tbuckley/cabot-search huggingface dataset:
Schizophrenia and the parvalbumin-containing class of cortical local circuit neurons
Authors: T U Woo, J L Miller, D A Lewis
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to test the hypothesis that abnormalities in the parvalbumin-containing subclass of local circuit neurons contribute to altered gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex of schizophrenic subjects.Profile counts and somal size measures were made of parvalbumin-immunoreactive neurons in areas 9, 46, and 17 from 15 matched pairs of schizophrenic and normal comparison subjects.No differences in relative density, laminar distribution, or somal size of labeled neurons were found in any region.These findings suggest that altered GABA neurotransmission in schizophrenia is due to either abnormalities in other sub-populations of prefrontal cortical GABA neurons or abnormalities in the parvalbumin-containing subclass that could not be detected in the present study.
Drug points: Rhabdomyolysis and multiple system organ failure with streptokinase
Authors: H E Montgomery, C W McIntyre, M K Almond, K Davies, C W Pumphrey, D Bennett
Journal: BMJ (1995)

Write: We report two cases of rhabdomyolysis and multiple system organ failure with streptokinase treatment.

A 47 year old normotensive (110/70 mm Hg) man with normal renal function suffered an inferoposterior myocardial infarction treated with oral aspirin (300 mg). Lumbar pain accompanied intravenous streptokinase (1.5x106 units over one hour). At three hours renal, respiratory, and high output circulatory failure with fever ensued despite inotropes and fluids. At 17 hours his temperature was 39.2°C, blood pressure 70/40 mm Hg, urea 22 mmol/l, creatinine 400 μmol/l; urine red+ and white cells+ …
Abstract 3549: Reduced Right Ventricular Systolic Function is the Best Predictor of Outcome in Patients with Prior Mitral Valve Surgery
Authors: Mohsin T Alhaddad, Yasir Batres, Jo Mahenthiran, Gradus-Pizlo Gradus-Pizlo, Masoor Kamalesh, Harvey Feigenbaum, Stephen G Sawada
Journal: Circulation (2006)

Background: Right ventricular systolic dysfunction commonly occurs in patients with prior mitral valve replacement and long-standing pulmonary hypertension. We assessed the prognostic impact of RV ...
Abstract 3880: GRK2 Inhibition Prevents Development Of Cardiac Insulin Resistance And Impaired Glucose Uptake In Post Ischemic Heart Failure
Authors: Michele Ciccarelli, Giuseppe Rengo, Kurt Chuprun, Gaetano Santulli, Bruno Trimarco, Guido Iaccarino, Walter J Koch
Journal: Circulation (2008)

The beta adrenergic receptor (βAR) kinase, GRK2, is upregulated and participates to the evolution of heart failure (HF) through downregulation and desensitization of βARs. Recent studies showed that this molecule affects insulin signaling and reduce glucose uptake in hepatocytes and adipocytes. We hypothesized that in HF, GRK2 reduces cardiac performance also through inhibition of cardiac glucose metabolism. In 12 week old Sprague/Dawley rats, we measured cardiac glucose uptake by PET 3 days, 3 and 6 weeks after myocardial infarction (MI). Function and cardiac dimensions were measured by echocardiography. We observed that glucose uptake was reduced in animal post-MI at 3 and 6 weeks respect to healthy animals (3 rd week: 1.3±0.22 vs 2.1±0.3; 6 th week: 1±0.1 vs 2.4±0.2, ml/min/g, p&lt;0.05). No difference was observed in glucose uptake acutely after surgery. Echo showed cardiac dilation and reduced function at 6 weeks (LVD: 9.2± 0.3 vs 7.2± 0.4 mm; EF: 42%±1.1 vs 66%±2.2, p&lt;0.05, Sham vs MI). To inhibit GRK2 in the heart during post-ischemic HF, we delivered the GRK2 inhibitor βARKct by adeno-associated type 6 virus (AAV6) to the left ventricle before induction of the MI. As a control we treated rats with AAV6 encoding for the green fluorescent protein (GFP). Cardiac dilation and function were preserved after 6 weeks post MI in AAV6 βARKct respect to AAV6GFP rats (LVD: 7.73 ±0.25 vs 9.9 ±0.8 mm; EF: 55%±2.25 vs 44%±2, p&lt;0.05). Glucose uptake was better preserved in AAV6βARKct rats after 3 and 6 weeks post MI respect to AAV6GFP group (3rd week: 2.3±0.3 vs 1.2±0.2; 6th week: 1.8±0.2 vs 1.1±0.05, ml/min/g, p&lt;0.05). Since Akt mediates most of the anabolic effects of insulin in cells, we evaluated the effects of GRK2 overexpression by adenovirus (ADGRK2) in neonatal cardiomyocytes (NRVMs) on Akt phosphorylation later on insulin stimulation (ins, 10 – 6 M). As control we induced overexpression of GFP by adenovirus (ADGFP). We observed reduced activation of Akt in presence of GRK2 overexpression as compared to the ADGFP treated cells (1.2±0.2- vs. 3.5±0.4- fold activation over basal, p&lt;0.05). Our data show that post MI, impaired glucose extraction precedes development of HF, and that early GRK2 inhibition prevents impaired myocardial glucose uptake and HF development.
Abstract 18681: Association Between Type of Coronary Artery Anomaly, Cardiac Surgery, and Death in Adults
Authors: Kristen Cotney, Todd M Brown, Hrudaya Nath, Steven Lloyd
Journal: Circulation (2013)

