bluuebunny/crossref_metadata_2025 huggingface dataset:
Basic fibroblast growth factor accelerates and improves second‐degree burn wound healing
Authors: Akita Sadanori , Akino Kozo , Imaizumi Toshifumi , Hirano Akiyoshi
Published: September 2008

Second‐degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second‐degree burn patients (average 57.8 ± 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 ± 0.9 days from the burn injury, compared with non‐bFGF use (12.0 ± 2.2 vs. 15.0 ± 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF‐treated and non‐bFGF–treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF‐treated scars than non‐bFGF–treated scars (0.23 ± 0.10 vs. 0.14 ± 0.06 mm, 0.59 ± 0.20 vs. 0.49 ± 0.15 mm: scar extension, scar elasticity, bFGF vs. non‐bFGF, p<0.01). The durometer reading was significantly lower in bFGF‐treated scars than in non‐bFGF–treated scars (16.2 ± 3.8 vs. 29.3 ± 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF‐treated than in non‐bFGF–treated scars (p<0.01).
Multiplexed analysis of matrix metalloproteinases in leg ulcer tissue of patients with chronic venous insufficiency before and after compression therapy
Authors: Beidler Stephanie K. , Douillet Christelle D. , Berndt Daniel F. , Keagy Blair A. , Rich Preston B. , Marston William A.
Published: September 2008

Elevated matrix metalloproteinases (MMP) levels have been implicated in the pathogenesis of chronic venous insufficiency ulcers. Quantitative measurements of a broad range of MMP proteins in human tissue treated with compression bandaging have not been reported. The goal of this study was to determine the expression of a wide range of proteases in untreated venous leg ulcer tissue and the changes in these levels after 4 weeks of high‐strength compression therapy. Twenty‐nine limbs with new or untreated chronic venous insufficiency and leg ulceration received therapy for 4 weeks with sustained high compression bandaging. Biopsies were obtained from healthy tissue and from ulcerated tissue before and after therapy. A novel multiplexed protein assay was used to measure multiple MMPs in a single sample. MMP protein activity, TIMP protein levels, and gene expression levels were also addressed. MMP1, 2, 3, 8, 9, 12, and 13 protein levels were elevated in ulcer tissue compared with healthy tissue. MMP8 and 9 were highly expressed in ulcer tissue. MMP3, 8, and 9 significantly decreased following treatment. Reduction in the levels of MMP1, 2, and 3 was associated with significantly higher rates of ulcer healing at 4 weeks. We conclude that compression therapy results in a reduction of the pro‐inflammatory environment characterizing chronic venous ulcers, and ulcer healing is associated with resolution of specific elevated levels of protease expression.
Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo
Authors: Sisco Mark , Kryger Zol B. , O'Shaughnessy Kristina D. , Kim Peter S. , Schultz Greg S. , Ding Xian‐Zhong , Roy Nakshatra K. , Dean Nicholas M. , Mustoe Thomas A.
Published: September 2008

Augmented expression of connective tissue growth factor (CTGF/CCN2) is observed in healing wounds and in a variety of fibrotic disorders. It appears to enhance many of the effects of transforming growth factor‐β and has been shown to have independent fibrogenic functions. Despite these observations, its importance to dermal wound healing and the transition from wound to scar remains poorly defined. In this study, we use established rabbit models to evaluate the roles of CTGF in dermal wound healing and hypertrophic scarring. We show that CTGF mRNA demonstrates persistent up‐regulation in hypertrophic scars. Treatment of wounds with antisense oligonucleotides to CTGF has no measurable effect on early wound closure. However, antisense therapy significantly limits subsequent hypertrophic scarring. Inhibition of CTGF is associated with a marked reduction in the number of myofibroblasts in scars and decreased transcription of TIMP‐1 and types I and III collagen. These findings confirm CTGF to be a key mediator of hypertrophic scarring in this model. Its effect on myofibroblasts in this setting suggests a mechanism whereby it plays this role. Its limited participation in early healing implies that it may be a useful and specific target for modulating hypertrophic scarring following injury.
Comparison of the effects of collagenase and extract ofCentella asiaticain an experimental model of wound healing: An immunohistochemical and histopathological study
Authors: Ermertcan Aylin Türel , Inan Sevinc , Ozturkcan Serap , Bilac Cemal , Cilaker Serap
Published: September 2008

