tbuckley/cabot-search huggingface dataset:
Abstract 9993: Friedreich Ataxia is Associated with Endothelial Dysfunction and Increased Arterial Stiffness
Authors: Gerasimos Siasos, Elias Gialafos, Dimitris Tousoulis, Evangelos Oikonomou, Stavroula Michalea, Christina Kollia, Constantina Aggeli, Konstantinos Maniatis, Thodoris Paraskevopoulos, Konstantinos Zisimos, Stamatios Kioufis, Athanasios G Papavassiliou, Christodoulos Stefanadis
Journal: Circulation (2011)

Purpose: Friedreich's ataxia (FA) is an autosomal recessive disorder characterized by spinocerebellar degeneration and increased oxidative status. However, vascular function in the syndrome remains unknown. In this study we assessed the hypothesis that FA patients have impaired vascular function. Methods: Nine teen FA patients diagnosed by molecular genetic analysis (aged 30 ± 10.88 years) were compared with thirty five age and sex matched healthy subjects. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness was evaluated by augmentation index (AIx). Left ventricle end diastolic diameter, intra ventricular septum and posterior wall were measured by echocardiography examination and left ventricle (LV) mass was calculated by Penn’s formula. LV mass index was calculated by subdivided LV mass with body surface area. Results: FA patients, compared to healthy subjects, had significantly lower FMD values (4.08 ± 1.08 % vs 9.46 ± 3.76 %, p&lt;0.001) and higher AIx values (10.93 ± 16.56 % vs 0.98 ± 14.19 %, p=0.05). FA patients also had significant thicker intra ventricular septum (9.8 ± 2.15 cm vs 8.2 ± 0.91 cm, p&lt;0.05), posterior wall (10.12 ± 2.00 vs 8.10 ± 0.73 cm, p&lt;0.05) and increased LV mass index (112.08±48,20 vs. 85.17±16.01, p=0.05). Conclusion: Friedreich's ataxia patients have impaired endothelial function, increased arterial stiffness and increased LV mass index. These results highlight the need for intense modification of cardiovascular risk factors in this population.
Abstract 10677: A Validation of Circumferential and Longitudinal Regional Strain in Pumped Hearts Modeling Normal Function Compared to Simulated Myocardial Infarction Generated From Three-Dimensional Echocardiographic Feature Tracking Compared to Sonomicrometry
Authors: Cole Streiff, Jill Panosian, Meihua Zhu, Muhammad Ashraf, David J Sahn
Journal: Circulation (2011)

Background: Three-dimensional (3D) echocardiography provides visualization of the complex anatomy of heart structures throughout the cardiac cycle. Quantitative global and regional strain values ma...
Abstract 1102: Atypical Presentation of Acute Coronary Syndrome: The Underestimated High Risk Group. Insights From a Multicenter, Multinational Observational Study
Authors: Ayman El-Menyar, Mohammad Zubaid, Wael Al Mahmeed, Kadhim Sulaiman, Ahmed Al-Motarreb, Haitham Amin, Khalid Al-Habib, Rashid Alhamdan, R Singh, Nidal Asaad, Jassim Al Suwaidi
Journal: Circulation (2009)
Abstract 4413: Accelerated Inactivation of the L-type Calcium due to a Mutation in CACNB2b Underlies the Development of a Brugada ECG Phenotype
Authors: Jonathan M Cordeiro, Mark Marieb, Ryan Pfeiffer, Kirstine Calloe, Elena Burashnikov, Charles Antzelevitch
Journal: Circulation (2008)

