bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-8 Is Associated with Non-Viremic State and IFN-γ with Biochemical Activity in HCV-Seropositive Blood Donors
Authors: Zarife Maria Alice S. , Reis Eliana A.G. , Meira Glenda C. , Carmo Theomira M.A. , Lopes Gisele B. , Malafaia Emilia C.O.B. , Silva Helder R. , Santana Nelma , Martins-Filho Olindo A. , Reis Mitermayer G.
Published: September 2010

Objective: The aim of this study was to explore a possible association between the pattern of serum cytokines with the virological and biochemical status of hepatitis C virus (HCV)-seropositive blood donors. Methods: 23 non-viremic and 33 viremic HCV-seropositive blood donors based on HCV-RNA tests, and 29 healthy individuals were included. Cytometric bead array assays were performed to detect cytokines. Results: The subjects were classified as low, medium or high cytokine producers based on the tertile distribution. The absence of detectable viremia was associated with high IL-1β and IL-8 producers. Conversely, elevated levels of IL-6, IL-10 and IL-12 were associated with detectable viremia. An increased frequency of high IL-1β producers was observed frequently in the non-viremic recombinant immunoblot assay (RIBA)-indeterminate subjects, while the high IL-4, IL-6, IL-8, IL-10 and IL-12 producers were more frequent in the non-viremic RIBA-positive subjects. Furthermore, the levels of IL-1β and IL-8 were higher in viremic subjects with a low level of alanine-aminotransferase (ALT), whereas the level of IFN-γ was increased among viremic subjects with a high ALT level. Conclusion: IL-1β and IL-8 were more likely to be associated with a non-viremic or less severe HCV infection, whereas IL-2 and IFN-γ levels correlated with a high ALT level.
An Adequate Calcium Intake Could Help Achieve Weight Loss in Overweight/Obese Women following Hypocaloric Diets
Authors: Rodríguez-Rodríguez Elena , Perea José M. , López-Sobaler Ana M. , Ortega Rosa M. ,   Research Group: 920030
Published: September 2010

Aim: To investigate the effect of calcium (Ca) intake and dairy product consumption modification on body composition in overweight/obese women following two types of hypocaloric diet. Methods: Study subjects were 57 women who were randomly assigned to follow one of two hypocaloric diets: diet V, in which the relative consumption of vegetables was increased, and diet C, which involved increasing the relative consumption of cereals (especially breakfast cereals). Dietetic and anthropometric data were collected at the start and at the end of the 6-week intervention period. Results: Ca density, Ca index of nutritional quality and Ca/protein improved with both diets. Dairy products, Ca intake, dairy Ca intake and Ca/protein were inversely correlated with body mass index at the end of the study. Among the women with an initial calcium intake below the 50th percentile, those who achieved a reduction in body mass index above the 50th percentile were those who most increased their total calcium intake, calcium intake from dairy sources, calcium density, calcium/protein ratio and the intake of total and skimmed dairy product consumption. Conclusion: Correcting an inadequate calcium intake could help improve weight loss in women following hypocaloric diets.
Antidepressants: Clinically Relevant Drug Interactions to Be Considered
Authors: Schellander Rene , Donnerer Josef
Published: September 2010

Drug interactions in clinical practice are common and have developed into an increasing challenge for the medical profession. Specifically antidepressant drugs (ADs), which are among the 5 most frequently prescribed drugs, are predestined for adverse drug interactions because of their multiple mechanisms of action and/or their influence on drug-metabolizing cytochrome P450 (CYP) enzymes. Although selective serotonin reuptake inhibitors (SSRIs) and other new-generation ADs have an overall improved safety profile, their potential for drug interactions is to be considered. A review of the current literature has been performed, and selected examples of clinically relevant interactions with ADs have been chosen. With regard to pharmacodynamic interactions, the serotonin syndrome, the risk of bleeding under SSRI therapy, and the corrected Q–T interval prolongation are discussed in this review. The inhibitory effects of new-generation ADs on CYP enzymes show great variability and might be relevant for prescription recommendations in elderly patients and in patients with polypharmacy. The CYP-enzyme-inducing effect of St. John’s wort, a popular over-the-counter herbal drug, may lead to decreased plasma levels of CYP substrates. When comparing prescription data and observed adverse drug events, there is fortunately a safety gap between the number of potential drug-drug interactions and the number of clinically observed side effects due to drug-drug interactions.
Analgesic and Antiallodynic Effects of Antidepressants after Infiltration into the Rat
Authors: Garcia Xavier , del Valle Jaume , Escribano Elvira , Domenech Josep , Queralt Josep
Published: September 2010

