tbuckley/cabot-search huggingface dataset:
Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia
Authors: C.-H. Pui, D. Pei, Jt T. Sandlund, Rc C. Ribeiro, Je E. Rubnitz, Sc C. Raimondi, M. Onciu, D. Campana, Le E. Kun, S. Jeha, C. Cheng, Sc C. Howard, Ml L. Metzger, D. Bhojwani, J. R. Downing, We E. Evans, Mv V. Relling
Journal: Leukemia (2009)
Regulatory Interdependence of Cloned Epithelial Na+ Channels and P2X Receptors
Authors: Scott S. Wildman, Joanne Marks, Linda J. Churchill, Claire M. Peppiatt, Ahmed Chraibi, David G. Shirley, Jean-Daniel Horisberger, Brian F. King, Robert J. Unwin
Journal: Journal of the American Society of Nephrology (2005)

Epithelial Na+ channels (ENaC) coexist with a family of ATP-gated ion channels known as P2X receptors in the renal collecting duct. Although ENaC is itself insensitive to extracellular ATP, tubular perfusion of ATP can modify the activity of ENaC. To investigate a possible regulatory relationship between P2X receptors and ENaC, coexpression studies were performed in Xenopus oocytes. ENaC generated a persistent inward Na+ current that was sensitive to the channel blocker amiloride (I(am-s)). Exogenous ATP transiently activated all cloned isoforms of P2X receptors, which in some cases irreversibly inhibited I(am-s). The degree of inhibition depended on the P2X receptor subtype present. Activation of P2X2, P2X(2/6), P2X4, and P2X(4/6) receptor subtypes inhibited I(am-s), whereas activation of P2X1, P2X3, and P2X5 receptors had no significant effect. The degree of inhibition of I(am-s) correlated positively with the amount of ionic charge conducted by P2X receptor subtypes. ENaC inhibition required Na+ influx through I(am-s)-inhibiting P2X ion channels but also Ca2+ influx through P2X4 and P2X(4/6) ion channels. P2X-mediated inhibition of I(am-s) was found to be due to retrieval of ENaC from the plasma membrane. Maximum amplitudes of ATP-evoked P2X-mediated currents (I(ATP)) were significantly increased for P2X2, P2X(2/6), and P2X5 receptor subtypes after coexpression of ENaC. The increase in I(ATP) was due to increased levels of plasma membrane-bound P2X receptor protein, suggesting that ENaC modulates protein trafficking. In summary, ENaC was downregulated by the activation of P2X2, P2X(2/6), P2X4, and P2X(4/6) receptors. Conversely, ENaC increased the plasma membrane expression of P2X2, P2X(2/6), and P2X5 receptors.
Manual Chest Compression vs Use of an Automated Chest Compression Device During Resuscitation Following Out-of-Hospital Cardiac Arrest
Authors: Al Hallstrom, Thomas D. Rea, Michael R. Sayre, James Christenson, Andy R. Anton, Vince N. Mosesso, Lois Van Ottingham, Michele Olsufka, Sarah Pennington, Lynn J. White, Stephen Yahn, James Husar, Mary F. Morris, Leonard A. Cobb
Journal: JAMA (2006)

High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes.To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR.Multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005.Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517).The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors.Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006).Use of an automated LDB-CPR device as implemented in this study was associated with worse neurological outcomes and a trend toward worse survival than manual CPR. Device design or implementation strategies require further evaluation.clinicaltrials.gov Identifier: NCT00120965.
Surgery Alone Versus Chemoradiotherapy Followed by Surgery for Stage I and II Esophageal Cancer: Final Analysis of Randomized Controlled Phase III Trial FFCD 9901
Authors: Christophe Mariette, Laetitia Dahan, Françoise Mornex, Emilie Maillard, Pascal-Alexandre Thomas, Bernard Meunier, Valérie Boige, Denis Pezet, William B. Robb, Valérie Le Brun-Ly, Jean-François Bosset, Jean-Yves Mabrut, Jean-Pierre Triboulet, Laurent Bedenne, Jean-François Seitz
Journal: Journal of Clinical Oncology (2014)

