bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical effects and outcomes with new P2Y12 inhibitors in ACS
Authors: Collet Jean‐Philippe , O’Connor Stephen 
Published: September 2011

AbstractThienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high‐risk percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral pro‐drug leading to irreversible blockade of the P2Y12 receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct‐acting and reversible inhibitor of the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y12 receptor providing the highest level of inhibition, and elinogrel is an intravenous and oral P2Y12 antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y12 inhibition led respectively to significant 19 and 16% relative risk reduction of a similar primary end point combining cardiovascular death, non‐fatal myocardial infarction, or non‐fatal stroke. Both drugs showed a significant 0.6% absolute excess of TIMI major bleeding not related to CABG surgery. Because in clinical trials, patients perceived to be at higher risk of bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a ‘real‐world’ setting, i.e. in the elderly patient with comorbidities. On the other hand, these newly developed P2Y12 inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for patients with STEMI.
Pharmacokinetic basis of the antiplatelet action of prasugrel
Authors: Schrör Karsten , Siller‐Matula Jolanta M. , Huber Kurt 
Published: September 2011

AbstractPrasugrel is the most recent development of thienopyridine‐type antiplatelet drugs. Like the earlier‐generation thienopyridines, i.e. ticlopidine and clopidogrel, prasugrel is also an inactive prodrug that requires metabolic processing in vivo to generate the active antiplatelet metabolite. The efficacy of this bioactivation is the key determinant for the pharmacodynamic potency of the compound, i.e. the irreversible blockade of the platelet P2Y12‐ADP receptor. Prasugrel is rapidly absorbed from the gut. After oral administration of standard‐loading doses of 60 mg, maximum plasma levels of the active metabolite are achieved within 1 h, effective, maximum inhibition of platelet aggregation at 1–2 h. Bioconversion of prasugrel into the active metabolite requires two metabolic steps that occur in sequence. The first is the generation of a thiolactone‐intermediate, mainly by carboxyesterases‐2 in the intestine, the second the cytochrome (CYP)‐dependent conversion of the thiolactone into the active metabolite. This second step involves several cytochromes, most notably CYP3A4, CYP2C19, CYP2B6, and CYP2C9. The enzymatic generation of the active metabolite of prasugrel is much more effective than that of clopidogrel where only about 5% of oral clopidogrel is transformed into the active compound by two‐step CYP‐dependent procedures. About 70% of prasugrel metabolites are excreted in the urine and 30% in the feces. The molar potency of the respective active metabolites of prasugrel and clopidogrel is identical. Thus, the more rapid onset, higher potency and lower interindividual variability of antiplatelet effects of prasugrel as compared to clopidogrel in vivo are entirely because of its more efficient pharmacokinetics.
Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues
Authors: Lin Ligen , Saha Pradip K. , Ma Xiaojun , Henshaw Iyabo O. , Shao Longjiang , Chang Benny H. J. , Buras Eric D. , Tong Qiang , Chan Lawrence , McGuinness Owen P. , Sun Yuxiang 
Published: September 2011

SummaryAging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show that ablation of the ghrelin receptor (growth hormone secretagogue receptor, GHS‐R) improves insulin sensitivity during aging. Compared to wild‐type (WT) mice, old Ghsr−/− mice have reduced fat and preserve a healthier lipid profile. Old Ghsr−/− mice also exhibit elevated energy expenditure and resting metabolic rate, yet have similar food intake and locomotor activity. While GHS‐R expression in white and brown adipose tissues was below the detectable level in the young mice, GHS‐R expression was readily detectable in visceral white fat and interscapular brown fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced glucose/lipid uptake and lipogenesis in white adipose tissues but increased thermogenic capacity in brown adipose tissues. Ghsr ablation prevents age‐associated decline in thermogenic gene expression of uncoupling protein 1 (UCP1). Cell culture studies in brown adipocytes further demonstrate that ghrelin suppresses the expression of adipogenic and thermogenic genes, while GHS‐R antagonist abolishes ghrelin’s effects and increases UCP1 expression. Hence, GHS‐R plays an important role in thermogenic impairment during aging. Ghsr ablation improves aging‐associated obesity and insulin resistance by reducing adiposity and increasing thermogenesis. Growth hormone secretagogue receptor antagonists may be a new means of combating obesity by shifting the energy balance from obesogenesis to thermogenesis.
Depressive symptomatology and service utilisation among refugee children and adolescents living in South Australia
Authors: Ziaian Tahereh , de Anstiss Helena , Antoniou Georgia , Sawyer Michael , Baghurst Peter 
Published: September 2011

