tbuckley/cabot-search huggingface dataset:
Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction.
Authors: J B Michel, A L Lattion, J L Salzmann, M L Cerol, M Philippe, J P Camilleri, P Corvol
Journal: Circulation Research (1988)

To explain how converting enzyme inhibition could improve the prognosis in cardiac insufficiency, the effect of converting enzyme inhibition (CEI) by S9490-3 (Perindopril) treatment for 2 months (treated infarctions, n = 18) on hormonal plasma variables and the quantitative and qualitative changes in myocardium were studied in an experimental model of left ventricular infarction in rats (untreated infarctions, n = 18) and compared to a sham-operated control group (n = 15). Induction of myocardial infarction was associated with a transient decrease in blood pressure. CEI treatment maintained a lower blood pressure throughout the experimental period. Plasma renin concentration was not significantly increased in the untreated infarct group (155.4 +/- 136.7 ng AI/ml/hr) as compared to the sham-operated group (47.6 +/- 15.9 ng AI/ml/hr). Plasma aldosterone did not change in the three experimental groups. The plasma level of immunoreactive atrial natriuretic factor increased in the untreated infarct group (185 +/- 245 pg/ml) as compared with the control group (76 +/- 40 pg/ml) and was normalized by CEI (66 +/- 60 pg/ml). Body weight was slightly decreased in both treated and untreated infarct groups, whereas the heart weight was significantly increased in the untreated group (1,540 +/- 310 mg) and normalized by treatment (1,145 +/- 180 mg) as compared with sham-operated controls (1,071 +/- 80 mg). The combined atria and right ventricular mass was significantly increased in the untreated infarct group (660 +/- 210 mg) and decreased by treatment (443 +/- 106 mg) but was not completely normalized (controls, 343 +/- 40 mg). Left ventricular isomyosin profiles were modified by myocardial infarction as compared with controls: V1 form decreased from 62.4 +/- 9.4% in the sham-operated group to 41.6 +/- 13.4% in the infarct group, and the V3 form increased from 13.0 +/- 4.7% in sham-operated animals to 27.4 +/- 11.8% in untreated infarct animals. CEI treatment partially, but significantly, reversed this modification of the isomyosin profile (V1, 53.0 +/- 14.4%; V3, 17.5 +/- 8.0%). Volume density of collagen was significantly increased in the untreated infarct rats (4.14 +/- 0.81% versus 2.68 +/- 0.49% in controls), and this was reversed by treatment (2.95 +/- 0.66%). Messenger RNA encoding for atrial natriuretic factor, measured by dot blot hybridization, was significantly increased in both the atria and the ventricles in the untreated infarct group, and treatment by CEI partially reversed this increase. Thus, myocardial infarction profoundly modified several variables of peripheral circulation and quantitative and qualitative myocardial protein expression.(ABSTRACT TRUNCATED AT 400 WORDS)
Impact of a Bladder Cancer Diagnosis on Smoking Behavior
Authors: Jeffrey C. Bassett, John L. Gore, Amanda C. Chi, Lorna Kwan, William McCarthy, Karim Chamie, Christopher S. Saigal
Journal: Journal of Clinical Oncology (2012)

Bladder cancer is the second most common tobacco-related malignancy. A new bladder cancer diagnosis may be an opportunity to imprint smoking cessation. Little is known about the impact of a diagnosis of bladder cancer on patterns of tobacco use and smoking cessation among patients with incident bladder cancer.A simple random sample of noninvasive bladder cancer survivors diagnosed in 2006 was obtained from the California Cancer Registry. Respondents completed a survey on history of tobacco use, beliefs regarding bladder cancer risk factors, and physician influence on tobacco cessation. Respondents were compared by smoking status. Those respondents smoking at diagnosis were compared with general population controls obtained from the California Tobacco Survey to determine the impact of a diagnosis of bladder cancer on patterns of tobacco use.The response rate was 70% (344 of 492 eligible participants). Most respondents (74%) had a history of cigarette use. Seventeen percent of all respondents were smoking at diagnosis. Smokers with a new diagnosis of bladder cancer were almost five times as likely to quit smoking as smokers in the general population (48% v 10%, respectively; P < .001). The bladder cancer diagnosis and the advice of the urologist were the reasons cited most often for cessation. Respondents were more likely to endorse smoking as a risk factor for bladder cancer when the urologist was the source of their understanding.The diagnosis of bladder cancer is an opportunity for smoking cessation. Urologists can play an integral role in affecting the patterns of tobacco use of those newly diagnosed.
Resistance to Chemotherapy Is Associated with Fibroblast Growth Factor Receptor 4 Up-Regulation
Authors: Andreas Roidl, Hans-Jürgen Berger, Sushil Kumar, Johannes Bange, Pjotr Knyazev, Axel Ullrich
Journal: Clinical Cancer Research (2009)