Background: Ion channelopathies are responsible for a number of genetic cardiac arrhythmia syndromes. Recent work demonstrated an association between mutations in CACNA1c and CACNB2b, the genes that encode the α and β subunits of the L-type calcium channel, and the Brugada syndrome (BrS). The mutations previously described all caused a loss of function secondary to a major reduction in peak calcium channel current (I Ca ). In the present study we describe a novel CACNB2b mutation associated with BrS in which loss of function was caused by accelerated inactivation of I Ca . Methods and Results: The proband, a 32 yo male, displayed a saddleback ST segment elevation in the right precordial leads that converted to a coved-type ECG following a procainamide challenge. His EP study was positive with double extrastimuli inducing polymorphic VT/VF. He was also diagnosed with vasovagal syncope. Genomic DNA was isolated from blood lymphocytes. All exons and intron borders of 12 ion channel genes were amplified and sequenced. The only mutation uncovered was a missense mutation (T11I) in CACNB2b. The effect of this mutation was studied by expression of WT or T11I CACNB2b in TSA201 cells co-transfected with WT CANCA1c and CACNA2d. Patch clamp analysis showed no difference in I Ca density between WT and T11I (17.9±1.8 vs 22.5±4.3 pA/pF, respectively at +20mV). Similarly, steady-state inactivation and channel recovery was not different between WT and T11I mutant channels. However, both the fast and slow decay of I Ca produced by T11I mutant were significantly faster compared to WT at potentials between −10 to +30 mV, suggesting a reduction in depolarizing current during the course of an action potential. Application of action potential voltage clamp pulses confirmed that T11I total charge was reduced by 42±2.3% compared to WT (p&lt;0.05). Conclusion: We report the first Brugada syndrome mutation in CaCNB2b resulting in accelerated inactivation of the L-type calcium channel. The T11I mutation caused a faster decay of cardiac L-type calcium current but did not significantly alter the magnitude of the peak current. Our results suggest that a reduced total charge carried by I Ca during the plateau of the action potential predisposes to the Brugada phenotype.
Follow up of people fitted with hearing aids
Authors: E. M Bond
Journal: BMJ (2002)

Emergency response to 999 calls Alternatives to the emergency 999 response can be seen in EuropeEditor-Snooks et al point out that the current 999 emergency response system has problems: increasing demand from the public and ever shorter response time targets. 1 They find a lack of evidence on alternative systems and responses in the English medical literature.By restricting their search, they overlook live examples only a few miles from these shores.France, since the mid-1960s, has had a system which incorporates many of the alternatives quoted by the authors: the Service d'Aide Medical Urgente (SAMU). 2 Calls to the control room are logged by trained telephone operators and then passed on to a "medical dispatcher": a doctor in emergency medicine, trained by the service.Medical dispatchers may simply provide medical advice to the caller, or they may decide to use one of a range of other responses to a call.These are referral to, or the dispatch of, a primary care doctor; arranging nonurgent transport by a private ambulance; urgent transport by pompiers (emergency technicians working through the fire service); or sending out a mobile intensive care unit with a doctor trained in emergency medicine.Medical dispatchers also coordinate the deployment of additional resources and decide on the most appropriate destination for a patient.In 2001 the service covering Paris received 300 000 calls (about 820 calls per day).Only 6% of the calls (50 per day) resulted in the dispatch of a mobile intensive care unit.In 16% of cases (130 per day) a primary care doctor was called.Altogether 205 calls per day were managed by the pompiers, by a private ambulance, or by giving medical advice.The remainder were
Does delay in the diagnosis of childhood testicular germ cell tumors (GCT) lead to more advanced disease stage and inferior survival?
Authors: S. L. Spunt, C. A. Billups, J. Wu, M. F. Walsh
Journal: Journal of Clinical Oncology (2005)

