tbuckley/cabot-search huggingface dataset:
Pallidal Deep-Brain Stimulation in Primary Generalized or Segmental Dystonia
Authors: Andreas Kupsch, Reiner Benecke, Jörg Müller, Thomas Trottenberg, Gerd-Helge Schneider, Werner Poewe, Wilhelm Eisner, Alexander Wolters, Jan-Uwe Müller, Günther Deuschl, Marcus O. Pinsker, Inger Marie Skogseid, Geir Ketil Roeste, Juliane Vollmer-Haase, Angela Brentrup, Martin Krause, Volker Tronnier, Alfons Schnitzler, Jürgen Voges, Guido Nikkhah, Jan Vesper, Markus Naumann, Jens Volkmann
Journal: New England Journal of Medicine (2006)

Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial.Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment.Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria.Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].).
The relative influence of the topography and chemistry of TiAl6V4 surfaces on osteoblastic cell behaviour
Authors: K. Anselme, P. Linez, M. Bigerelle, D. Le Maguer, A. Le Maguer, P. Hardouin, H.F. Hildebrand, A. Iost, J.M. Leroy
Journal: Biomaterials (2000)
Low Penetrance in the Long-QT Syndrome
Authors: Silvia G. Priori, Carlo Napolitano, Peter J. Schwartz
Journal: Circulation (1999)

It is still currently held that most patients affected by the long-QT syndrome (LQTS) show QT interval prolongation or clinical symptoms. This is reflected by the assumption in linkage studies of a penetrance of 90%. We had previously suggested that a larger-than-anticipated number of LQTS patients might be affected without showing clinical signs. We have now exploited the availability of molecular diagnosis to test this hypothesis.We identified 9 families with "sporadic" cases of LQTS, ie, families in which, besides the proband, none of the family members had clinical signs of the disease. Mutation screening by conventional single-strand conformational polymorphism and sequencing was performed on DNA of probands and family members to identify mutation carriers. Of 46 family members considered on clinical grounds to be nonaffected, 15 (33%) were found instead to be gene carriers. Penetrance was found to be 25%. In these families, conventional clinical diagnostic criteria had a sensitivity of only 38% in correctly identifying carriers of the genetic defect.This study demonstrates that in some families, LQTS may appear with a very low penetrance, a finding with multiple clinical implications. The family members considered to be normal and found to be silent gene carriers are unexpectedly at risk of generating affected offspring and also of developing torsade de pointes if exposed to either cardiac or noncardiac drugs that block potassium channels. It is no longer acceptable to exclude LQTS among family members of definitely affected patients on purely clinical grounds. Conversely, it now appears appropriate to perform molecular screening in all family members of genotyped patients.
Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.
Authors: H N Sabbah, H Shimoyama, T Kono, R C Gupta, V G Sharov, G Scicli, T B Levine, S Goldstein
Journal: Circulation (1994)

BACKGROUND Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P &lt; .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P &lt; .001, and 61 +/- 6 versus 78 +/- 8 mL, P &lt; .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P &lt; .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.
Quinin in Cholera.
Authors: Erskine B. Fullerton
Journal: JAMA (1906)

Columbus, Ohio, Feb. 5, 1906. <h3>To the Editor:</h3> —I see inThe Journal, February 3, what I have looked for for a generation—some acknowledgment of the truth that quinin sulphate is a specific for Asiatic cholera. In brief, Dr. Ussher, a medical missionary at Van, Asiatic Turkey, found himself, about a year since, in the midst of an outbreak of cholera, so severe that in the first week of its prevalence all that were seized with the disease died—100 per cent. mortality. On Saturday night at midnight he began to treat the disease according to my directions (10 gr. quinin every hour until discharges were controlled), with the result that the mortality fell to less than 10 per cent. Some of your readers may recall that in my article in the<i>New York Medical Journal</i>, Aug. 18, 1904, I set the necessary mortality from the disease at somewhere between 5
Abstract B42: The lineage-specific transcription factor ASCL1 defines a subtype of neuroendocrine non-small cell lung cancers with poor prognosis and points to potential therapeutic targets
Authors: Alexander Augustyn, John Minna, Christopher Tan, James Sullivan, Mark Borromeo, Luc Girard, Jane Johnson, Carmen Behrens, Ignacio Wistuba, Yang Xie
Journal: Clinical Cancer Research (2012)