Establishment of antiapoptotic signaling pathways in tumor cells is a major cause for the failure of chemotherapy against cancer. To investigate the underlying mechanisms, we developed an experimental approach that is based on the genetic plasticity of cancer cells and the selection for cell survival on treatment with chemotherapeutic agents.Gene expression changes of surviving cell clones were analyzed by macroarrays. Involvement of fibroblast growth factor receptor 4 (FGFR4) in antiapoptotic pathways was elucidated by apoptosis assays, small interfering RNA experiments, and an antagonistic antibody.We show that FGFR4 gene expression is up-regulated in doxorubicin-treated, apoptosis-resistant cancer cell clones. Ectopic expression of FGFR4 in cancer cells led to reduced apoptosis sensitivity on treatment with doxorubicin or cyclophosphamide, whereas knockdown of endogenous FGFR4 expression in breast cancer cell lines had the opposite effect. FGFR4 overexpression resulted in Bcl-xl up-regulation at both mRNA and protein levels. Knockdown of FGFR4 expression by small interfering RNA caused a decrease in phospho-extracellular signal-regulated kinase 1/2 levels and reduced Bcl-xl expression. Moreover, an antagonistic FGFR4 antibody suppressed the resistance of cancer cells with endogenous FGFR4 expression against apoptosis-inducing chemotherapeutic agents.Based on these findings, we propose an antiapoptotic signaling pathway that is initiated by FGFR4 and regulating the expression of Bcl-xl through the mitogen-activated protein kinase cascade. Our findings are exemplary for a novel strategy toward the elucidation of diverse signaling pathways that define antiapoptotic potential in cancer cells. These observations open new avenues toward the diagnosis of chemoresistant tumors and therapies targeting FGFR4-overexpressing cancers.
Pharmacogenetics of Warfarin
Authors: Farhad Kamali, Hilary Wynne
Journal: Annual Review of Medicine (2009)

Warfarin is a drug with a narrow therapeutic index and a wide interindividual variability in dose requirement. Because it is difficult to predict an accurate dose for an individual, patients starting the drug are at risk of thromboembolism or bleeding associated with underdosing or overdosing, respectively. Single nucleotide polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) genes have been shown to have a significant effect on warfarin dose requirement. Other genes mediating the action of warfarin make either little or no contribution to dose requirement. Although the polymorphisms in CYP2C9 and VKORC1 explain a significant proportion of the interindividual variability in warfarin dose requirement, currently available evidence based on a few small studies relating to the use of pharmacogenetics-guided dosing in the initiation of warfarin therapy has not shown improved outcomes in either safety or efficacy of therapy. Better clinical evidence of beneficial effects on patient outcome, particularly at the extremes of the dose requirements in geographically and ethnically diverse patient populations, is needed before the role of a pharmacogenomic approach to oral anticoagulation therapy in clinical practice can be established.
New arrangements for prison health care
Authors: Nick de Viggiani, Judy Orme, Jane Powell, Debra Salmon
Journal: BMJ (2005)