Background:  Young refugees resettled in Western countries are at increased risk of mental health problems. However, most research has centred on post traumatic stress disorder (PTSD), with depression, other mental health disorders, and problems receiving comparatively less attention.Method:  Depressive symptomatology was assessed using the Children’s Depression Inventory (CDI) in a multiethnic community sample of 348 refugee children (n = 180) and adolescents (n = 168) aged 7–17 years living in South Australia.Results:  According to parent reports, 7.1% of children and adolescents had depressive symptomatology for which services were available and yet only 21.5% of these accessed services.Conclusions:  Young refugees need improved access to culturally appropriate mental health care.
Remains of Hipparion (Equidae, Perissodactyla) from Puente Minero (Teruel Province, Spain) and their implications for the systematics of the Turolian Hipparionini
Authors: PESQUERO MARÍA D. , ALBERDI MARÍA T. , ALCALÁ LUIS 
Published: September 2011

Abstract:  Morphological and biometrical variability of the equid Hipparion from Puente Minero and other localities from the Teruel Basin, Spain (MN10–MN13), is analysed. Three species of Hipparion are recognized in Puente Minero, H. laromae, H. matthewi and Hipparion sp. cf. H. longipes, through comparison with other Spanish and Eurasian species (Samos, Greece; Höwenegg, Germany; Pavlodar, Kazakhstan, small and large forms; Akkaşdaği, Turkey; and the following Spanish sites, La Roma 2, Los Aljezares, Concud, Milagros, Las Casiones and Venta de Moro). The majority of the Hipparion remains from Puente Minero and determined to be Hipparion laromae based on their size and morphology. This interpretation was confirmed by bivariate and multivariate analyses. These results suggest a Eurasian immigration of different Hipparion species into the Teruel Basin.
Retracted: Unrecognized High Brachial Artery Bifurcation is Associated with Higher Rate of Dialysis Access Failure
Authors: Kirksey Lee 
Published: September 2011

AbstractA thorough consideration of all factors contributing to successful dialysis access creation is necessary to achieve optimal outcomes. A high bifurcation of the brachial artery (brachioradial variant) occurs in greater than 20% of patients. Dialysis access was created in 22 limbs with this variant—15 fistula, and 7 prosthetic grafts. Nonmaturation occurred in 33% of fistula. Early thromboses occurred in 29% of prosthetic bridge grafts. In this experience, the brachioradial variant is associated with a relatively higher rate of fistula nonmaturation and prosthetic graft thromboses. These findings reinforce the critical role of preoperative imaging studies in dialysis access creation. A sound algorithm for the surgical management of the brachioradial variation facilitates decision making and will improve dialysis access outcomes.
A Vascular Access Coordinator Improves the Prevalent Fistula Rate
Authors: Dwyer Amy , Shelton Paula , Brier Michael , Aronoff George 
Published: September 2011