In this study, we compared the effects of collagenase andCentella asiaticain the rat model. Twenty‐seven female rats were divided into three groups, and two full‐thickness wounds were made for each animal. Collagenase ointment was applied topically to Group I andC. asiaticaointment to Group II rats. In Group III, no treatment was applied. On the third day of treatment, wounds on the left side of three animals of each group were excised. On the fifth and eighth day of the treatments, the same procedure was performed for the remaining animals. Indirect immunohistochemical examination was performed to detect transforming growth factor beta (TGF)‐β, endothelial and inducible nitric oxide synthase (eNOS and iNOS), vascular endothelial growth factor, TGF‐α, laminin, fibronectin, collagen I, and interleukin‐1β. According to the measurements of the wound areas and wound healing periodo, collagenase was superior to the control group. Immunohistochemical examinations showed strong (+++) iNOS and TGF‐β immunoreactivities inC. asiaticagroup. eNOS immunoreactivity was moderate (++) in this group. For the collagenase group, iNOS, eNOS, and TGF‐β immunoreactivities were moderate (++). In the collagenase group, while TGF‐β and iNOS immunoreactivities were weaker, laminin and fibronectin reactivities were stronger than inC. asiaticaand control groups. Collagenase was superior toC. asiaticaaccording to the immunohistochemical findings. Collagenase ointment significantly improves the quality of wound healing and scar formation and is a more appropriate treatment choice than extract ofC. asiaticain the early stages of the wound healing process.
Exogenous metallothionein‐IIA promotes accelerated healing after a burn wound
Authors: Morellini Natalie M. , Giles Natalie L. , Rea Suzanne , Adcroft Katharine F. , Falder Sian , King Carolyn E. , Dunlop Sarah A. , Beazley Lyn D. , West Adrian K. , Wood Fiona M. , Fear Mark W.
Published: September 2008

Severe injury to the epidermal barrier often results in scarring and life‐long functional deficits, the outcome worsening with a number of factors including time taken to heal. We have investigated the potential of exogenous metallothionein IIA (Zn7‐MT‐IIA), a naturally occurring small cysteine‐rich protein, to accelerate healing of burn wounds in a mouse model. Endogenous MT‐I/II expression increased in basal keratinocytes concurrent with reepithelialization after a burn injury, indicating a role for MT‐I/II in wound healing. In vitro assays of a human keratinocyte cell line indicated that, compared with saline controls, exogenous Zn7‐MT‐IIA significantly increased cell viability by up to 30% (p<0.05), decreased apoptosis by 13% (p<0.05) and promoted keratinocyte migration by up to 14% (p<0.05), all properties that may be desirable to promote rapid wound repair. Further in vitro assays using immortalized and primary fibroblasts indicated that Zn7‐MT‐IIA did not affect fibroblast motility or contraction (p>0.05). Topical administration of exogenous Zn7‐MT‐IIA (2 μg/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate‐buffered saline (PBS), 8.9±0.3 mm diameter vs. MT‐I/II, 7.1±0.7 mm; 7 days: PBS 5.8±0.98 mm vs. MT‐I/II, 3.6±1.0 mm, p<0.05) and reduced epidermal thickness (MT‐I/II: 45±4 μm vs. PBS: 101±19 μm, p<0.05) compared with controls. Our data suggest that exogenous Zn7‐MT‐IIA may prove a valuable therapeutic for patients with burns and other skin injuries.
Anti‐apoptotic role of EGF in HaCaT keratinocytes via a PPARβ‐dependent mechanism
Authors: Liang Pengfei , Jiang Bimei , Huang Xu , Xiao Weimin , Zhang Pihong , Yang Xinghua , Long Jianhong , Xiao Xianzhong , Huang Xiaoyuan
Published: September 2008

Epidermal growth factor (EGF) plays an important role in epithelial cell proliferation and apoptosis. Our recent studies found that EGF‐attenuated tumor necrosis factor‐α induced HaCaT keratinocyte apoptosis, and this effect was accompanied by up‐regulation of the expression of peroxisome proliferator‐activated receptor β (PPARβ). However, little is known about whether PPARβ is functionally involved in the inhibition of keratinocyte apoptosis by EGF. Here, we showed that EGF up‐regulated the DNA‐binding and transcriptional regulation activities of PPARβ. Antisense phosphorothioate oligonucleotides against PPARβ markedly inhibited de novo synthesis of PPARβ and attenuated the protective effect of EGF on tumor necrosis factor‐α–induced apoptosis. L165041, a specific PPARβ ligand, significantly enhanced the transcriptional regulation activity of PPARβ and increased the protective effect of EGF. These results suggest a molecular mechanism by which EGF protects HaCaT keratinocytes against apoptosis in a PPARβ‐dependent manner.
Enhanced wound healing by an epigallocatechin gallate‐incorporated collagen sponge in diabetic mice
Authors: Kim HakHee , Kawazoe Takeshi , Han Dong‐Wook , Matsumara Kazuaki , Suzuki Shigehiko , Tsutsumi Sadami , Hyon Suong‐Hyu
Published: September 2008