Tricyclic antidepressants (TCA) have potent local anesthetic properties and may produce a long-lasting pain blockade that could be of interest in relieving chronic pain states such as neuropathic pain, but there are only few data comparing their dose-response curves of analgesic activity under the same experimental conditions. This study examines the time course of pain-relieving properties of 7 TCA in heat-induced paw withdrawal after subcutaneous administration. Mixed inhibitors of norepinephrine and serotonin uptake (amitriptyline, nortriptyline, imipramine, desipramine, doxepin) and selective inhibitors of serotonin uptake (fluoxetine and fluvoxamine) were assayed. The TCA with the longest analgesic activity were selected to test its antiallodynic effect in the neuropathic pain model of chronic sciatic nerve constriction injury. Bupivacaine was used as a reference drug in both experiments. A dose versus time of maximal analgesic effect curve was constructed for each drug. The longest analgesic effect was obtained for doxepin and imipramine. Although low doses of amitriptyline showed the same activity than doxepin, higher doses failed to reach the same effect. Selective inhibitors of serotonin showed no action at all doses tested. In the chronic sciatic nerve constriction injury model, doxepin and, to a smaller degree, amitriptyline and imipramine protected from allodynia; bupivacaine was ineffective. The antiallodynic effect always lasted less long than the analgesic effect. These observations provide support for the potential use of TCA as durable analgesics. Doxepin overall showed the most outstanding results in pain relief.
agr-Dependent Interactions of Staphylococcus aureus USA300 with Human Polymorphonuclear Neutrophils
Authors: Pang Yun Yun , Schwartz Jamie , Thoendel Matthew , Ackermann Laynez W. , Horswill Alexander R. , Nauseef William M.
Published: September 2010

The emergence of serious infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has fueled interest in the contributions of specific staphylococcal virulence factors to clinical disease. To assess the contributions of agr-dependent factors to the fate of organisms in polymorphonuclear neutrophils (PMN), we examined the consequences for organism and host cells of feeding PMN with wild-type CA-MRSA (LAC) or CA-MRSA (LAC agr KO) at different multiplicities of infection (MOIs). Phagocytosed organisms rapidly increased the transcription of RNAIII in a time- and MOI-dependent fashion; extracellular USA300 (LAC) did not increase RNAIII expression despite having the capacity to respond to autoinducing peptide-enriched culture medium. HOCl-mediated damage and intracellular survival were the same in the wild-type and USA300 (LAC agr KO). PMN lysis by ingested USA300 (LAC) was time- and MOI-dependent and, at MOIs >1, required α-hemolysin (hla) as USA300 (LAC agr KO) and USA300 (LAC hla KO) promoted PMN lysis only at high MOIs. Taken together, these data demonstrate activation of the agr operon in human PMN with the subsequent production of α-hemolysin and PMN lysis. The extent to which these events in the phagosomes of human PMN contribute to the increased morbidity and mortality of infections with USA300 (LAC) merits further study.
Early Feeding Practices and Severe Early Childhood Caries in Four-Year-Old Children from Southern Brazil: A Birth Cohort Study
Authors: Feldens C.A. , Giugliani E.R.J. , Vigo Á. , Vítolo M.R.
Published: September 2010

The aim of this study was to investigate the relationship between feeding practices in the first year of life and the occurrence of severe early childhood caries (S-ECC) at 4 years of age. A birth cohort study (n = 500) was conducted in children who were born within the public health system in São Leopoldo, Brazil. Feeding practices were assessed using standardized methods at 6 and 12 months of age. A total of 340 children were examined at 4 years of age. S-ECC was defined as recommended by an expert panel for research purposes: ≧1 cavitated, missing or filled smooth surfaces in primary maxillary anterior teeth or d1+ mfs ≧5. Poisson regression with robust variance was used in order to determine the early feeding practices which represent risk factors for the occurrence of S-ECC at 4 years of age. The multivariable model showed a higher adjusted risk of S-ECC for the following dietary practices at 12 months: breastfeeding ≧7 times daily (RR = 1.97; 95% CI = 1.45–2.68), high density of sugar (RR = 1.43; 95% CI = 1.08–1.89), bottle use for liquids other than milk (RR = 1.41; 95% CI = 1.08–1.86), as well as number of meals and snacks >8 (RR = 1.42; 95% CI = 1.02–1.97). Mother’s education ≤8 years was also associated with the outcome. The present study identified early feeding practices which represent risk factors for caries severity in subsequent years. These findings may contribute to developing general and oral health interventions, with special attention to families with low maternal education.
Mutans Streptococci and Caries Prevalence in Children after Early Maternal Caries Prevention: A Follow-Up at Eleven and Fifteen Years of Age
Authors: Köhler B. , Andréen I.
Published: September 2010

Aim: The efficacy of early maternal caries prevention in children was evaluated. Methods: First-time mothers selected on the basis of a high level of salivary mutans streptococci (MS) and mothers excluded at screening due to a low level of MS (‘low’) were recalled when their children were 11 years old. The salivary MS level was determined in the mothers. Their children were examined for salivary MS and lesion prevalence (decayed and filled surfaces, DFS) at the ages of 11 and 15 years. Results: More ‘high control’ mothers displayed ≧106 MS than the ‘high interventional’ and ‘low control’ mothers and, vice versa, more ‘interventional’ and ’low control’ mothers had MS counts of <3 × 105 than ’high control’ mothers. More of ‘interventional’ and ’low control’ children had <105 MS/ml as compared with the ’high control’ children. All the ’high control’ children had detectable MS. MS were undetected in 5 ‘interventional’ and 5 ’low control’ children at 15 years. Significantly fewer ’high control’ than ‘interventional’ and ’low control’ children were caries free at 11 and 15 years of age. Non-MS-colonised children at 3 years of age, irrespective of group identity, displayed statistically lower MS counts and less DFS at 15 years than those colonised at 3 years of age. Children with clinical caries/fillings at 15 years had had a significantly higher level of MS at 11 years of age than those without clinical caries/fillings. Conclusion: The clinical trial, focusing on the mothers, resulted in long-term benefits for their children. Children colonised by MS at an early stage developed more caries than those colonised at a later stage.
Retention of Antimicrobial Activity in Plaque and Saliva following Mouthrinse Use in vivo
Authors: Otten M.P.T. , Busscher H.J. , van der Mei H.C. , Abbas F. , van Hoogmoed C.G.
Published: September 2010

