tbuckley/cabot-search huggingface dataset:
Drug points: Drug induced psychosis with doxazosin
Authors: M Evans, P W Perera, J Donoghue
Journal: BMJ (1997)

Objective: To quantify the effectiveness and safety of corticosteroids in the treatment of acute traumatic brain injury.Design: Systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury.Summary odds ratios were estimated as an inverse variance weighted average of the odds ratios for each study.Setting: Randomised trials available by March 1996.Subjects: The included trials with outcome data comprised 2073 randomised participants. Results:The effect of corticosteroids on the risk of death was reported in 13 included trials.The pooled odds ratio for the 13 trials was 0.91 (95% confidence interval 0.74 to 1.12).Pooled absolute risk reduction was 1.8% ( -2.5% to 5.7%).For the 10 trials that reported death or disability the pooled odds ratio was 0.90 (0.72 to 1.11).For infections of any type the pooled odds ratio was 0.92 (0.69 to 1.23) and for the seven trials reporting gastrointestinal bleeding it was 1.05 (0.44 to 2.52).With only those trials with the best quality of concealment of allocation, the pooled odds ratio estimates for death and death or disability became closer to unity.Conclusions: This systematic review of randomised controlled trials of corticosteroids in acute traumatic brain injury shows that there remains considerable uncertainty over their effects.Neither moderate benefits nor moderate harmful effects can be excluded.The widely practicable nature of the drugs and the importance of the health problem suggest that large simple trials are feasible and worth while to establish whether there are any benefits from use of corticosteroids in this setting.
Genetic Risk Assessment and <i>BRCA</i> Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement
Journal: Annals of Internal Medicine (2005)

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility, along with the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis available through the USPSTF Web site (www.preventiveservices.ahrq.gov). The recommendation is also posted on the Web site of the National Guideline Clearinghouse (www.guideline.gov). *For a list of the members of the U.S. Preventive Services Task Force, see the Appendix.
Comparison of dose distributions in IMRT planning using the gamma function.
Authors: C Andenna, M Benassi, B Caccia, S Marzi, M Pedrini, C Zicari
Journal: Journal of experimental & clinical cancer research (2006)

Intensity-modulated radiotherapy (IMRT) (1) is an advanced form of 3-D conformal radiotherapy. It uses non uniform spatial modifications in the intensity of the beams across the irradiated field. Consequently, it is necessary to develop sophisticated tools to compare measured and calculated dose distributions in order to verify the accuracy of the results of the planned dose distribution. Different methods have been developed to evaluate the accordance between measured and calculated doses, such as the point-to-point dose difference or the evaluation of the distance between two closed points having the same dose value (2-4). The verification method proposed by Low (5-7) seems to be more complete since it takes into account both the dose difference (DD) and the distance to agreement (DTA), allowing to define a "score", the gamma value, at each point of interest. A software tool (DDE: Dose Distribution Evaluator), based on Low's method, to evaluate the agreement between dose distribution matrices has been implemented. In particular, the proposed gamma curve, as a function of the isodose levels, gives real-time information useful for decision making about the treatment plan. The paper describes the software, and reports the obtained results in a simple geometry and in several clinical cases (head-neck and prostate). Comparison between measured data (film and MapCheck) and calculated data (CadPlan) using DDE has shown very good agreements. Thanks to its higher resolution, film dosimetry showed better accuracy than the MapCheck technique. Similar results can be obtained also with the MapCheck technique when proper measurement methods are used.
Abstract 1613: Activation of a Novel Estrogen Receptor, GPR30, is Cardioprotective in the Rat
Authors: Anne M Deschamps, Elizabeth Murphy
Journal: Circulation (2008)