8554 Background Stage I testicular GCT in childhood is readily curable with orchiectomy alone. Stage II-IV disease requires the addition of chemotherapy that may cause long-term toxicity, and survival is slightly less favorable. It is unknown if a prolonged time interval from initial symptoms to diagnosis (TSD) is associated with more advanced disease stage and a lower likelihood of cure. Methods Single institution retrospective chart review of 49 pediatric patients with testicular germ cell tumors treated between 12/68 and 12/03. The relationships between TSD (as a continuous variable), tumor size, disease stage, age group (< 10 years or ≥ 10 years), and survival were examined using the Spearman correlation coefficient, the Wilcoxon rank sum test, Fisher’s exact test, and Cox regression, as appropriate. Results Median age at diagnosis was 2.1 years (range, 0.3–19.9 years), and 22 patients were ≥10 years. TSD range was 1 to 447 days (median 52 days). Twenty-nine patients had stage I disease and 20 patients had stage II-IV. Longer TSD was correlated with larger tumor volume (p<0.001). TSD was longer in patients with stage II-IV disease than in patients with stage I disease (median 122 vs. 41 days, p=0.001). Patients ≥ 10 years of age had a longer TSD than younger patients (median 106 vs. 33 days, p=0.001) and were more likely to have high stage disease (p<0.001). TSD was significantly predictive of survival (p=0.03). Conclusions In pediatric testicular GCT patients, longer TSD is associated with larger tumor volume, higher disease stage, and inferior survival. Patients ≥ 10 years of age are at the greatest risk for long TSD. Interventions aimed at early diagnosis, particularly in adolescents, may improve the likelihood of survival. Early diagnosis may also reduce the proportion of patients requiring chemotherapy, thereby diminishing long-term morbidity in survivors. No significant financial relationships to disclose.
Rapid Effects of Atorvastatin on Tetrahydrobiopterin-Mediated eNOS Coupling in Human Arteries, is Mediated by Stimulation of Vascular GTP-Cyclohydrolase
Authors: Charalambos Antoniades, Costantinos Bakogiannis, Ashley Hale, Dimitris Tousoulis, Michael Demosthenous, Alexios S Antonopoulos, Regent Lee, Costas Psarros, Christodoulos Stefanadis, Keith M Channon
Journal: Circulation (2011)

Background: Statins improve survival of patients with atherosclerosis, but their direct effects on human arterial wall are unclear. We examined the effect of atorvastatin on the mechanisms regulati...
Telomere Length Is Reduced In Endothelial Progenitor Cells (EPCs) from Subjects with Prehypertension and Hypertension and Relates to Impaired Epc In Vivo Re-Endothellalisation Capacity
Authors: Giovanna Giannotti, Maja Muller, Hong Jiang, Tibor Horvath, Carola Dorries, Christian Besler, Costantina Manes, Mario Marzilli, Thomas F Luscher, Helmut Drexler, Lenhard K Rudolph, Ulf Landmesser
Journal: Circulation (2008)
Atrial Fibrillation in the Setting of Acute Myocardial Infarction: The GUSTO-I Experience fn1fn1This study was funded by grants from Genentech, South San Francisco, California; Bayer Corporation, New York, New York; CIBA-Corning, Medfield, Massachusetts; ICI Pharmaceuticals, Wilmington, Delaware; and Sanofi Pharmaceuticals, Paris, France.
Authors: Brian S. Crenshaw, Samuel R. Ward, Christopher B. Granger, Amanda L. Stebbins, Eric J. Topol, Robert M. Califf
Journal: Journal of the American College of Cardiology (1997)
Treatment with Anti-CD19 BiTE Antibody Blinatumomab (MT103 / MEDI-538) Is Able to Eliminate Minimal Residual Disease (MRD) in Patients with B-Precursor Acute Lymphoblastic Leukemia (ALL): First Results of An Ongoing Phase II Study.
Authors: Max Topp, Nikola Goekbuget, Peter Kufer, Gerhard Zugmaier, Evelyn Degenhard, Svenja Neumann, Heinz A Horst, Andreas Viardot, Mathias Schmid, Oliver G. Ottmann, Margit Schmidt, Carsten Reinhardt, Patrick A Baeuerle, Dirk Nagorsen, Dieter Hoelzer, Ralf C. Bargou
Journal: Blood (2008)
Fortnightly Review: Development of review criteria: linking guidelines and assessment of quality
Authors: R. Baker, R. C Fraser
Journal: BMJ (1995)