New arrangements for prison health careProvide an opportunity and a challenge for primary care trusts F rom April, responsibility for prison health care in England has shifted from the Prison Service to primary care trusts.Under the new arrangements, primary care trusts are expected to develop prison healthcare delivery plans based on assessment and analyses of healthcare needs. 1 Given the extensive range of health problems reported among prisoners, this will be a major challenge for primary care trusts.Furthermore, in the light of the recent public health white paper, Choosing Health, 2 primary care trusts are expected to take a public health approach and aim to find the causes of health inequalities and social exclusion among prisoners and try and prevent them.Health needs of prisoners are diverse and complex.4][5][6] Moreover, prisoners are reported to be more preoccupied with their health and to place much greater demands on primary and secondary healthcare services than the general population. 4 7 Recent research has highlighted three key areas where primary care trusts should prioritise resourcesthe staff who provide prison health care; the systems
Predicting mortality in the elderly with community-acquired pneumonia: should we design a new car or set a new 'speed limit'?
Authors: V. Brito, M. S. Niederman
Journal: Thorax (2010)

Community-acquired pneumonia (CAP) is a common illness associated with increasing mortality rates that parallel the site of care. While outpatients have a risk of dying of <5%, those in hospital have a mortality rate of 12% and those managed in the ICU can have a chance of dying that exceeds 30%.1 In addition, delayed recognition of severe illness can add to mortality, with those admitted to the ICU late in the course of disease having a higher mortality than those admitted early.2 Thus, patient outcome is dependent on making an accurate assessment about where patients should be initially managed and the intensity of care that they should receive. To this end, a number of prognostic scoring systems have been developed for patients with CAP that can predict the mortality risk, which is then often applied as a surrogate for deciding the initial site of care.1 3 4 Unfortunately, the risk of death is not always correlated with the need for a high level of care including need for ICU admission. In fact, patients who are young and otherwise healthy may benefit from ICU admission yet have a much lower predicted mortality risk than older patients with multiple medical comorbidities who may benefit little from admission to a hospital unit that provides a high level of care. Accurate definition of the site of care not only impacts mortality, but also the cost of care which rises incrementally from outpatient to inpatient to ICU management.

The most commonly used tools for predicting mortality—the CURB-65 (confusion, elevated blood urea nitrogen, elevated respiratory rate, low blood pressure and age >65 years), derived from the British Thoracic Society rule,5 and the Pneumonia Severity Index (PSI)1—predict mortality by giving a point …
Role of the peripheral vasculature in changes in venous return caused by isoproterenol, norepinephrine, and methoxamine in anesthetized dogs.
Authors: Y Imai, K Satoh, N Taira
Journal: Circulation Research (1978)

We studied effects on venous return of alpha- and beta-adrenergic agonists in anesthetized dogs. Blood from the superior and inferior venae cavae (venous return) was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant rate. Isoproterenol infused into the ascending aorta or the right atrium increased the venous return and heart rate and decreased systemic blood pressure. The increase in venous return produced by isoproterenol given into the right atrium was not significantly different from that produced by isoproterenol administered into the ascending aorta, although the increase in heart rate was more marked with the latter route of administration. Norepinephrine infused into the ascending aorta increased the systemic blood pressure, venous return, and heart rate. Methoxamine infused into the ascending aorta increased the systemic blood pressure and decreased the venous return but produced no change in heart rate. Isoproterenol increased the venous return even when the sinoaortic baroreceptor reflex was eliminated. Propranolol abolished the increase in venous return caused by isoproterenol and reversed the increase in venous return caused by norepinephrine. The results suggest that a decrease in venous resistance mediated through a beta-adrenergic mechanism is important in increasing venous return, whereas an increase in venous resistance mediated through an alpha-adrenergic mechanism is responsible for a decrease in venous return.
Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure, secondary failure or intolerance to etanercept
Authors: P.P.M. Van Lümig, L.L.A. Lecluse, R.J.B. Driessen, P.I. Spuls, J.B. Boezeman, P.C.M. Van De Kerkhof, E.M.G.J. De Jong
Journal: British Journal of Dermatology (2010)

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.
Prevalence, Comorbidity, and Correlates of DSM-5 Proposed Disruptive Mood Dysregulation Disorder
Authors: William E. Copeland, Adrian Angold, E. Jane Costello, Helen Egger
Journal: American Journal of Psychiatry (2013)

