tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Mortality and Readmission of Patients With Heart Failure, Atrial Fibrillation, or Coronary Artery Disease Undergoing Noncardiac Surgery: An Analysis of 38 047 Patients”
Authors: Sean van Diepen, Justin A. Ezekowitz, Jeffrey A. Bakal, Finlay A. McAlister
Journal: Circulation (2012)

Patients"We thank Drs Chatterjee and Chakraborty for their insightful comments.We acknowledge that studies on the general epidemiology of heart failure demonstrate that patients with an ischemic pathogenesis for heart failure have a worse prognosis than those with nonischemic heart failure; however, there are few publications that explore this relationship in the perioperative setting.A cohort from the United States with the use of administrative data reported no difference in perioperative outcomes between ischemic heart failure and nonischemic heart failure patients. 1Our study used up to 13 years of inpatient and procedural administrative data, rather than a single data source, to create our ischemic heart failure and nonischemic heart failure cohorts. 2 We hypothesize this observed difference may be explained, in part, by the comprehensive methods used to separate the ischemic heart failure and nonischemic heart failure cohorts in our study.Irrespective of this difference, our study adds to evidence that patients with heart failure are at increased risk of adverse perioperative outcomes.Information regarding perioperative ␤-blocker management, heart rhythm, heart rate, or blood pressure control is not available in our dataset, and to date this has not been extensively studied as to the relative risks, benefits, or harms of any of these items.Finally, our dataset does not distinguish between paroxysmal or permanent atrial fibrillation, nor does it include patients with nonhospitalized atrial fibrillation.We believe that this question merits future evaluation in a dataset with these additional data points.
Abstract 1325: Organ, species and sex differences in mutagenesis induced by butyl-hydroxybutyl-N-nitrosamine in big blue transgenic rodents as the basis for the strict organ specificity of this environmental carcinogen metabolite
Authors: Zhiming He, Zhong-Lin Zhao Strasberg-Rieber, Wieslawa Kosinska, Xue-Ru Wu, Joseph B. Guttenplan
Journal: Cancer Research (2011)

Abstract Although butyl-hydroxybutyl-N-nitrosamine (BBN) is a powerful carcinogen that specifically causes bladder cancer in rodents, the reason for such a high degree of organ specificity is unclear. Mutagenesis induced by BBN in a chromosomally incorporated mutagenesis reporter gene was measured in bladder urothelial cells and smooth muscle cells of mice or rats and compared with mutagenesis in liver, kidney, ureter and forestomach. BBN was administered as a 0.05% solution in water for 2 weeks followed by 4 weeks of water to 6 male and female mice and 4 male rats. All animals were euthanized at 6 weeks. Since mutagenesis in the reporter gene is a surrogate for mutagenesis in general, we hypothesized that mutations also induced in critical growth control genes would contribute to the tumor formation induced by BBN. The mutant fractions in urothelial cells were: 257 +/- 25 mutants / 105 pfu for male mice, 276 +/- 43 for female mice and 54 +/- 6 for rats. In contrast, the mutant fractions in bladder smooth muscle cells were 8-9 fold lower than these values in all animals. In non-bladder tissues such as liver, kidney, ureter and forestomach, the mutant fractions were between 2 and 5 mutants / 105 pfu, a level comparable to the control groups without BBN treatment. Hence mutagenesis correlated extremely well with the organ specificity for cancer induction by BBN. Additionally, mutagenesis level was found to be significantly higher in mice than in rats, consistent with the fact that BBN is a much more potent bladder carcinogen in mice. Finally, no significant difference in mutagenicity of BBN between male and female mice was observed, suggesting that post-initiation processes may be responsible for the gender difference in bladder tumor susceptibility. BBN is a primary metabolite of the environmental carcinogen, dibutylnitrosamine and hence a potential human carcinogen. These results provide molecular explanations to the bewildering organ and species specificity of BBN, and indicate that BBN-induced mutagenesis in the urinary bladder represents a highly appropriate model for initiation of bladder cancer, and combined with other models can help elucidate distinct steps in bladder carcinogenesis. Supported by an NYU Centers of Excellence Seed Grant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1325. doi:10.1158/1538-7445.AM2011-1325
Impact of Screening Colonoscopy on Outcomes in Colon Cancer Surgery
Authors: Ramzi Amri, Liliana G. Bordeianou, Patricia Sylla, David L. Berger
Journal: JAMA Surgery (2013)