Epigallocatechin‐3‐O‐gallate (EGCG), the major polyphenolic compound present in green tea, has potent anti‐oxidant and free radical‐scavenging activities. In this study, various concentrations (10, 100, and 1,000 ppm) of EGCG were incorporated into a collagen sponge (CS) in order to investigate its healing effects on full‐thickness wounds created in type 2 diabetic mice. After 14 days, the residual wound size of the mice treated with 10 ppm EGCG‐incorporated collagen sponge (E‐CS) decreased significantly faster than that of the other mice. Moreover, significant increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of the capillaries were also histologically observed in the wound sites exposed to 10 ppm E‐CS in comparison with the others. Furthermore, 10 ppm E‐CS resulted in significant increases in the immunoreactivity of Ki‐67 (reepithelialization at the wound site), CD31 (formation of blood vessels), and α‐smooth muscle actin (the induction of myofibroblasts across the dermis). These results suggest that a CS incorporated with EGCG at low concentrations can enhance wound healing in diabetic mice by accelerating reepithelialization and angiogenesis as well as improving the cellular reorganization of granulation tissue by triggering the activity of myofibroblasts.
Observation‐Based Nocturnal Sleep Inventory: Screening Tool for Sleep Apnea in Elderly People
Authors: Onen S.‐Hakki , Dubray Claude , Decullier Evelyne , Moreau Thierry , Chapuis François , Onen Fannie
Published: September 2008

OBJECTIVES: To measure the ability of the Observation‐based Nocturnal Sleep Inventory (ONSI) to detect the presence or absence of sleep apnea syndrome (SAS) in older adults.

DESIGN: Cross‐sectional blinded study.

SETTING: University hospital–based geriatric sleep center.

PARTICIPANTS: All participants aged 70 and older were referred by physicians for suspicion of SAS.

MEASUREMENTS: ONSI performed by nurses; overnight polysomnography. SAS was defined as an apnea‐hypopnea index of 15 events or more per hour of sleep.

RESULTS: A total of 121 consecutive patients were evaluated for study participation. Six were excluded because of technical difficulties with polysomnography or too‐frequent awakenings related to medical conditions. One hundred eleven patients completed the validation process. Polysomnography identified 68 patients as having SAS and 43 patients as not having SAS. The nurse‐administered ONSI demonstrated good levels of sensitivity (90%), specificity (81%), positive predictive value (88%), and negative predictive value (83%) in screening older adults for SAS.

CONCLUSION: The ONSI is the first valid SAS screening tool proposed for older persons in hospitals and nursing homes. This study demonstrates that the ONSI provides accurate information; is a simple, easy‐to‐use bed‐side tool; and is highly sensitive and specific in screening SAS when compared with overnight polysomnography results.
A Short Functional Survey Is Responsive to Changes in Functional Status in Vulnerable Older People
Authors: Min Lillian C. , Wenger Neil S. , Reuben David B. , Saliba Debra
Published: September 2008

OBJECTIVES: To investigate whether an abbreviated five‐item functional status survey consisting of five activities of daily living (ADLs) reflects changes measured over time in a full 12‐item functional status survey.

DESIGN: Longitudinal evaluation with mean follow‐up of 11 months.

SETTING: Two managed‐care organizations in the United States.

PARTICIPANTS: Four hundred twenty community‐dwelling older people at moderate to high risk of death and functional decline enrolled in the Assessing Care of Vulnerable Elders (ACOVE) observational study.

MEASURES: Number of ADL abilities according to the short (range 0–5) and full functional status surveys (range 0–12); change in function as defined according to a 1‐point change in short score and 1‐ to 2‐point change in full survey scores.

RESULTS: Changes in short functional status survey scores were highly correlated to changes in long survey scores (correlation coefficient=0.88). On average, a 1‐point change in the short survey score was associated with a 1.4‐point change on the long survey score (P<.001). The short survey correctly classified 93% of those who declined according to the long survey, adjusting for chance agreement (κ=0.82) and was responsive to decline in function (sensitivity 82–94%, specificity 94–97%, and area under the receiver operating curve 0.91–0.93 for 1‐ to 2‐point decreases in full survey ADL counts).

CONCLUSION: The short functional status survey is an efficient way to detect changes in functional status in vulnerable older populations for clinical and research purposes.
Blood components produced from whole blood using the Atreus processing system
Authors: Thomas Stephen , Beard Martin , Garwood Margaret , Callaert Martine , Waeg Geert van , Cardigan Rebecca
Published: September 2008

BACKGROUND: The Atreus 2C+ system (Gambro BCT) automates whole blood (WB) processing into a single device. This study compared the quality of red blood cells (RBCs), fresh‐frozen plasma (FFP), and buffy coats (BCs) made from WB held with or without active cooling.

STUDY DESIGN AND METHODS: WB was collected into Atreus disposables and stored with (n = 20) or without (n = 20) active cooling for 14 to 18 hours at 22 ± 2°C before processing with the Atreus. Two RBC leukodepletion filters were assessed, and markers of RBC quality were tested to Day 42. BCs were held for 3 hours before testing, plasma was tested, and samples were frozen for coagulation analysis.

RESULTS: RBCs met UK specifications for volume, hemoglobin content (48 ± 5 g), and hematocrit (Hct). Hemolysis, adenosine triphosphate, 2,3‐diphosphoglycerate, potassium, glucose, and lactate throughout storage were all within expected ranges. No differences were seen in RBC produced from WB held with or without active cooling. FFP units met UK specification for volume, total protein, cellular contamination, and coagulation factors. No differences were seen in FFP produced from WB held with or without active cooling. The Hct of BCs produced from WB held without active cooling was lower than in BCs from WB held with active cooling; no differences in activation were seen.