It has been well documented that pre-menopausal females have a lower incidence of cardiovascular disease than their male counterparts. However, post-menopausal women reach the rates of disease in men suggesting a protective role of estrogen. Numerous animal studies have also demonstrated that estrogen is cardioprotective. Historically, estrogen has been thought to signal through two nuclear receptors, ERa and ERb; however, a third, membrane bound receptor, GPR30, has been identified and shown to bind estrogen with high affinity. GPR30 is a G protein coupled receptor localized to the plasma membrane and endoplasmic reticulum. To date, there is little information on GPR30 in the heart and no study has looked at the effect of GPR30 activation during myocardial ischemia and reperfusion. Therefore, the goal of this study was to determine whether activation of GPR30 results in a cardioprotective phenotype in rats. A highly specific GPR30 agonist, G-1, was administered to Sprague Dawley (200–300g) rat hearts 10 minutes prior to 20 minutes of ischemia followed by 120 minutes of reperfusion using a Langendorff model. Recovery of post-ischemic function was significantly better in G-1 treated hearts compared to controls (39.4±5.5 vs 23.6±2.5% of pre-ischemic rate pressure product, p&lt;0.05). Additionally, infarct size was reduced in the G-1 treated animals when compared to control (16.5±4.4 vs 30.6±3.3% p&lt;0.05). The protection afforded by G-1 was blocked by co-administration of a PI3K inhibitor (wortmannin 100nM). Through western blot analysis, it was demonstrated that G-1 induced the activation of both Akt and Erk1/2 and was blocked by PI3K inhibition. Taken together, the data show that G-1 activation of GPR30 improved functional recovery and reduced infarct size in isolated rat hearts following ischemia and reperfusion through a PI3K dependent mechanism.
Abstract 1057: Specific Targeting of Gi Signaling in Normal and Dysfunctional Myocardium
Authors: Brent R DeGeorge, Erhe Gao, Matthieu Boucher, Leif E Vinge, J. K Chuprun, Philip Raake, Jeffrey S Martini, David M Harris, Stephen Soltys, Andrea D Eckhart, Walter J Koch
Journal: Circulation (2007)

Evidence has accumulated to suggest that cardiomyocyte apoptosis contributes significantly to the progression of heart failure. A salient characteristic of the failing heart is an upregulation of the adenylyl cyclase inhibitory G protein alpha subunit, Galpha(i2); however this upregulation has yet to be established as beneficial or deleterious. Of note, G protein-coupled receptor (GPCR) signaling through Gi has been implicated in the cardioprotective properties of adenosine, opioids, and bradykinin; however to date there has been no in vivo evidence that increased Gi in ischemic myocardium is cardioprotective. We have created a novel molecular tool to specifically address this question and other Gi-related mechanisms in the heart. We have developed a Gi inhibitor, GiCT - the carboxyl-terminal 63 amino acids of Galphai(i2), which represents the region of Gi that interacts specifically with GPCRs. Gi selectivity of GiCT has been shown in vitro as Gi signals are inhibited while Gs and Gq signals are not. Thus, a class-specific Gi inhibitor has been developed. We next created a transgenic mouse line with inducible, cardiac-specific expression of GiCT (Tg-GiCT mice). At baseline, Tg-GiCT mice display a structural and functional phenotype consistent with non-transgenic (nTg) mice. However, when subjected to stress in the form of myocardial ischemia/reperfusion (I/R) injury, Tg-GiCT mice demonstrate a significant increase in infarct size as compared to nTg mice. Furthermore, Tg-GiCT mice demonstrate increased myocardial apoptosis in response to I/R, with a resultant decrease in contractile performance. These results indicate first that ischemic damage induces apoptotic signals that can be countered by GPCR signaling specifically through Gi. Moreover, the beneficial survival effects of Gi signaling on the prevention of myocardial apoptosis in ischemia appears to outweigh any potential detrimental effects that Gi upregulation may have on contractility through inhibition of cAMP. Overall, our results demonstrate the in vivo utility of GiCT - to elucidate the novel finding that upregulation of Gi seen in dysfunctional myocardium induces survival signals and appears to be an adaptive mechanism post-ischemia to protect myocytes from apoptosis.
Do depressed men and women respond similarly to cognitive behavior therapy?
Authors: M E Thase, C F Reynolds, E Frank, A D Simons, J McGeary, A L Fasiczka, G G Garamoni, J R Jennings, D J Kupfer
Journal: American Journal of Psychiatry (1994)