The aim of this study was to determine the contribution of plaque and saliva towards the prolonged activity, also called substantivity, of three antimicrobial mouthrinses (Listerine®, Meridol®, Crest Pro Health®), used in combination with a toothpaste (Prodent Coolmint®). Volunteers brushed for 4 weeks with a toothpaste without antimicrobial claims, while during the last 2 weeks half of the volunteers used an antimicrobial mouthrinse in addition to brushing. At the end of the experimental period, plaque and saliva samples were collected 6 h after oral hygiene, and bacterial concentrations and viabilities were determined. The contribution of plaque and saliva towards substantivity was assessed by combining plaque obtained after mechanical cleaning only with plaque and saliva obtained after additional use of an antimicrobial rinse. Subsequently, resulting viabilities of the combined plaques were determined. The viabilities of plaque samples after additional rinsing with mouthrinses were lower than of plaque obtained after mechanical cleaning only, regardless of the rinse involved. Moreover, plaque collected 6 h after rinsing with antimicrobial mouthrinses contained a surplus of antimicrobial activity. Only Listerine showed decreased viability in saliva, but none of the mouthrinses showed any residual antimicrobial activity in saliva. The findings indicate that plaque left behind after mechanical cleaning contributes to the prolonged substantivity of antimicrobial mouthrinses.
Computer-Assisted Sleep Classification according to the Standard of the American Academy of Sleep Medicine: Validation Study of the AASM Version of the Somnolyzer 24 × 7
Authors: Anderer Peter , Moreau Arnaud , Woertz Michael , Ross Marco , Gruber Georg , Parapatics Silvia , Loretz Erna , Heller Esther , Schmidt Andrea , Boeck Marion , Moser Doris , Kloesch Gerhard , Saletu Bernd , Saletu-Zyhlarz Gerda M. , Danker-Hopfe Heidi , Zeitlhofer Josef , Dorffner Georg
Published: September 2010

Background: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). Methods: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21–86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. Results: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen’s kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). Conclusion: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.
Patient and Clinician Perceptions of Therapeutic Alliance as Predictors of Improvement in Depression
Authors: De Bolle Marleen , Johnson Jeffrey G. , De Fruyt Filip
Published: September 2010

Background: Meta-analyses have consistently concluded that a positive therapeutic alliance is associated with better clinical outcomes and progress. To date, however, very few studies have focused on sociodemographic or clinical patient characteristics as moderators of alliance. Method: A multicenter longitudinal treatment outcome study was conducted to investigate the associations of patient and clinician perceptions of the therapeutic alliance with improvement in depression, and to investigate whether these associations were influenced by sociodemographic or clinical characteristics of the patient. Clinician-rated Montgomery Åsberg Depressive Rating Scale scores and both patient- and therapist-rated Helping Alliance Questionnaire (HAQ-I) scores were obtained from 567 outpatients with major depressive disorder who received 6 months of combined psycho- and pharmacotherapy. Results: Multilevel repeated-measures analyses indicated that patient- and therapist-rated HAQ-I scores, 4 weeks after treatment began, positively predicted subsequent clinical change, controlling for the effect of early improvement and a range of patient characteristics. Next to alliance, early improvement, initial depressive symptom severity, a history of psychiatric disorders, and occupational status affected the rate of clinical improvement. Personality pathology comorbidity, marital and occupational status, and the atypical character of the major depressive episode (MDE) moderated the alliance-outcome relationship, depending on the informant (patient or therapist) of therapeutic alliance. Conclusions: The present findings suggest that therapist and patient ratings of therapeutic alliance predict therapeutic progress, and that this relation may be moderated by client characteristics, including personality pathology comorbidity, marital status, occupational status, and the atypical character of the MDE.
Plasma haemoxygenase-1 in coronary artery disease
Authors: Idriss Naglaa , Lip Gregory , Balakrishnan Balu , Jaumdally Rumi , Boos Christopher , Blann Andrew
Published: September 2010

It was the aim of this study to determine plasma haemoxygenase-1 (HO-1) across the spectrum of health, angina but normal coronary arteries (NCA), stable coronary artery disease (CAD), and acute coronary syndromes (ACS), and relationships with angiogenin, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1, and vascular endothelial growth factor. Plasma markers were measured (ELISA) in peripheral venous citrated plasma from 50 healthy subjects, 30 with NCA, 70 with stable CAD and 24 with an ACS, and from patient’s aortic root, coronary ostium, coronary sinus and femoral artery. Human umbilical vein endothelial cells (HUVECs) were cultured with or without tumour necrosis factor (TNF), and platelets were probed. HO-1 was raised in stable CAD (p<0.05) and increased further in ACS (p<0.01) compared to healthy controls and NCA. HO-1 correlated only with MMP-9, and then only in the healthy controls. There were no major differences from cardiac or peripheral sites. HO-1 was present in HUVECs and 24-hour HUVEC supernatants but release was abolished by TNF. Platelets had no HO-1. In conclusion, HO-1 is raised in stable CAD and ACS and may arise from the endothelium but not the platelet. This may have implications for our understanding of the pathophysiology of CAD and its acute presentation as ACS.
Studies on Fletcher trait and Fitzgerald trait
Authors: Saito Hidehiko
Published: September 2010