CONCLUSION: From these in vitro data, blood components produced using the Atreus appear suitable for clinical use, with no clinically significant difference in the quality of components from WB held at ambient temperature overnight with or without active cooling.
Coagulation factor levels in plasma frozen within 24 hours of phlebotomy over 5 days of storage at 1 to 6°C
Authors: Yazer Mark H. , Cortese‐Hassett Andrea , Triulzi Darrell J.
Published: September 2008

BACKGROUND: The use of plasma frozen within 24 hours after phlebotomy (FP24) is likely to increase as male donors become the predominant source of plasma products. This study was performed to investigate the levels of clotting factors in thawed plasma (TP) prepared from FP24 during 5 days of storage at 1 to 6°C.

STUDY DESIGN AND METHODS: Five units of A, B, and O and 3 units of AB FP24 were obtained from the local blood provider. They were thawed and maintained at 1 to 6°C for a total of 5 days. Within 6 hours of thawing and every 24 hours thereafter for 5 days, each unit was assayed for the following clotting factors: Factor (F)II, FV, FVII, FVIII, F IX, FXI, FXII, antithrombin (AT), protein C (PC), and protein S (PS). ADAMTS‐13 was assayed on Days 2, 4, and 5. Time is expressed as mean hours or days (standard deviation).

RESULTS: On average the units were frozen 21.3 (3.8) hours after phlebotomy and had been frozen for a mean of 30.1 (32.3) days before thawing. The activities of all procoagulant factors including FVIII, along with AT, PC, and ADAMTS‐13, were well maintained in their normal range during the 5‐day storage. The activity of PS was slightly below the normal range by Day 5.

CONCLUSIONS: The activity of all factors assayed, except for PS, were within their normal range during the 5‐day storage period. These results show comparable factor assay levels in TP prepared from fresh‐frozen plasma and FP24.
Transfusion efficacy of ABO major‐mismatched platelets (PLTs) in children is inferior to that of ABO‐identical PLTs
Authors: Julmy Friedgard , Ammann Roland A. , Taleghani Behrouz Mansouri , Fontana Stefano , Hirt Andreas , Leibundgut Kurt
Published: September 2008

BACKGROUND: ABO major compatibility is essential in transfusions of red blood cells but is not requisite in PLT transfusions. In adults there is some evidence that transfusion efficacy of ABO blood group–identical platelets (PLTs) is superior to major‐mismatched PLTs. However, in children this question has not been investigated for more than 30 years.

STUDY DESIGN AND METHODS: In a prospective study, the efficacy (based on the 1‐hour percentage of PLT recovery [PPR1hr]) of 400 eligible ABO blood group–identical or out‐of‐group apheresis PLT concentrates (APCs), transfused mainly prophylactically to 50 children with hematologic malignancies, solid tumors, or aplastic anemia was investigated. The primary objective was to compare PPR1hr between ABO‐identical and major‐mismatched transfusions.

RESULTS: After ABO major‐mismatched transfusions, PPR1hr was significantly lower than after ABO blood group–identical transfusions (median 21% vs. 32%; p = 0.034). Multivariate analysis showed major‐mismatched transfusions to be significantly more often unsuccessful than identical transfusions (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.52‐10.39; p = 0.005). Using flow cytometry and fluorescent microscopy, it could be demonstrated that PLTs of subgroup A1, significantly expressing A antigen on their surface, were rapidly cleared from the circulation of group O or B recipients. In contrast, major‐mismatched transfusions of A2 PLTs, expressing no detectable A antigen, were as successful as identical transfusions (OR, 1.13; 95% CI, 0.16‐7.88; p = 0.90).

CONCLUSION: These data clearly indicate that in children ABO major‐mismatched PLT transfusions result in inferior transfusion efficacy, with the only exception of group A2 PLTs. ABO minor‐mismatched PLTs showed comparable efficacy to identical transfusions.
Cardiac Resynchronization Therapy (and Multisite Pacing) in Pediatrics and Congenital Heart Disease: Five Years Experience in a Single Institution
Authors: CECCHIN FRANK , FRANGINI PATRICIA A. , BROWN DAVID W. , FYNN‐THOMPSON FRANCIS , ALEXANDER MARK E. , TRIEDMAN JOHN K. , GAUVREAU KIMBERLEE , WALSH EDWARD P. , BERUL CHARLES I.
Published: September 2008

Introduction:
Clinical evidence supports the use of cardiac resynchronization therapy (CRT) in adults with heart failure, but experience in pediatrics and congenital heart disease (CHD) is limited in terms of patient numbers and follow‐up. We sought to determine the functional assessment and clinical outcomes in pediatric and CHD CRT patients followed uniformly at one institution.

Methods:
Retrospective review of 60 consecutive patients who underwent CRT between 2002 and 2007.

