tbuckley/cabot-search huggingface dataset:
Comment on Kramer et al. Glucagon Response to Oral Glucose Challenge in Type 1 Diabetes: Lack of Impact of Euglycemia. Diabetes Care 2014;37:1076–1082
Authors: Nobuyuki Takahashi, Tetsuro Tsujimoto, Hiroshi Kajio
Journal: Diabetes Care (2014)

We have read the study by Kramer et al. (1) concerning glucagon response to oral glucose challenge in type 1 diabetes with great interest. Although a paradoxical increase in glucagon in response to oral glucose may be one of the significant causes of hyperglycemia in patients with type 1 diabetes, its results should be carefully interpreted …
A Phase I Study of the First-in-Class Antimitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies
Authors: Timothy S. Pardee, King Lee, John Luddy, Claudia Maturo, Robert Rodriguez, Scott Isom, Lance D. Miller, Kristin M. Stadelman, Denise Levitan, David Hurd, Leslie R. Ellis, Robin Harrelson, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L. Powell
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the MTD, pharmacokinetics, and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design: Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results: CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3,780 mg/m2, there were two dose-limiting toxicities (DLT). At a dose of 2,940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of approximately 1.34 hours. Of the 21 evaluable, heavily pretreated patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion: CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. Clin Cancer Res; 20(20); 5255–64. ©2014 AACR.
Government pledges extra £34m to tackle health inequalities in England
Authors: Deborah Cohen
Journal: BMJ (2008)

Inequalities in health persist and, in some cases, have widened, a government report launched this week has said. This is despite record spending in the NHS in England, which will further increase from just over £90bn (€113, $176) in 2007-8 to £100bn in 2010-11.

The report, Health inequalities: progress and next steps , sets out the government’s plans to tackle health inequalities and help the most deprived communities. The report renewed the government’s pledge to reduce inequalities in health outcomes by 10% as measured by infant mortality and life expectancy at birth by 2010.

Speaking at the launch health secretary, Alan Johnson, …
Book Review Contracting a Cure: Patients, healers, and the law in early modern Bologna By Gianna Pomata. Translated from the Italian by the author, with the assistance of Rosemarie Foy and Anna Taraboletti-Segre. 294 pp. Baltimore, Johns Hopkins University Press, 1998. $42.50. 0-8018-5858-5
Authors: Richard M. Ratzan
Journal: New England Journal of Medicine (1999)
Endemic pemphigus foliaceus (fogo seivagem). I. Clinical features and immunopathology
Authors: Luis A. Diaz, Sebastiao A. Sampaio, Evandro A. Rivitti, Ciro R. Martins, Paulo R. Cunha, Clovis Lombardi, Fernando A. Almeida, Raymundo Martins Castro, Mario L. Macca, Carlos Lavrado, Gunther H. Filho, Paulo Borges, Lorivaldo Minelli, Julio C. Empinotti, Horacio Friedman, Iphis Campbell, Ramzy S. Labib, Grant J. Anhalt
Journal: Journal of the American Academy of Dermatology (1989)
Short-Term Deployment of Self-Expanding Metallic Stents Facilitates Healing of Bronchial Dehiscence
Authors: Majid M. Mughal, Thomas R. Gildea, Sudish Murthy, Gosta Pettersson, Malcom DeCamp, Atul C. Mehta
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Bronchial dehiscence after lung transplantation is difficult to treat and associated with high mortality. We describe our experience using self-expanding metallic stents to treat post-lung transplant bronchial dehiscence. From January 1995 to June 2004, 189 single and 118 double lung transplants were performed in our institution, totaling 425 at-risk bronchial anastomoses. Seven (1.6%) incidents of life-threatening bronchial dehiscence were treated with self-expanding metallic stents. The interval between transplant and diagnosis of dehiscence was 29.1 +/- 18.5 days. All patients presented with respiratory distress, and three required mechanical ventilation. Self-expanding metallic stent placement resulted in complete bronchial healing. All three patients with respiratory failure requiring mechanical ventilation were successfully weaned after stent placement. In two later cases, the stents were electively removed after adequate healing of the dehiscence. Complications included stent migration (one patient) and in-stent stenosis (three patients). Two of these patients required repeat stent insertion after removal, due to bronchomalacia. In patients with life-threatening bronchial dehiscence, self-expanding metallic stents offer prospects for a successful outcome. Self-expanding metallic stents are known to be associated with significant granulation tissue formation, and this property provides a platform for healing of dehiscence and, in time, peribronchial soft tissue grows in to cover the defect, allowing stent removal.
Self-Study from Web-Based and Printed Guideline Materials
Authors: Douglas S. Bell, Gregg C. Fonarow, Ron D. Hays, Carol M. Mangione
Journal: Annals of Internal Medicine (2000)