The way by which contact of blood with foreign surface accelerates clotting has been elucidated from the discovery of four rare disorders of blood coagulation; Hageman trait, plasma thromboplastin antecedent (PTA) deficiency, Fletcher trait, and Fitzgerald trait. Interestingly, it was unexpectedly found that Fletcher factor is plasma prekallikrein and Fitzgerald factor is high-molecular-weight kininogen; components of the kinin-generating system, thus disclosing intimate relationships among clotting, fibrinolysis and kinin generation which may be viewed as body’s defense reactions against injury. This review mainly reflects our research on Fletcher trait and Fitzgerald trait during the 1970s in Cleveland.
2B or not to be – The 45-year saga of the Montreal Platelet Syndrome
Authors: Rand Margaret , Jackson Shannon , Poon Man-Chiu
Published: September 2010

Over 45 years ago, Montreal Platelet Syndrome was first described as a rare inherited platelet disorder characterised by macrothrombocytopenia with spontaneous platelet clumping, abnormal platelet shape change upon stimulation and a defect in platelet calpain. This syndrome has now been reclassified as type 2B von Willebrand disease with the V1316M VWF mutation in the only kindred ever reported. We herein revisit the historical platelet characteristics originally described in Montreal Platelet Syndrome in light of the new diagnosis. This paper will review the 45-year saga of Montreal Platelet Syndrome, a story that highlights the value of revisiting a rare diagnosis to look for a more common explanation.
Differential endocytosis of tissue plasminogen activator by serpins PAI-1 and PAI-2 on human peripheral blood monocytes
Authors: Lee Jodi A. , Croucher David R. , Ranson Marie
Published: September 2010

Generation of the broad spectrum protease plasmin is facilitated by the tissue (t-PA) and urokinase (u-PA) plasminogen activators, within multiple physiological and disease states. Finely tuned control of this proteolytic cascade is exerted by the plasminogen activator inhibitors type-1 (PAI-1/SERPINE1) and 2 (PAI-2/SERPINB2). Expression of this network of activators and inhibitors by cells of myeloid lineage appears to be highly interchangeable between physiological environments, and whilst the role of PAI-1 and PAI-2 in regulating u-PA-dependent functions is well established, the interaction between t-PA and PAI-2 on these cell types is poorly characterised. To this end, we used freshly isolated peripheral blood monocytes (PBM) as a model of a t-PA-dependent cellular environment. We demonstrate that while both PAI-1 and PAI-2 could inhibit surface-bound t-PA and are internalised predominately via low-density-lipoprotein receptor family members, PAI-1 enhanced the endocytosis of t-PA, whereas PAI-2 did not. Surface plasmon resonance analyses revealed differential binding affinities between the very-low-density-lipoprotein receptor and t-PA and t-PA:PAI-1 complexes in addition to those previously described with low-density-lipoprotein receptor-related protein. Moreover, t-PA:PAI-2 bound to both endocytosis receptors with similar kinetics to t-PA. These differential biochemical interactions between t-PA and the t-PA:PAI complexes may underlie the observed differences in endocytosis mechanisms on the PBMs. This suggests that while PAI-1 and PAI-2 function similarly in the control of cellular plasmin generation by t-PA, they may have disparate effects on the alternative functions of t-PA via modulation of its engagement with endocytosis receptors.
Von Willebrand factor-containing factor VIII concentrates and inhibitors in haemophilia A
Authors: Lippi Giuseppe , Franchini Massimo
Published: September 2010

The development of inhibitors that neutralise the function of factor VIII (FVIII) is currently not only the most challenging complication associated with the treatment of haemophilia A but it also increases the disease-related morbidity as bleeding episodes do not respond to standard therapy. The main short-term goal of the treatment of inhibitor patients is to control bleeding episodes while the long-term one is to permanently eradicate the inhibitor by immune tolerance induction, particularly in the case of high-titer antibodies. Due to some in vitro studies and clinical observations, some investigators have suggested that FVIII concentrates containing von Willebrand factor (VWF) may be less immunogenic than high-purity or recombinant FVIII products. It has also been suggested that success rates for immune tolerance induction are higher when plasma-derived FVIII products are used. The currently available data from laboratory and clinical studies on the role of VWF in inhibitor development and eradication in haemophilia A is critically analysed in this review. As a result, we have not found definitive evidence supporting a role for product type on inhibitor incidence and inhibitor eradication in haemophilia A patients.
Platelets enhance lymphocyte adhesion and infiltration into arterial thrombus
Authors: Hu Hu , Zhu Linjing , Huang Zhangsen , Ji Qiushang , Chatterjee Madhumita , Zhang Wei , Li Nailin
Published: September 2010