Review criteria are designed to enable clinicians and others to assess care. However, there is no established method for developing criteria, and they are often confused with guidelines. Criteria should comprise measurable activities that are appropriate for the setting in which they are to be used. They should also be based on research evidence and prioritised according to the strength of that evidence and effect on outcome. Good criteria can be used to aid implementation of guidelines by providing a standard against which to monitor performance and enabling clinical audit.
Abstract 5770: The Platelet Activity After Clopidogrel Termination (PACT) Study
Authors: Andrew L Frelinger, Marc R Barnard, Marsha L Fox, Alan D Michelson
Journal: Circulation (2009)

“Rebound” platelet hyperreactivity upon discontinuation of clopidogrel has been proposed to lead to increased thrombotic risk including late stent thrombosis. However the hypothesis that discontinuation of clopidogrel results in platelet hyperreactivity has never been rigorously tested. To test this, we performed a prospective, randomized, double-blind, placebo-controlled, crossover study: the Platelet Activity after Clopidogrel Termination (PACT) study. Platelet reactivity was measured before, during clopidogrel 75 mg or placebo daily for 14 days, and on days 1, 4, 8, 11, 15 and 45 after discontinuation of clopidogrel or placebo in 15 healthy subjects. All subjects received aspirin 81 mg daily. Platelet reactivity was assessed by platelet surface activated GPIIb-IIIa and surface P-selectin, measured by whole blood flow cytometry, in response to ADP 0.5, 1, and 20 μ M, thrombin receptor activating peptide (TRAP) 1 and 20 μ M, and both collagen 5 μ g/mL and epinephrine 5 μ M, and by light transmission platelet aggregation with ADP 2.5, 5, and 20 μ M, TRAP 2 and 20 μ M, and collagen 6 μ g/mL. Immature platelet fraction (IPF) was measured in the Sysmex XE-2100. At no time point after discontinuation of clopidogrel was platelet reactivity, as determined by all assay end points, or the IPF significantly greater than after discontinuation of placebo. The figure shows representative results. In conclusion, this double-blind, placebo-controlled, crossover study demonstrates that discontinuation of clopidogrel does not result in “rebound” platelet hyperreactivity -as determined by multiple time points, assays, agonists, and agonist concentrations. Fig. ADP 1 μM-stimulated platelet surface activated GPIIb-IIIa before, during, and after treatment with placebo or clopidogrel .
Eye Care for Elderly Americans with Diabetes Mellitus
Authors: Fang Wang, Jonathan C. Javitt
Journal: Ophthalmology (1996)

The purpose of the study is to understand current pattern of eye care use among people with diabetes.Study population included 175,015 Medicare beneficiaries who had physician-diagnosed diabetes. The authors estimated overall rate of eye care visits among these beneficiaries in 1992 and 1993 using Medicare physician claims data. In combination of Area Resource File, the authors examined association of eye care use with demographic characteristics, regional socio-economic characteristics, and regional eye care provider supply.Fifty-three percent of the population had at least 1 eye care visit in a 1-year period and 67% in a 2-year period. Younger age (ages < 75 years), male gender, black race, high regional poverty, and fewer ophthalmologist supply were related to lower rate of eye care use. There was no association between eye care use and regional education level and optometrist supply.The findings suggest that a large portion of elderly people with diabetes is not obtaining the necessary eye care, especially blacks, men, and those residing in poor areas with fewer ophthalmologists.
Abstract P184: Rescue of Reductive Stress by Nrf2 Deficiency in Protein Aggregation Cardiomyopathy Mice
Authors: Rajasekaran Namakkal Soorappan, Gayatri D Khanderao, Corey J Miller, Curtis Olson, Vasanthi Rajasekaran, Sankaranarayanan Kannan, Sheldon E Litwin, Christopher J Davidson
Journal: Circulation Research (2011)

