tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin and Oral Anticoagulants for Prevention of Thromboembolic Complications in Cardioversion of Nonvalvular Atrial Fibrillation
Authors: Christoph Stellbrink, Uwe Nixdorff, Thomas Hofmann, Walter Lehmacher, Werner Günther Daniel, Peter Hanrath, Christoph Geller, Andreas Mügge, Walter Sehnert, Caroline Schmidt-Lucke, Jan-André Schmidt-Lucke
Journal: Circulation (2004)

Anticoagulation in cardioversion of atrial fibrillation is currently performed with unfractionated heparin (UFH) and oral anticoagulants, with or without guidance by transesophageal echocardiography (TEE). Low-molecular-weight heparins may reduce the risk of bleeding, may obviate the need for intravenous access, and do not require frequent anticoagulation monitoring.In a randomized, prospective multicenter trial, we compared the safety and efficacy of enoxaparin administered subcutaneously with intravenous UFH followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for cardioversion of atrial fibrillation of >48 hours' and < or =1 year's duration. Patients were stratified to cardioversion with (n=431) and without (n=65) guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin compared with UFH+phenprocoumon with regard to the incidence of embolic events, all-cause death, and major bleeding complications. Secondary end points included successful cardioversion, maintenance of sinus rhythm until study end, and minor bleeding complications. Of 496 randomized patients, 428 were analyzed per protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the incidence of the composite primary end point in a per-protocol analysis (7 of 216 patients versus 12 of 212 patients, respectively; P=0.016) and in an intention-to-treat analysis (7 of 248 patients versus 12 of 248 patients, respectively; P=0.013). There was no significant difference between the 2 groups in the number of patients reverted to sinus rhythm.Enoxaparin is noninferior to UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding complications, and death in TEE-guided cardioversion of atrial fibrillation. Its easier application and more stable anticoagulation may make it the preferred drug for initiation of anticoagulation in this setting.
The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults
Authors: Symeon Tournis, Asimina Mitrakou
Journal: Diabetes Care (2007)

In their recent article, Pittas et al. (1) reported on the effect of calcium and vitamin D supplementation on glycemic status in nondiabetic elderly subjects. Because vitamin D supplementation, though mainly in subjects with relatively low vitamin D levels, improves muscle …
Association of a Cancer Diagnosis With Vulnerability and Frailty in Older Medicare Beneficiaries
Authors: S. G. Mohile, Y. Xian, W. Dale, S. G. Fisher, M. Rodin, G. R. Morrow, A. Neugut, W. Hall
Journal: JNCI Journal of the National Cancer Institute (2009)

Few studies have evaluated the independent effect of a cancer diagnosis on vulnerability and frailty, which have been associated with adverse health outcomes in older adults.We used data in the 2003 Medicare Current Beneficiary Survey from a nationally representative sample of 12,480 community-dwelling elders. Multivariable logistic regression models were used to evaluate whether cancer was independently associated with vulnerability and frailty. Measures of vulnerability and frailty included disability, geriatric syndromes, self-rated health, and scores on two assessment tools for elderly cancer patients-the Vulnerable Elders Survey-13 (VES-13) and the Balducci frailty criteria. All statistical tests were two-sided.Diagnosis of a non-skin cancer was reported by 18.8% of the respondents. Compared with respondents without a cancer history, respondents with a personal history of cancer had a statistically significantly higher prevalence of limitations in activities of daily living (31.9% vs 26.9%), limitations in instrumental activities of daily living (49.5% vs 42.3%), geriatric syndromes (60.8% vs 53.9%), low self-rated health (27.4% vs 20.9%), score of 3 or higher on the VES-13 (45.8% vs 39.5%), and satisfying criteria for frailty as defined by Balducci (79.6% vs 73.4%) (P < .001 for all characteristics). After adjustment for confounders, a cancer diagnosis was found to be associated with low self-rated health (adjusted odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.30 to 1.64; relative risk [RR] = 1.33), limitations in activities of daily living (adjusted OR = 1.19, 95% CI = 1.06 to 1.33; RR = 1.13), limitations in instrumental activities of daily living (adjusted OR = 1.25, 95% CI = 1.13 to 1.38; RR = 1.13), a geriatric syndrome (adjusted OR = 1.27, 95% CI = 1.15 to 1.41; RR = 1.11), VES-13 score of 3 or higher (adjusted OR = 1.26, 95% CI = 1.13 to 1.41; RR = 1.14), and frailty (adjusted OR = 1.46, 95% CI = 1.29 to 1.65; RR = 1.09) as defined by Balducci criteria.Diagnosis of a non-skin cancer was associated with increased levels of having disability, having geriatric syndromes, and meeting criteria for vulnerability and frailty.
Identification of a dominant epitope of glutamic acid decarboxylase (GAD-65) recognized by autoantibodies in stiff-man syndrome.
Authors: M H Butler, M Solimena, R Dirkx, A Hayday, P De Camilli
Journal: The Journal of Experimental Medicine (1993)