Lymphocytes are present in atherosclerotic lesion. We hypothesise that platelets may facilitate lymphocyte infiltration into the arterial wall. Reconstituted human blood or whole blood was perfused through a collagen-coated parallel-plate flow chamber at different shear rates. Adhered platelets markedly enhanced lymphocyte adhesion that increased lymphocyte deposition from 10 ± 3 cells/mm2 of platelet-depleted blood to 38 ± 11 cells/mm2 of platelet-containing blood at the arterial shear rate of 500 s-1. Platelet-dependent lymphocyte adhesion was inhibited by P-selectin, CD40L, and GPIIb/IIIa-blocking agents, suggesting the involvement of multiple adhesion molecules in this heterotypic interaction. Lymphocyte deposition was more marked among T cells, and seen in both small and large cells. B and natural killer cell adhesion was, however, mainly seen in small cells. Platelet-conjugation facilitated lymphocyte adhesion, as suggested by the selective deposition of platelet-conjugated lymphocytes. In a mouse model of arterial thrombosis, FeCl3-induced thrombus formation markedly enhanced lymphocyte adhesion and infiltration into platelet thrombi, which was abolished by GPIIb/IIIa inhibition. In conclusion, platelets support lymphocyte adhesion under arterial flow conditions, which is selective among T cells and involves multiple adhesion molecules. Our data imply that platelets may facilitate the recruitment of circulating lymphocytes at the arterial injured sites.
Post–Heart Transplant Survival Is Inferior at Low-Volume Centers Across All Risk Strata
Authors: Russo Mark J. , Iribarne Alexander , Easterwood Rachel , Ibrahimiye Ali N. , Davies Ryan , Hong Kimberly N. , Ascheim Deborah D. , Gelijns Annetine C. , Naka Yoshifumi
Published: September 2010

Background—

Previous studies have demonstrated a relationship between increasing center volume and cardiac transplant outcomes. The purpose of this study was to confirm a relationship between post–heart transplant outcomes and center experience and to determine whether this relationship persists among low- and high-risk heart transplant recipient–donor pairs.

Methods and Results—

The United Network for Organ Sharing (UNOS) provided deidentified patient-level data. Analysis included 8029 heart transplant recipients aged ≥18 years and transplanted between January 1, 2001 and December 31, 2006 with follow-up available through February 3, 2009. The primary outcome was observed 1-year posttransplant graft survival. Multivariable logistic regression was used to calculate expected 1-year survival for recipients. Threshold analysis identified 3 discrete risk groups of transplant recipients: high-risk, moderate-risk, and low-risk. Three discrete risk strata for center volume: low (<10.5 recipients/yr), intermediate (10.5 to 47 recipients/yr), and high (>47 recipients/yr) were also identified. χ
2
test was used to compare 1-year survival at low- and intermediate- with high-volume centers. In multivariable logistic regression analysis, annual center volume was significantly associated with posttransplant graft survival at 1 year (odds ratio [OR]=0.995, 0.992 to 0.999;
P
=0.010) and primary graft failure (OR=0.985, 0.972 to 0.997;
P
=0.015), but not stroke (OR=0.996, 0.990 to 1.003;
P
=0.295), infection (OR=1.001, 0.998 to 1.003;
P
=0.613), or dialysis (OR=1.001, 0.997 to 1.005;
P
=0.522). Log-rank test demonstrated significant difference in survival between volume groups with respect to high-risk (
P
=0.0032) and low-risk (
P
=0.00415), but not moderate-risk (
P
=0.128) patients.

Conclusions—

A direct relationship existed between increasing center volume and improved graft survival. Across all recipient–donor pair risk strata, posttransplant graft survival at 1 year was significantly lower at low-volume centers. The volume–outcomes relationship was strongest in the highest-risk recipient–donor category.
Sustained Inhibition of ε Protein Kinase C Inhibits Vascular Restenosis After Balloon Injury and Stenting
Authors: Deuse Tobias , Koyanagi Tomoyoshi , Erben Reinhold G. , Hua Xiaoqin , Velden Joachim , Ikeno Fumiaki , Reichenspurner Hermann , Robbins Robert C. , Mochly-Rosen Daria , Schrepfer Sonja
Published: September 2010

Background—

ε Protein kinase C (εPKC) is involved in vascular smooth muscle cell (VSMC) activation, but little is known about its function in vascular pathology. We aimed at assessing the role of εPKC in the development of restenosis.

Methods and Results—

Rat models of aortic balloon injury with or without subsequent stenting were used. Rats were treated with the selective εPKC activator ψε receptor for activated protein kinase C (ψεRACK), the selective εPKC inhibitor εV1–2, or saline. Both down-stream cascades of the platelet-derived growth factor receptor via extracellular signal-regulated kinase and Akt, respectively, were evaluated in vivo and in VSMC cultures. Intimal hyperplasia with luminal obliteration developed in saline-treated balloon-injured rat aortas (20.3±8.0%), and ψεRACK significantly promoted neointima development (32.4±4.9%,
P
=0.033), whereas εV1–2 significantly inhibited luminal narrowing (9.2±4.3%,
P
=0.039). εPKC inhibition led to significantly reduced VSMC extracellular signal-regulated kinase phosphorylation in vivo, whereas Akt phosphorylation was not markedly affected. Neointimal proliferation in vivo and platelet-derived growth factor-induced VSMC proliferation/migration in vitro were significantly inhibited by εV1–2. The inhibition of the platelet-derived growth factor pathway was mediated by inhibiting down-stream extracellular signal-regulated kinase and Akt phosphorylation. In vitro, εV1–2 showed inhibitory properties on endothelial cell proliferation, but that did not prevent reendothelialization in vivo. εV1–2 showed proapoptotic effects on VSMC in vitro. After stent implantation, luminal restenosis (quantified by optical coherence tomography imaging) was significantly reduced with εV1–2 (8.0±2.0%) compared with saline (20.2±9.8%,
P
=0.028).