Background: We recently discovered that the overexpression of human mutant αB-crystallin (hR120GCryAB) in mouse resulted in protein aggregation cardiomyopathy (PAC) and reductive stress (RS) in the heart tissue (Rajasekaran et.al Cell, 2007). Further, we identified that sustained activation of Nrf2 (nuclear erythroid 2 related factor 2)/ARE signaling as a causal mechanism for RS in the MPAC mice. We hypothesize that abolishing Nrf2 could prevent RS in R120GTG mice and thereby rescue them from cardiomyopathy and heart failure. Methods: To elucidate loss-of-function mechanisms for Nrf2 on RS and MPAC, we produced (1) NTG/WT, (2) R120GTG/WT, (3) R120GTG/Nrf2+/- and (4) R120GTG/Nrf2-/- mice by intercrossing R120GTG X Nrf2-KO. Primarily, we determined the rate of survival and performed echocardiography to understand the degree of pathogenesis and cardiac function over time (n=6-10). Next, we analyzed the redox state and protein/mRNA expression for major antioxidants including enzymes that are involved in glutathione metabolism in the heart. Results: Disruption of Nrf2 prolonged the survival of MPAC mice along with no signs of cardiac dysfunction (by ECHO). The R120GTG mice with Nrf2 deficiency (either Nrf2+/- or Nrf2-/-; n=4) had significantly decreased glutathione (but equal to NTG) levels when compared with R120GTG/WT cohorts. Such a decline in GSH resulted in quenching of “reducing power” to prevent “reductive stress” and facilitated redox homeostasis in the myocardium. Interestingly, the intercross mice showed no cardiac hypertrophy even at 12 months while the R120GTG exhibited 90% mortality due to PAC/heart failure. Further, protein and mRNA levels for major antioxidants were found to be normal in the R120GTG/Nrf2+/- while there was significant down regulation of these parameters in the R120GTG/Nrf2-/- mice when compared to NTG/WT suggesting that Nrf2-independent pathways are inadequate to maintain the antioxidant capacity under stressed conditions. Conclusions: These results demonstrate a critical role for Nrf2 underlying antioxidant potential in the myocardium. Abrogating RS via Nrf2 might be highly relevant to cure the protein aggregation diseases that are coupled with elevated intracellular reducing potential.
Abstract 18034: Clinical, Angiographic and Genetic Determinants of Early Coronary Stent Thrombosis: the ONASSIST Study
Authors: Gullaume Cayla, Stuart Scott, Stephen O'Connor, Jean-Sebastien Hulot, Johanne Silvain, Farzin Beygui, Olivier Barthelemy, Frederick Allanic, Gilles Montalescot, Jean-Phlippe Collet
Journal: Circulation (2011)