Results:
At implantation, median age was 15.0 years (5 months to 47 years). Overall, 46 patients had CHD (77%) and 14 had dilated cardiomyopathy. Prior to CRT, 92% were on heart failure treatment drugs and 55% had pacemakers. Median follow‐up time was 0.7 years (1 day–5.3 years). Median QRS width decreased from 149 to 120 ms (P < 0.001). Median ejection fraction (EF) increased from 36% to 42% (P < 0.001) and improvement was particularly evident in the group with CHD. Of note, 8 of 13 patients with single ventricle morphology had a “strong CRT response,” defined as either an improvement of 2–3 ordinal points in NYHA classification and/or increased ventricular function by ≥ 10 EF units. Overall, an improvement in functional status was observed in 39 of 45 patients (87%) with sufficient follow‐up data.

Conclusions:
Children and CHD patients treated with CRT have acute improvement in ventricular function, but implantation may require individualized planning and unconventional approaches. Future important goals include preimplant determination of CRT responders in pediatric and CHD patients, optimizing lead placement and programing, as well as long‐term CRT device management issues.
Real‐Time Rotational ICE Imaging of the Relationship of the Ablation Catheter Tip and the Esophagus During Atrial Fibrillation Ablation
Authors: HELMS ADAM , WEST J. JASON , PATEL AMIT , MOUNSEY J. PAUL , DIMARCO JOHN P. , MANGRUM J. MICHAEL , FERGUSON JOHN D.
Published: September 2008

Introduction:
Atrioesophageal fistula is a rare complication of atrial fibrillation (AF) ablation that should be avoided. We investigated whether rotational intracardiac echocardiography (ICE) can help to minimize ablation close to the esophagus.

Methods and Results:
We studied 41 patients referred for catheter ablation of refractory AF. A rotational ICE catheter was inserted into the (LA) to determine the location of the esophagus. The esophagus was identified to be either adjacent to the pulmonary vein (PV) ostium or to a cuff 2 cm outside the ostium. Circumferential ablation was performed at the PV ostium, with the exact ablation location determined by ICE. The relationship of the catheter tip to the esophagus was imaged during energy delivery, allowing interruption when respiration moved the tip closer to the esophagus. Out of 41 patients, the esophagus was seen near left‐sided PVs in 32 and near right‐sided PVs in three patients. The median distance from LA endocardium to esophagus was 2.2 mm (range, 1.4–6 mm). In 21 of 35 patients with a closely related esophagus, ablation over the esophagus was avoided by ablating either lateral or medial to the esophagus. In 14 patients, the esophagus could not be avoided, and risk was minimized by limiting lesion size. Significant movement (>10 mm) of the esophagus during the procedure occurred in 3/41 cases.

Conclusion:
Rotational ICE can accurately determine the distance of ablation sites from the esophagus. Real‐time imaging of the relationship of the ablation catheter tip to the esophagus may reduce the incidence of esophageal injury.
Long‐ and Short‐Term Temporal Stability of Complex Fractionated Atrial Electrograms in Human Left Atrium During Atrial Fibrillation
Authors: SCHERR DANIEL , DALAL DARSHAN , CHEEMA AAMIR , NAZARIAN SAMAN , ALMASRY IBRAHIM , BILCHICK KENNETH , CHENG ALAN , HENRIKSON CHARLES A. , SPRAGG DAVID , MARINE JOSEPH E. , BERGER RONALD D. , CALKINS HUGH , DONG JUN
Published: September 2008

Background:
Complex fractionated atrial electrograms (CFAEs) have been reported as targets for catheter ablation of atrial fibrillation (AF). However, the temporal stability of CFAE sites remains poorly defined.

Methods and Results:
The study consisted of two phases. In the initial phase, two automated software algorithms, namely the interval confidence level (ICL) and the average interpotential interval (AIPI) were assessed for their diagnostic accuracy for automated CFAE detection. The AIPI was found to be superior to the ICL, and an AIPI of ≤100 ms was associated with a sensitivity and specificity of both 92% for detection of CFAEs. In the second phase of the study, 12 patients (2 females, mean age 54 ± 12 years) who underwent catheter ablation for persistent AF were studied to investigate the temporal stability of CFAEs. Two consecutive left atrial (LA) three‐dimensional CFAE maps coded with AIPI readings were reconstructed during ongoing AF in each study patient, with a mean time difference of 34.3 ± 8.7 minutes between the two maps. Among a total of 149 CFAE sites and 238 non‐CFAE sites on the first CFAE map that were precisely revisited during the repeat mapping process, 135 (90.6%) and 225 (94.5%) remained as CFAE sites and non‐CFAE sites, respectively. RF ablation at the selected stable CFAE sites significantly prolonged AF cycle length (181 ± 26 ms to 199 ± 29 ms, P < 0.0001).

Conclusion:
CFAEs recorded in the LA during AF display high temporal stability in patients with persistent AF. The clinical significance of our findings warrants further investigation.
Predictors of Complications of Endovascular Chronic Lead Extractions from Pacemakers and Defibrillators: A Single‐Operator Experience
Authors: AGARWAL SUNIL K. , KAMIREDDY SWAPNA , NEMEC JAN , VOIGT ANDREW , SABA SAMIR
Published: September 2008

Background:
National trends in chronic lead extractions from cardiac rhythm management (CRM) devices are on the rise.