Conclusions—

εPKC seems to be centrally involved in the development of neointimal hyperplasia. We suggest that εPKC inhibition may be mediated via inhibition of extracellular signal-regulated kinase and Akt activation. εPKC modulation may become a new therapeutic target against vascular restenosis.
Impact of Early Surgery on Embolic Events in Patients With Infective Endocarditis
Authors: Kim Dae-Hee , Kang Duk-Hyun , Lee Myung-Zoon , Yun Sung-Cheol , Kim Yong-Jin , Song Jong-Min , Song Jae-Kwan , Lee Jae-Won , Sohn Dae-Won
Published: September 2010

Background—

Surgical indications to prevent systemic embolism in infective endocarditis (IE) remain controversial. We sought to compare clinical outcomes of early surgery with conventional treatment in IE patients with embolic indications only.

Methods and Results—

From 1998 to 2006, we prospectively enrolled 132 consecutive patients (86 men; age, 49±17 years) with definite IE. Patients were included if they had a left-sided native valve endocarditis with vegetation. The choice of early surgery or conventional treatment was at the discretion of attending physician. Early surgery was performed on 64 patients (OP group) within 7 days of diagnosis, and conventional management was chosen for 68 patients (CONV group). The OP group had larger vegetations and a higher percentage of patients with severe valvular disease (88% versus 62%,
P
=0.001). During initial hospitalization, there were no embolic events and 2 in-hospital deaths in the OP group and 14 embolic events and 2 in-hospital deaths in the CONV group. During a median follow-up of 1402 days, there were 2 cardiovascular deaths, 2 embolic events, and 1 recurrence of IE in the CONV group, and 1 cardiovascular death and 2 embolic events in the OP group. The 5-year event-free survival rate was significantly higher in the OP group (93±3%) than in the CONV group (73±5%,
P
=0.0016). For 44 propensity score–matched pairs, the OP group had a lower event rate (hazard ratio, 0.18;
P
=0.007).

Conclusions—

Compared with conventional treatment, an early surgery strategy is associated with improved clinical outcomes by effectively decreasing systemic embolism in patients with IE.
Effects of Cardiopulmonary Bypass on Endothelin-1–Induced Contraction and Signaling in Human Skeletal Muscle Microcirculation
Authors: Feng Jun , Chu Louis M. , Robich Michael P. , Clements Richard T. , Khabbaz Kamal R. , Hagberg Robert , Liu Yuhong , Osipov Robert M. , Sellke Frank W.
Published: September 2010

Background—

We investigated the effects of cardiopulmonary bypass (CPB) on the contractile response of human peripheral microvasculature to endothelin-1 (ET-1), examined the role of specific ET receptors and protein kinase C-alpha (PKC-α), and analyzed ET-1–related gene/protein expression in this response.

Methods and Results—

Human skeletal muscle arterioles (90 to 180 μm in diameter) were dissected from tissue harvested before and after CPB from 30 patients undergoing cardiac surgery. In vitro contractile response to ET-1 was assessed by videomicroscopy, with and without an endothelin-A (ET-A) receptor antagonist, an endothelin-B (ET-B) antagonist, or a PKC-α inhibitor. The post-CPB contractile response of peripheral arterioles to ET-1 was significantly decreased compared with pre-CPB response. The response to ET-1 was significantly inhibited in the presence of the ET-A antagonist BQ123 but unchanged in the presence of the ET-B receptor antagonist BQ788. Pretreatment with the PKC-α inhibitor safingol reversed ET-1–induced response from contraction to relaxation. The total protein levels of ET-A and ET-B receptors were not altered after CPB. Microarray analysis showed no significant changes in the gene expression of ET receptors, ET-1–related proteins, and protein kinases after CPB.

Conclusions—

CPB decreases myogenic contractile function of human peripheral arterioles in response to ET-1. The contractile response to ET-1 is through activation of ET-A receptors and PKC-α. CPB has no effects on ET-1–related gene/protein expression. These results provide novel mechanisms of ET-1–induced contraction in the setting of vasomotor dysfunction after cardiac surgery.
Profound Cardioprotection With Chloramphenicol Succinate in the Swine Model of Myocardial Ischemia-Reperfusion Injury
Authors: Sala-Mercado Javier A. , Wider Joseph , Reddy Undyala Vishnu Vardhan , Jahania Salik , Yoo Wonsuk , Mentzer Robert M. , Gottlieb Roberta A. , Przyklenk Karin
Published: September 2010

Background—

Emerging evidence suggests that “adaptive” induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction.