OBJECTIVES: To perform a comprehensive analysis of all determinants of definite early stent thrombosis (ST) to identify the risk and the modifiable factors of early EST. Methods: Using a web-based case collection and reporting system, 123 patients with definite early ST on dual antiplatelet therapy were matched 2:1 according to age and gender with 246 controls. All patients were genotyped for 23 genetic variants involved in clopidogrel metabolism ( CYP2C19 , CYP2C9, CYP2B6, CYP3A5, POR, ABCB1, PON1 ), platelet receptor function ( P2Y12, ITGB3 ), and the coagulation and fibrinolytic system ( MTHFR , Factor V, Fibrinogen, Prothrombin, PAI1 and VKORC1 ). Results: CYP2C19*2 (OR und =2.53, 95% CI [1.61-3.97], p&lt;0.0001) and ABCB1 TT3435 (OR und =2.01, 95% CI [1.22-3.30], p=0.006) carriers were more frequent among patients with EST than controls while CYP2C19*17 (OR und =0.53, 95% CI [0.31-0.88], p=0.01) and ITGB3 PlA2 (OR und =0.50, 95% CI [0.29-0.87], p=0.01) carriers were less frequent. Percutaneous coronary intervention in acute setting, complex lesions, impaired left ventricular function &lt; 35%, high clopidogrel loading doses and use of proton pump inhibitor were non genetic independent correlates of early ST. The accuracy of the clinical model to discriminate between early ST and controls (AUC 0.72, 95% CI [0.66-0.77] did not differ significantly from the genetic model (AUC 0.68, 95% CI [0.62-0.73] (p=0.34), although combining both led to a significant improvement in the discriminatory power of the model (AUC 0.78, 95% CI [0.73-0.83], p=0.004). Among all independent predictors of early ST, the use of high clopidogrel loading doses (OR=0.73, 95% CI[0.57-0.94], p=0.01) and proton pump inhibitors (OR=2.19, 95% CI [1.28-3.72], p=0.004) were the only modifiable factors. Conclusion: In addition to established clinical and angiographic factors, three genes involved in clopidogrel metabolism and platelet receptor function (CYP2C19, ABCB1, ITGB3) significantly improved the ability to predict early ST. PPI use and clopidogrel dose were both independently correlated with the risk of early ST, suggesting that the final amount of active metabolite generated is a major factor of prevention.
Preventing RhD haemolytic disease of the newborn
Authors: D. Lee, J S Craig, B G McClure, T R J Tubman
Journal: BMJ (1998)

Editor—In his editorial van Dijk advocates routine antenatal prophylaxis with anti-D immunoglobulin of all pregnant women who are RhD negative and refers to the consensus conference at the Royal College of Physicians in Edinburgh in April 1997.1 He states that two dose schedules were considered—two doses of 500 IU of anti-D immunoglobulin, one at 28 weeks’ gestation and the other at 34 weeks, and one dose of 1000 IU given between 28 and 30 weeks—both options being equally effective. He implies that the second option reflects Bowman’s practice in Canada.2 Bowman’s programme in fact uses a dose of 1500 IU given at 28 weeks; maternal anti-D immunoglobulin concentrations are then monitored and additional anti-D immunoglobulin is given at around 36 weeks to those women in whom passive anti-D immunoglobulin is no longer detectable. 

In my presentation to the conference the second option considered was a single dose of 1500 IU—not 1000 IU—of anti-D immunoglobulin at 30 weeks. In the final consensus statement the panel did not indicate a preference between these options and was satisfied that “both seem to work.” A dose of 1000 IU of anti-D immunoglobulin was never considered as the rate of its decay would mean that little or none would remain in a woman’s circulation towards the end of pregnancy, when fetomaternal haemorrhage is known to occur more frequently. 

Revised guidelines on the use of anti-D immunoglobulin from the British Blood Transfusion Society and the Royal College of Obstetricians and Gynaecologists agree that the preferred option is two doses of 500 IU of anti-D immunoglobulin.3 This option was chosen partly because it uses less anti-D immunoglobulin—a scarce resource—than a single dose of 1500 IU and partly because two doses of 500 IU given at 28 and 34 weeks achieve a higher circulating concentration of anti-D immunoglobulin as term approaches than does the single larger dose. The revised guidelines were also prompted by the absence of published data on the clinical outcome of giving a single dose of 1500 IU at 30 weeks.
Enriching Careers in General Practice A career structure for general practice
Authors: S Handysides
Journal: BMJ (1994)

Training for general practitioners usually provides little experience in research, business management, or dealing with chronic disease. It is these areas that could provide scope for further training after becoming a general practitioner principal and provided career goals. Formally recognised research practices, perhaps with one partner coordinating research but all participating, and district research facilitators could increase both the quality and the quantity of research in general practice. Recognising the different skills of doctors in the partnership and referring patients to the most appropriate partner will improve care for patients as well as provide career development. Further training could be aimed at filling gaps in the practice's pool of skills. Good management skills are becoming more important as practice teams get bigger and fundholding spreads. Some doctors may wish to become full time or part time managers and the idea of accredited courses for management has been raised.