Objective:
The main objective of the study was to identify the predictors of complications of chronic lead extractions.

Methods:
All patients who underwent endovascular chronic CRM lead extraction at our institution between 2002 and 2008 were included in this analysis. Demographic data as well as details of the extraction procedure and its complications within the ensuing 30 days were collected on all patients.

Results:
Data of 212 consecutive patients (456 leads, age = 65 ± 17 years, men 75%, left ventricular ejection fraction = 36 ± 16%, coronary artery disease 80%, defibrillators 49%) were analyzed. There were a total of 26 (11.8%) complications in 25 patients including 9 (4.2%) major complications (death 1, hemothorax 4, pneumothorax 2, tamponade 1, stroke 1) and 17 (8.0%) minor complications. Independent predictors of any complications included a higher number of explanted right ventricular leads (HR = 3.51, P = 0.013). Explantation of ICD as opposed to a pacemaker device showed a strong trend toward significance (HR = 2.57, P = 0.053). An elevated white blood cell count also predicted major complications (HR = 1.52, P = 0.005).

Conclusion:
Predictors of complications after lead extraction procedures include a higher number of extracted leads and the presence of defibrillator as opposed to pacemaker leads. A new paradigm of the removal of all leads not connected to a device may, therefore, reduce the risk of complications from lead extraction procedures and deserves to be tested prospectively.
A Systematic Review of Randomized Trials Comparing Radiofrequency Ablation with Antiarrhythmic Medications in Patients with Atrial Fibrillation
Authors: NAIR GIRISH M. , NERY PABLO B. , DIWAKARAMENON SYAMKUMAR , HEALEY JEFFREY S. , CONNOLLY STUART J. , MORILLO CARLOS A.
Published: September 2008

Introduction: Atrial fibrillation (AF) is the most frequent arrhythmia seen in clinical practice. Until recently, antiarrhythmic medications have been the only commonly employed treatment for maintaining sinus rhythm. However, antiarrhythmic medications have a modest long‐term efficacy and the potential for serious side effects. Radiofrequency (RF) ablation is now emerging as a viable alternative to antiarrhythmic medications in maintaining sinus rhythm in patients with AF. Several randomized trials comparing RF ablation with antiarrhythmic medications have now been published.

Objectives: To perform a systematic review of published randomized trials comparing RF ablation with antiarrhythmic medications in the treatment of AF.

Methods: A systematic review of the literature was performed and two authors independently abstracted the data from trials. A statistical analysis was performed using Comprehensive Meta‐Analysis Software™ (BIOSTAT, Englewood, NJ, USA).

Results: A total of six trials were identified. Overall, RF ablation reduced the risk of AF recurrence by 65% at 1 year compared with antiarrhythmic medications.

Conclusions: In selected patients with AF, RF ablation reduced the risk of AF recurrence at 1 year by 65% compared with antiarrhythmic medications.
Acute Stent Thrombosis in the Setting of Cocaine Abuse Following Percutaneous Coronary Intervention
Authors: MAKARYUS JOHN N. , VOLFSON ARIY , AZER VICTOR , BOGACHUK ELENA , LEE ALEXANDER
Published: September 2008

The treatment of acute coronary syndrome (ACS) in patients with documented cocaine abuse has always presented significant challenges. Issues related to medication compliance, the potential risks of beta adrenergic blockade, and possible continued cocaine abuse postmyocardial infarction necessitate a unique, individualized approach to these patients. Recent data in the era of extensive percutaneous coronary interventions (PCI) and intracoronary stent (ICS) implantation have raised questions regarding the safety of ICS in patients who may revert to cocaine abuse postacute coronary syndrome as a result of the potentially higher risk of stent thrombosis in these patients. While the precise reason as to why cocaine use may increase the risk of stent thrombosis is not fully understood, it is likely the result of a confluence of factors, including coronary vessel vasoconstriction, impaired vascular compliance, as well as the platelet‐activating effect of cocaine. We present the case a 46‐year‐old male with a history of cocaine abuse who presented with an acute stent thrombosis 2 days post‐PCI likely as a result of cocaine abuse on the day of discharge following initial stent implantation for a non‐ST‐elevation myocardial infarction (NSTEMI). We also review the literature regarding the safety of PCI in cocaine abusers.
Increased activated Akt expression in renal cell carcinomas and prognosis
Authors: Hager Martina , Haufe Heike , Kemmerling Ralf , Hitzl Wolfgang , Mikuz Gregor , Moser Patrizia L. , Kolbitsch Christian
Published: September 2008