AbstractThe Centers for Medicare and Medicaid Services set the prevalent arteriovenous fistula (AVF) rate of 66% as a national standard. To test the hypothesis that the use of a clinical vascular access coordinator could increase the rate of AVF in a large Nephrology group practice, we implemented an aggressive, multidisciplinary vascular access improvement program led by a trained vascular access coordinator (VAC). In early 2009, we established protocols, approved by all physicians, for the care of vascular access and implemented by a nurse VAC. We retrospectively reviewed Network vascular access data reports from January 2008 through December 2010. The data show that after the implementation of a comprehensive access program led by a VAC, the prevalent AVF rate increased from 50% to 65%. The number of grafts decreased while the percentage of dialysis catheters used for more than 90 days was cut in half. These data suggest that despite an unchanged catheter rate at dialysis initiation, the use of a VAC implementing an aggressive, multidisciplinary access program can significantly increase the AVF rate while decreasing grafts and prevalent catheter use.
Clonality of Staphylococcus aureus Colonization over Time in Attendees of a Camp for Children with Chronic Dermatoses
Authors: Graber Christopher J. , Shane Andi L. , Weintrub Peggy , Chambers Henry F. 
Published: September 2011

Abstract:  Chronic dermatoses are risk factors for Staphylococcus aureus colonization; little is known about the significance of transmission between persons with chronic dermatoses (CD) and their contacts. We collected nasal, axillary, and skin swabs for S. aureus from 50 attendees of a camp for children with CD and their families at three time points: start and end of 2005 camp and start of 2006 camp (times A, B, and C, respectively). Thirty‐one persons had CD, including epidermolysis bullosa (n = 14), atopic dermatitis (n = 7), ichthyosis (n = 5), and psoriasis (n = 5). Methicillin susceptibility and genotype were determined for all S. aureus isolates. Seventy‐one unique S. aureus isolate from 10 clonal complexes (CC) were isolated; 14 (20%) were methicillin‐resistant (MRSA). Persons with CD were more likely than those without CD to be colonized with S. aureus at the start of the 2005 (p = 0.01) and 2006 (p = 0.02) camp or at any time or site (p = 0.04) or to be persistently colonized with the same S. aureus CC at the start and end of the 2005 camp. Persons with atopic dermatitis had the highest burden of S. aureus colonization, whereas MRSA was isolated most frequently from attendees with epidermolysis bullosa. Three hospitalizations for skin infections were noted in people with CD between the 2005 and 2006 camps, versus three hospitalizations in the 6 months before the 2005 camp. Although S. aureus colonization was frequent among camp attendees (and in persons with CD in particular), it was diverse and variable. Camp attendance did not appear to affect infection‐related clinical outcomes.
Atrial Fibrillation Hospitalization Is Not Increased with Short‐Term Elevations in Exposure to Fine Particulate Air Pollution
Authors: BUNCH T. JARED , HORNE BENJAMIN D. , ASIRVATHAM SAMUEL J. , DAY JOHN D. , CRANDALL BRIAN G. , WEISS J. PETER , OSBORN JEFFREY S. , ANDERSON JEFFREY L. , MUHLESTEIN JOSEPH B. , LAPPE DONALD L. , POPE III C. ARDEN 
Published: September 2011

Background: Previous studies have observed that short‐term exposure to elevated concentrations of particulate matter (PM) air pollution increases risk of acute ischemic heart disease events and heart failure hospitalization, alters cardiac autonomic function, and increases risk of arrhythmias. This study explored the potential associations between short‐term elevations in PM exposure and atrial fibrillation (AF).
Methods and Results: A case‐crossover study design was used to explore associations between fine PM (PM2.5, particles with an aerodynamic diameter ≤2.5 μm) and 10,457 AF hospitalizations from 1993 to 2008 of patients who lived on Utah's Wasatch Front. Patients were hospitalized at Intermountain Healthcare facilities with a primary diagnosis of AF. Concurrent day exposure and cumulative lagged exposures for up to 21 days were explored and the data were stratified by sex, age, and previous or subsequent admission for myocardial infarction. Although the estimated associations between PM2.5 and AF hospitalizations for the various lag structures and strata were consistently positive suggestive of risk, they were not statistically significant and they were extremely small compared to previously observed associations with ischemic heart disease events and heart failure hospitalizations. Further, we observed no additive risk between PM2.5 and AF hospitalization in those with respiratory disease or sleep apnea.
Conclusions: Unlike previously observed associations with ischemic heart disease events and heart failure hospitalizations using similar study design and approaches, this study found that hospitalization for AF was not significantly associated with elevations in short‐term exposure to fine PM air pollution. (PACE 2011; 34:1475–1479)
Ranolazine Reduces Ventricular Tachycardia Burden and ICD Shocks in Patients with Drug‐Refractory ICD Shocks
Authors: BUNCH T. JARED , MAHAPATRA SRIJOY , MURDOCK DAVID , MOLDEN JAMIE , WEISS J. PETER , MAY HEIDI T. , BAIR TAMI L. , MADER KATY M. , CRANDALL BRIAN G. , DAY JOHN D. , OSBORN JEFFREY S. , MUHLESTEIN JOSEPH B. , LAPPE DONALD L. , ANDERSON JEFFREY L. 
Published: September 2011