Introduction: Anomalies of coronary artery origin where the artery arises from the opposite aortic cusp are associated with adverse cardiac events; those of the left main and the left anterior descending coronary arteries (LMCA and LAD) are thought to be at particular risk. However, there are few outcomes data on anomalies identified in adulthood; existing outcomes data are derived from the pediatric population. We determined the relationship between anomaly type, cardiac surgery, and death in adults. Methods: 73 individuals ≥19 years of age with anomalies of coronary artery origin were identified from the institutional imaging and catheterization databases. Anomaly type and whether surgery was performed were ascertained by chart review. Anomalies were grouped into 3 categories: 1) left circumflex coronary artery arising from right cusp (n=26); 2) right coronary artery (RCA) arising from left cusp (n=32); and 3) all other anomalies (n=15). Vital status was ascertained from the Social Security Death Index. Association between type of anomaly and mortality was investigated by Cox proportional hazards models, adjusting for surgical management and age at diagnosis. Results: Mean age at diagnosis was 56±14 years (55% male, 59% white). As of November 5, 2012, 27 had died. The relationship between anomaly type, surgical management, and mortality is in the table. After adjustment, RCA anomaly (hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.2, 9.9) was associated with increased mortality; undergoing surgery (HR 0.07, 95% CI 0.01, 0.56) was associated with decreased mortality. Conclusion: This represents the largest outcomes study of adults with anomalous coronary artery origin. In this group, anomalous RCA is associated with higher incidence of overall mortality than other types of anomalies, including those of LMCA and LAD. This finding is surprising, since the prevailing view suggests that RCA anomaly carries less risk than those of the LMCA or LAD.
Abstract 447: Sonic Hedgehog Carried By Microparticles Corrects Endothelial Injury Through Nitric Oxide Release
Authors: Abdelali Agouni, Hadj A Mostefai, Chiarra Porro, Nunzia Carusio, Julie Favre, Maria C Martinez, Ramaroson Andriantsitohaina
Journal: Circulation (2007)