Purpose Although often investigated in locally advanced esophageal cancer (EC), the impact of neoadjuvant chemoradiotherapy (NCRT) in early stages is unknown. The aim of this multicenter randomized phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II EC. Methods The primary end point was overall survival. Secondary end points were disease-free survival, postoperative morbidity, in-hospital mortality, R0 resection rate, and prognostic factor identification. From June 2000 to June 2009, 195 patients in 30 centers were randomly assigned to surgery alone (group S; n = 97) or NCRT followed by surgery (group CRT; n = 98). CRT protocol was 45 Gy in 25 fractions over 5 weeks with two courses of concomitant chemotherapy composed of fluorouracil 800 mg/m 2 and cisplatin 75 mg/m 2 . We report the long-term results of the final analysis, after a median follow-up of 93.6 months. Results Pretreatment disease was stage I in 19.0%, IIA in 53.3%, and IIB in 27.7% of patients. For group CRT compared with group S, R0 resection rate was 93.8% versus 92.1% (P = .749), with 3-year overall survival rate of 47.5% versus 53.0% (hazard ratio [HR], 0.99; 95% CI, 0.69 to 1.40; P = .94) and postoperative mortality rate of 11.1% versus 3.4% (P = .049), respectively. Because interim analysis of the primary end point revealed an improbability of demonstrating the superiority of either treatment arm (HR, 1.09; 95% CI, 0.75 to 1.59; P = .66), the trial was stopped for anticipated futility. Conclusion Compared with surgery alone, NCRT with cisplatin plus fluorouracil does not improve R0 resection rate or survival but enhances postoperative mortality in patients with stage I or II EC.
Much Ado About Not ... Enough Data: High-Dose Chemotherapy With Autologous Stem Cell Rescue for Breast Cancer
Authors: JoAnne Zujewski, Jeffrey Abrams, Anita Nelson
Journal: JNCI Journal of the National Cancer Institute (1998)

High-dose chemotherapy with autologous bone marrow or stem cell rescue (HDC/ASCR) has been proposed as a promising treatment strategy for breast cancer. Despite the frequency with which this procedure is performed, the role of HDC/ASCR in the treatment of breast cancer remains undefined. The purpose of this review is to examine the rationale for the procedure, the research progress to date, and the limitations of available data. A literature search of Medline from January 1966 through May 1997, CancerLit from January 1983 through May 1997, and Current Contents through May 1997 identified more than 600 English language papers or abstracts on this topic. Our review focuses on the preclinical and clinical data that explore the concept of chemotherapy dose intensity and the role of dose intensity in treating breast cancer. HDC/ASCR is based on the hypothesis that high-dose chemotherapy will overcome drug resistance, eradicate metastatic disease, and increase the proportion of women with breast cancer who are “cured.” To date, results from only one phase 3 trial of HDC/ASCR compared with more conventional therapy have been published. Phase 2 and some phase 3 data on HDC/ASCR in the treatment of high-risk primary breast cancer and metastatic breast cancer are discussed. However, the results are inconclusive. The completion of national and international randomized trials is urgently needed to establish definitively the role of HDC/ASCR in the treatment of breast cancer.
Expression and Function of the Developmental Gene Wnt-4 during Experimental Acute Renal Failure in Rats
Authors: Yoshio Terada, Hiroyuki Tanaka, Tomokazu Okado, Haruko Shimamura, Seiji Inoshita, Michio Kuwahara, Sei Sasaki
Journal: Journal of the American Society of Nephrology (2003)

The Wnt-beta-catenin pathway plays key roles in embryogenesis. Wnt-4 is known to be expressed in the mesonephric duct in embryonic development. It is tempting to speculate that the Wnt-4-beta-catenin pathway contributes to the recovery from acute renal failure (ARF). This study used an in vivo model of ARF rats to clarify the significance of the Wnt-4-beta-catenin pathway in ARF. ARF was induced by clamping the rat left renal artery for 1 h. At 3, 6, 12, 24, 48, and 72 h after reperfusion, whole kidney homogenate and total RNA were extracted for examination by Western blot analysis and real-time RT-PCR. Wnt-4 mRNA and protein expression were strongly increased at 3 to 12 h and 6 to 24 h after ischemia, respectively. In immunohistologic examination, Wnt-4 was expressed in the proximal tubules and co-expressed with aquaporin-1, GM130, and PCNA. Cyclin D1 and cyclin A were expressed at 24 to 48 h after reperfusion. In addition, the overexpression of Wnt-4 and beta-catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Taken together, these data suggest that the Wnt-4-beta-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Wnt-4-beta-catenin pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF.
A micropuncture study of collecting tubule function in rats with hereditary diabetes insipidus
Authors: Rex L. Jamison, John Buerkert, Frank Lacy, Dan Marcus, Betty Henton
Journal: Journal of Clinical Investigation (1971)