Glutamic acid decarboxylase (GAD) is the enzyme that synthesizes the neurotransmitter gamma-aminobutyric acid (GABA) in neurons and in pancreatic beta cells. It is a major target of autoimmunity in Stiff-Man syndrome (SMS), a rare neurological disease, and in insulin-dependent diabetes mellitus. The two GAD isoforms, GAD-65 and GAD-67, are the products of two different genes. GAD-67 and GAD-65 are very similar to each other in amino acid sequence and differ substantially only at their NH2-terminal region. We have investigated the reactivity of autoantibodies of 30 Stiff-Man syndrome patients to GAD. All patient sera contained antibodies that recognize strongly GAD-65, but also GAD-67, when tested by immunoprecipitation on brain extracts and by immunoprecipitation or immunocytochemistry on cells transfected with either the GAD-65 or the GAD-67 gene. When tested by Western blotting, all patient sera selectively recognized GAD-65. Western blot analysis of deletion mutants of GAD-65 demonstrated that autoantibodies are directed predominantly against two regions of the GAD-65 molecule. All SMS sera strongly recognized a fragment contained between amino acid 475 and the COOH terminus (amino acid 585). Within this region, amino acids 475-484 and 571-585 were required for reactivity. The requirement of these two discontinuous segments implies that the epitope is influenced by conformation. This reactivity is similar to that displayed by the monoclonal antibody GAD 6, suggesting the presence of a single immunodominant epitope (SMS-E1) in this region of GAD-65. In addition, most SMS sera recognized at least one epitope (SMS-E2) in the NH2-terminal domain of GAD-65 (amino acids 1-95). The demonstration in SMS patients of a strikingly homogeneous humoral autoimmune response against GAD and the identification of dominant autoreactive target regions may help to elucidate the molecular mechanisms of GAD processing and presentation involved in GAD autoimmunity. Moreover, the reactivity reported here of GAD autoantibodies in SMS partially differs from the reactivity of GAD autoantibodies in insulin-dependent diabetes mellitus, suggesting a link between the pattern of humoral autoimmunity and the clinical condition.
NHS efficiency savings may be at expense of service cuts and staff pay, say MPs
Authors: A. O'Dowd
Journal: BMJ (2013)

Progress so far in making efficiency savings in the NHS in England may have been achieved only by reducing some services for patients and freezing staff pay, MPs have warned.

More substantial long term changes to the way the NHS provides services in a more cost effective and efficient way are far less certain, said a report published by the parliamentary Public Accounts Committee on 22 March.1

In their report on progress in making NHS efficiency savings, the MPs said that there seemed to be positive movement towards the government’s goal for the NHS to make efficiency savings of £20bn (€23bn; $30bn) in the four years to 2014-15 to allow the NHS to keep pace with growing demand.