Screening colonoscopy seemingly decreases colorectal cancer rates in the United States. In addition to removing benign lesions and preventing progression to malignancy, screening colonoscopy theoretically identifies asymptomatic patients with early-stage disease, potentially leading to higher survival rates.To assess the effect of screening colonoscopy on outcomes of colon cancer surgery by reviewing differences in staging, disease-free interval, risk of recurrence, and survival and to identify whether diagnosis through screening improves long-term outcomes independent of staging.Retrospective review of prospectively maintained, institutional review board-approved database.Tertiary care center with high patient volume.All patients who underwent colon cancer surgery at Massachusetts General Hospital from January 1, 2004, through December 31, 2011.Colon cancer surgery.Postoperative staging, death, and recurrence, measured as incidence and time to event.A total of 1071 patients were included, with 217 diagnosed through screening. Patients not diagnosed through screening were at risk for a more invasive tumor (≥T3: relative risk [RR] = 1.96; P < .001), nodal disease (RR = 1.92; P < .001), and metastatic disease on presentation (RR = 3.37; P < .001). In follow-up, these patients had higher death rates (RR = 3.02; P < .001) and recurrence rates (RR = 2.19; P = .004) as well as shorter survival (P < .001) and disease-free intervals (P < .001). Cox and logistic regression controlling for staging and baseline characteristics revealed that death rate (P = .02) and survival duration (P = .01) were better stage for stage with diagnosis through screening. Death and metastasis rates also remained significantly lower in tumors without nodal or metastatic spread (all P < .001).Patients with colon cancer identified on screening colonoscopy not only have lower-stage disease on presentation but also have better outcomes independent of their staging. Compliance to screening colonoscopy guidelines can play an important role in prolonging longevity, improving quality of life, and reducing health care costs through early detection of colon cancer.
Response to Fukui et al.
Authors: Oral Öncül, Cihan Top, Saban Cavuslu
Journal: Diabetes Care (2002)

In response to the letter by Fukui et al. (1) in this issue of Diabetes Care , we first must comment on the possible interaction between leptin and insulin, independent of body fatness. Leptin is mainly an adipocyte-secreted protein. Leptin, the obese ( ob ) gene product, is an adipose tissue hormone that has been closely linked to the amount of body-fat stores. Most of the research following the discovery of leptin was focused on the role it plays in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more data are emerging that show that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function in metabolism, as well as in normal sexual maturation and reproduction. Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation. A possible interaction between leptin and insulin was first suggested by the …
Adoptive Transfer of Type 1 CTL Mediates Effective Anti–Central Nervous System Tumor Response: Critical Roles of IFN-Inducible Protein-10
Authors: Fumihiko Nishimura, Jill E. Dusak, Junichi Eguchi, Xinmei Zhu, Andrea Gambotto, Walter J. Storkus, Hideho Okada
Journal: Cancer Research (2006)

Abstract The development of effective immunotherapeutic strategies for central nervous system (CNS) tumors requires a firm understanding of factors regulating the trafficking of tumor antigen–specific CTLs into CNS tumor lesions. Using C57BL/6 mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1 or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor–transgenic OT-1 mice. We also tested our hypothesis that intratumoral (i.t.) delivery of dendritic cells that had been transduced with IFN-α cDNA (DC-IFN-α) would enhance the tumor-homing and antitumor effectiveness of adoptively transferred Tc1 via induction of an IFN-γ-inducible protein 10 (IP-10). In vitro, DC-IFN-α induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1. In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. M05 and mediated antitumor responses more effectively than Tc2, and their effect was IP-10 dependent. I.t. injections of DC-IFN-α remarkably enhanced the tumor homing, therapeutic efficacy, and in situ IFN-γ production of i.v. delivered Tc1, resulting in the long-term survival and persistence of systemic ovalbumin-specific immunity. These data suggest that Tc1-based adoptive transfer therapy may represent an effective modality for CNS tumors, particularly when combined with strategies that promote a type 1 polarized tumor microenvironment. (Cancer Res 2006; 66(8): 4478-87)
Perforin-Mediated Target Cell Lysis by Cytolytic T Lymphocytes
Authors: Jürg Tschopp, Markus Nabholz
Journal: Annual Review of Immunology (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Factors Affecting the Errors in the Estimation of Evolutionary Distances Between Sequences
Authors: D. C. Hoyle, P. G. Higgs
Journal: Molecular Biology and Evolution (2003)