Microparticles (MPs) are small fragments generated from the plasma membrane of cells upon stimulation. Among the candidate proteins harboured by MPs, we have recently shown that Sonic Hedgehog (Shh) is present in MPs generated from activated/apoptotic human T CEM lymphocytes. MPs were isolated following serial centrifugations. Eahy 926 endothelial cells were grown for 24h in the absence or presence of 10 μg/mL MPs pre-incubated (or not) either with inhibitors of PI3-kinase (LY294002, 20 μM), MEK 1/2 (U0126, 10 μM), cyclopamine (30 μM), a specific antagonist of the Sonic Hedgehog receptor (Patched), or siRNA of Patched. Cell lysates were analyzed by Western blot. Cells were used for direct measurement of nitric oxide (NO), and oxidative stress was determined by flow cytometry. In other experiments, after 24h of intravenous injection of MPs to mice, endothelium-dependent relaxation was determined in aortic rings. In addition, ischemia/reperfusion was induced in mice by ligating the left anterior descending coronary artery proximal to its origin and endothelial function of the distal coronary artery was assessed. We show that Shh carried by MPs: a) induces NO release from endothelial cells under basal (2.5 fold) and after a bradykinin-stimulation (20 μM) conditions (2.6 fold) b) increases both the expression and the phosphorylation of enzymes related to the NO pathway, and c) decreases the production of reactive oxygen species (38.6 ± 1.4 % of positive cells in treated vs. 51.4 ± 0.2 % in control). Inhibition of PI3-kinase and ERK signalling reversed the effects of MPs. Injection of MPs to mice improved endothelial function in aorta (EC 50 ; 8.5 x 10 −8 M of acetylcholine in control vs. 7.05 x 10 −8 M in treated mice) and elevated NO release in blood, heart and lungs (1.4, 1.9 and 2.6-fold, respectively). Mice treated with Shh MPs had reduced coronary endothelial dysfunction after ischaemia/reperfusion. Silencing Shh with either cyclopamine or siRNA of Patched caused a 35 % reduction of NO release elicited by MPs. Based on our findings, we propose that the cardiovascular effects of MPs harbouring Shh may represent a new therapeutic approach against endothelial dysfunction caused by endothelial injury e.g. during cardiac ischemia.
Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials
Authors: Gregory J. Dore, Brian Conway, Yan Luo, Ewa Janczewska, Brygida Knysz, Yan Liu, Adrian Streinu-Cercel, Florin Alexandru Caruntu, Manuela Curescu, Richard Skoien, Wayne Ghesquiere, Włodzimierz Mazur, Alejandro Soza, Francisco Fuster, Susan Greenbloom, Adriana Motoc, Victoria Arama, David Shaw, Istvan Tornai, Joseph Sasadeusz, Olav Dalgard, Danielle Sullivan, Xuan Liu, Mudra Kapoor, Andrew Campbell, Thomas Podsadecki
Journal: Journal of Hepatology (2015)

Telaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV.Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0-4% and 34-47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV.Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.
Abstract 17756: Incidence and Progression of Aortic Valve Calcification among the Elderly: a Prospective Analysis of the Age, Gene-Environment Susceptibility (AGES)-Reykjavik Study
Authors: Kathleen Kearney, Sigurdur Sigursdsson, Guny EirIksdOttir, Kevin D O'Brien, Vilmundur Gudnason, David S Owens
Journal: Circulation (2012)

Background: There are currently no effective treatments for calcific aortic valve disease, and determinants of aortic valve calcium (AVC) initiation and progression in the elderly are poorly unders...
Abstract 2793: Increasing Levels of Hemoglobin A1C are associated with the Presence of Mixed Coronary Plaques in Asymptomatic Individuals without Diabetes Mellitus
Authors: Juan J Rivera, Khurram Nasir, Yeonyee Yoon, Song A Chang, Eue-Keun Choi, Sang-il Choi, Eun-Ju Chun, Dong-Joo Choi, Roger Blumenthal, Hyuk-Jae Chang
Journal: Circulation (2008)
Effects of Race and Sex on Features of Eosinophilic Esophagitis
Authors: Fouad J. Moawad, Evan S. Dellon, Sami R. Achem, Tony Ljuldjuraj, Daniel J. Green, Corinne L. Maydonovitch, Diana R. Brizuela, Sandeep K. Gupta, Mirna Chehade
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract 3017: Na+-H+ Exchange Inhibition by Cariporide Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine in Heart Failure: Assessment by Pressure-Volume Analysis
Authors: Che-Ping Cheng, Heng-Jie Cheng, Hiroshi Hasegawa, Atsushi Morimoto, Peng Zhou, Michael Cross, William C Little
Journal: Circulation (2009)

Background. Inability of failing hearts to respond to positive inotropic agents such as dobutamine (DOB) represents a major clinical problem. We have shown previously that in addition to intracellu...
The independent inquiry into inequalities in health
Authors: G. D. Smith, J. N Morris, M. Shaw
Journal: BMJ (1998)

News p 1471 

Twenty years ago the secretary of state for social services of the last Labour government appointed Sir Douglas Black to chair a working group to review information on inequalities in health and suggest policy and research that should follow from this review.1 The report appeared in 1980 and received a cold reception from the new Conservative government.2 The climate for the reception of the Black report's successor—the independent inquiry into inequalities in health, chaired by Sir Donald Acheson and published this week3—is hopefully different. How do its findings and recommendations compare?