During the committee’s inquiry the Department of Health had reported that the NHS made savings of £5.8bn in 2011-12 and that it was …
Arterial Baroreceptor Fibers from the Aortic Region of the Dog in the Cervical Vagus Nerve
Authors: CYRIL S. ITO, ALLEN M. SCHER
Journal: Circulation Research (1973)

The neural pathways followed by sensory fibers from arterial baroreceptors in the aortic region of the dog were investigated with neurophysiological recording. Systemic arterial baroreceptor fibers separate from the depressor nerve were found in the left cervical vagus in each of five dogs investigated; at most two fibers were isolated from each dog due to the difficulty of the dissection. These fibers originated from or above the aortic arch region. One baroreceptor fiber had its arterial sensory ending below the fifth rib. In the right cervical vagus in six dogs, visual evidence of fiber activity from systemic arterial baroreceptors could not be produced; only subjective (auditory) evidence for the presence of systemic arterial baroreceptor fibers was obtained. The number of these arterial baroreceptor fibers, which run in the vagus nerve but are not part of the depressor nerve, appeared to be smaller than the number of arterial baroreceptor fibers in the depressor nerve.
Pegylated Interferon Alfa-2a Yields High Rates of Hematologic and Molecular Response in Patients With Advanced Essential Thrombocythemia and Polycythemia Vera
Authors: Alfonso Quintás-Cardama, Hagop Kantarjian, Taghi Manshouri, Rajyalakshmi Luthra, Zeev Estrov, Sherry Pierce, Mary Ann Richie, Gautam Borthakur, Marina Konopleva, Jorge Cortes, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2009)

Purpose We conducted a phase II study of pegylated interferon alfa-2a (PEG-IFN-α-2a) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Patients and Methods Seventy-nine patients (40 with PV and 39 with ET) have been treated. Median time from diagnosis to PEG-IFN-α-2a was 54 months in patients with PV and 33 months in patients with ET. Eighty-one percent of patients had received prior therapy. The first three patients received PEG-IFN-α-2a at 450 μg weekly. As a result of poor tolerance, this dose was decreased in a stepwise manner to a current starting dose of 90 μg weekly. Seventy-seven patients are evaluable and have been observed for a median of 21 months. Results The overall hematologic response rate was 80% in PV and 81% in ET (complete in 70% and 76% of patients, respectively). The JAK2 V617F mutation was detected in 18 patients with ET and 38 patients with PV; sequential measurements by a pyrosequencing assay were available in 16 patients with ET and 35 patients with PV. The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2 V617F ) in 6% and 14%, respectively. The JAK2 V617F mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability of PEG-IFN-α-2a at 90 μg weekly was excellent. Conclusion PEG-IFN-α-2a resulted in remarkable clinical activity, high rates of molecular response, and acceptable toxicity in patients with advanced ET or PV. The ability of PEG-IFN-α-2a to induce complete molecular responses suggests selective targeting of the malignant clone.
FoxO1 is crucial for sustaining cardiomyocyte metabolism and cell survival
Authors: Prasanth Puthanveetil, Andrea Wan, Brian Rodrigues
Journal: Cardiovascular Research (2012)

Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentially switching on protein targets like FoxOs, initiators of cell death. FoxO1, a prominent member of the forkhead box family and subfamily O of transcription factors and produced from the FKHR gene, is involved in regulating metabolism, cell proliferation, oxidative stress response, immune homeostasis, pluripotency in embryonic stem cells, and cell death. In this review we describe distinctive functions of FoxOs, specifically FoxO1 under conditions of nutrient excess, insulin resistance and diabetes, and its manipulation to restore metabolic equilibrium to limit cardiac damage due to cell death. Because FoxO1 helps cardiac tissue to combat a variety of stress stimuli, it could be a major determinant in regulating diabetic cardiomyopathy. In this regard, we highlight studies from our group and others who illustrate how cardiac tissue-specific FoxO1 deletion protects the heart against cardiomyopathy and how its down-regulation in endothelial tissue could prevent against atherosclerotic plaques. In addition, we also describe studies that show FoxO1's beneficial qualities by highlighting their role in inducing anti-oxidant, autophagic, and anti-apoptotic genes under stress conditions of ischaemia–reperfusion and myocardial infarction. Thus, the aforementioned FoxO1 traits could be useful in curbing cardiac tissue-specific impairment of function following diabetes.
Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy
Authors: Guillaume Ploussard, Stéphane Terry, Pascale Maillé, Yves Allory, Nanor Sirab, Laurence Kheuang, Pascale Soyeux, Nathalie Nicolaiew, Estelle Coppolani, Bernard Paule, Laurent Salomon, Stéphane Culine, Ralph Buttyan, Francis Vacherot, Alexandre de la Taille
Journal: Cancer Research (2010)

Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human PCa cell lines using a human βIII-tubulin expression vector or βIII-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.
MAINTENANCE THERAPY OF CHRONIC PSYCHOTICS WITH PERPHENAZINE
Authors: J. PIUS BARBOUR
Journal: American Journal of Psychiatry (1963)

Perphenazine was used to treat 300 psychotic patients. The dosage usually ranged between 16 and 4 mg. three times daily, for 1 to 9 months. Remission or significant improvement occurred among 80% of first-admission patients and among 70% of those who had had one or several previous admissions. Mild pseudoparkinsonism during high dosage was the only significant side effect.
Selective Activation of the c-Jun NH2-terminal Protein Kinase Signaling Pathway by Stimulatory KIR in the Absence of KARAP/DAP12 in CD4+ T Cells
Authors: Melissa R. Snyder, Mathias Lucas, Eric Vivier, Cornelia M. Weyand, Jörg J. Goronzy
Journal: The Journal of Experimental Medicine (2003)

Activation of CD4(+) T cells is governed by interplay between stimulatory and inhibitory receptors; predominance of stimulatory signals favors autoimmune reactions. In patients with rheumatoid arthritis, expression of the critical costimulatory molecule, CD28, is frequently lost. Instead, CD4(+)CD28(null) T cells express killer immunoglobulin-like receptors (KIRs) with a preferential expression of the stimulatory receptor, CD158j. The frequency of CD4(+)CD28(null) T cells in rheumatoid arthritis (RA) correlates with the risk for more severe disease. Moreover, the KIR2DS2 gene, which encodes for CD158j, is a genetic risk factor for rheumatoid vasculitis. CD158j signals through the adaptor molecule, KARAP/DAP12, to positively regulate cytotoxic activity in NK cells. However, the majority of CD4(+)CD28(null) T cell clones lacked the expression of KARAP/DAP12. Despite the absence of KARAP/DAP12, CD158j was functional and augmented interferon-gamma production after T cell receptor stimulation. Cross-linking of CD158j resulted in selective phosphorylation of c-Jun NH(2)-terminal protein kinase (JNK) and its upstream kinase, MKK4 that led to the expression of ATF-2 and c-Jun, all in the absence of extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Mutation of the lysine residue within the transmembrane domain of CD158j abolished JNK activation, suggesting that an alternate adaptor molecule was being used. CD4(+)CD28(null) T cells expressed DAP10 and inhibition of phosphatidylinositol 3-kinase, which acts downstream of DAP10, inhibited JNK activation; however, no interaction of DAP10 with CD158j could be detected. Our data suggest that CD158j in T cells functions as a costimulatory molecule through the JNK pathway independent of KARAP/DAP12 and DAP10. Costimulation by CD158j may contribute to the autoreactivity of CD4(+)CD28(null) T cells in RA.
Increased respiratory chemosensitivity induced by infusing almitrine intravenously in healthy man.
Authors: N N Stanley, J M Galloway, B Gordon, N Pauly
Journal: Thorax (1983)

The respiratory effects of intravenously infused almitrine were evaluated in healthy volunteers. In the dose range 0.25-1.0 mg/kg/hour it caused large and dose-dependent increases in hypoxic chemosensitivity, which were longlasting and more persistent than the drug9s retention in the plasma. Increases in sensitivity to hypercapnia were much less and were detected only when the plasma almitrine exceeded 200 ng/ml. Small increases in resting ventilation and metabolic rate with a decrease in mixed venous carbon dioxide tension occurred only at the highest infusion rate. The findings accord with an action of almitrine in the peripheral chemoreceptors, which may be of therapeutic value in managing some cases of respiratory failure.
Assessing people's ability to drive after stroke.
Authors: R J Irvine
Journal: BMJ (1993)