The reabsorption of water and solute by the papillary collecting duct was studied during water diuresis and vasopressin-induced antidiuresis in young rats with hereditary hypothalamic diabetes insipidus. The tip of the left renal papilla was exposed and fluid was obtained by micropuncture from loops of Henle and from collecting ducts at the papillary tip, and at an average of 1 mm proximal to the tip. In water diuresis the ratio of tubule fluid to plasma (TF/P) osmolality (osm) of loop fluid was 1.73 +/-0.058 (SE); of fluid from the proximal collecting duct, 0.63 +/-0.027; and from the tip, 0.55 +/-0.024; indicating a substantial osmotic pressure difference across the collecting duct epithelium. The fraction of filtered water reabsorbed (x 100) by the terminal collecting duct was 1.58% +/-0.32. In antidiuresis the TF/P osm of loop fluid was 2.65 +/-0.109; of fluid from the proximal collecting duct, 2.20 +/-0.093; and from the tip, 2.71 +/-0.111; indicating a marked decrease in the driving force for water reabsorption. The fraction of filtered water reabsorbed (x 100) by the terminal collecting duct was reduced to 0.58% +/-0.08, while the delivery of solute to the same segment was unchanged from that in water diuresis. The glomerular filtration rate (GFR) of the right kidney declined from 327 +/-24.4 mul/min in water diuresis to 274 +/-24.4 mul/min in antidiuresis (P < 0.005); similar results were obtained in a study comparing right and left GFRs in five additional rats. Thus, fractional reabsorption (and very likely the absolute volume) of water reabsorbed by the terminal collecting duct was less in antidiuresis than in water diuresis (mean difference, 1.01% +/-0.29, P < 0.005).
The future of London medical education
Authors: Isambard Owen
Journal: BMJ (2004)

sclerosants such as povidone iodine, talcum powder, or doxycycline.w8 w9 w10 ConclusionsSurgical management of inguinal lymph nodes forms a key element in the treatment algorithm for several malignancies.Clinicians should be aware of the indications for surgery, the high postoperative morbidity, and the need for further randomised controlled trials to ascertain the role of sentinel lymph node biopsy in the management of nodal disease.Acknowledgements: We thank the patients who consented to involvement with this review, and Nick White from Oxford Medical Illustration for
The Role of Posttraumatic Stress in Acute Postconcussive Symptoms following Blast Injury in Combat
Authors: Richard A. Bryant, Monty T. Baker, Jim Mintz, Jeffrey Barth, Stacey Young-McCaughan, Brian Creasy, Gerald Grant, William Isler, Steffany L. Malach, Alan L. Peterson
Journal: Psychotherapy and Psychosomatics (2015)

Abstract : Mild traumatic brain injury (mTBI) has been called the signature injury of recent wars in Iraq and Afghanistan. Estimates of mTBI in deployed personnel are as high as 20%. Postconcussive symptoms (PCS), regarded as the core problem following mTBI, comprise headaches, dizziness, sensitivity to light and sound, fatigue, and concentration deficits. Although PCS have traditionally been presumed to result from neurological insult, evidence points to a role of psychological factors in these symptoms. Current military evidence is limited by the reliance on retrospective reports collected after deployment through surveys. Research on mTBI in combat setting is needed to more accurately determine the nature of blast-related mTBI. This study reports the first analysis of military personnel assessed in theatre shortly after exposure to a blast.
The role of the sympathetic nervous system in hypoglycaemia-stimulated gastric secretion
Authors: A. J. Hodge, J. R. Masarei, B. N. Catchpole
Journal: Gut (1972)

The gastric secretory response to insulin is mediated predominantly by the vagus. The associated hypoglycaemia stress response is mediated by the sympathetic nervous system. Inhibition of the sympathetic response by simultaneous alpha and beta receptor blockade was studied in five healthy young adults. No appreciable modification of gastric secretory output resulted.
Severe and refractory solar urticaria treated with intravenous immunoglobulins: A phase II multicenter study
Authors: François Aubin, Raphaël Porcher, Michel Jeanmougin, Fabienne Léonard, Christophe Bedane, Anne Moreau, Jean-Luc Schmutz, Marie-Claude Marguery, Henri Adamski, Manuelle Viguier
Journal: Journal of the American Academy of Dermatology (2014)
Adherence to Mediterranean diet and health status: meta-analysis
Authors: F. Sofi, F. Cesari, R. Abbate, G. F. Gensini, A. Casini
Journal: BMJ (2008)

<b>Objective</b> To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention setting. <b>Design</b> Meta-analysis of prospective cohort studies. <b>Data sources</b> English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. <b>Studies reviewed</b> Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574 299 subjects followed for a time ranging from three to 18 years were included. <b>Results</b> The cumulative analysis among eight cohorts (514 816 subjects and 33 576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson's disease and Alzheimer's disease (0.87, 0.80 to 0.96). <b>Conclusions</b> Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson's disease and Alzheimer's disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.
Association of Primary Breast Cancer of the Vulva With Hereditary Breast and Ovarian Cancer
Authors: Amanda Lamb, Christopher J. Darus, Silvia Skripenova, Tracey Weisberg, Susan Miesfeldt
Journal: Journal of Clinical Oncology (2013)