Abstract The future of cancer therapy relies on identifying certain patient populations that will respond to one treatment but not another based on the properties of the tumor and additionally creating specific drugs that target genetic pathways required for a particular tumor's formation, growth, and maintenance. We have developed a pre-clinical model for a genetically identifiable clade of non-small cell lung cancer that exhibits neuroendocrine features. We utilized whole-genome mRNA expression array data from 119 NSCLC cell lines to identify a class of NSCLC lines that fit the neuroendocrine phenotype (NE-NSCLC). We identified 11 NSCLC cell lines (9.2%) that display a distinct neuroendocrine gene signature. A gene expressed in all putative NE-NSCLC cell lines is the potent neural-specific transcription factor ASCL1. We hypothesize that ASCL1 acts as a “lineage dependent oncogene” for NE-NSCLC and that associated with ASCL1's function in the molecular pathogenesis of these lung cancers will be a gene expression profile that contributes to the malignant phenotype, which will provide insight towards therapeutic targeting of this subset of NSCLC. In this regard, ASCL1 ChIP-Seq data combined with genome wide mRNA expression data identified a subset of genes whose expression appears to be regulated by ASCL1. In NSCLC patient populations, tumors expressing ASCL1 and the neuroendocrine gene signature demonstrated impaired prognosis compared to the other NSCLCs. Knockdown of ASCL1 in representative NSCLC cell lines reduced target gene expression, caused significant cell cycle defects, and induced marked apoptosis. NSCLC cell lines expressing ASCL1 demonstrate a cancer stem cell marker phenotype similar to that of small cell lung cancer, providing clues to the pathogenesis of the NE-NSCLC disease subset. Our results suggest that neuroendocrine gene expression in NSCLC is of clinical relevance, that ASCL1 is required for survival of the NE-NSCLC disease subset, while the integrated ASCL1 ChIP-Seq and mRNA expression data provide a roadmap for systematically searching for therapeutic targets for this phenotype and their mechanistic role in a cancer stem cell (initiating cell) subpopulation within these tumors.
Immunotherapy With Tolerogenic Apolipoprotein B-100–Loaded Dendritic Cells Attenuates Atherosclerosis in Hypercholesterolemic Mice
Authors: Andreas Hermansson, Daniel K. Johansson, Daniel F.J. Ketelhuth, John Andersson, Xinghua Zhou, Göran K. Hansson
Journal: Circulation (2011)

Background— Atherosclerosis is a chronic inflammatory disease characterized by a massive intimal accumulation of low-density lipoprotein that triggers chronic vascular inflammation with an autoimmune response to low-density lipoprotein components. Methods and Results— To dampen the inflammatory component of atherosclerosis, we injected hypercholesterolemic huB100 tg × Ldlr −/− mice (mice transgenic for human apolipoprotein B100 [ApoB100] and deficient for the low-density lipoprotein receptor) intravenously with dendritic cells (DCs) that had been pulsed with the low-density lipoprotein protein ApoB100 in combination with the immunosuppressive cytokine interleukin-10. DCs treated with ApoB100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-γ, and increased de novo generation of regulatory T cells in vitro. Spleen cells from mice treated with DCs plus ApoB100 plus interleukin-10 showed diminished proliferative responses to ApoB100 and significantly dampened T-helper 1 and 2 immunity to ApoB100. Spleen CD4 + T cells from these mice suppressed activation of ApoB100-reactive T cells in a manner characteristic of regulatory T cells, and mRNA analysis of lymphoid organs showed induction of transcripts characteristic of these cells. Treatment of huB100 tg × Ldlr −/− mice with ApoB100-pulsed tolerogenic DCs led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4 + T-cell infiltration and signs of reduced systemic inflammation. Conclusions— Tolerogenic DCs pulsed with ApoB100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis.
Risk Score for In-Hospital Ischemic Stroke Mortality Derived and Validated Within the Get With The Guidelines–Stroke Program
Authors: Eric E. Smith, Nandavar Shobha, David Dai, DaiWai M. Olson, Mathew J. Reeves, Jeffrey L. Saver, Adrian F. Hernandez, Eric D. Peterson, Gregg C. Fonarow, Lee H. Schwamm
Journal: Circulation (2010)

