tbuckley/cabot-search huggingface dataset:
Threats and opportunities of the NHS reforms
Authors: N. Dudley
Journal: BMJ (2011)

Diuron, a widely used herbicide and antifouling biocide, has been shown to persist in the environment and contaminate drinking water. It has been characterized as a “known/likely” human carcinogen. Whereas its environmental transformation and toxicity have been extensively examined, its metabolic characteristics in mammalian livers have not been reported. This study was designed to investigate diuron biotransformation and disposition because metabolic routes, metabolizing enzymes, interactions, interspecies differences, and interindividual variability are important for risk assessment purposes. The only metabolic pathway detected by liquid chromatography/mass spectometry in human liver homogenates and seven types of mammalian liver microsomes including human was demethylation at the terminal nitrogen atom. No other phase I or phase II metabolites were observed. The rank order of <i>N</i>-demethyldiuron formation in liver microsomes based on intrinsic clearance (<i>V</i><sub>max</sub>/<i>K</i><sub>m</sub>) was dog &gt; monkey &gt; rabbit &gt; mouse &gt; human &gt; minipig &gt; rat. All tested recombinant human cytochrome P450s (P450s) catalyzed diuron <i>N</i>-demethylation and the highest activities were possessed by CYP1A1, CYP1A2, CYP2C19, and CYP2D6. Relative contributions of human CYP1A2, CYP2C19, and CYP3A4 to hepatic diuron <i>N</i>-demethylation, based on average abundances of P450 enzymes in human liver microsomes, were approximately 60, 14, and 13%, respectively. Diuron inhibited relatively potently only CYP1A1/2 (IC<sub>50</sub> 4 μM). With human-derived and quantitative chemical-specific data, the uncertainty factors for animal to human differences and for human variability in toxicokinetics were within the range of the toxicokinetics default uncertainty/safety factors for chemical risk assessment.
DRG Creep
Authors: Donald W. Simborg
Journal: New England Journal of Medicine (1981)

"Diagnostic related groups" (DRGs) have become the watchwords of the health-services research, regulatory, and planning agencies. Introduced in 1975 by Thompson et al.,1 they were intended as a means of grouping patients by discharge diagnosis to measure a hospital's output. These measurements are useful in analyzing and monitoring the hospital's resource utilization, performance, and costs. Today, the use of DRGs is virtually synonymous with case-mix measurement, and it has become the standard method to describe hospital outputs for any use.This article is intended to provide a case report of "DRG creep," a new phenomenon that is expected to occur . . .
Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB
Authors: Liping Pan, Hongyan Jia, Fei Liu, Huishan Sun, Mengqiu Gao, Fengjiao Du, Aiying Xing, Boping Du, Qi Sun, Rongrong Wei, Shuxiang Gu, Zongde Zhang
Journal: Journal of Infection (2015)
Factors in Pathogenesis of Central-nervous-system Leukaemia
Authors: R. J. West, J. Graham-Pole, R. M. Hardisty, M. C. Pike
Journal: BMJ (1972)

Eighty-three (50%) of 165 children with acute lymphoblastic or acute stem-cell leukaemia presenting during 1958-70 developed leukaemia of the central nervous system (C.N.S.). The rate of incidence of this complication is fairly constant throughout the first two-and-a-half years of the disease, but falls thereafter. The incidence of C.N.S. leukaemia is inversely correlated with the platelet count at the time of initial diagnosis of leukaemia, and directly correlated with the total leucocyte count and the presence of lymph-node enlargement. The major effect of initial leucocyte count is on the time of onset of clinical symptoms. It is suggested that leukaemic cells usually enter the C.N.S. from the blood as a result of intracranial petechial haemorrhage occurring around the time of initial diagnosis of leukaemia, and that the time for subsequent development of symptoms of C.N.S. disease is largely determined by the number and replication rate of leukaemic cells which gain access to the C.N.S. at that time. The increasing frequency of diagnosis of C.N.S. leukaemia in recent years is not wholly explained by increasing survival, and may in part be related to changes in the pattern of antileukaemic therapy.Prophylaxis for C.N.S. leukaemia should be instituted as early as practicable after diagnosis; the identification of a high-risk group may permit this to be done selectively.
Extraocular Muscle Imbalance after Scleral Buckling Surgery
Authors: William E. Smiddy, Donna Loupe, Ronald G. Michels, Cheryl Enger, Bert M. Glaser, Serge deBustros
Journal: Ophthalmology (1989)