Renal carcinogenesis is promoted by overexpression of the activated serine/threonine kinase Akt (p‐Akt) and supposedly a concomitant reduction in phosphatase and tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN), which normally inhibits the activation of Akt. Because promising anti‐cancer therapies increasingly focus on pathways involving p‐Akt and PTEN, the present study evaluated the expression of p‐Akt in renal cell carcinomas and compared it with prognosis. P‐Akt and PTEN expression were analysed in a tissue microarray (TMA) from renal cell carcinoma (n= 386) and adjacent uninvolved renal tissue (n= 32) specimens. Increased p‐Akt was found more often in the nucleus than in the cytoplasm, and PTEN was concomitantly reduced in about 50% of cases. Neither tumour grade nor stage influenced p‐Akt expression, whereas the clear cell and papillary subtypes showed increased p‐Akt more often than did the chromophobe or sarcomatoid types. Increased cytoplasmic and nuclear p‐Akt levels were independent prognostic factors for diminishing patient survival. The present study found significantly increased nuclear but also cytoplasmic p‐Akt expression in renal cell carcinoma subtypes. Increased nuclear and cytoplasmic p‐Akt was an independent prognostic factor for diminishing patient survival. The considerable number of high‐grade and high‐stage RCC showing increased p‐Akt and reduced PTEN would justify further evaluation of therapeutic concepts based on inhibitors of the PI3K/p‐Akt/mTOR pathway.
Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRα1‐Nox1 pathway
Authors: Wang Xiuqing , Sun Zhongjie
Published: September 2008

Thyroid hormone (T3) can stimulate protein synthesis and cell growth. NOX1 is a mitogenic oxidase. The aim of this study was to test a novel hypothesis that T3 induces artery smooth muscle cell proliferation by up‐regulating NOX1. Immunofluoresence confocal microscopy was used to visualize the sub‐cellular localization of NOX1 and TRα1 in rat aorta smooth muscle (RASM) cells. Optical sectioning showed that TRα1 and NOX1 co‐localized around the nucleus. T3 promoted RASM cell proliferation as determined by the fact that T3 significantly increased the number of cytokinesis cells, proliferating cellular nuclear antigen (PCNA) and smooth muscle α‐actin (SM α‐actin). T3 increased NOX1 expression at both the transcription (mRNA) and translation (protein) levels as evaluated by RT‐PCR and Western blot, respectively. T3 also significantly increased the intracellular ROS production based on the oxidation of 2’,7’‐dichlorodihydrofluoresein (H2DCF) to a fluorescent 2’,7’‐dichlorofluoresein (DCF). RNAi silence of TRα1 or NOX1 abolished T3‐induced intracellular ROS generation and PCNA and SM α‐actin expression, indicating that TRα1 and NOX1 mediated T3‐induced RASM cell proliferation. Notably, RNAi silence of TRα1 blocked the T3‐induced increase in NOX1 expression, whereas silence of NOX1 did not affect TRα1 expression, disclosing a new pathway, i.e. T3‐TRα1‐NOX1‐cell proliferation. TRα1 and NOX1 co‐localized around the nucleus. T3 induced RASM cell proliferation by up‐regulating NOX1 in a TRα1‐dependent manner.
Oxidative stress in NPC1 deficient cells: protective effect of allopregnanolone
Authors: Zampieri Stefania , Mellon Synthia H. , Butters Terry D. , Nevyjel Marco , Covey Douglas F. , Bembi Bruno , Dardis Andrea
Published: September 2008

Niemann‐Pick C disease (NPC) is an autosomal recessive neurodegenerative disorder caused by the abnormal function of NPC1 or NPC2 proteins, leading to an accumulation of unesterified cholesterol and glycosphingolipids (GSLs) in the lysosomes. The mechanisms underlying the pathophysiology in NPC disease are not clear. Oxidative damage is implicated in the pathophysiology of different neurological disorders and the effect of GSL accumulation on the intracellular redox state has been documented. Therefore, we determined whether the intracellular redox state might contribute to the NPC disease pathophysiology. Because the treatment of NPC mice with allopregnanolone (ALLO) increases their lifespan and delays the onset of neurological impairment, we analysed the effect of ALLO on the oxidative damage in human NPC fibroblasts. Concentrations of reactive oxygen species (ROS) and lipid peroxidation were higher in fibroblasts from NPC patients than in fibroblasts from normal subjects. Fibroblasts from NPC patients were more susceptible to cell death through apoptosis after an acute oxidative insult. This process is mediated by activation of the NF‐κB signalling pathway. Knockdown of NPC1 mRNA both in normal fibroblasts and in human SH‐SY5Y neuroblastoma cells caused increased ROS concentrations. ALLO treatment of fibroblasts from NPC patients or NPC1 knockdown cells reduced the levels of ROS and lipid peroxidation and prevented peroxide‐induced apoptosis and NF‐kB activation. Thus, these findings suggest that oxidative stress might contribute to the NPC disease and ALLO might be beneficial in the treatment of the disease, at least in part, due to its ability to restore the intracellular redox state.
Hepcidin suppression and defective iron recycling account for dysregulation of iron homeostasis in heme oxygenase‐1 deficiency
Authors: Kartikasari Apriliana E. R. , Wagener Frank A. D. T. G. , Yachie Akihiro , Wiegerinck Erwin T. G. , Kemna Erwin H. J. M. , Winkels Dorine W.
Published: September 2008

