical species and in environments retaining large predators to support generalizations about factors influencing ungulate life-history patterns. [source] Estimating survival and movements using both live and dead recoveries: a case study of oystercatchers confronted with habitat changeJOURNAL OF APPLIED ECOLOGY, Issue 1 2009Olivier Duriez Summary 1Animals facing partial habitat loss can try to survive in the remaining habitat or emigrate. Effects on survival and movements should be studied simultaneously since survival rates may be underestimated if emigrants are not considered, and since emigrants may experience reduced survival. 2We analysed movements and survival of adult wintering oystercatcher Haematopus ostralegus in response to the 1986,1987 partial closure of the Oosterschelde in the Dutch Delta. This reduced by one-third the tidal area of this major European wintering area for waders. 3We developed a novel variant of a multistate capture,recapture model allowing simultaneous estimation of survival and movement between sites using a mixture of data (live recaptures and dead recoveries). We used a two-step process, first estimating movements between sites followed by site-specific survival rates. 4Most birds were faithful to their ringing site. Winter survival was negatively affected by winter severity and was lowest among birds changing wintering site (i.e. moving outside of the Oosterschelde). 5During mild winters, survival rates were very high, and similar to before the closure in both changed and unchanged sectors of the Oosterschelde. However, the combined effect of habitat loss with severe winters decreased the survival of birds from changed sectors and induced emigration. 6The coastal engineering project coincided with three severe winters and high food stock, making assessment of its effects difficult. However, the habitat loss seems to have had less impact on adult survival and movements than did winter severity. 7 Synthesis and applications. Human-induced habitat change may result in population decline through costly emigration or reduced survival or reproduction of individuals that stay. Long-term monitoring of marked individuals helps to understand how populations respond to environmental change, but site-specific survival and movement rates should be integrated in the same model in order to maximize the information yield. Our modelling approach facilitates this because it allows the inclusion of recoveries from outside the study area. [source] ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancerJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2007N. Valkovskaya Abstract ADAM8 belongs to a family of transmembrane proteins implicated in cell,cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT-PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis-sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI-TOF-MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3-fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy. [source] Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone diseaseJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2010A. Rio Abstract Background: Motor neurone disease (MND) is a progressive neurodegenerative disease leading to limb weakness, wasting and respiratory failure. Prolonged poor nutritional intake causes fatigue, weight loss and malnutrition. Consequently, disease progression requires decisions to be made regarding enteral tube feeding. The present study aimed to investigate the survival, nutritional status and complications in patients with MND treated with enteral tube feeding. Methods: A retrospective case note review was performed to identify patients diagnosed with MND who were treated with enteral tube feeding. A total of 159 consecutive cases were identified suitable for analysis. Patients were treated with percutaneous endoscopic gastrostomy (PEG), radiologically inserted gastrostomy (RIG) or nasogastric feeding tube (NGT). Nutritional status was assessed by body mass index (BMI) and % weight loss (% WL). Serious complications arising from tube insertion and prescribed daily energy intake were both recorded. Results: Median survival from disease onset was 842 days [interquartile range (IQR) 573,1263]. Median time from disease onset to feeding tube was PEG 521 days (IQR 443,1032), RIG 633 days (IQR 496,1039) and NGT 427 days (IQR 77,781) (P = 0.28). Median survival from tube placement was PEG 200 (IQR 106,546) days, RIG 216 (IQR 83,383) days and NGT 28 (IQR 14,107) days. Survival between gastrostomy and NGT treated patients was significant (P , 0.001). Analysis of serious complications by nutritional status was BMI (P = 0.347) and % WL (P = 0.489). Conclusions: Nutritional factors associated with reduced survival