Pneumatic retinopexy is advocated to treat some retinal detachment cases, in part to avoid the complication of induced strabismus sometimes associated with scleral buckling procedures (SBPs). Prospective evaluation of postoperative muscle imbalance was performed in 76 eyes of 69 patients undergoing SBP. Measureable limitation of ductions occurred in 40 (73%) of the 55 eyes for which a full set of duction measurements could be obtained. Among 53 patients without previous retinal surgery in either eye, postoperative deviations were associated with encircling scleral buckles (P = 0.00003), but not with radial scleral buckles (P = 0.6). Significant strabismus occurred in 12 patients (23%), and three required surgery or prism therapy. Candidates for pneumatic retinopexy can usually be treated by a radial scleral buckling procedure, and therefore the risk of postoperative strabismus is low if this technique is selected.
Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions
Authors: William L. Trepicchio, Maki Ozawa, Ian B. Walters, Toyoko Kikuchi, Patricia Gilleaudeau, Judith L. Bliss, Ullrich Schwertschlag, Andrew J. Dorner, James G. Krueger
Journal: Journal of Clinical Investigation (1999)

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from skin infiltration by type I T lymphocytes and release of associated cytokines. A multifunctional cytokine, rhIL-11, modulates macrophage and type I T-lymphocyte function in cell culture and shows anti-inflammatory activity in animal models. We are testing subcutaneous delivery of rhIL-11to patients with psoriasis in a phase 1 open-label dose-escalation clinical trial. Tissue was obtained from lesional and uninvolved skin before and during treatment with rhIL-11 and was examined by histology/immunohistochemistry and quantitative RT-PCR. Expression of over 35 genes was examined in all patients, and multiple genetic markers of psoriasis were identified. Expression of numerous proinflammatory genes was elevated in psoriatic tissue compared with nonlesional skin. Seven of 12 patients responded well to rhIL-11 treatment. Amelioration of disease by rhIL-11, as shown by reduced keratinocyte proliferation and cutaneous inflammation, was associated with decreased expression of products of disease-related genes, including K16, iNOS, IFN-γ, IL-8, IL-12, TNF-α, IL-1β, and CD8, and with increased expression of endogenous IL-11. We believe that this is the first study in humans to indicate that type I cytokines can be selectively suppressed by an exogenous immune-modifying therapy. The study highlights the utility of pharmacogenomic monitoring to track patient responsiveness and to elucidate anti-inflammatory mechanisms.
Prospective, randomized controlled trial of interferon-α in children with chronic hepatitis B
Authors: Mercedes Ruiz-Moreno, Maria José Rua, Josefina Molina, Gloria Moraleda, Alberto Moreno, Jaime García-aguado, Vicente Carréño
Journal: Hepatology (1991)