Phylogenetic methods that use matrices of pairwise distances between sequences (e.g., neighbor joining) will only give accurate results when the initial estimates of the pairwise distances are accurate. For many different models of sequence evolution, analytical formulae are known that give estimates of the distance between two sequences as a function of the observed numbers of substitutions of various classes. These are often of a form that we call "log transform formulae". Errors in these distance estimates become larger as the time t since divergence of the two sequences increases. For long times, the log transform formulae can sometimes give divergent distance estimates when applied to finite sequences. We show that these errors become significant when t ∼ 1/2 |λmax|−1 logN, where λmax is the eigenvalue of the substitution rate matrix with the largest absolute value and N is the sequence length. Various likelihood-based methods have been proposed to estimate the values of parameters in rate matrices. If rate matrix parameters are known with reasonable accuracy, it is possible to use the maximum likelihood method to estimate evolutionary distances while keeping the rate parameters fixed. We show that errors in distances estimated in this way only become significant when t ∼ 1/2 |λ1|−1 logN, where λ1 is the eigenvalue of the substitution rate matrix with the smallest nonzero absolute value. The accuracy of likelihood-based distance estimates is therefore much higher than those based on log transform formulae, particularly in cases where there is a large range of timescales involved in the rate matrix (e.g., when the ratio of transition to transversion rates is large). We discuss several practical ways of estimating the rate matrix parameters before distance calculation and hence of increasing the accuracy of distance estimates.
Adherence to CONSORT Adverse Event Reporting Guidelines in Randomized Clinical Trials Evaluating Systemic Cancer Therapy: A Systematic Review
Authors: Julien Péron, Denis Maillet, Hui K. Gan, Eric X. Chen, Benoit You
Journal: Journal of Clinical Oncology (2013)