For 17 years of Conservative government the Labour party made political capital out of the non-implementation of the recommendations of the Black report. The announcement before the 1997 election that, if elected, Labour would commission an independent review into inequalities in health was therefore welcome.4 When launching the inquiry in July 1997 the minister for public health criticised the health strategy of the previous administration for “its excessive emphasis on lifestyle issues” which “cast the responsibility back on to the individual.”5 Given the history of the Black report—released with no press release and only 260 copies—the commitment to publish the new report was encouraging, as was the statement that “its conclusions, based on evidence, will contribute to the development of a new strategy for health.”3 The review's terms of reference, however, included the stipulation that it must …
Assessing Eligibility for Anticoagulation After Diagnosis of Atrial Fibrillation—Reply
Authors: Gregory Y. H. Lip, Deirdre A. Lane
Journal: JAMA (2015)

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Abstract 29: Inhibition of Mst1 Kinase by Protein-l-Isoaspartate (d-aspartate) O-Methyltransferase Protects Cardiomyocytes from Hypoxia-Induced Apoptosis
Authors: Qing Qin, Guijun Yan, Bing Yi, Kurt Chuprun, Haixiang Sun, Shengdong Huang, Jianxin Sun
Journal: Circulation (2012)

Background: Mammalian sterile 20-like kinase 1 (Mst1) is a mammalian homolog of Hippo kinase from Drosophila and it is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression in mammals. Activation of Mst1 causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart is not known. Method and result: In a yeast two-hybrid screen of a human heart cDNA library with a dominant-negative Mst1 (K59R) mutant used as bait, protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) was identified as an Mst1-interacting protein. The interaction of PCMT1 with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK-293 cells and native cardiomyocytes, in which PCMT1 interacted with the kinase domain of Mst1, but not with its C-terminal regulatory domain. Knockdown of PCMT1 augments hypoxia/reoxygenation induced Mst1 activation and apoptosis. Overexpression of PCMT1 did not affect the Mst1 expression, but significantly attenuated the Mst1 activation and its apoptotic effects in response to the hypoxia/reoxygenation induced injury in cardiomyocytes. Moreover, upregulation of PCMT1 by CGP3466B, a compound related to the anti-Parkinson’s drug R-(-)-deprenyl with potent antiapoptotic effects, inhibited the hypoxia/reoxygenation induced Mst1 activation and cardiomyocyte apoptosis. Conclusion: PCMT1 is a novel inhibitor of Mst1 activation in cardiomyocytes and suggest that targeting PCMT1 may prevent myocardial apoptosis through inhibition of Mst1.
Abstract 2521: A Multicentre Randomized Study comparing Efficacy Of Telmisartan versus Carvedilol In Preventing Atrial Fibrillation Recurrence In Hypertensive Patients.
Authors: Domenico Galzerano, Gabriele Conforti, Roberto Breglio, Salvatore Caselli, Gabriele Saetta, Giuseppe Carbone, Bernardino Tuccillo, Diana Lama, Paolo Tammaro, Paolo Capogrosso
Journal: Circulation (2007)