Thirty-six children with chronic hepatitis B were entered into a randomized controlled trial of recombinant human interferon-α All patients had hepatitis B virus DNA and increased levels of aminotransferases in serum for at least 1 yr. Twelve children received 10 MU of interferon-α 2b/m 2 body surface area three times a week (group I); 12 children received 5 MU/m 2 under the same conditions (group II); and 12 children served as controls (group III). During 6 mo of therapy, 12 of 24 (50%) treated patients (7 from group I, 58%, and 5 from group II, 42%) and 2 of 12 (17%) controls lost hepatitis B virus DNA from serum and subsequently remained negative. Comparison of the rate of response in group I vs. controls showed a statistically significant difference (p &lt; 0.05). Eleven of 12 (92%) treated patients who cleared hepatitis B virus DNA from serum lost HBeAg, seroconverted to anti-HBe and had improvement in liver histological findings with loss of hepatitis B virus DNA from liver. In 10, serum ALT levels became normal. Interferon-α was well tolerated and all children finished therapy. These findings indicate that a 6-mo course of interferon-α is effective in inducing a serological, biochemical and histological remission of disease in approximately 50% of children with chronic hepatitis B. (Hepatology 1991;13:1035-1039.)
Renal Disease, Mononucleosis, and the Guillain-Barré-Strohl Syndrome
Authors: MICHAEL V. FERNANDES
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 June 1973Renal Disease, Mononucleosis, and the Guillain-Barré-Strohl SyndromeMICHAEL V. FERNANDES, M.D., BRIAN GRIMMETT, M.D., JAMES E. CLARK, M.D., F.A.C.P.MICHAEL V. FERNANDES, M.D.Search for more papers by this author, BRIAN GRIMMETT, M.D.Search for more papers by this author, JAMES E. CLARK, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-6-982_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The paper by Bernardo Rodríguez-Iturbe and his associates (1) has been of considerable interest to us. Being aware of consistent reports linking infectious mononucleosis to the Guillain-Barré-Strohl syndrome (2) and also to renal disease (3), which was later shown to be of the "immune complex" type (4), we were interested to know whether the patients manifested the clinical and serologic features of infectious mononucleosis.Our specific argument is that, if acute neural and renal involvement is the effect of a presumable viral disease, infectious mononucleosis should be considered in the diagnosis....References1. RODRÍGUEZ-ITURBE B, GARCÍA R, and RUBIO L: Acute glomerulonephritis in the Guillain-Barré-Strohl syndrome. Report of nine cases. Ann Intern Med 78:391-395, 1973 LinkGoogle Scholar2. RICKER W, BLUMBERG A, and PETERS C: The association of the Guillain-Barré syndrome with infectious mononucleosis. Blood 2:217-226, 1947 CrossrefMedlineGoogle Scholar3. ERWIN W, WEBER R, and MANNING R: Complications of infectious mononucleosis. Am J Med Sci 238:699-712, 1959 CrossrefMedlineGoogle Scholar4. RANDALL R, BRIDIG S, and STILL W: Glomerulonephritis following infectious mononucleosis. Abstracts. 3rd Meeting American Society of Nephrology, 1969. Pg. 56 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MICHAEL V. FERNANDES, M.D.; BRIAN GRIMMETT, M.D.; JAMES E. CLARK, M.D., F.A.C.P.Affiliations: Department of Medicine Division of Nephrology Crozer-Chester Medical Center Chester, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1973Volume 78, Issue 6Page: 982-982KeywordsImmune complexInfectious diseasesRenal diseasesViral diseases ePublished: 1 December 2008 Issue Published: 1 June 1973 PDF downloadLoading ...
BIVALIRUDIN VERSUS HEPARIN PLUS GLYCOPROTEIN IIB/IIIA INHIBITORS IN PATIENTS WITHOUT “ADEQUATE” CLOPIDOGREL PRETREATMENT: A META-ANALYSIS
Authors: Luke Kim, S. Chiu Wong, Edward Wingfield, Hasan Ahmad, Robert M. Minutello, Geoffrey Bergman, Issam Moussa, Dmitriy N. Feldman
Journal: Journal of the American College of Cardiology (2010)
Prospective Study of Clinical Predictors of Suicidal Acts After a Major Depressive Episode in Patients With Major Depressive Disorder or Bipolar Disorder
Authors: Maria A. Oquendo, Hanga Galfalvy, Stefani Russo, Steven P. Ellis, Michael F. Grunebaum, Ainsley Burke, J. John Mann
Journal: American Journal of Psychiatry (2004)

