tbuckley/cabot-search huggingface dataset:
Introduction of Surgical Safety Checklists in Ontario, Canada
Authors: David R. Urbach, Anand Govindarajan, Refik Saskin, Andrew S. Wilton, Nancy N. Baxter
Journal: New England Journal of Medicine (2014)

Evidence from observational studies that the use of surgical safety checklists results in striking improvements in surgical outcomes led to the rapid adoption of such checklists worldwide. However, the effect of mandatory adoption of surgical safety checklists is unclear. A policy encouraging the universal adoption of checklists by hospitals in Ontario, Canada, provided a natural experiment to assess the effectiveness of checklists in typical practice settings.We surveyed all acute care hospitals in Ontario to determine when surgical safety checklists were adopted. Using administrative health data, we compared operative mortality, rate of surgical complications, length of hospital stay, and rates of hospital readmission and emergency department visits within 30 days after discharge among patients undergoing a variety of surgical procedures before and after adoption of a checklist.During 3-month periods before and after adoption of a surgical safety checklist, a total of 101 hospitals performed 109,341 and 106,370 procedures, respectively. The adjusted risk of death during a hospital stay or within 30 days after surgery was 0.71% (95% confidence interval [CI], 0.66 to 0.76) before implementation of a surgical checklist and 0.65% (95% CI, 0.60 to 0.70) afterward (odds ratio, 0.91; 95% CI, 0.80 to 1.03; P=0.13). The adjusted risk of surgical complications was 3.86% (95% CI, 3.76 to 3.96) before implementation and 3.82% (95% CI, 3.71 to 3.92) afterward (odds ratio, 0.97; 95% CI, 0.90 to 1.03; P=0.29).Implementation of surgical safety checklists in Ontario, Canada, was not associated with significant reductions in operative mortality or complications. (Funded by the Canadian Institutes of Health Research.).
THE PATHOGENESIS OF HYPERTENSION INDUCED BY RENAL CONSTRICTION
Authors: L. J. Rather
Journal: The Journal of Experimental Medicine (1950)

Blood pressures were determined on forty-two young male albino rats and a basal level established. The rats were then divided into four groups and subjected to one of the following operations: (a) unilateral nephrectomy with exposure and handling of the opposite kidney; (b) unilateral nephrectomy and constriction of the remaining kidney with a silk figure-of-eight ligature; (c) unilateral renal constriction with a silk figure-of-eight ligature, the other kidney being left intact after exposure and handling; (d) unilateral nephrectomy and removal of the poles of the contralateral kidney (three-quarters nephrectomy). The animals were followed for 50 days, during which blood pressures were measured on twenty occasions, then killed by exsanguination under ether anesthesia. The organs were weighed according to a standardized procedure and studied histologically. Individual determinations of serum creatinine and of the hematocrit levels were made. Mean lines and frequency distributions of blood pressure were subjected to statistical analysis. A definitely significant increase in blood pressure developed in the group subjected to operation (b) within 4 days postoperative. In none of the other groups did hypertension develop. Analysis of the individual renal weights and creatinine levels indicates the independence of the development of hypertension from the total mass of functioning renal tissue. Nor is it dependent on the prevention of renal hypertrophy or the presence of fibrous perinephritis. The effect is probably due to the production of a disturbance of hemodynamics or tissue tension with the liberation of a pressor substance by the injured kidney.
Type 2 Diabetes and the Risk of Renal Cell Cancer in Women
Authors: Hee-Kyung Joh, Walter C. Willett, Eunyoung Cho
Journal: Diabetes Care (2011)