Purpose The Consolidated Standards of Reporting Trials (CONSORT) guidance was extended in 2004 to provide a set of 10 specific and comprehensive guidelines regarding adverse event (AE) reporting in randomized clinical trials (RCTs). Limited data exist regarding adherence to these guidelines in publications of oncology RCTs. Methods All phase III RCTs published between 2007 and 2011 were reviewed using a 16-point AE reporting quality score (AERQS) based on the 2004 CONSORT extension. Multivariable linear regression was used to identify features associated with improved reporting quality. Results A total of 325 RCTs were reviewed. The mean AERQS was 10.1 on a 16-point scale. The most common items that were poorly reported were the methodology of AE collection (adequately reported in only 10% of studies), the description of AE characteristics leading to withdrawals (15%), and whether AEs are attributed to trial interventions (38%). Even when reported, the methods of AE collection and analysis were highly heterogeneous. The multivariable regression model revealed that industry funding, intercontinental trials, and trials in the metastatic setting were predictors of higher AERQS. The quality of AE reporting did not improve significantly over time and was not better among articles published in journals with a high impact factor. Conclusion Our findings show that some methodologic aspects of AE collection and analysis were poorly reported. Given the importance of AEs in evaluating new treatments, authors should be encouraged to adhere to the 2004 CONSORT guidelines regarding AE reporting.
Activating Transcription Factor 3 Confers Protection against Ventilator-induced Lung Injury
Authors: Ali Akram, Bing Han, Hussain Masoom, Claudia Peng, Emily Lam, Michael L. Litvack, Xiaohui Bai, Yuexin Shan, Tsonwin Hai, Jane Batt, Arthur S. Slutsky, Haibo Zhang, Wolfgang M. Kuebler, Jack J. Haitsma, Mingyao Liu, Claudia C. dos Santos
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Ventilator-induced lung injury (VILI) significantly contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury. Understanding the molecular basis for response to cyclic stretch (CS) and its derangement during high-volume ventilation is of high priority.Objectives: To identify specific molecular regulators involved in the development of VILI.Methods: We undertook a comparative examination of cis-regulatory sequences involved in the coordinated expression of CS-responsive genes using microarray analysis. Analysis of stretched versus nonstretched cells identified significant enrichment for genes containing putative binding sites for the transcription factor activating transcription factor 3 (ATF3). To determine the role of ATF3 in vivo, we compared the response of ATF3 gene–deficient mice to wild-type mice in an in vivo model of VILI.Measurements and Main Results: ATF3 protein expression and nuclear translocation is increased in the lung after mechanical ventilation in wild-type mice. ATF3-deficient mice have greater sensitivity to mechanical ventilation alone or in conjunction with inhaled endotoxin, as demonstrated by increased cell infiltration and proinflammatory cytokines in the lung and bronchoalveolar lavage, and increased pulmonary edema and indices of tissue injury. The expression of stretch-responsive genes containing putative ATF3 cis-regulatory regions was significantly altered in ATF3-deficient mice.Conclusions: ATF3 deficiency confers increased sensitivity to mechanical ventilation alone or in combination with inhaled endotoxin. We propose ATF3 acts to counterbalance CS and high volume–induced inflammation, dampening its ability to cause injury and consequently protecting animals from injurious CS.
Experimental Malaria: Recurrence after Nine Months
Authors: P. T. Manson
Journal: BMJ (1901)

Dr. Eustace Talbot reported two cases of haemorrhage into the suprarenal capsules in the St. Bartholomew's Hospital -Reports for i9oo, in which he also refers to two cases reported by Drs.Andrews, Garrod, and Drysdale in the Pathological Society's Transactions for I898.These four cases were all un- vaccinated, were apparently healthy children, suddenly taken ill, with a rapid and fatal termination.Subcutaneous hlemorrhages occurred in the two latter cases only, and convulsions seem to have been a prominent symptom in the two cases reported by Dr. Talbot.It will be noted that in our cases no convulsions occurred.The only morbid changes found post mortem, in all these four cases was haemorrhage into the supra- renal capsules, all the other organs being apparentlyhealthy.In conclusion, we desire to express our gratitude to Drs.Eustace Smith and J. A.
Mechanical Ventilation Protects against Diaphragm Injury in Sepsis
Authors: SATORU EBIHARA, SABAH N. A. HUSSAIN, GAWIYOU DANIALOU, WON-KYUNG CHO, STEWART B. GOTTFRIED, BASIL J. PETROF
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Overproduction of nitric oxide (NO) with attendant oxidative and nitrosative stress has been implicated in sepsis-induced diaphragm dysfunction. Here we determined the impact of controlled mechanical ventilation (MV) on rat diaphragm sarcolemmal injury, inducible NO synthase (iNOS) expression, and oxidative stress during endotoxemia. At 4 h after injection of endotoxin, impaired sarcolemmal integrity and decreased force production by the diaphragm were observed in spontaneously breathing rats. The use of MV during endotoxemia largely eliminated sarcolemmal damage and significantly improved diaphragm force production. These benefits were not associated with alterations in either iNOS expression or protein carbonyls (marker of oxidation), which remained abnormally elevated in septic diaphragms despite MV. Therefore, we hypothesized that the protection afforded by MV was due to its ability to decrease the level of mechanical stress placed on the sarcolemma, because the latter could be hyperfragile in the setting of increased oxidative stress. Using an in vitro system to independently modulate oxidative and mechanical stresses, we confirmed that these two factors act together in a synergistic fashion to favor sarcolemmal injury. Accordingly, our data suggest that MV protects the diaphragm during sepsis by abrogating an injurious interaction between oxidative and biomechanical stresses imposed on the sarcolemma.
Effectiveness of a Short Message Reminder in Increasing Compliance with Pediatric Cataract Treatment
Authors: Haotian Lin, Weirong Chen, Lixia Luo, Nathan Congdon, Xinyu Zhang, Xiaojian Zhong, Zhaochuan Liu, Wan Chen, Changrui Wu, Danying Zheng, Daming Deng, Shaobi Ye, Zhuoling Lin, Xia Zou, Yizhi Liu
Journal: Ophthalmology (2012)
Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis
Authors: Bruce A. Runyon
Journal: Hepatology (1988)