Background:
There are limited options for patients who present with antiarrhythmic‐drug (AAD)‐refractory ventricular tachycardia (VT) with recurrent implantable cardioverter defibrillator (ICD) shocks. Ranolazine is a drug that exerts antianginal and antiischemic effects and also acts as an antiarrhythmic in isolation and in combination with other class III medications. Ranolazine may be an option for recurrent AAD‐refractory ICD shocks secondary to VT, but its efficacy, outcomes, and tolerance are unknown.
Methods and Results:
Twelve patients (age 65 ± 9.7 years) were treated with ranolazine. Eleven (92%) were male, and 10 (83%) had ischemic heart disease with an average ejection fraction of 0.34 ± 0.13. All patients were on a class III AAD (11 amiodarone, one sotalol), with six (50%) receiving mexilitene or lidocaine. Five patients had a prior ablation and two were referred for a VT ablation at the index presentation. The QRS increased nonsignificantly from 128 ± 31 ms to 133 ± 31 ms, and the QTc increased nonsignificantly from 486 ± 32 ms to 495 ± 31 ms after ranolazine initiation. Over a follow‐up of 6 ± 6 months, 11 (92%) patients had a significant reduction in VT and no ICD shocks were observed. VT ablation was not required in those referred. In two patients, gastrointestinal side effects limited long‐term use. Of these two patients, one died due to progressive heart failure. In one patient, severe hypoglycemia limited dosing to 500 mg daily, but this was sufficient for VT control.
Conclusion:
Ranolazine proved effective in reducing VT burden and ICD shocks in patients with AAD‐refractory VT. Ranolazine should be further tested for this indication and considered for clinical application when other options have proven ineffective. (PACE 2011; 34:1600–1606)
Immune response to human embryonic stem cell‐derived cardiac progenitors and adipose‐derived stromal cells
Authors: Calderon Damelys , Planat‐Benard Valérie , Bellamy Valérie , Vanneaux Valérie , Kuhn Chantal , Peyrard Severine , Larghero Jéröome , Desnos Michel , Casteilla Louis , Pucéat Michel , Menasché Philippe , Chatenoud Lucienne 
Published: September 2011

AbstractTransplantation of allogeneic human embryonic stem cell‐derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of adipose‐derived stromal cells (ADSC). Peripheral blood mononuclear cells were collected from 40 patients with coronary artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15+ Mesp1+) were generated as already reported from the I6 cell line treated with bone morphogenetic protein (BMP)‐2. Adipose‐derived stromal cells were obtained from abdominal dermolipectomies. We assessed the proliferative response of peripheral lymphocytes from patients and controls to cardiac progenitors cultured on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac progenitors cultured on a monolayer of ADSC triggered a proliferation of lymphocytes from both patients and controls albeit lower than that induced by allogeneic lymphocytes. When cultured alone, ADSC did not induce any proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes, ADSC significantly inhibited the alloantigen or mitogen‐induced proliferative response. Compared to healthy controls, lymphocytes from patients presenting CAD expressed a decreased proliferative capacity, in particular to mitogen‐induced stimulation. Adipose‐derived stromal cells express an immunomodulatory effect that limits both alloantigen and mitogen‐induced lymphocyte responses. Furthermore, lymphocytes from patients with CAD are low responders to conventional stimuli, possibly because of their age and disease‐associated treatment regimens. We propose that, in combination, these factors may limit the in vivo immunogenicity of cardiac progenitors co‐implanted with ADSC in patients with CAD.
Anthropometric measurements as predictors of cephalopelvic disproportion
Authors: BENJAMIN SANTOSH J , DANIEL ANJALI B , KAMATH ASHA , RAMKUMAR VANI 
Published: September 2011