Background : The possibility of addressing blood pressure(BP) control and lower incidence of atrial fibrillation(AF) should be a suitable pharmacological goal in antihypertensive therapy. The renin-angiotensin-aldosterone system (RAAS) play an important role as a mediator of atrial remodeling in AF AIM: this prospective , randomized, multicentre study sought to assess the effect of an antihypertensive treatment with Telmisartan (Telm) and Carvedilol (Carv) in preventing the recurrence of AF in hypertensive pts with a history of recent atrial fibrillation. Methods and Results : We studied 154 mild hypertensive (SBP&gt;130&lt;160 mmHg and\or DBP&gt;80&lt;100 mmHg) out patients. All pts were in sinus rhytm but with at least from one to four Ecg documented episodes of AF in the previous six months. The two groups didn’t differ dealing with left ventricular(LV) mass, LV Ejection fraction and left atrial diameter. After one week placebo period, they were randomized to telmisartan 80mg once day(od) or to Carv 25 mg od and followed for one year period. BP and 24 hour EKG was monthly recorded. Every pt was asked to report any episode of symptomatic AF and to perform an Ekg as early as possible . 132 pts completed the study ,70 in Telm group and 62 in Carv group.After 12 months the BP mean values were significantly reduced in both group without any difference between the two group. (Telm : 154\97 to 123\75 mmHg P&lt;0.001; Carv Group: 153\94 to 125\78 , p&lt;0,001) Left atrial diameter as assessed by echocardiography was lower in Telm group but didn’t differ statistically significant with Carv Group (Telm: 3,4±2,3 cm ; Carv: 3,6 ±2,4 cm). In 10\70(14,2 %) pts in the Telm group and in 23±62(37,09%) pts in Carv group an episode (symptomatic or asymptomatic )was reported (P&lt;0,005, χ 2 test). Conclusion: Telm seems to be more effective than Carv in preventing new episodes of AF in hyp with recurrent AF . Our results suggest that the angiotensin II receptor blockers (ARBs), also target the RAAS by binding to angiotensin type 1 (AT 1 ) receptors could be favourably interfere the electrical and structural atrial remodeling in hyp pts suggesting an own effect on this phenomen.
Portal vein and systemic thromboses in hepatocellular carcinoma
Authors: G. C. Connolly, A. Khorana, P. Mantry, A. Bozorgzadeh, P. Abt, R. Chen, O. Hyrien
Journal: Journal of Clinical Oncology (2007)

15048 Background: Hemostatic activation may be important for tumor growth and metastasis. Hepatocellular carcinoma (HCC) is commonly associated with portal vein thrombosis (PVT). Very little is known about factors predictive for PVT in patients with HCC or its correlation with systemic venous thromboembolism (VTE). Methods: We conducted a retrospective chart review of 194 patients diagnosed with HCC at the University of Rochester between 1998 and 2004. The primary endpoints of this study were presence of PVT and any systemic VTE. The secondary endpoint was overall survival calculated from time of diagnosis. Univariate and multivariate logistic regression analyses were conducted to assess the association of PVT with a set of clinical covariates, and the survival curve was estimated using the method of Kaplan-Meier. Results: The mean age of the total population was 60.4 ± 11.9, and one-third of the patients underwent liver transplant. The incidence of PVT in the total population was 31% (60/194) with a higher incidence in the non-transplant group compared to transplanted patients (34% vs. 24%; p= 0.08). In univariate analysis, advanced stage, major vessel involvement, higher MELD score, higher Child-Turcotte-Pugh (CTP) classification, lower serum albumin, elevated serum bilirubin, elevated serum alpha-fetoprotein (AFP) level, and elevated INR were associated with development of PVT (p &lt;0.05 for each). In multivariate analysis CTP class, stage, major vessel involvement, serum albumin, and serum AFP were independently and significantly associated with PVT (p &lt;0.05 for each). The presence of PVT was associated with reduced survival (median survival 4.61 months for those with PVT versus 17.55 months for those without PVT, HR 2.01, p &lt;0.001). The incidence of systemic VTE in the total population was 6.7%, and patients with PVT had a higher rate of systemic VTE compared to patients without PVT (11.5% vs. 4.4%; p 0.044). Conclusions: PVT is common in patients with HCC and is associated with worse outcomes. The correlation between PVT and systemic VTE suggests a common mechanism of hemostatic activation. Advanced stage, higher CTP class, major vessel involvement, and serum albumin and AFP levels are predictive of PVT. Identifying patients at high-risk for PVT and instituting prophylaxis may affect HCC outcomes. No significant financial relationships to disclose.