Background— There are few validated models for prediction of in-hospital mortality after ischemic stroke. We used Get With the Guidelines–Stroke Program data to derive and validate prediction models for a patient's risk of in-hospital ischemic stroke mortality. Methods and Results— Between October 2001 and December 2007, there were 1036 hospitals that contributed 274 988 ischemic stroke patients to this study. The sample was randomly divided into a derivation (60%) and validation (40%) sample. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model. We also separately derived and validated a model in the 109 187 patients (39.7%) with a National Institutes of Health Stroke Scale (NIHSS) score recorded. Model discrimination was quantified by calculating the C statistic from the validation sample. In-hospital mortality was 5.5% overall and 5.2% in the subset in which NIHSS score was recorded. Characteristics associated with in-hospital mortality were age, arrival mode (eg, via ambulance versus other mode), history of atrial fibrillation, previous stroke, previous myocardial infarction, carotid stenosis, diabetes mellitus, peripheral vascular disease, hypertension, history of dyslipidemia, current smoking, and weekend or night admission. The C statistic was 0.72 in the overall validation sample and 0.85 in the model that included NIHSS score. A model with NIHSS score alone provided nearly as good discrimination (C statistic 0.83). Plots of observed versus predicted mortality showed excellent model calibration in the validation sample. Conclusions— The Get With the Guidelines–Stroke risk model provides clinicians with a well-validated, practical bedside tool for mortality risk stratification. The NIHSS score provides substantial incremental information on a patient's short-term mortality risk and is the strongest predictor of mortality.
Renin-angiotensin system inhibition in acute myocardial infarction in dogs. Effects on systemic hemodynamics, myocardial blood flow, segmental myocardial function and infarct size.
Authors: C S Liang, H Gavras, J Black, L G Sherman, W B Hood
Journal: Circulation (1982)

Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.
Estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes.
Authors: Shigeyuki Kitamura, Motoko Ohmegi, Seigo Sanoh, Kazumi Sugihara, Shin'ichi Yoshihara, Nariaki Fujimoto, Shigeru Ohta
Journal: Environmental Health Perspectives (2002)

In this study we examined estrogenic activity of styrene oligomers after metabolic activation by rat liver microsomes. Trans-1,2-diphenylcyclobutane (TCB), cis-1,2-diphenylcyclobutane (CCB), 1,3-diphenylpropane, 2,4-diphenyl-1-butene, 2,4,6-triphenyl-1-hexene, and 1-alpha-phenyl-4ss-(1 -phenylethyl)tetralin were negative in the yeast estrogen screening assay and estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7. However, TCB exhibited estrogenic activity after incubation with liver microsomes of phenobarbital-treated rats in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Minor activity was observed when liver microsomes of untreated or 3-methylcholanthrene-treated rats were used instead of those from phenobarbital-treated rats. CCB, 1,3-diphenylpropane, and 2,4-diphenyl-1-butene also exhibited estrogenic activity after metabolic activation by liver microsomes, but the activity was lower than that of TCB. 2,4,6-Triphenyl-1-hexene and 1-alpha-phenyl-4ss-(1 -phenylethyl)tetralin did not show estrogenic activity after such incubation. When TCB was incubated with liver microsomes of phenobarbital-treated rats in the presence of NADPH, three metabolites were detected by high-performance liquid chromatography (HPLC). One metabolite isolated by HPLC exhibited a significant estrogenic activity. The active metabolite was identified as trans-1-(4-hydroxyphenyl)-2-phenylcyclobutane by mass and nuclear magnetic resonance spectral analysis. These results suggest that the estrogenic activity of TCB was caused by the formation of the 4-hydroxylated metabolite.
A&amp;E doctor is suspended for nine months after series of incidents that alarmed colleagues
Authors: C. Dyer
Journal: BMJ (2013)

A middle grade accident and emergency doctor who gave a wrong diagnosis to a woman with an ectopic pregnancy and to a man with a broken neck has been ordered to be suspended from the medical register for nine months, after a Medical Practitioners Tribunal Service panel found her professional performance to be deficient.

Camelia Jurcut, who qualified in Romania in 1999, was working at Skegness and Scunthorpe Hospitals between June and November 2011 when a string of incidents took place that alarmed colleagues.