A great majority of the evidence pertaining to the effectiveness of the time-limited psychotherapies as treatments of major depression are derived from studies of either predominantly or entirely female subject groups. Depressed men and women differ in a number of important respects that may alter the course of affective disorder, and as a result, they may also differ in their responses to psychotherapy. In this study the outcomes of 40 men and 44 women treated with cognitive behavior therapy were compared.The patients were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed according to the Research Diagnostic Criteria and DSM-III-R criteria. Subsequently, they were assessed every other week (with the Hamilton Depression Rating Scale, Beck Depression Inventory, and Global Assessment Scale) during a standardized, time-limited cognitive behavior therapy protocol. The outcomes of the men and women were compared by means of a series of analyses of variance and covariance and survival analyses.There were several significant pretreatment differences, and the men attended significantly fewer therapy sessions than the women. Although the men and women generally had comparable responses, patients with higher pretreatment levels of depressive symptoms, particularly women, had poorer outcomes.This study provides further evidence of gender-specific differences in depressed patients' symptoms and treatment utilization. Cognitive behavior therapy appears to be a comparably useful outpatient treatment for men and women. However, either more intensive cognitive behavior therapy or alternative methods of treatment may be warranted for patients with more severe syndromes.
Abstract 17302: A Meta-Analysis of Major Adverse Cardiovascular and Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation Using Edwards SAPIEN valve versus Medtronic CoreValve for Severe Aortic Stenosis
Authors: Hemang B Panchal, Neil Barry, Samit Bhatheja, Kais Albalbissi, Timir Paul
Journal: Circulation (2014)

Background: In patients with severe aortic stenosis (AS) who are at high risk for surgery, a transcatheter aortic valve implantation (TAVI) is an emerged alternative procedure using Edwards SAPIEN valve (EV) or Medtronic CoreValve (CV). The purpose of this meta-analysis is to compare early major adverse cardiovascular and cerebrovascular events (MACCE) between EV and CV. Methods: PubMed and the Cochrane Center Register of Controlled Trials were searched through May 2014. Seventeen studies (n=6211) comparing TAVI procedure that used EV (n=2693) and CV (n=3518) were included. End points were post-procedural all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, major bleeding and major vascular events. The odds ratio (OR) with 95% confidence interval (CI) was computed and p&lt;0.05 was considered as a level of significance. Results: The studies were homogeneous for all outcomes except all-cause mortality. There was no significant difference between EV and CV for post-procedural all-cause mortality (OR: 0.82, CI: 0.6-1.13, p=0.23), cardiovascular mortality (OR: 0.7, CI: 0.41-1.2. p=0.2), myocardial infarction (OR: 1.13, CI: 0.51-2.51, p=0.76), stroke (OR: 0.97, CI: 0.66-1.42, p=0.86) (Figure), major bleeding (OR: 1.13, CI: 0.81-1.58, p=0.48) and major vascular complications (OR: 1.22, CI: 0.94-1.58, p=0.14). Conclusion: The results of our meta-analysis of 6211 patients suggest that the types of valve used to perform TAVI procedures do not affect early mortality and MACCE outcomes. Further studies are needed to evaluate long-term outcomes.
Abstract 1710: Pharmacologic Profile of SCH 530348, a Novel Oral Antiplatelet Agent Selective for the Protease-Activated Receptor-1 (PAR-1)
Authors: Madhu Chintala, Ho-Sam Ahn, Carolyn Foster, Jacqueline Agans, George Boykow
Journal: Circulation (2008)

Antiplatelet agents are a cornerstone of therapy for atherothrombotic disease. However, despite the proven efficacy of agents targeting the thromboxane A2 (aspirin) and P2Y12 ADP (clopidogrel, prasugrel) platelet activation pathways, the residual risk for ischemic events remains considerable. Binding of thrombin to the platelet PAR-1 is an important platelet activation pathway not targeted by existing agents. Inhibition of PAR-1 may thus provide incremental clinical benefits over aspirin and ADP receptor antagonists. PAR-1 receptors expressed on endothelial cells, smooth muscle cells, monocytes and neutrophils have been reported to mediate the pro-inflammatory and chemotactic responses to thrombin. In the present study, we report pharmacologic characterization of SCH 530348, a novel thrombin receptor antagonist (TRA) selective for PAR-1, using in vitro assays with human platelet membranes and cultured human coronary artery smooth muscle cells (HCASMC), and ex vivo platelet aggregation assays in cynomolgus monkeys. The affinity of SCH 530348 for the PAR-1 receptor was determined in human platelet membranes. Functional studies involving calcium transients, thymidine incorporation, and receptor kinetics were performed in HCASMC. The oral antiplatelet effects of SCH 530348 in cynomolgus monkeys were evaluated in ex vivo platelet aggregation assays. SCH 530348 exhibited high affinity for PAR-1 receptor. SCH 530348 potently inhibited thrombin-stimulated calcium transients and thymidine incorporation in HCASMC, and displayed slow dissociation from PAR-1 receptor. In cynomolgus monkeys, SCH 530348 administered orally at doses ranging from 0.1 mg/kg to 3 mg/kg, provided rapid, complete, and sustained inhibition of thrombin receptor agonist peptide (TRAP)-induced ex vivo platelet aggregation for 24 hours. Significant inhibition of TRAP-induced platelet aggregation was maintained at 48 hours after dosing of SCH 530348. SCH 530348 is a highly selective, potent, and orally active PAR-1 antagonist. Inhibition of PAR-1 by SCH 530348 may translate into beneficial clinical effects in patients with atherothrombotic disease, and this hypothesis is currently being evaluated in 2 large trials.
Abstract 12157: Impact of a Hybrid Nurse-Led Home and Clinic-based Intervention on Hospitalization and Related Hospital Stay: Results From a Pragmatic, Randomized Trial (the NIL-CHF Study)
Authors: Simon Stewart, Carrington Melinda, Yih Kai Chan, Garry Jennings, Chiew Wong
Journal: Circulation (2014)