Background: On-line physician education is increasing, but its efficacy in comparison with existing self-study methods is unknown. Objective: To compare knowledge, learning efficiency, and learner satisfaction produced by self-study of World Wide Web–based and print-based guidelines for care after acute myocardial infarction. Design: Randomized, controlled trial. Setting: 12 family medicine and internal medicine residency programs at four universities. Participants: 162 residents. Interventions: In proctored sessions, participants were randomly assigned to study from printed materials or from SAGE (Self-Study Acceleration with Graphic Evidence), a Web-based tutorial system. Both methods used identical self-assessment questions and answers and guideline text, but SAGE featured hyperlinks to specific guideline passages and graphic evidence animations. Measurements: Scores on multiple-choice knowledge tests, score gain per unit of study time, and ratings on a learner satisfaction scale. Results: Immediate post-test scores on a 20-point scale were similar in the SAGE and control groups (median score, 15.0 compared with 14.5; P > 0.2), but SAGE users spent less time studying (median, 27.0 compared with 38.5 minutes; P < 0.001) and therefore had greater learning efficiency (median score gain, 8.6 compared with 6.7 points per hour; P = 0.04). On a scale of 5 to 20, SAGE users were more satisfied with learning (median rating, 17.0 compared with 15.0; P < 0.001). After 4 to 6 months, knowledge had decreased to the same extent in the SAGE and control groups (median score, 12.0 compared with 11.0; P = 0.12). Conclusions: On-line tutorials may produce greater learning efficiency and satisfaction than print materials do, but one self-study exposure may be insufficient for long-term knowledge retention. Further research is needed to identify instructional features that motivate greater final learning and retention.
Pathogenetic Mechanisms of Septic Shock
Authors: Franklin H. Epstein, Joseph E. Parrillo
Journal: New England Journal of Medicine (1993)

One of the most frequent and serious problems confronting clinicians is the management of a serious infection and the systemic response to infection, a syndrome termed sepsis. When this syndrome results in hypotension and organ dysfunction, it is called septic shock. Septic shock is the most common cause of death in intensive care units,1 and it is the 13th most common cause of death in the United States2. The incidence of the two disorders continues to rise: 400,000 cases of sepsis and 200,000 episodes of septic shock are estimated to occur annually, resulting in more than 100,000 deaths1. . . .
Control of Breast Cancer Through Mass Screening
Authors: George E. Moore
Journal: JAMA (1976)

<h3>To the Editor.—</h3> I am disturbed by a prominent omission in the article "Control of Breast Cancer Through Mass Screening"; namely, the lack of any definitive facts concerning the effectiveness or lack of effectiveness of thermography. A similar hiatus is present in several current articles. In the present study, the author states that an abnormal thermogram "alerts the physician to the possible presence of cancer in a stage not yet detectable by palpation or mammography." Such a selective test would be wonderful and apparently would reduce numerous "excessive" mammograms. Further, if the observation was correct, the author should have found more interval cancers in the positive thermography group—a finding of great importance. The statement that a biopsy is never done on the basis of a positive thermogram is incomplete; no reason is given. One strongly suspects this technique may be an expensive failure and should be discontinued unless there is
Drugs in the Institutionalized Elderly
Authors: Nicholas L. Owen
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Although few nursing home medical directors would argue that all patients in their institutions are receiving optimal drug therapy, many of us have been attuned to the problem of overmedication and abuse of chemical restraints (psychotropic medications and other sedating drugs) for a long time. The study by Beers et al<sup>1</sup>is illuminating, but Dr Riesenberg's<sup>2</sup>editorial takes a myopic view of the problem. There are some 20 000 nursing homes in the United States containing an everincreasing number of patients, a significant percentage of whom are agitated and noisy to the point of being antisocial and hard to live with. There are strict federal and state regulations regarding the chemical and physical restraint of nursing home residents. These are enforced by federal and state surveyors with varying but generally strict interpretation of the regulations, both from a pharmacy and nursing point of view. The
When to Perform Biopsies of Enlarged Peripheral Lymph Nodes in Young Patients
Authors: Gail B. Slap
Journal: JAMA (1984)