Type 2 diabetes is associated with increased risks of several types of cancer; however, its relationship to renal cell cancer remains unclear.A total of 118,177 women aged 30 to 55 years at baseline (1976) were followed up through 2008 in the Nurses' Health Study. Self-reports of physician-diagnosed diabetes were collected at baseline and updated biennially. Hazard ratios (HRs) were calculated using Cox proportional hazards models with adjustment for age, BMI, hypertension, smoking, and parity.During 32 years of follow-up (3,531,170 person-years), 16,819 cases of type 2 diabetes and 330 cases of pathology-confirmed incident renal cell cancer were documented. After multivariate adjustment, type 2 diabetes was significantly associated with an increased risk of renal cell cancer (HR 1.60 [95% CI 1.19-2.17]). These associations were consistent across different strata of BMI, smoking, and hypertension (Pinteraction≥0.32). The risk of renal cell cancer increased with an increasing number of comorbidities, including obesity, hypertension, and type 2 diabetes (Ptrend<0.001). When compared with women without any comorbidity, women who had all three conditions had a HR of 4.13 (2.76-6.18) for renal cell cancer.Type 2 diabetes is independently associated with an increased risk of renal cell cancer in women. In addition, comorbidity of obesity, hypertension, and type 2 diabetes substantially elevates the risk of renal cell cancer.
Age at Development of Type 1 Diabetes– and Celiac Disease–Associated Antibodies and Clinical Disease in Genetically Susceptible Children Observed From Birth
Authors: Satu Simell, Sanna Hoppu, Tuu Simell, Marja-Riitta Ståhlberg, Markku Viander, Taina Routi, Ville Simell, Riitta Veijola, Jorma Ilonen, Heikki Hyöty, Mikael Knip, Olli Simell
Journal: Diabetes Care (2010)

OBJECTIVE To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND METHODS We observed 2,052 children carrying genetic risks for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease–associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by World Health Organization criteria and celiac disease by duodenal biopsies. RESULTS Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease–associated antibody at the median ages of 3.0 and 1.5 years, respectively (P &amp;lt; 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease–associated antibodies, 3 progressed to both diabetes and celiac disease. CONCLUSIONS Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease–associated antibodies mostly at a younger age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.
Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study
Authors: Martin H Brutsche, Ingrid Carlen Brutsche, Mohamed Munawar, Stephen J Langley, Catherine M Masterson, Peter T Daley-Yates, Ronan Brown, Adnan Custovic, Ashley Woodcock
Journal: The Lancet (2000)
The impact of match-play tennis in a hot environment on indirect markers of oxidative stress and antioxidant status
Authors: Wade L Knez, JP Périard
Journal: British Journal of Sports Medicine (2014)

The purpose of this study was to determine the impact of changes in oxidative stress and antioxidant status in response to playing tennis in HOT (∼36°C and 35% relative humidity (RH)) and COOL (∼22°C and 70% RH) conditions.10 male tennis players undertook two matches for an effective playing time (ie, ball in play) of 20 min, corresponding to ∼122 and ∼107 min of total play in HOT and COOL conditions, respectively. Core body temperature, body mass and indirect markers of oxidative stress (diacrons reactive oxygen metabolic test) and antioxidant status (biological antioxidant potential test) were assessed immediately prematch, midmatch and postmatch, and 24 and 48 h into recovery.Regardless of the condition, oxidative stress remained similar throughout play and into recovery. Likewise, match-play tennis in the COOL had no impact on antioxidant status. However, antioxidants status increased significantly in the HOT compared with COOL environment (p<0.05). Body mass losses (∼0.5 kg) were similar between conditions. Rectal temperature increased during both matches (p<0.05), but with a greater magnitude in the HOT (39.3±0.5°C) versus COOL (38.7±0.2°C) environment (p<0.05).Match-play tennis in the heat does not exacerbate the development of oxidative stress, but significantly increases antioxidant status. These data suggest that the heat stress observed in the HOT environment may provide a necessary signal for the upregulation of antioxidant defence, dampening cellular damage.
Urokinase Plasminogen Activator Receptor (uPAR) Targeted Nuclear Imaging and Radionuclide Therapy
Authors: Dan Li, Shuanglong Liu, Hong Shan, Peter Conti, Zibo Li
Journal: Theranostics (2013)

Urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein.Besides regulating proteolysis, uPAR could also activate many intracellular signaling pathways that promote cell motility, invasion, proliferation, and survival through cooperating with transmembrane receptors.uPAR is overexpressed across a variety of tumors and is associated with cancer invasion and metastasis.In order to meet the demand for a rapid development and potential clinical application of anti-cancer therapy based on uPA/uPAR system, it is desirable to develop non-invasive imaging methods to visualize and quantify uPAR expression in vivo.In this review, we will discuss recent advances in the development of uPAR-targeted nuclear imaging and radionuclide therapy agents.The successful development of molecular imaging probes to visualize uPAR expression in vivo would not only assist preclinical researches on uPAR function, but also eventually impact patient management.
Dehydroepiandrosterone in the treatment of steroid resistant asthma: Whether synthetic nanoform can replace the natural hormone?
Authors: Galina Shmarina, Alexander Pukhalsky, Anastasia Utekhina, Gleb Sergeev, Olga Kozyreva, Tamara Vylegzhanina, Vladimir Alioshkin
Journal: European Respiratory Journal (2013)

Efficiency of dehydroepiandrosterone (DHEA) in asthma treatment has been recently shown in multicenter randomized, placebo-controlled trial [1]. But the poor solubility of DHEA and its metabolites restrains the progress in this area. The problem may be resolved by the synthesis of nanoparticles of the hormone using the methods of cryochemical synthesis. The aim of this study was to evaluate peripheral blood lymphocyte (PBL) sensitivity to antiproliferative effect of Dexamethasone (Dx) and DHEA metabolites in asthmatic patients resistant to steroid therapy. Individual PBL susceptibility to Dx and DHEA metabolites including androstendiol (ADL), ADL in the form of nanoparticles (nADL), and β-thiol was evaluated by ED 50  calculation. PBL from both sensitive and resistant patients were investigated. Susceptibility to Dx of sensitive cells was high (ED 50 =8.9 nM); ED 50  for resistant patient was impossible to calculate. However, the cells obtained from resistant patients were sensitive to DHEA metabolites (Table).  The data show that DHEA metabolites reveal high anti-proliferative activity against human PBL including the cells isolated from steroid resistant asthmatic patients. Anti-proliferative activities of nADL and β-thiol (the most active but unstable DHEA metabolite) were comparable. It has been noted that nanophorm of the hormone demonstrated higher activity than natural metabolite. Such effect may be explained by the greater bioavailability of nADL.  References:  1. Wenzel et al. Allergy Asthma Proc. 2010; 31:461-471.
Atypical teratoid/rhabdoid tumor evolving from an optic pathway ganglioglioma: Case study1
Authors: Jeffrey C. Allen, Alexander R. Judkins, Marc K. Rosenblum, Jaclyn A. Biegel
Journal: Neuro-Oncology (2006)

We report an atypical teratoid/rhabdoid tumor arising in a ganglioglioma from an 11-year-old male who had been treated over a nine-year period.A combined histologic, immunohistochemical, and molecular genetic analysis confirmed this diagnosis.Molecular genetic studies demonstrated a mutation in exon 9 of the INI1 gene in the tumor, which was not present in the patient's blood.This report is the first to describe progression of a ganglioglioma to atypical teratoid/rhabdoid tumor.
ARC Inhibits Cytochrome <i>c</i> Release From Mitochondria and Protects Against Hypoxia-Induced Apoptosis in Heart-Derived H9c2 Cells
Authors: Daryoush Ekhterae, Zhiwu Lin, Martha S. Lundberg, Michael T. Crow, Frank C. Brosius, Gabriel Núñez
Journal: Circulation Research (1999)