were weight loss, malnutrition and severe dysphagia. Serious complications were not related to nutritional status but to method of tube insertion. There was no difference in survival between PEG and RIG treated patients. [source] Cysteine-mutations in von Willebrand factor associated with increased clearanceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2005C. J. VAN SCHOOTEN Summary.,Background:,von Willebrand disease (VWD) is a bleeding disorder caused by the decrease of functional von Willebrand factor (VWF). Low levels of VWF can result from decreased synthesis, impaired secretion, increased clearance or combinations thereof. Several mutations lead to impaired synthesis or secretion of VWF, however, little is known about the survival of VWF in the circulation. Objectives:,To evaluate the effect of several VWF mutations on VWF clearance. Patients/methods:,The effect of three cysteine-mutations (C1130F, C1149R or C2671Y) on the in vivo survival of VWF was studied in patients carrying these mutations and in a VWF-deficient mice model. Results:,In patients carrying these mutations, we observed increased propeptide/mature VWF ratios and rapid disappearance of VWF from the circulation after desmopressin treatment. Detailed analysis of in vivo clearance of recombinant VWF in a VWF-deficient mice model revealed a fourfold increased clearance rate of the mutants. The mutations C1130F, C1149R and C2671Y are each associated with reduced survival of VWF in the circulation. Detailed analysis of the recombinant mutant VWF demonstrated that increased clearance was not due to increased proteolysis by ADAMTS-13. We did not identify functional or structural characteristics that the mutant proteins have in common and could be associated with the phenomenon of increased clearance. Conclusions:,Cysteine-mutations in VWF may result in reduced in vivo survival. The observation that various mutations are associated with increased in vivo clearance may have major implications for the therapeutic strategies that rely on the rise of endogenous VWF after desmopressin administration. [source] Outcomes of living donor liver transplantation for acute liver failure: The adult-to-adult living donor liver transplantation cohort study,,§LIVER TRANSPLANTATION, Issue 9 2008Jeffrey Campsen For acute liver failure (ALF), living donor liver transplantation (LDLT) may reduce waiting time and provide better timing compared to deceased donor liver transplantation (DDLT). However, there are concerns that a partial graft would result in reduced survival of critically ill LDLT recipients and that the rapid evolution of ALF would lead to selection of inappropriate donors. We report outcomes for ALF patients (and their donors) evaluated for LDLT between 1998 and April 2007 from the Adult-to-Adult Living Donor Liver Transplantation Cohort. Of the 1201 potential LDLT recipients, 14 had ALF, only 6 of whom had an identified cause. The median time from listing to first donor evaluation was 1.5 days, and the median time from evaluation to transplantation was 1 day. One patient recovered without liver transplant, 3 of 10 LDLT recipients died, and 1 of 3 DDLT recipients died. Five of the 10 living donors had a total of 7 posttransplant complications. In conclusion, LDLT is rarely performed for ALF, but in selected patients it may be associated with acceptable recipient mortality and donor morbidity. Liver Transpl 14:1273,1280, 2008. © 2008 AASLD. [source] Erythropoiesis stimulating agents are associated with reduced survival in patients with multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008Eirini Katodritou The impact of erythropoiesis-stimulating agent (ESA) on cancer patients' survival has recently become a matter of extensive discussion. Studies in solid tumors demonstrated that ESA adversely affects survival. This issue has not been sufficiently studied in patients with multiple myeloma. In this study, which included 323 multiple myeloma patients followed in our Institution between 1988 and 2007, we demonstrated by using a proportional hazards model including multiple covariates (age, LDH, Hb, platelets, serum creatinine, ISS score, ,2 microglobulin, and ESA administration) that ESA administration is associated with reduced survival (hazards ratio: 1.88, 95% CI: 1.28,2.77). Anemia, which is considered a predictor for survival, platelets, serum creatinine, ISS score, and LDH, were not significant, whereas, age and ,2 microglobulin confirmed their predicting value in the multivariate analysis. With a median follow-up of 31 months (range 1,238), the median survival of patients in the ESA group was 31 months (95% CI: 25,37), whereas in the group without ESA administration it was 67 months (95% CI: 55,79) (P < 0.001). The