AbstractObjective. We assessed the efficacy of maternal anthropometric measurements and clinical estimates of fetal weight in isolation and in combination as predictors of cephalopelvic disproportion (CPD). Design. Prospective cohort study. Setting. Tertiary care teaching hospital, two affiliated hospitals with facilities for conducting cesarean delivery and seven affiliated primary care facilities with no operation theaters. Sample. Primigravidae over 37 weeks’ gestation attending these facilities during a 20‐month period with a singleton pregnancy in vertex presentation. Methods. Several anthropometric measurements were taken in 249 primigravidae. Fetal weight was estimated. Differences in these measurements between the vaginal delivery and CPD groups were analyzed. The validity of these measurements in predicting CPD was analyzed by plotting receiver operating characteristic curves and by logistic regression analysis. Main outcome measure. Mode of delivery. Results. Maternal height, foot size, inter‐trochanteric diameter and bis‐acromial diameter showed the highest positive predictive values for CPD. Combining some maternal measurements with estimates of fetal weight increased predictive values modestly, which are likely to be greater if the estimates of fetal weight are close to the actual birth weight. Based on multivariate analysis the risk factors for CPD in our population were foot length ≤23cm, inter‐trochanteric diameter ≤30cm and estimated fetal weight ≥3 000g. Conclusions. Maternal anthropometric measurements can predict CPD to some extent. Combining maternal measurements with clinical estimates of fetal weight only enhances the predictive value to a relatively modest degree (positive predictive value 24%).
Platelet antibodies and fetal growth: maternal antibodies against fetal platelet antigen 1a are strongly associated with reduced birthweight in boys
Authors: TILLER HEIDI , KILLIE METTE KJÆR , HUSEBEKK ANNE , SKOGEN BJØRN , NI HEYU , KJELDSEN‐KRAGH JENS , ØIAN PÅL 
Published: September 2011

AbstractObjective. To assess whether maternal HPA 1a alloimmunization is associated with birthweight. Design. A retrospective observational cohort study. Setting. The national reference laboratory for clinical platelet immunology at a university hospital. Population. 165 HPA 1a incompatible pregnancies identified from a recent screening study of 100 448 women (124 pregnancies) and the national reference laboratory for clinical platelet immunology (41 pregnancies). Methods. A linear mixed model analysis was used to assess whether maternal anti‐HPA 1a antibodies were associated with birthweight. A generalized linear model was used to assess maternal anti‐HPA 1a antibodies as risk factor for small‐for‐gestational age neonates. Both models were adjusted for gestational age at time of delivery, maternal age, parity, smoking habits during pregnancy, preeclampsia, diabetes mellitus and fetal sex. Main outcome measures. Maternal anti‐HPA 1a antibody as risk factor of reduced birthweight and small‐for‐gestational age neonates. Results. The level of maternal anti‐HPA 1a antibodies was significantly associated with birthweight and risk of small‐for‐gestational age neonates after correcting for confounding variables (p<0.001). However, this association was only significant for boys. When the mother had high levels of anti‐HPA 1a antibodies during pregnancy, the adjusted mean birthweight in boys was 530g lower compared with anti‐HPA 1a antibody negative pregnancies (p<0.001). Conclusions. A linear relation between maternal anti‐HPA 1a antibody levels and reduced birthweight in boys was demonstrated. Reduced birthweight should be considered a possible complication of fetal and neonatal alloimmune thrombocytopenia.