Background: Beyond pharmacological treatment, there is a paucity of data to support the application of disease management programs that bridge (predominantly short-term) cardiac rehabilitation and chronic heart failure (CHF) management programs. Methods: The NIL-CHF Study was a pragmatic randomized trial that tested the hypothesis that relative to Standard Care a nurse-led, multidisciplinary management program for hospitalized patients aged ≥ 45 years with pre-existing CVD and/or common antecedents of CHF, will reduce the incidence of admission for CHF or all-cause mortality (primary endpoint) and secondary endpoints of rehospitalization and recurrent hospital stay (specific focus on emergency and cardiovascular-related events) during mean 4.3 years follow-up. Results: A total of 611 subjects (mean age 66±11 years and 71% male) without baseline CHF (echocardiography confirmation), of whom 70% had an acute coronary syndrome and 62% were hypertensive, were randomized to Standard Care (n=310) or NIL-CHF inte...
Abstract 20876: Genomewide Analysis Finds a Variant in the KCNC2 Gene Associated With Sex-Dependent Differences in HDL Cholesterol Levels
Authors: Dhananjay Vaidya, Lisa R Yanek, Rasika A Mathias, Lewis C Becker, Diane M Becker
Journal: Circulation (2010)

Background:  HDL-cholesterol (HDL-C) levels differ between men and women suggesting sex-specific differences in lipoprotein metabolism. We tested for sex-specific effects of genetic variants with HDL-C in a genomewide association approach.   Methods:  We studied 1780 healthy European American individuals (18-84 years, 52% women) from 466 families ascertained from a proband with premature coronary artery disease ( −6 ); (2) a second stage testing for heterogeneity by sex correcting for the significance of the screening test (Bonferroni threshold: 0.05/n where n = number of SNPs passing the screening test).   Results:  12 SNPs passed the screening threshold, of which one passed the second stage (p −4 , original interaction p = 9.2×10 −8 ) in the KCNC2 gene, which is involved in the reactivity of islet cells in the pancreas. Table 1 presents genotypic distributions for HDL-C by sex for rs7304239.   Conclusion:  The minor allele [A] of rs7304239 in intron 2 the KCNC2 gene is associated with low HDL-C in women, but the opposite trend in men. This finding strongly suggests sex specific regulation of lipoprotein pathways involving pancreatic beta cell function.
Abstract 286: Resuscitation After Traumatic Cardiac Arrest
Authors: Jan-Thorsten Gräsner, Patrick Meybohm, Stephan Seewald, Jan Wnent, Matthias Fischer, Thomas Paffrath, Rolf Lefering
Journal: Circulation (2011)