Identification of young patients with peripheral lymphadenopathy who will benefit from lymph node biopsy often is difficult. A model was developed to differentiate patients whose biopsy results do not lead to treatment (normal, hyperplastic, or benign inflammatory lymph nodes) from those whose biopsy results do lead to treatment (granulomatous or malignant nodes). The medical records and histopathology slides of 123 nine- to 25-year-old patients who underwent biopsies of enlarged peripheral lymph nodes were reviewed for pathological diagnosis and 22 clinical findings. Seventy-two (58%) patients had biopsy results that did not lead to treatment, and 51 (42%) had results that did lead to treatment. Using stepwise discriminant analysis, a predictive model was developed that assigned 95% of the cases to the correct biopsy group based on lymph node size; history of recent ear, nose, and throat symptoms; and chest roentgenogram. When tested prospectively on new patients, the model correctly classified 32 (97%) of 33. We conclude that this simple model can help select adolescents and young adults with peripheral lymphadenopathy for biopsy. (<i>JAMA</i>1984;252:1321-1326)
Severe Streptococcal Disease
Authors: Paul H. Black, Morton N. Swartz, John T. Sharp, Lawrence J. Kunz, Joseph Stokes, Robert B. McFarland
Journal: New England Journal of Medicine (1961)

IN recent years the nonsuppurative complications of streptococcal disease have received considerably more attention than acute infections caused by the Group A beta-hemolytic streptococcus. This is in contrast to the preantibiotic experience, when severe streptococcal infections were commonly encountered and were frequently fatal.During the winter and spring of 1958–1959, when a streptococcal epidemic occurred in the Boston area, many of the classic forms of severe Streptococcus pyogenes infections were observed. The purpose of this report is to emphasize the fact that during an epidemic both unusual and fulminating forms of streptococcal disease may be encountered. It is also worth . . .
Abstract 3518: Preclinical pharmacology of the novel, potent &amp; selective CHK1 inhibitor SAR-020106
Authors: Michael I. Walton, Paul D. Eve, Angela Hayes, Melanie Valenti, Alexis De Haven Brandon, Gary Box, G Wynne Aherne, Suzanne A. Eccles, Florence I. Raynaud, David H. Williams, John C. Reader, Ian Collins, Michelle D. Garrett
Journal: Cancer Research (2010)

Abstract Genotoxic antitumor agents continue to be the mainstay of current cancer chemotherapy. These drugs cause DNA damage and activate numerous cell cycle checkpoints facilitating DNA repair and the maintenance of genomic integrity. Most human tumors lack functional p53 and consequently have compromized G1/S checkpoint control. This has led to the hypothesis that S and G2/M checkpoint abrogation may selectively enhance genotoxic cell killing in a p53 deficient background, as normal cells would be rescued at the G1/S checkpoint. CHK1 is a serine/threonine kinase associated with DNA damage linked S and G2/M checkpoint control. SAR-020106 (the structure will be shown on the poster) is an ATP competitive, potent and selective CHK1 inhibitor with an IC50 of 13.3nM on the isolated human enzyme. This compound abrogates an etoposide-induced G2 arrest with an IC50 of 55nM in HT29 cells, and significantly enhances the cell killing of gemcitabine and SN38 by 3.0 to 29-fold in a number of colon tumor lines in vitro and in a p53 dependent fashion. Biomarker studies have shown that SAR-020106 inhibits cytotoxic drug induced autophosphorylation of CHK1 at S296 and blocks phosphorylation of CDK1 at Y15 in a dose-dependent fashion both in vitro and in vivo. Cytotoxic drug combinations were associated with increased γH2AX and PARP cleavage consistent with SAR-020106 enhanced DNA damage and tumor cell death. Irinotecan and gemcitabine antitumor activity was enhanced by SAR-020106 in vivo with minimal toxicity. Orally bioavailable analogues of SAR-02106 are currently under development. In conclusion SAR-020106 represents a novel class of CHK1 inhibitors which can enhance antitumor activity with selected anticancer drugs in vivo and may therefore have clinical utility. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3518.
A pain in the bottom
Authors: F. Iqbal, A. D. Beggs, T. Holt, D. M. Bowley
Journal: BMJ (2013)