Methods and Results—

Anesthetized pigs underwent 45 minutes of coronary artery occlusion and 3 hours of reperfusion. In the first component of the study, pigs received chloramphenicol succinate (CAPS) (an agent that purportedly upregulates autophagy; 20 mg/kg) or saline at 10 minutes before ischemia. Infarct size was delineated by tetrazolium staining and expressed as a % of the at-risk myocardium. In separate animals, myocardial samples were harvested at baseline and 10 minutes following CAPS treatment and assayed (by immunoblotting) for 2 proteins involved in autophagosome formation: Beclin-1 and microtubule-associated protein light chain 3-II. To investigate whether the efficacy of CAPS was maintained with “delayed” treatment, additional pigs received CAPS (20 mg/kg) at 30 minutes after occlusion. Expression of Beclin-1 and microtubule-associated protein light chain 3-II, as well as infarct size, were assessed at end-reperfusion. CAPS was cardioprotective: infarct size was 25±5 and 41±4%, respectively, in the CAPS-pretreated and CAPS-delayed treatment groups versus 56±5% in saline controls (
P
<0.01 and
P
<0.05 versus control). Moreover, administration of CAPS was associated with increased expression of both proteins.

Conclusion—

Our results demonstrate attenuation of ischemia-reperfusion injury with CAPS and are consistent with the concept that induction of autophagy may provide a novel strategy to confer cardioprotection.
Sex Differences in Mortality in Children Undergoing Congenital Heart Disease Surgery
Authors: Marelli Ariane , Gauvreau Kimberlee , Landzberg Mike , Jenkins Kathy
Published: September 2010

Background—

The changing demographics of the adult congenital heart disease (CHD) population requires an understanding of the factors that impact patient survival to adulthood. We sought to investigate sex differences in CHD surgical mortality in children.

Methods and Results—

Children <18 years old hospitalized for CHD surgery were identified using the Kids’ Inpatient Database in 2000, 2003, and 2006. Demographic, diagnostic, and procedural variables were grouped according to RACHS-1 (Risk Adjustment for Congenital Heart Surgery) method. Logistic regression was used to determine the odds ratio of death in females versus males adjusting for RACHS-1 risk category, age, prematurity, major noncardiac anomalies, and multiple procedures. Analyses were stratified by RACHS-1 risk categories and age. Of 33 848 hospitalizations for CHD surgery, 54.7% were in males. Males were more likely than females to have CHD surgery in infancy, high-risk CHD surgery, and multiple CHD procedures. Females had more major noncardiac structural anomalies and more low-risk procedures. However, the adjusted risk of in-hospital death was higher in females (odds ratio, 1.21; 95% confidence interval, 1.08 to 1.36) on account of the subgroup with high-risk surgeries who were <1 year of age (odds ratio, 1.39; 95% confidence interval, 1.16 to 1.67).

Conclusions—

In this large US population study, more male children underwent CHD surgery and had high-risk procedures. Female infants who had high-risk procedures were at higher risk for death, but this accounted for a small proportion of females and is therefore unlikely to have a major impact on the changing demographics in adults in CHD.
Effect of Thrombin Fragment (TP508) on Myocardial Ischemia Reperfusion Injury in a Model of Type 1 Diabetes Mellitus
Authors: Chu Louis M. , Osipov Robert M. , Robich Michael P. , Feng Jun , Sheller Michael R. , Sellke Frank W.
Published: September 2010

Background—

We investigated the efficacy of novel thrombin fragment TP508 on ischemia-reperfusion injury using a porcine model of type 1 diabetes mellitus.

Methods and Results—

Alloxan-induced diabetic male Yucatan swine underwent 60 minutes of mid-left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. Fifty minutes into ischemia, animals received either placebo (DM; n=8) or TP508 as a bolus of 1 mg/kg followed by infusion at 2.5 mg/kg per hour (DMT; n=8). Hemodynamic parameters and myocardial function were monitored. Monastryl blue/triphenyl tetrazolium chloride staining was used to assess sizes of the areas at risk and infarction. Coronary microvascular reactivity was measured and expression of cell survival and proapoptotic proteins quantified. Preoperative serum glucose values were similar between groups (309±57 mg/dL in DM versus 318±67 mg/dL in DMT;
P
=0.92). Infarct size was smaller in the TP508-treated group (5.3±1.9% in DMT versus 19.4±5.6% in DM;
P
=0.03). There was no statistically significant difference in global or regional left ventricular function between groups. Endothelium-dependent microvessel relaxation was moderately improved in the DMT group (
P
=0.09), whereas endothelium-independent relaxation was similar between groups. The expression of cell survival proteins Akt, phospho-p38, and mammalian target of rapamycin was higher in the areas at risk of DMT animals compared with DM animals (
P
<0.05), and expressions of proapoptotic glycogen synthase kinase 3β and caspase 3 were lower in the DMT group (
P
<0.05).

Conclusions—

This study demonstrates that, in type 1 diabetic swine, TP508 reduces infarct size after ischemia-reperfusion. Thus, TP508 may offer a novel approach in cardioprotection from ischemia-reperfusion injury in diabetic patients.
Rapid-Response Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in Children With Cardiac Disease
Authors: Kane David A. , Thiagarajan Ravi R. , Wypij David , Scheurer Mark A. , Fynn-Thompson Francis , Emani Sitaram , del Nido Pedro J. , Betit Peter , Laussen Peter C.
Published: September 2010

Background—

Survival of children with in-hospital cardiac arrest that does not respond to conventional cardiopulmonary resuscitation (CPR) is poor. We report on survival and early neurological outcomes of children with heart disease supported with rapid-response extracorporeal membrane oxygenation (ECMO) to aid cardiopulmonary resuscitation (ECPR).