The young woman, named only as Patient A, presented with severe lower abdominal pain in the first trimester of a second pregnancy. Jurcut failed to take a proper …
Sodium Nitroprusside Treatment of Ergotamine-Induced Peripheral Ischemia
Authors: Nathan H. Carliner
Journal: JAMA (1974)

A 50-year-old woman was admitted to the hospital with severe peripheral ischemia of all four extremities due to an overdose of suppositories containing ergotamine tartrate and caffeine (Cafergot) (total dose of ergotamine, 36 mg). Fluids were given intravenously but, because of recurrent seizures, anticoagulants were not given. Signs of ischemia increased and were unaffected by intravenously given hydralazine hydrochloride. A continuous intravenous infusion of the potent vasodilator sodium nitroprusside was then initiated, with subsequent complete resolution of all signs and symptoms of peripheral ischemia.
The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety
Authors: Michael Davis
Journal: Trends in Pharmacological Sciences (1992)

Over the past several years, major advances have been made in understanding the pharmacology of anxiety, involving three broad classes of experimental approach. One approach studies the mechanism of action of drugs that are known to treat anxiety clinically, such as the benzodiazepines. A second approach uses various animal models of fear or anxiety that are sensitive to known anxiolytic drugs, to see if they will detect new compounds. A third approach involves describing the neural pathways and neurotransmitters that are active in a state of fear or anxiety; importantly, this approach is not derived from the mechanisms of known anxiolytics. In this review, Michael Davis describes such a 'neural systems' approach to the study of fear or anxiety that uses the paradigm of fear-potentiated startle.
Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload
Authors: T. Doenst, G. Pytel, A. Schrepper, P. Amorim, G. Farber, Y. Shingu, F. W. Mohr, M. Schwarzer
Journal: Cardiovascular Research (2009)

Left ventricular hypertrophy is a risk factor for heart failure. However, it also is a compensatory response to pressure overload, accommodating for increased workload. We tested whether the changes in energy substrate metabolism may be predictive for the development of contractile dysfunction. Chronic pressure overload was induced in Sprague–Dawley rats by aortic arch constriction for 2, 6, 10, or 20 weeks. Contractile function in vivo was assessed by echocardiography and by invasive pressure measurement. Glucose and fatty acid oxidation as well as contractile function ex vivo were assessed in the isolated working heart, and respiratory capacity was measured in isolated cardiac mitochondria. Pressure overload caused progressive hypertrophy with normal ejection fraction (EF) at 2, 6, and 10 weeks, and hypertrophy with dilation and impaired EF at 20 weeks. The lung-to-body weight ratio, as marker for pulmonary congestion, was normal at 2 weeks (indicative of compensated hypertrophy) but significantly increased already after 6 and up to 20 weeks, suggesting the presence of heart failure with normal EF at 6 and 10 weeks and impaired EF at 20 weeks. Invasive pressure measurements showed evidence for contractile dysfunction already after 6 weeks and ex vivo cardiac power was reduced even at 2 weeks. Importantly, there was impairment in fatty acid oxidation beginning at 2 weeks, which was associated with a progressive decrease in glucose oxidation. In contrast, respiratory capacity of isolated mitochondria was normal until 10 weeks and decreased only in hearts with impaired EF. Pressure overload-induced impairment in fatty acid oxidation precedes the onset of congestive heart failure but mitochondrial respiratory capacity is maintained until the EF decreases in vivo. These temporal relations suggest a tight link between impaired substrate oxidation capacity in the development of heart failure and contractile dysfunction and may imply therapeutic and prognostic value.
Rapid Correction of Hyponatremia in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Authors: DAVID HANTMAN
Journal: Annals of Internal Medicine (1973)

In the syndrome of inappropriate secretion of antidiuretic hormone, life-threatening cerebral dysfunction may necessitate rapid elevation of the serum sodium concentration. Treatment with fluid restriction may be too slow, and infusions of hypertonic saline are excreted because these patients already have volume expansion. Severe hyponatremia in five patients was corrected by inducing a diuresis with furosemide and by replacing the urinary electrolyte losses. The mean plasma sodium concentration increased in these patients from 120 ± 1 to 133 ± 2 meq/litre (P < 0.001) in 6 to 8 hours. Before treatment one of these patients was semicomatose and had grand mal seizures, symptoms that subsided as the serum sodium concentration was rapidly elevated. Although the furosemide diuresis consistently diminished urine to plasma osmolality ratios, a negative water balance may be achieved at all levels of urinary osmolality, provided the urinary electrolyte losses are replaced in a more concentrated solution.