A 44 year old man presents to primary care with a four week history of severe, intermittent episodes of anorectal pain, each lasting for some 10 minutes without pain between episodes. Symptoms persist despite use of over the counter medications. Anorectal pain is common, with an estimated prevalence of around 7%. It can usually be managed in general practice. However, presentation may be confounded by embarrassment and fear of serious pathology, requiring a sensitive and focused approach. In this case, the most likely diagnoses are anal fissure, haemorrhoids, or functional anorectal pain (chronic proctalgia or proctalgia fugax). Less common possibilities are listed in the box. Functional anorectal pain occurs in the absence of any pathology; it is relatively common, affecting about 18% of patients with anorectal pain, but can be disabling. Chronic proctalgia is defined as chronic or recurrent pain or aching localised to the anus or lower rectum, with episodes lasting ≥20 minutes. The pain in proctalgia fugax lasts from seconds to minutes, without pain between episodes. #### Unusual causes of anorectal pain ##### Anorectal sexually transmitted infections Risk factors:
Potential Impact of Adding Genetic Markers to Clinical Parameters in Predicting Prostate Biopsy Outcomes in Men Following an Initial Negative Biopsy: Findings from the REDUCE Trial
Authors: A. Karim Kader, Jielin Sun, Brian H. Reck, Paul J. Newcombe, Seong-Tae Kim, Fang-Chi Hsu, Ralph B. D’Agostino, Sha Tao, Zheng Zhang, Aubrey R. Turner, Greg T. Platek, Colin F. Spraggs, John C. Whittaker, Brian R. Lane, William B. Isaacs, Deborah A. Meyers, Eugene R. Bleecker, Frank M. Torti, Jeffery M. Trent, John D. McConnell, S. Lilly Zheng, Lynn D. Condreay, Roger S. Rittmaster, Jianfeng Xu
Journal: European Urology (2012)
Some haematological characteristics of competitive swimmers
Authors: P. L. T. Willan, K. M. Bagnall, M. Mahon, D. W. Kellett
Journal: British Journal of Sports Medicine (1981)

Some basic haematological characteristics of a group of competitive swimmers were compared with haematological “normal standards” and with a “control” group of non-athletes, unmatched for age. In the women, the values for red blood cell count, haemoglobin concentration, and mean red cell volume for both the swimmers and the controls were not significantly different from the normal standards. In the groups of men, both swimmers and controls, red cell counts were significantly lower than the normal standard values, although individual values lay within the “normal range” (mean ± 2 standard deviations). The ranges of the values for individuals were found to be narrow. There were no significant differences between these ranges over periods of five consecutive weeks and five consecutive months. Relatively large changes in results for individuals could occur before the results would be considered abnormal, that is, before the results fall outside the “normal range”. Early detection of changes may perhaps be facilitated if the range of values for individual athletes is determined by monitoring.
Evolution of Vault RNAs
Authors: P. F. Stadler, J. J.-L. Chen, J. Hackermuller, S. Hoffmann, F. Horn, P. Khaitovich, A. K. Kretzschmar, A. Mosig, S. J. Prohaska, X. Qi, K. Schutt, K. Ullmann
Journal: Molecular Biology and Evolution (2009)