Introduction In severe trauma patients with cardiac arrest (CA), pre-hospital CPR is performed infrequently and resuscitation outcome is much worse compared to cardiac causes. The purpose of the present study is to analyze CPR outcome in trauma patients with CA using two large German Registries - the German Resuscitation Registry (GRR) and the Trauma Registry of the German Society for Trauma Surgery (TR-DGU). Methods We combined two independent l registries to analyze outcome of trauma patients with CA. The GRR includes patients with pre-hospital CA followed by any resuscitation attempt, whereas the TR-DGU includes patients with severe trauma who reached a hospital alive. Combining both registries may have the potential to enable follow up of patients outcome from scene up to hospital discharge. Individual patients in both registries, however, were not identical. Results and Conclusions Within the GRR database data from 368 (2.8%) trauma CA patients were identified out of 13,329 CA patients. Compared to CA patients with cardiac cause (n=8637), trauma patients had a mean age of 51.2 +/-22.4 years (vs. 68.4 +/-15.2 years in cardiac patients, p&lt;0.001), initial return of spontaneous circulation could be restored in 107(29,1%) patients (vs. 3980 (46,1%) in cardiac patients), and 95 (25,8%) trauma patients had ROSC on admission at hospital (vs. 3673 (42,5%) in cardiac patients). Within the TR-DGU resuscitation attempts were reported in 814 trauma patients (3%) out of 27,592 documented trauma patients. The overall in-hospital mortality rate of these trauma CA patients was 72.9% (n=593 of 814). A two-step approach including both registries revealed that 13% survived 24 hours and 2% had good neurological outcome at hospital discharge out of 100% with a pre-clinical traumatic CA. Trauma patients with CA, however, were significant younger than CA patients with cardiac origin. Therefore, starting CPR in each CA patient, irrespective of the primary cause of CA, should be recommended.
Abstract 1974: Comparisons of Ultrasound Radio Frequency Analysis between Integrated Backscatter Intravascular Ultrasound and Virtual Histology Intravascular Ultrasound for Tissue Characterization of Coronary Plaques
Authors: Munenori Okubo, Masanori Kawasaki, Yoshiyuki Ishihara, Urara Mori, Tomoki Kubota, Takahiko Yamaki, Shinji Yasuda, Shinichiro Tanaka, Shinsuke Ojio, Kunihiko Tsuchiya, Genzou Takemura, Kazuhiko Nishigaki, Masanao Saio, Tsuyoshi Takami, Shinya Minatoguchi, Hisayoshi Fujiwara
Journal: Circulation (2006)
Epidemiologic Study of 100 Cases of Toxoplasmic Uveitis: Implications for Diagnosis and Prevention
Authors: J B CHODOS, H E HABEGGER-CHODOS
Journal: JAMA (1963)

An epidemiologic study of 100 patients with active chorioretinitis, positive Sabin-Feldman methylene-blue dye-test, and favourable response to antitoxoplasmic drugs (spiramycin) was undertaken to establish a basis for rapid clinical diagnosis and institution of preventive measures for toxoplasmic uveitis. Eighty-two of the 100 patients, but only 19 of 100 controls, gave positive histories of exposure to likely sources of toxoplasmosis, such as hunting and handling of wild game, ingestion of raw meat, etc. Seventy-six of these 82 patients had positive toxoplasmin skin tests, but all subsequently had positive dye-tests. The important practical conclusion was reached that all cases with active chorioretinitis, positive toxoplasmin skin test, or history of exposure to known reservoirs of toxoplasmosis should be treated immediately, as dye-tests in such cases will almost invariably be positive. This clinical approach greatly improves the visual prognosis of toxoplasmic chorioretinitis, since specific therapy need not be delayed for several weeks until the result of the dye-test is known.
Abstract 16051: Potential of Pre-Contrast T1 Mapping as a Marker of Interstitial Fibrosis in Severe Aortic Stenosis
Authors: Andrew Jabbour, Callum Ettles, Tevfik Ismail, Ankur Gulati, Pedro Ferreira, Ricardo Wage, Saman Zaman, Pierre Croisille, Carl Shakespeare, Raad Mohiaddin, Taigang He, Dudley Pennell, David Firmin, Sanjay Prasad
Journal: Circulation (2011)

Introduction: Aortic stenosis (AS) is associated with increased interstitial myocardial fibrosis (IMF). Although detectable after gadolinium administration by equilibrium-contrast CMR, protocols ar...
Abstract 21652: DPP4 Inhibition Improves Adipose Inflammation and Insulin Resistance via GLP-1 Independent Mechanisms
Authors: Zubair Shah, Thomas Kampfrath, Jeffrey Deiuliis, Andrei Maiseyeu, Colleen Pineda, Zhekang Ying, Rekha Durairaj, Xiaohua Xu, Qinghua Sun, Sanjay Rajagopalan
Journal: Circulation (2010)

Objective: Inflammation of the adipose milieu in obesity is believed to play an etiologic role in insulin resistance and type 2 diabetes (T2DM). Dipeptidyl peptidase-4 (DPP4, CD26) inhibitors are a...
Wave Reflection Predicts Cardiovascular Events in Hypertensive Individuals Independent of Blood Pressure and Other Cardiovascular Risk Factors
Authors: Charlotte Manisty, Jamil Mayet, Robyn J. Tapp, Kim H. Parker, Peter Sever, Neil H. Poulter, Simon A. McG. Thom, Alun D. Hughes
Journal: Journal of the American College of Cardiology (2010)