Case ReportA 59-year-old woman of French-Canadian ancestry, with a family history of breast cancer and a documented BRCA2 mutation in a first-degree relative, sought care for a 5-month history of a 1-cm, raised, and erythematous mass lateral to the left labium majus.Excisional biopsy results revealed infiltrating mammary adenocarcinoma with mucinous differentiation (Fig 1A).The tumor cells were positive for cytokeratin 7 (CK7), mammoglobin (Fig 1B), estrogen receptor (90%; Fig 1C), and progesterone receptor (30%), and were negative for CK20, Wilms tumor 1, gross cystic disease fluid protein 15, and human epidermal growth factor receptor 2 (HER2)/neu (1ϩ).The tumor infiltrated through the epithelium, and specimen biopsy margins were focally positive.She had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy at age 51 years because of abnormal vaginal bleeding.Pathology was nondiagnostic.She was without a history of breast problems and had regular mammograms in the past.On referral to gynecologic oncology, a minimal scar without underlying mass was noted at the biopsy site.Otherwise, physical examination, including examination of the breasts and the remainder of the external genitalia, anus, and inguinal regions was negative for clinical evidence of malignancy.Breast magnetic resonance imaging, body computed tomography, and bone scan were nondiagnostic.She underwent a radical local vulvar excision of the scar with left inguinofemoral lymphadenectomy.There was no residual tumor noted in the vulva, and left groin lymph nodes were negative.Following an uneventful postoperative course, she was started on tamoxifen, 20 mg daily.Her family history was significant for breast cancer in her sister at age 59 years, and her mother's history of bilateral breast cancer at ages 39 and 49 years (Fig 2 ).A close relative had previously undergone comprehensive BRCA analysis.This result returned with a BRCA2 mutation (8765delAG) that is a founder mutation in breast and ovarian cancer families of French-Canadian descent. 1 Following her final surgery, the patient underwent single-site testing for this BRCA2 mutation and was found to be positive.
PWE-114 Factors Affecting the Risk of Relapse to Drinking Alcohol Following Listing for Transplantation for Alcohol-Related Liver Disease
Authors: A Sainsbury, K L Rothwell, M A Aldersley
Journal: Gut (2013)

<h3>Introduction</h3> Alcohol-related liver disease (ALD) is one of the commonest indications for liver transplantation, but relapse to drinking alcohol in this group of patients is a significant concern. Clarification of risk factors that can predict relapse is needed in the UK, so that additional support can be provided for those at increased risk. <h3>Methods</h3> Patients being considered for liver transplantation as a result of ALD in Leeds undergo thorough assessment by an alcohol professional. Particular emphasis is placed on the risk of recidivism to drinking, using 2 scoring systems. One of these, the High-risk Alcohol Relapse (HRAR) Score, focuses on prior alcohol consumption history, whereas the Relative Risk Factors for Relapse (RRFR) Score addresses psychosocial dysfunction. However, neither of these scoring systems is used to determine suitability for transplantation. Scores were evaluated in those known to have returned to drinking alcohol after listing for transplantation, either by self-report or by random blood alcohol testing. These scores were compared to listed patients considered to be abstinent. We also assessed whether duration of self-reported abstinence or family history of alcoholism were greater in those who relapsed. <h3>Results</h3> Between September 2008 and August 2010, 58 people with ALD were listed for liver transplantation. Of these, 12 are known to have returned to drinking alcohol, either whilst listed or post-transplant. There was no significant difference in the relapsers compared to the non-relapsers according to gender (0.67% vs 0.73% were males, P = 0.45) or age (median 50 vs 54 years, P = 0.09). The median RRFR scores were significantly higher in the relapsers compared to the non-relapsers (14.5/27 vs 12/27; P = 0.01). The median HRAR scores were identical in the 2 groups (median scores 2/6; P = 0.28). There was no significant difference in duration of self-reported abstinence between relapsers and non-relapsers (13 vs 10 months; P = 0.26). There was also no difference in family history (where known) of alcoholism between the 2 groups (1/10 vs 8/39; P = 0.4). <h3>Conclusion</h3> Psychosocial dysfunction is significantly greater in patients with ALD who relapse to drinking alcohol following listing for transplantation. Psychological support may therefore reduce the risk of relapse in these patients. The predictive utility of the HRAR score was poor in this cohort of patients. <h3>Disclosure of Interest</h3> None Declared.
Study identifies why child heart operations go wrong
Authors: C. Dyer
Journal: BMJ (1999)

Human and organisational factors have a significant role in determining whether a surgical operation has a good or bad outcome, according to research outlined last week to the public inquiry into child heart surgery at Bristol.

Marc de Leval, professor of cardiothoracic surgery at Great Ormond Street children's hospital in London, previewed the results of a study which looked at all the arterial switch operations performed in the United Kingdom over an 18 month period. Of 230 operations, 165 were studied in detail. The research is to be published soon in the Journal of Cardiothoracic Surgery.

The switch, performed in the first month of life to correct transposition of the great arteries of the heart, is one of two paediatric heart operations looked into by the General Medical Council in its …