Vault RNAs (vtRNAs) are small, about 100 nt long, polymerase III transcripts contained in the vault particles of eukaryotic cells. Presumably due to their enigmatic function, they have received little attention compared with most other noncoding RNA (ncRNA) families. Their poor sequence conservation makes homology search a complex and tedious task even within vertebrates. Here we report on a systematic and comprehensive analysis of this rapidly evolving class of ncRNAs in deuterostomes, providing a comprehensive collection of computationally predicted vtRNA genes. We find that all previously described vtRNAs are located at a conserved genomic locus linked to the protocadherin gene cluster, an association that is conserved throughout gnathostomes. Lineage-specific expansions to small vtRNA gene clusters are frequently observed in this region. A second vtRNA locus is syntenically conserved across eutherian mammals. The vtRNAs at the two eutherian loci exhibit substantial differences in their promoter structures, explaining their differential expression patterns in several human cancer cell lines. In teleosts, expression of several paralogous vtRNA genes, most but not all located at the syntenically conserved protocadherin locus, was verified by reverse transcriptase–polymerase chain reaction.
Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca <sup>2</sup> Influx
Authors: David Jho, Dolly Mehta, Gias Ahmmed, Xiao-Pei Gao, Chinnaswamy Tiruppathi, Michael Broman, Asrar B. Malik
Journal: Circulation Research (2005)

Angiopoietin-1 (Ang1) exerts a vascular endothelial barrier protective effect by blocking the action of permeability-increasing mediators such as vascular endothelial growth factor (VEGF) through unclear mechanisms. Because VEGF may signal endothelial hyperpermeability through the phospholipase C (PLC)-IP 3 pathway that activates extracellular Ca 2+ entry via the plasmalemmal store-operated channel transient receptor potential canonical-1 (TRPC1), we addressed the possibility that Ang1 acts by inhibiting this Ca 2+ entry mechanism in endothelial cells. Studies in endothelial cell monolayers demonstrated that Ang1 inhibited the VEGF-induced Ca 2+ influx and increase in endothelial permeability in a concentration-dependent manner. Inhibitors of the PLC-IP 3 Ca 2+ signaling pathway prevented the VEGF-induced Ca 2+ influx and hyperpermeability similar to the inhibitory effects seen with Ang1. Ang1 had no effect on PLC phosphorylation and IP 3 production, thus its permeability-decreasing effect could not be ascribed to inhibition of PLC activation. However, Ang1 interfered with downstream IP 3 -dependent plasmalemmal Ca 2+ entry without affecting the release of intracellular Ca 2+ stores. Anti-TRPC1 antibody inhibited the VEGF-induced Ca 2+ entry and the increased endothelial permeability. TRPC1 overexpression in endothelial cells augmented the VEGF-induced Ca 2+ entry, and application of Ang1 opposed this effect. In immunoprecipitation studies, Ang1 inhibited the association of IP 3 receptor (IP 3 R) and TRPC1, consistent with the coupling hypothesis of Ca 2+ entry. These results demonstrate that Ang1 blocks the TRPC1-dependent Ca 2+ influx induced by VEGF by interfering with the interaction of IP 3 R with TRPC1, and thereby abrogates the increase in endothelial permeability.
Identification of two major populations of mucins in respiratory secretions.
Authors: D J Thornton, P L Devine, C Hanski, M Howard, J K Sheehan
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Two populations of reduced subunits were present in the mucins purified from pooled normal secretions and asthmatic and chronic bronchitic sputa; their relative level differed between samples. To investigate the nature of this heterogeneity, an asthmatic respiratory mucin preparation from a single individual was reduced and alkylated with 14C-iodoacetamide. This preparation was analyzed by gel filtration, agarose gel electrophoresis, immunoblotting, rate-zonal- and density-gradient centrifugation, and HPLC ion-exchange- and reverse-phase chromatography. Two populations (A and B) of reduced mucin subunits and a high-M(r)protein-rich fraction were identified. Species A has the higher molecular mass, is slowest migrating on agarose electrophoresis, has longer oligosaccharide chains, and expresses the carbohydrate structure sialyl-Le(x). Species B has a lower molecular mass, migrates faster in agarose electrophoresis Species B has a lower molecular mass, migrates faster in agarose electrophoresis, has shorter chains, and does not express sialyl-Le(x). The two subunits have similar but not identical amino acid compositions and 14C-tryptic peptide maps indicating they have different protein cores. The anti-sialyl-Le(x) antibody selectively precipitated subunit A not only from the reduced but also from the nonreduced mucin preparation, demonstrating that subunits A and B are present in different intact mucins.