The authors investigated the predictive potential of a stress-diathesis model for suicidal behavior based on correlates of past suicidal acts. In this model, suicidal acts are precipitated by stressors such as life events or a major depressive episode in the setting of a propensity for acting on suicidal urges. This diathesis is expressed as the tendency to develop more pessimism in response to a stressor and/or the presence of aggressive/impulsive traits. The predictive potential of the diathesis was tested by determining whether clinical correlates of past suicidal behavior predict suicidal acts during a 2-year follow-up of patients with a major depressive episode.Patients with DSM-III-R major depressive disorder or bipolar disorder (N=308) were assessed at presentation for treatment of a major depressive episode. Potential predictors of suicidal acts in the 2 years after study enrollment were identified on the basis of an association with previous suicidal behavior and were tested by using Cox proportional hazards regression analysis. In addition, pessimism and aggression/impulsivity factors were generated, and their predictive ability was tested by using Cox proportional hazards regression analysis.The three most powerful predictors of future suicidal acts were a history of suicide attempt, subjective rating of the severity of depression, and cigarette smoking, each of which had an additive effect on future risk. The pessimism and aggression/impulsivity factors both predicted suicidal acts, and each factor showed an additive effect.In addition to obtaining a history of suicidal behavior, clinicians may find it useful to assess patients' current level of pessimism, aggressive/impulsive traits, and comorbidity with substance use disorders, including nicotine-related disorders, to help identify patients at risk for suicidal behavior after major depression. Interventions such as aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptoms may protect such at-risk individuals from future suicidal behavior.
Explorative Genome Scan to Detect Candidate Loci for Adaptation Along a Gradient of Altitude in the Common Frog (Rana temporaria)
Authors: A. Bonin
Journal: Molecular Biology and Evolution (2006)

Today, with the rapid development of population genomics, the genetic basis of adaptation can be unraveled directly at the genome level, without any prerequisites about the selectively advantageous genes or traits. For nonmodel species, it is now possible to screen many markers randomly scattered across the genome and to distinguish between the neutral genetic background and outlier loci displaying an atypical behavior (e.g., a higher differentiation between populations). This study investigated the genetic frame of adaptation to a gradient of altitude in the common frog (Rana temporaria) by means of a genome scan based on 392 amplified fragment length polymorphism markers. Using two outlier detection methods never applied to dominant data so far, we sought for loci with a genetic differentiation diverging from neutral expectations when comparing populations from different altitudes. All the detected loci were sorted out according to their most probable cause for outlier behavior and classified as false positives, outliers due to local effects, or outliers associated with altitude. Altogether, eight good candidate loci were identified as potentially involved in adaptation to altitude because they were picked out in several independent interaltitude comparisons. This result illustrated the potential of genome-wide surveys to reveal selection signatures along selection gradients, where the association between environmental variables and fitness-related traits may be complex and/or cryptic. In this article, we also underlined the need for confirmation of the selection footprints for the outlier loci. Finally, we provided some preliminary insights into the genetic basis of adaptation along an altitudinal cline in the common frog.
THE CONTROL OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION IN NORMAL MAN
Authors: Herbert Chasis, Hilmert A. Ranges, William Goldring, Homer W. Smith
Journal: Journal of Clinical Investigation (1938)

This report is concerned with the effective renal blood flow and rate of glomerular filtration in normal man, as determined by the diodrast and inulin clearances (26) during diuresis and during the action of phlorizin, adrenin, caffeine, nitrite, and typhoid vaccine.The observations not only throw light on the action of these agents, but also afford information concerning the physiological control of renal blood flow and glomerular activity.Typical data are reported graphically.On the assumption that the diodrast plasma clearance (indicated by D in the figures) is a complete clearance, this value is taken as equal to the effective renal plasma flow, i.e., the flow of plasma to active excretory tissue.To convert this figure to the effective whole blood flow it is only necessary to divide it by the per cent of plasma in the blood.For brevity, the term " effective " will be omitted from the discussion without, however, neglecting the physiological distinction between the diodrast clearance and the actual plasma flow which must be somewhat larger than the former in conse- quence of the inclusion of inert tissue.The filtract.
The Orthopaedic Training Study
Authors: George E. Miller
Journal: JAMA (1968)