Abstract —Ischemia induces apoptosis as well as necrosis of cardiac myocytes. We recently reported the cloning of a cDNA that encodes an apoptotic inhibitor, ARC, that is expressed predominantly in cardiac and skeletal muscle. In the present study, we examined the ability of ARC to protect rat embryonic heart–derived H9c2 cells from apoptosis induced by hypoxia, a component of ischemia. We found that H9c2 cells express ARC and that exposure to hypoxia substantially reduces ARC expression while inducing apoptosis. Transfected H9c2 cells in which cytosolic ARC protein levels remain elevated during hypoxia were significantly more resistant to hypoxia-induced apoptosis than parental H9c2 cells or H9c2 cells transfected with a control vector. Loss of endogenous ARC in the cytosol of H9c2 cells was associated with translocation of ARC from the cytosol to intracellular membranes, release of cytochrome c from the mitochondria, activation of caspase-3, poly(ADP-ribose)polymerase (PARP) cleavage, and DNA fragmentation. All of these events were inhibited in H9c2 cells overexpressing ARC when compared with control cells. In contrast, caspase inhibitors prevented PARP cleavage but not cytochrome c release, suggesting that exogenously expressed ARC acts upstream of caspase activation in this model of apoptosis. These results demonstrate that ARC can protect heart myogenic H9c2 cells from hypoxia-induced apoptosis, and that ARC prevents cytochrome c release by acting upstream of caspase activation, perhaps at the mitochondrial level. The full text of this article is available at http://www.circresaha.org.
Diabetic Patients Detected by Population-Based Stepwise Screening Already Have a Diabetic Cardiovascular Risk Profile
Authors: Annemieke M.W. Spijkerman, Marcel C. Adriaanse, Jacqueline M. Dekker, Giel Nijpels, Coen D.A. Stehouwer, Lex M. Bouter, Robert J. Heine
Journal: Diabetes Care (2002)

OBJECTIVE—To describe a population-based two-step screening procedure for type 2 diabetes and to study the cardiovascular risk profile of the patients identified by the screening. RESEARCH DESIGN AND METHODS—The first step of the screening procedure consisted of the Symptom Risk Questionnaire (SRQ), and the second step was a fasting capillary glucose measurement. In subjects with an SRQ score of &amp;gt;6 and a capillary glucose level of &amp;gt;5.5 mmol/l, an oral glucose tolerance test was performed. RESULTS—A total of 11,679 inhabitants of the West-Friesland region of the Netherlands, aged 50–75 years, were invited. Of the inhabitants, 9,169 (78%) responded, and, of those, 417 had previously diagnosed diabetes. The SRQ score was calculated for 7,736 participants, and 3,301 of those had a score of &amp;gt;6. A total of 2,885 subjects (87.3%) attended for capillary glucose measurement. Diagnostic testing was carried out in 509 participants, and we identified 217 diabetic patients. In these patients detected by screening, mean HbA1c was 6.7% (±1.4). Hypertension and high total cholesterol levels (&amp;gt;5.0 mmol/l) were present in 70%, 33% had high triglyceride (&amp;gt;3.0 mmol/l) or low HDL cholesterol levels (&amp;lt;1.0 mmol/l in men and &amp;lt;1.1 mmol/l in women), and 40% were obese (BMI ≥30 kg/m2). CONCLUSIONS—The high response rate was the main feature of the screening by means of the Symptom Risk Questionnaire and fasting capillary glucose measurement followed by diagnostic testing. The 217 diabetic patients detected by the screening were characterized by relatively low HbA1c levels and by a cardiovascular risk profile typical of diabetic patients.
Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement
Authors: Arti Hurria, Laura A. Levit, William Dale, Supriya G. Mohile, Hyman B. Muss, Louis Fehrenbacher, Allison Magnuson, Stuart M. Lichtman, Suanna S. Bruinooge, Enrique Soto-Perez-de-Celis, William P. Tew, Michael A. Postow, Harvey J. Cohen
Journal: Journal of Clinical Oncology (2015)