among outpatients was not associated with any measurable benefits to patients, but 43% of doctors used information on functional status to change treatment.5It is not appropriate to generalise from American experience to British hospitals, where geriatric services are more multidisciplinary and training is longer.Similar trials are urgently needed.It would be useful to know more detail of the patterns of compliance with both measures at both times in Wessex as this may indicate where resistance lies and where research may be most usefully targeted.Interviews with the 40 consult- ants in Wessex would also be useful to explore their views on the reasons for poor compliance and to define research needs.The main weakness of the consensus approach adopted by the Royal College of Physicians and the British Geriatrics Society (and other prestigious groups in other aspects of medicine) is that acts of faith are required to bridge gaps in scientific evidence.Spending resources in applying new technologies of unknown efficacy cannot be defended unless there is a planned evaluation of the technologies' value.The NHS Research and Development division's newly constituted health technology assessment boards should provide a useful source of new funding for this purpose.
DEPTH OF ANAESTHESIA FOR VARIOUS OPERATIONS
Authors: C. L. Hewer
Journal: BMJ (1937)

It is frequently stated that the least possible quantity of the least toxic drug or combination of drugs should be administered to produce just sufficient depth of anaesthesia for any given operation.Like most generalizations this is only a half-truth.At first sight it appears most laudable to produce the lightest degree of narcosis which will enable the surgeon to perform his task, as it is evident that the less a patient inhales of a toxic drug the less there is to eliminate, and consequently metabolic Zhanges will be minimized.
The Effect of Diphenylhydantoin Sodium (Dilantin), Procaine Hydrochloride, Procaine Amide Hydrochloride, and Quinidine Hydrochloride upon Ouabain-Induced Ventricular Tachycardia in Unanesthetized Dogs
Authors: LOIS MOSEY, MYRA D. TYLER
Journal: Circulation (1954)

Ventricular tachycardia has been produced in unanesthetized dogs by the intravenous injection of ouabain, and the ability of various agents to produce reversion to normal sinus rhythm has been tested. Diphenylhydantoin sodium, procaine amide hydrochloride, procaine hydrochloride and quinidine hydrochloride were approximately equally effective; however the procaine hydrochloride effect was shorter and the drug was more toxic than the other three. It is suggested that diphenylhydantoin sodium may merit a trial for the treatment of digitalis-induced ventricular arrhythmias.
Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC)
Authors: S Resta-Lenert
Journal: Gut (2003)

<b>Background:</b> The colonic epithelium maintains a life long reciprocally beneficial interaction with the colonic microbiota. Disruption is associated with mucosal injury. <b>Aims:</b> We hypothesised that probiotics may limit epithelial damage induced by enteroinvasive pathogens, and promote restitution. <b>Methods:</b> Human intestinal epithelial cell lines (HT29/cl.19A and Caco-2) were exposed to enteroinvasive <i>Escherichia coli</i> (EIEC 029:NM), and/or probiotics (<i>Streptococcus thermophilus</i> (ST), ATCC19258, and <i>Lactobacillus acidophilus</i> (LA), ATCC4356). Infected cells and controls were assessed for transepithelial resistance, chloride secretory responses, alterations in cytoskeletal and tight junctional proteins, and responses to epidermal growth factor (EGF) stimulation. <b>Results:</b> Exposure of cell monolayers to live ST/LA, but not to heat inactivated ST/LA, significantly limited adhesion, invasion, and physiological dysfunction induced by EIEC. Antibiotic killed ST/LA reduced adhesion somewhat but were less effective in limiting the consequences of EIEC invasion of cell monolayers. Furthermore, live ST/LA alone increased transepithelial resistance, contrasting markedly with the fall in resistance evoked by EIEC infection, which could also be blocked by live ST/LA. The effect of ST/LA on resistance was accompanied by maintenance (actin, ZO-1) or enhancement (actinin, occludin) of cytoskeletal and tight junctional protein phosphorylation. ST/LA had no effect on chloride secretion by themselves but reversed the increase in basal secretion evoked by EIEC. EIEC also reduced the ability of EGF to activate its receptor, which was reversed by ST/LA. <b>Conclusions:</b> Live ST/LA interact with intestinal epithelial cells to protect them from the deleterious effect of EIEC via mechanisms that include, but are not limited to, interference with pathogen adhesion and invasion. Probiotics likely also enhance the barrier function of naïve epithelial cells not exposed to any pathogen.