Methods and Results—

Children with heart disease supported with ECPR were identified from our ECMO database. Demographic, CPR, and ECMO details associated with mortality were evaluated using multivariable logistic regression. Pediatric overall performance category and pediatric cerebral performance category scores were assigned to ECPR survivors to assess neurological outcomes. There were 180 ECPR runs in 172 patients. Eighty-eight patients (51%) survived to discharge. Survival in patients who underwent ECPR after cardiac surgery (54%) did not differ from nonsurgical patients (46%). Survival did not vary by cardiac diagnosis and CPR duration did not differ between survivors and nonsurvivors. Factors associated with mortality included noncardiac structural or chromosomal abnormalities (OR, 3.2; 95% CI, 1.3–7.9), use of blood-primed ECMO circuit (OR, 7.1; 95% CI, 1.4–36), and arterial pH <7.00 after ECMO deployment (OR, 6.0; 95% CI, 2.1–17.4). Development of end-organ injury on ECMO and longer ECMO duration were associated with increased mortality. Of pediatric overall performance category/pediatric cerebral performance category scores assigned to survivors, 75% had scores ≤2, indicating no to mild neurological injury.

Conclusions—

ECPR may promote survival in children with cardiac disease experiencing cardiac arrest unresponsive to conventional CPR with favorable early neurological outcomes. CPR duration was not associated with mortality, whereas patients with metabolic acidosis and noncardiac structural or chromosomal anomalies had higher mortality.
Influence of Mesoscale Dynamics and Turbulence on Fine Dust Transport in Owens Valley
Authors: Jiang Qingfang , Liu Ming , Doyle James D.
Published: September 2010

Fine dust particles emitted from Owens (dry) Lake in California documented during the Terrain-Induced Rotor Experiment (T-REX) of 2006 have been examined using surface observations and a mesoscale aerosol model. Air quality stations around Owens (dry) Lake observed dramatic temporal and spatial variations of surface winds and dust particulate concentration. The hourly particulate concentration averaged over a 2-month period exhibits a strong diurnal variation with a primary maximum in the afternoon, coincident with a wind speed maximum. The strongest dust event documented during the 2-month-long period, with maximum hourly and daily average particulate concentrations of 7000 and 1000 μg m−3, respectively, is further examined using output from a high-resolution mesoscale aerosol model simulation. In the morning, with the valley air decoupled from the prevailing westerlies (i.e., cross valley) above the mountaintop, fine particulates are blown off the dry lake bed by moderate up-valley winds and transported along the valley toward northwest. The simulated strong westerlies reach the western part of the valley in the afternoon and more fine dust is scoured off Owens (dry) Lake than in the morning. Assisted by strong turbulence and wave-induced vertical motion in the valley, the westerlies can transport a substantial fraction of the particulate mass across the Inyo Mountains into Death Valley National Park.
An Ensemble Cumulus Convection Parameterization with Explicit Cloud Treatment
Authors: Wagner Till M. , Graf Hans-F.
Published: September 2010

The paper describes a convection parameterization employing a new formulation of the quasi-equilibrium closure hypothesis of Arakawa and Schubert. The scheme models a full spectrum of different cumulus clouds and its evolution within one time step of the host global climate model. Each cloud is simulated using a one-dimensional Lagrangian entraining parcel model, which includes mixed phase microphysics and vertical velocity. Hence, the model delivers explicit information on distribution of vertical velocities, precipitation intensities, cloud heights, and cloud coverage. The parameterization is evaluated in the ECHAM single-column model for midlatitude summer and tropical convection. Results show an improved temporal distribution, including the diurnal cycle, of convective heating and moistening in comparison to the Tiedtke–Nordeng scheme, which is the standard convection parameterization within ECHAM. The amount and temporal distribution of precipitation are clearly improved compared with the original parameterization. The convective cloud field model (CCFM) does not produce spurious convection events occurring with the standard parameterization.
Using and Designing GCM–RCM Ensemble Regional Climate Projections
Authors: Kendon Elizabeth J. , Jones Richard G. , Kjellström Erik , Murphy James M.
Published: September 2010

Multimodel ensembles, whereby different global climate models (GCMs) and regional climate models (RCMs) are combined, have been widely used to explore uncertainties in regional climate projections. In this study, the extent to which information can be enhanced from sparsely filled GCM–RCM ensemble matrices and the way in which simulations should be prioritized to sample uncertainties most effectively are examined.

A simple scaling technique, whereby the local climate response in an RCM is predicted from the large-scale change in the GCM, is found to often show skill in estimating local changes for missing GCM–RCM combinations. In particular, scaling shows skill for precipitation indices (including mean, variance, and extremes) across Europe in winter and mean and extreme temperature in summer and winter, except for hot extremes over central/northern Europe in summer. However, internal variability significantly impacts the ability to determine scaling skill for precipitation indices, with a three-member ensemble found to be insufficient for identifying robust local scaling relationships in many cases.

This study suggests that, given limited computer resources, ensembles should be designed to prioritize the sampling of GCM uncertainty, using a reduced set of RCMs. Exceptions are found over the Alps and northeastern Europe in winter and central Europe in summer, where sampling multiple RCMs may be equally or more important for capturing uncertainty in local temperature or precipitation change. This reflects the significant role of local processes in these regions. Also, to determine the ensemble strategy in some cases, notably precipitation extremes in summer, better sampling of internal variability is needed.