The Orthopaedic Training Study, a joint enterprise of the American Board of Orthopaedic Surgery and the Center for the Study of Medical Education of the University of Illinois, is now four years old. As a new phase is about to be undertaken, it seems fitting to describe to the medical profession at large what has been accomplished in this critical examination of one facet of graduate medical education, as well as what is proposed. In the interest of perspective, it is useful to begin with a reminder that the study was launched to explore a set of issues about efficiency in the use of limited manpower resources, issues which were serious in 1963 but have reached critical dimensions in 1968. The facts are simple. More man years are now devoted to postdoctoral than to predoctoral professional education in medicine. These years are under the control of specialty boards whose distinguished
Multiple small bowel strictures in a child and accidental potassium chloride ingestion.
Authors: J Tresadern, A M Rickwood, L Spitz
Journal: BMJ (1977)

occasions; in none of these cases was S dysenteriae type 1 the causative organism.Two patients had bacteraemia.'-3Petechial rashes have been seen on some occasions in shigellosis,4 but they are quite different from rose spots-which have sharply defined borders and disappear on applying pressure.The size of the spots and absence of itching differentiate them from allergic rashes due to ampicillin.An upsurge of shigellosis due to S dysenteriae 1 has been recorded in Bangladesh since the end of war in 1971.5 Nevertheless, rose spots were not detected in any one of over 4000 patients seen during the last five years.
End of life care in the acute hospital setting
Authors: P. Edmonds, R. Burman, W. Prentice
Journal: BMJ (2009)

An update of the Liverpool care pathway does much to tackle recent criticisms

Most deaths occur in hospital, yet effective management of dying patients in this environment is challenging. The Liverpool care pathway was developed as a framework to guide practice and extend the excellence of hospice care into hospital, where there was evidence of poor quality care.1 2

An updated version (version 12) of this care pathway was ratified on 2 December 2009. A recent media debate during the consultation period raised criticisms that the pathway is prescriptive and inevitably leads to the patient’s death; it also highlighted concerns about inappropriate sedation and dehydration. The debate has produced welcome political and professional interest in the care of the dying.

The Liverpool care pathway offers a framework that helps non-specialists manage the dying process, with the aim of ensuring a minimum standard of care for people who are dying. If correctly used it should not hasten a patient’s death. Research from the United Kingdom and international data show that the pathway reduces symptom burden, improves multidisciplinary working, and increases anticipatory prescribing for key symptoms that may develop in the last hours or days of life. It also improves nurses’ confidence in caring for the dying.3 4 5 Two national audits have benchmarked data …
Mapping Community Determinants of Heat Vulnerability
Authors: Colleen E. Reid, Marie S. O’Neill, Carina J. Gronlund, Shannon J. Brines, Daniel G. Brown, Ana V. Diez-Roux, Joel Schwartz
Journal: Environmental Health Perspectives (2009)

BackgroundThe evidence that heat waves can result in both increased deaths and illness is substantial, and concern over this issue is rising because of climate change. Adverse health impacts from heat waves can be avoided, and epidemiologic studies have identified specific population and community characteristics that mark vulnerability to heat waves.ObjectivesWe situated vulnerability to heat in geographic space and identified potential areas for intervention and further research.MethodsWe mapped and analyzed 10 vulnerability factors for heat-related morbidity/mortality in the United States: six demographic characteristics and two household air conditioning variables from the U.S. Census Bureau, vegetation cover from satellite images, and diabetes prevalence from a national survey. We performed a factor analysis of these 10 variables and assigned values of increasing vulnerability for the four resulting factors to each of 39,794 census tracts. We added the four factor scores to obtain a cumulative heat vulnerability index value.ResultsFour factors explained > 75% of the total variance in the original 10 vulnerability variables: a) social/environmental vulnerability (combined education/poverty/race/green space), b) social isolation, c) air conditioning prevalence, and d) proportion elderly/diabetes. We found substantial spatial variability of heat vulnerability nationally, with generally higher vulnerability in the Northeast and Pacific Coast and the lowest in the Southeast. In urban areas, inner cities showed the highest vulnerability to heat.ConclusionsThese methods provide a template for making local and regional heat vulnerability maps. After validation using health outcome data, interventions can be targeted at the most vulnerable populations.
Hepatocytic TGFβ1 is involved in interferon alfa-2B (IFN)-induced apoptosis on rat preneoplastic liver
Authors: M.L. Alvarez, M.T. Ronco, J. Monti, J.E. Ochoa, C. Carnovale, G. Pisani, M.C. Lugano, M.C. Carrillo
Journal: Journal of Hepatology (2003)