median progression-free survival for patients in the ESA group was 14 months (95% CI: 12,16), and for the group without ESA it was 30 months (95% CI: 24,36) (P < 0.001). These results indicate that ESA may have a detrimental impact on MM patients' outcomes and, thus, in this context, they should be used with rigorous criteria. © 2008 Wiley-Liss, Inc. Am. J. Hematol., 2008. [source] Photobleaching of Melanosomes from Retinal Pigment Epithelium: II.PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2007Effects on the Response of Living Cells to Photic Stress Melanosomes of the retinal pigment epithelium (RPE) are long lived organelles that may undergo photobleaching with aging, which can diminish the antioxidant efficiency of melanin. Here, isolated porcine RPE melanosomes were experimentally photobleached with visible light to simulate aging and compared with untreated granules or control particles (black latex beads) for their effects on the survival of photically stressed ARPE-19 cultures. Particles were delivered to cultures for uptake by phagocytosis then cells were exposed to violet light and analyzed by a new live cell imaging method to identify the time of apoptotic blebbing as a dynamic measure of reduced cell survival. Results indicated that untreated melanosomes did not decrease photic injury to ARPE-19 cells when compared with cells lacking particles or with cells containing control particles, as might be expected if melanin performed an antioxidant function. Instead cells with untreated melanosomes showed reduced survival indicated by an earlier onset of blebbing and a lower fraction of surviving cells after photic stress. Cell survival was reduced even further in stressed cells containing melanosomes that were photobleached, and survival decreased with increasing photobleaching time. Photobleaching of RPE melanosomes therefore makes cells containing them more sensitive to light-induced cytotoxicity. This observation raises the possibility that aged melanosomes increase RPE cell photic stress in situ, perhaps contributing to reduced tissue function and to degeneration of the adjacent retina that the RPE supports. How melanosomes (photobleached or not) interact with their local subcellular environment to modify RPE cell survival is poorly understood and is likely determined by the physicochemical state of the granule and its constituent melanin. The live cell imaging method introduced here, which permitted detection of a graded effect of photobleaching, provides a sensitive bioassay for probing the effects of melanosome modifications. [source] Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical FactorAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010E. Vibert Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ,progression' of AFP was defined by >15 ,g/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 ,g/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 ,g/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness. [source] Histidine-Tryptophan-Ketoglutarate (HTK) Is Associated with Reduced Graft Survival in Pancreas TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009Z. A. Stewart Prior single-center studies have reported that pancreas allograft survival is not affected by preservation in histidine-tryptophan-ketoglutarate (HTK) versus University of Wisconsin (UW) solution. To expand on these studies, we analyzed the United Network for Organ Sharing (UNOS) database of pancreas transplants from July 2004, through February 2008, to determine if preservation with HTK (N = 1081) versus UW (N = 3311) impacted graft survival. HTK preservation of pancreas allografts increased significantly in this time frame, from 15.4% in 2004 to 25.4% in 2008. After adjusting for other recipient, donor, graft and transplant center factors that impact graft survival, HTK preservation was independently associated with an increased risk of pancreas graft loss (hazard ratio [HR] 1.30, p = 0.014), especially in pancreas allografts with cold ischemia time (CIT) ,12 h (HR 1.42, p = 0.017). This reduced survival with HTK preservation as compared to UW preservation was seen in both simultaneous pancreas-kidney (SPK) transplants and pancreas alone (PA) transplants. Furthermore, HTK preservation was also associated with a 1.54-fold higher odds of early (<30 days) pancreas graft loss as compared to UW (OR 1.54, p = 0.008). These results suggest that the increasing use of HTK for abdominal organ preservation should be re-examined. [source] Outcome in Cardiac Recipients of Donor Hearts With Increased Left Ventricular Wall ThicknessAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2007S. S. Kuppahally The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT ,1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 ± 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT , 1.4 cm. By Cox regression, donor LVWT > 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients. [source] Modelling impacts of long-line fishing: what are the effects of pair-bond disruption and sex-biased mortality on albatross fecundity?ANIMAL CONSERVATION, Issue 4 2005Michael S. L. Mills Long-line fishing mortality poses a significant threat to many large procellariiform seabirds. To date, estimates of impacts have concentrated on lower survival rates, largely ignoring the costs to fecundity resulting from disruption of breeding pairs and skews in sex ratio. A comparative, stochastic, individual-based model was used to investigate these costs for the wandering albatross Diomedea exulans. Ignoring the time taken to replace a lost mate overestimates fecundity by 13,18%, resulting in annual population growth rates (,) being 0.006,0.007 too high. Long-line mortality exacerbates this cost, which becomes more substantial with increasing demographic skew resulting from female-biased mortality. At moderate levels of long-line mortality (2,4% per year), 80% female-biased mortality reduces fecundity by 9,27% and , by 0.003,0.010 relative to models with random mortality. Biased sex ratios accumulate and, unlike reduced survival, their impacts on albatross demography persist after long-line mortality ceases. Estimates of the demographic costs of long-line mortality should incorporate individual-level effects, especially where mortality is sex-biased. [source] Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomasAPMIS, Issue 11 2003HELGA B. SALVESEN Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours. [source] Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: Impact of interstitial lung diseaseARTHRITIS & RHEUMATISM, Issue 2 2009Stephen C. Mathai Objective Pulmonary hypertension (PH) is an important cause of mortality in systemic sclerosis (SSc), where it can be isolated (pulmonary arterial hypertension [PAH]) or associated with interstitial lung disease (ILD). This study was undertaken to characterize determinants of survival among SSc patients with either type of PH who received PAH-specific therapy. Methods Consecutive SSc patients with PAH or ILD-associated PH confirmed by right heart catheterization were included in the study. Kaplan-Meier and Cox proportional hazards models were used to compare survival between SSc patients with PAH and those with ILD-associated PH and to identify predictors of survival. Results Fifty-nine patients (39 with PAH and 20 with ILD-associated PH) were identified. The majority (15 of 20 with ILD-associated PH and 27 of 39 with PAH) received an endothelin receptor antagonist as initial therapy. Median followup time was 4.4 years (range 2.7,7.4 years). Survival was significantly worse in SSc patients with ILD-associated PH than in those with PAH (1-, 2-, and 3-year survival rates 82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank test). In a multivariable analysis, ILD-associated PH was associated with a 5-fold increase in risk of death compared with PAH. Pulmonary vascular resistance index was also an independent predictor of mortality in the overall cohort (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in each group separately. Type of initial PAH therapy and the use of warfarin were not related to survival. Conclusion Survival in SSc complicated by PH remains poor despite currently available treatment options. While therapy may be associated with improved survival in PAH compared with historical controls, the prognosis for patients with ILD-associated PH is particularly grim. Early diagnosis and treatment may improve outcomes since worsening hemodynamic factors were associated with reduced survival. [source] Bone marrow cyclooxygenase-2 levels are elevated in chronic-phase chronic myeloid leukaemia and are associated with reduced survivalBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2002Francis J. Giles Summary., Increased angiogenesis is important in the pathophysiology of haematological malignancies. Cyclooxygenase-2 (Cox-2) converts arachidonic acid to prostaglandins, which induce expression of angiogenic factors, including vascular endothelial growth factor (VEGF), basic-fibroblast growth factor, transforming growth factor-, and interleukin 6. Cox-2 may also reduce apoptosis and reduce cellular attachment to the extracellular matrix (ECM). Increased bone marrow (BM) vascularity, increased BM cellular and plasma VEGF levels, and decreased progenitor adherence to BM ECM have all been observed in chronic myeloid leukaemia (CML). We investigated the prognostic significance of levels of Cox-2 in BM cells from patients with CML. Western blot