To assess the risk of development of spontaneous bacterial peritonitis in relation to ascitic fluid opsonic activity, routine admission abdominal paracentesis was performed on 119 patients during 141 hospitalizations. Paracentesis was repeated if evidence of peritonitis developed during the hospitalization. The ascitic fluid opsonic activity (0.2 +/- 0.5 log kill) of 24 spontaneously infected specimens was significantly (p less than 0.001) lower than that of the group with sterile portal hypertension-related ascites (0.8 +/- 1.1 log kill), and significantly lower than the group with ascites of miscellaneous type (2.4 +/- 1.0 log kill, p less than 0.001). The C3 and C4 concentrations of the spontaneous peritonitis specimens were also significantly lower than in the specimens from the other groups. Of the 55 patients whose initial sterile ascitic fluid opsonic activity was less than 0.2 log kill, 8 (14.5%) developed spontaneous bacterial peritonitis during the hospitalization; whereas none of the 70 patients with sterile ascitic fluid opsonic activity greater than or equal to 0.2 log kill developed spontaneous peritonitis. This difference in the risk of development of peritonitis was significant (p less than 0.01). Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.
Subcellular distribution of endogenous long chain acylcarnitines during hypoxia in adult canine myocytes
Authors: J. McHowat, K. A Yamada, J. E Saffitz, P. B Corr
Journal: Cardiovascular Research (1993)

Objective: Previous studies from our laboratory showed a pronounced increase in the sarcolemmal accumulation of long chain acylcarnitines in isolated neonatal rat myocytes after a prolonged (60 minute) hypoxic interval. Because much shorter intervals of hypoxia are associated with electrophysiological alterations in adult cells, the present study was performed to assess the extent of sarcolemmal accumulation of long chain acylcarnitines during hypoxia in adult canine myocytes. Methods: Cells were incubated (for 24 hours) with 3H-carnitine and the uniformity of incorporation into carnitine fractions was verified biochemically. Cells were exposed to hypoxia (Po2<15 mm Hg) for 10 or 20 minutes in the presence or absence of sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA; 10 μM), an inhibitor of carnitine acyltransferase I. Cells were processed for electron microscopical autoradiography with a technique to spatially fix endogenous long chain acylcarnitines with selective and complete removal of short chain and free carnitine. Grain distributions were analysed by the maximum likelihood method from digitised micrographs. Results: Total mass of long chain acylcarnitines increased ninefold [42.3(3.3) to 374(42) pmol·mg−1 protein] by 10 minutes of hypoxia and 15-fold [to 632(36) nmol·mg−1 protein] by 20 minutes of hypoxia. Normoxic cells exhibited little long chain acylcarnitines in the sarcolemma, and modest amounts in mitochondria and cytoplasm. In hypoxic cells, content of long chain acylcarnitines in mitochondria and cytoplasm increased by a maximum of twofold. By contrast, long chain acylcarnitines increased 100-fold in the sarcolemma to 4.18×106 molecules·μm−3 after 10 minutes of hypoxia. The increase in long chain acylcarnitines with hypoxia was completely prevented by pretreatment with POCA. Conclusion: Hypoxia in adult ventricular myocytes induces a rapid and preferential increase in endogenous long chain acylcarnitines within the sarcolemma. Cardiovascular Research 1993;27:1237-1243