The American Society of Clinical Oncology (ASCO) convened a subcommittee to develop recommendations on improving the evidence base for treating older adults with cancer in response to a critical need identified by the Institute of Medicine. Older adults experience the majority of cancer diagnoses and deaths and make up the majority of cancer survivors. Older adults are also the fastest growing segment of the US population. However, the evidence base for treating this population is sparse, because older adults are underrepresented in clinical trials, and trials designed specifically for older adults are rare. The result is that clinicians have less evidence on how to treat older adults, who represent the majority of patients with cancer. Clinicians and patients are forced to extrapolate from trials conducted in younger, healthier populations when developing treatment plans. This has created a dearth of knowledge regarding the risk of toxicity in the average older patient and about key end points of importance to older adults. ASCO makes five recommendations to improve evidence generation in this population: (1) Use clinical trials to improve the evidence base for treating older adults with cancer, (2) leverage research designs and infrastructure for generating evidence on older adults with cancer, (3) increase US Food and Drug Administration authority to incentivize and require research involving older adults with cancer, (4) increase clinicians' recruitment of older adults with cancer to clinical trials, and (5) use journal policies to improve researchers' reporting on the age distribution and health risk profiles of research participants.
Efficient gene transfer into myocardium by direct injection of adenovirus vectors.
Authors: R J Guzman, P Lemarchand, R G Crystal, S E Epstein, T Finkel
Journal: Circulation Research (1993)

Previous studies have established that gene transfer into myocardial cells in vivo is detectable after direct injection of plasmid DNA. Recently, adenovirus vectors have been shown to provide an efficient method for gene transfer into a wide range of tissues. Therefore, this study sought to assess the efficiency and stability of adenovirus-mediated gene transfer into myocardium and to compare this method with that using plasmid-based gene transfer techniques. Adult rats underwent myocardial injection via a subdiaphragmatic approach. Gene transfer efficiency was compared using direct injection of an adenovirus vector encoding for the marker gene beta-galactosidase (beta-gal), a control adenovirus vector encoding for the cystic fibrosis transmembrane conductance regulator gene, a plasmid encoding for beta-gal, or a control plasmid. Hearts infected with an adenovirus vector containing the beta-gal gene showed significantly increased beta-gal enzymatic activity compared with hearts injected with beta-gal plasmid. Histological examination revealed that cardiac myocytes were the target of adenovirus-mediated gene transfer. A time course of gene expression showed that beta-gal enzymatic activity peaked during the first week following injection. Adenovirus vectors provide an efficient but transient method for in vivo gene expression in myocardium.
Gliomas Promote Immunosuppression through Induction of B7-H1 Expression in Tumor-Associated Macrophages
Authors: Orin Bloch, Courtney A. Crane, Rajwant Kaur, Michael Safaee, Martin J. Rutkowski, Andrew T. Parsa
Journal: Clinical Cancer Research (2013)

Gliomas are known to induce local and systemic immunosuppression, inhibiting T-cell-mediated cytotoxic responses to tumor growth. Tumor-associated macrophages are a significant component of the immune infiltrate in gliomas and may express immunosuppressive surface ligands, such as B7-H1.Tumor and peripheral blood samples from patients with glioblastoma (GBM) were analyzed by flow cytometry to evaluate the expression of B7-H1 in circulating and tumor-infiltrating macrophages. Human monocytes from healthy patients were stimulated with conditioned media from glioma cells to evaluate B7-H1 expression. Production of interleukin (IL)-10 by stimulated monocytes was measured by ELISA, and stimulation with IL-10 alone was evaluated for the ability to induce B7-H1 expression. The effect of inhibiting IL-10 and its receptor on glioma-induced B7-H1 expression in monocytes was evaluated.Circulating monocytes in patients with GBM had significantly increased expression of B7-H1 compared with healthy control patients. Tumor-associated macrophages from matched GBM tissue had even greater B7-H1 expression. Treatment of normal monocytes with glioma-conditioned media could significantly increase B7-H1 expression. Stimulation of monocytes with conditioned media resulted in substantial production of IL-10 and upregulation of the IL-10 receptor. Stimulation of monocytes with IL-10 alone could significantly increase B7-H1 expression, sufficient to induce T-cell apoptosis when cocultured with stimulated monocytes. Inhibition of IL-10 and the IL-10 receptor could knock down the effect of glioma media on B7-H1 by more than 50%.Gliomas can upregulate B7-H1 expression in circulating monocytes and tumor-infiltrative macrophages through modulation of autocrine/paracrine IL-10 signaling, resulting in an immunosuppressive phenotype.