and solid-phase radioimmunoassay (RIA) were used to measure Cox-2 BM levels in 149 patients with chronic phase CML (CP CML). Results were compared with those of normal controls. Expression of Cox-2 was significantly higher in CML than in normal controls (P < 0·0001). Increasing levels of Cox-2 were significantly associated with shorter survival (P = 0·0002, Cox proportional hazard model). A multivariate model based on Cox-2 and degree of splenomegaly was developed for survival in patients with early CP CML. Agents that inhibit Cox-2 activity merit investigation in patients with CP CML. [source] High preoperative prevalence of deep venous thrombosis in patients with colorectal cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 9 2007M. T. Stender Background: Deep venous thrombosis (DVT) is a major complication of cancer and a predictor of reduced survival. The postoperative prevalence of DVT in colorectal cancer surgery is high, but the preoperative prevalence is unknown. The aim of this observational study was to estimate the preoperative prevalence of DVT in patients with colorectal cancer. Methods: Some 193 consecutive patients with newly diagnosed colorectal cancer admitted for intended curative surgery were examined with compression ultrasonography for DVT before surgery. Results: DVT was detected in 15 (7·8 per cent) of the 193 patients, with a prevalence of 16 per cent in women (12 of 76) versus 2·6 per cent in men (three of 117 (adjusted odds ratio (OR) 5·8 (95 per cent confidence interval (c.i.) 1·4 to 23·2)). The risk of DVT was strongly correlated with increasing American Society of Anesthesiologists (ASA) risk score: adjusted OR 6·8 (95 per cent c.i. 1·6 to 28·7 for ASA group III or IV versus ASA group I or II). Pulmonary embolism was detected in two patients (1·0 per cent). Conclusion: A high preoperative prevalence of DVT was observed in patients with colorectal cancer, especially among women and patients in ASA groups III and IV. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumorsCANCER, Issue 8 2005Variables affecting response rates, survival Abstract BACKGROUND The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE) or chemoembolization (HACE). METHODS Patients with metastatic neuroendocrine tumors who underwent HAE or HACE were included in this retrospective study. Follow-up imaging studies were compared with baseline imaging to determine the radiologic response. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan,Meier method. Univariate and multivariate analyses were performed to assess the prognostic variables that affected response and survival. RESULTS The study included 69 patients with carcinoid tumors and 54 patients with pancreatic islet cell carcinomas. Patients who had carcinoid tumors had a higher response rate (66.7% vs. 35.2%; P = 0.0001) and had longer PFS (22.7 mos vs. 16.1 mos; P = 0.046) and OS (33.8 mos vs. 23.2 mos; P = 0.012) compared with patients who had islet cell carcinomas. For patients with carcinoid tumors, multivariate analysis identified male gender as the only independent risk factor for poor survival (P = 0.05). Octreotide was predictive marginally for PFS (P = 0.06). Patients who were treated with HAE had a higher response rate than patients who were treated with HACE (P = 0.004). For patients with islet cell carcinoma, an intact primary tumor, , 75% liver involvement, and extrahepatic metastases were associated with reduced OS in the univariate analysis; the presence of bone metastases was the only risk factor (P = 0.031) in the multivariate analysis. Patients who were treated with HACE had a prolonged OS (31.5 mos vs. 18.2 mos) and improved response (50% vs. 25%) compared with patients who were treated with HAE, although the differences did not reach statistical significance. CONCLUSIONS Patients with carcinoid tumors had better outcomes than patients with islet cell carcinomas. The addition of intraarterial chemotherapy to HAE did not improve the outcome of patients with carcinoid tumors, but it seemed to benefit patients with islet cell carcinomas. In patients who had carcinoid tumors, male gender predicted a poor outcome, and a trend toward prolonged PFS was observed in patients who received concomitant octreotide. An intact primary tumor, extensive liver disease, and bone metastases were associated with reduced survival in patients with islet cell carcinomas. Cancer 2005. © 2005 American Cancer Society. [source] Prognostic factors in patients with Hürthle cell neoplasms of the thyroidCANCER, Issue 5 2003Luis Lopez-Penabad M.D. Abstract BACKGROUND Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy. Cancer 2003;97:1186,94. © 2003 American Cancer Society. DOI 10.1002/cncr.11176 [source] | ||||||||||||||||||||||||||||