The low prevalence rates in three large community samples of children (0.8% to 3.3%) for the new proposed diagnosis of disruptive mood dysregulation disorder suggest that the diagnosis will not be extensively applied to children with normal behavior. Although the core symptoms are common, the criteria regarding frequency, duration, and context exclude most children. The diagnosis is associated with high levels of social impairment, school suspension, service use, and poverty. It frequently co-occurs with other psychiatric conditions, especially oppositional defiant disorder and depressive disorders, but overlapped only partially with severe mood dysregulation, the research diagnosis on which it was based.
Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics
Authors: Leo Kager, Meyling Cheok, Wenjian Yang, Gianluigi Zaza, Qing Cheng, John C. Panetta, Ching-Hon Pui, James R. Downing, Mary V. Relling, William E. Evans
Journal: Journal of Clinical Investigation (2005)

The ability of leukemia cells to accumulate methotrexate polyglutamate (MTXPG) is an important determinant of the antileukemic effects of methotrexate (MTX). We measured in vivo MTXPG accumulation in leukemia cells from 101 children with acute lymphoblastic leukemia (ALL) and established that B-lineage ALL with either TEL-AML1 or E2A-PBX1 gene fusion, or T-lineage ALL, accumulates significantly lower MTXPG compared with B-lineage ALL without these genetic abnormalities or compared with hyperdiploid (fewer than 50 chromosomes) ALL. To elucidate mechanisms underlying these differences in MTXPG accumulation, we used oligonucleotide microarrays to analyze expression of 32 folate pathway genes in diagnostic leukemia cells from 197 children. This revealed ALL subtype–specific patterns of folate pathway gene expression that were significantly related to MTXPG accumulation. We found significantly lower expression of the reduced folate carrier (SLC19A1, an MTX uptake transporter) in E2A-PBX1 ALL, significantly higher expression of breast cancer resistance protein (ABCG2, an MTX efflux transporter) in TEL-AML1 ALL, and lower expression of FPGS (which catalyzes formation of MTXPG) in T-lineage ALL, consistent with lower MTXPG accumulation in these ALL subtypes. These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome these potential causes of treatment failure in childhood ALL.
Do IgA antigliadin and IgA antiendomysium antibodies show there is latent coeliac disease in primary IgA nephropathy?
Authors: C Sategna-Guidetti, G Ferfoglia, M Bruno, R Pulitano, D Roccatello, A Amore, R Coppo
Journal: Gut (1992)

The finding in primary IgA nephropathy of increased levels of IgA to food antigens and particularly to gliadin prompted the hypothesis that a subgroup of these patients may have latent coeliac disease. The observation that gliadin may experimentally induce IgA mesangial deposits supported this hypothesis. We evaluated specific immunological markers of coeliac disease (antiendomysium antibodies) which parallel histological changes of gluten sensitive enteropathy, and an IgA immunofluorescent test for antigliadin antibodies in 18 patients with IgA nephropathy, in 56 untreated coeliac disease patients, in 254 controls (58 healthy and 196 disease controls). Antiendomysium antibodies were positive in 89.28% of coeliac patients, but negative in all IgA nephropathies and controls. IgA immunofluorescent test for antigliadin antibodies, negative in all IgA nephropathy patients, was positive in 76.78% of coeliac patients and in 4.91% of controls. ELISA IgA antigliadin antibodies were negative in controls, but positive in 22.22% of IgA nephropathy patients and in 60.71% of coeliac patients. Our data would suggest that in most patients with IgA nephropathy there is no evidence of latent coeliac disease.
Spain launches national plan for palliative care
Authors: X. Bosch
Journal: BMJ (2000)

The Spanish health ministry is to launch a national plan on palliative care aimed at improving the quality of life of terminally ill patients on a “rational, planned, and effective” basis and at ensuring that palliative care constitutes a “legal and individual right” of patients.

Special attention will also be paid to improving the quality of life of relatives of terminally ill patients. The report highlights the necessity of a …
Gene expression–based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study
Authors: Kerby Shedden, Jeremy M.G. Taylor, Steven A. Enkemann, Ming Sound Tsao, Timothy J. Yeatman, William L. Gerald, Steven Eschrich, Igor Jurisica, Thomas J. Giordano, David E. Misek, Andrew C. Chang, Chang Qi Zhu, Daniel Strumpf, Samir Hanash, Frances A. Shepherd, Keyue Ding, Lesley Seymour, Katsuhiko Naoki, Nathan Pennell, Barbara Weir, Roeland Verhaak, Christine Ladd-Acosta, Todd Golub, Michael Gruidl, Anupama Sharma, Janos Szoke, Maureen Zakowski, Valerie Rusch, Mark Kris, Agnes Viale, Noriko Motoi, William Travis, Barbara Conley, Venkatraman E. Seshan, Matthew Meyerson, Rork Kuick, Kevin K. Dobbin, Tracy Lively, James W. Jacobson, David G. Beer
Journal: Nature Medicine (2008)
Local Ca <sup>2+</sup> Entry Through L-Type Ca <sup>2+</sup> Channels Activates Ca <sup>2+</sup> -Dependent K <sup>+</sup> Channels in Rabbit Coronary Myocytes
Authors: Antonio Guia, Xiaodong Wan, Marc Courtemanche, Normand Leblanc
Journal: Circulation Research (1999)

Abstract —Large-conductance Ca 2+ -dependent K + channels (K Ca ), which are abundant on the sarcolemma of vascular myocytes, provide negative feedback via membrane hyperpolarization that limits Ca 2+ entry through L-type Ca 2+ channels ( I CaL ). We hypothesize that local accumulation of subsarcolemmal Ca 2+ during I CaL openings amplifies this feedback. Our goal was to demonstrate that Ca 2+ entry through voltage-gated I CaL channels can stimulate adjacent K Ca channels by a localized interaction in enzymatically isolated rabbit coronary arterial myocytes voltage clamped in whole-cell or in cell-attached patch clamp mode. During slow-voltage-ramp protocols, we identified an outward K Ca current that is activated by a subsarcolemmal Ca 2+ pool dissociated from bulk cytosolic Ca 2+ pool (measured with indo 1) and is dependent on L-type Ca 2+ channel activity. Transient activation of unitary K Ca channels in cell-attached patches could be detected during long step depolarizations to +40 mV (holding potential, −40 mV; 219 pS in near-symmetrical K + ). This local interaction between the channels required the presence of Ca 2+ in the pipette solution, was enhanced by the I CaL agonist Bay K 8644, and persisted after impairment of the sarcoplasmic reticulum by incubation with 10 μmol/L ryanodine and 30 μmol/L cyclopiazonic acid for at least 60 minutes. Furthermore, we provide the first direct evidence of simultaneous openings of single K Ca (67 pS) and I CaL (3.9 pS) channels in near-physiological conditions, near resting membrane potential. Our data imply a novel sensitive mechanism for regulating resting membrane potential and tone in vascular smooth muscle.
Rehabilitation of scapular dyskinesis: from the office worker to the elite overhead athlete
Authors: Ann M J Cools, Filip Struyf, Kristof De Mey, Annelies Maenhout, Birgit Castelein, Barbara Cagnie
Journal: British Journal of Sports Medicine (2013)

The scapula functions as a bridge between the shoulder complex and the cervical spine and plays a very important role in providing both mobility and stability of the neck/shoulder region. The association between abnormal scapular positions and motions and glenohumeral joint pathology has been well established in the literature, whereas studies investigating the relationship between neck pain and scapular dysfunction have only recently begun to emerge. Although several authors have emphasised the relevance of restoring normal scapular kinematics through exercise and manual therapy techniques, overall scapular rehabilitation guidelines decent for both patients with shoulder pain as well as patients with neck problems are lacking. The purpose of this paper is to provide a science-based clinical reasoning algorithm with practical guidelines for the rehabilitation of scapular dyskinesis in patients with chronic complaints in the upper quadrant.