Heme oxygenase‐1 (HO‐1) contribution to iron homeostasis has been postulated, because it facilitates iron recycling by liberating iron mostly from heme catabolism. This enzyme also appears to be responsible for the resolution of inflammatory conditions. In a patient with HO‐1 deficiency, inflammation and dysregulation of body iron homeostasis, including anemia and liver and kidney hemosiderosis, are evidenced. Here we postulated that HO‐1 is critical in the regulation of ferroportin, the major cellular iron exporter, and hepcidin, the key regulator of iron homeostasis central in the pathogenesis of anemia of inflammation. Our current experiments in human THP‐1 monocytic cells indicate a HO‐1‐induced iron‐mediated surface‐ferroportin expression, consistent with the role of HO‐1 in iron recycling. Surprisingly, we observed low hepcidin levels in the HO‐1‐deficient patient, despite the presence of inflammation and hemosiderosis, both inducers of hepcidin. Instead, we observed highly increased soluble transferrin receptor levels. This suggests that the decreased hepcidin levels in HO‐1 deficiency reflect the increased need for iron in the bone marrow due to the anaemia. Using human hepatoma cells, we demonstrate that HO‐activity did not have a direct modulating effect on expression of HAMP, the gene that encodes for hepcidin. Therefore, we argue that the decreased iron recycling may, in part, have contributed to the low hepcidin levels. These findings indicate that dysregulation of iron homeostasis in HO‐1 deficiency is the result of both defective iron recycling and erythroid activity‐associated inhibition of hepcidin expression. This study therefore shows a crucial role for HO‐1 in maintaining body iron balance.
High‐dose therapy and autologous stem cell transplantation for follicular lymphoma undergoing transformation to diffuse large B‐cell lymphoma
Authors: Hamadani Mehdi , Benson Jr. Don M. , Lin Thomas S. , Porcu Pierluigi , Blum Kristie A. , Devine Steven M.
Published: September 2008

The transformation of follicular lymphoma (FL) to high‐grade histology occurs in up to 70% of patients. The role of hematopoietic stem cell transplantation (HSCT) in transformed FL is poorly defined. Twenty‐four FL patients with histologically confirmed transformation to diffuse large B‐cell lymphoma underwent unpurged autologous HSCT at our institution. Their median age was 56 yr. The median number of prior chemotherapies was 2 (range 1–6). Thirteen patients had residual nodal disease measuring more than 2 cm and four patients had bulky disease at the time of HSCT. Six patients had refractory disease at transplantation. At a median follow‐up of 38 months, 3‐yr progression‐free survival following autologous HSCT was 40%. The 3‐yr overall survival was 52%. The cumulative incidence of relapse and non‐relapse mortality rate was 41% and 25%, respectively.
Mn2+ regulates myeloma cell adhesion differently than the proadhesive cytokines HGF, IGF‐1, and SDF‐1α
Authors: Slørdahl Tobias S. , Hov Håkon , Holt Randi U. , Baykov Vadim , Syversen Tore , Sundan Anders , Waage Anders , Børset Magne
Published: September 2008

Adhesion of multiple myeloma (MM) cells in the bone marrow (BM) is important for the growth and survival of the myeloma cells. Very late antigen‐4 (VLA‐4) is one of the main adhesion receptors that mediate MM cell binding to fibronectin (FN). In this study we have examined the effect of divalent cations on adhesion of MM cells to FN, and compared this type of adhesion with the adhesion induced by the cytokines HGF, IGF‐1 and SDF‐1α. Mn2+ induced adhesion in all cell lines tested. Cytokine‐ and Mn2+‐induced VLA‐4‐mediated adhesion were different in many respects, including binding specificity, adhesion kinetics and the activation state of VLA‐4. To study a potential role of divalent cations in vivo, we measured the concentrations of divalent cations in BM plasma from 14 MM patients. We also found that Mn2+‐mediated adhesion to FN activated the MAPK pathway, indicating that the interaction of MM‐cells with FN mediated by Mn2+ could play a critical role for growth and proliferation. In conclusion, this study shows a potential important role of divalent cations in MM cell biology and supports earlier studies pointing to activated VLA‐4 as a key for homing of MM cells to the BM.
Validity and clinical feasibility of the ADHD rating scale (ADHD‐RS) A Danish Nationwide Multicenter Study
Authors: Szomlaiski N , Dyrborg J , Rasmussen H , Schumann T , Koch SV , Bilenberg N
Published: September 2008

Aim: To establish the validity of a Danish version of the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD‐RS), secondly to present national norm scores compared to that of United States and other European data and thirdly to evaluate ADHD‐RS when used for monitoring treatment effectiveness.

Methods: A Danish translation of the ADHD‐RS was used on a normative sample of 837 children. Two clinical samples, 138 hyperkinetic disorder (HKD) cases and 110 clinical controls were recruited from eleven Danish Child and Adolescent Mental Health (CAMH) centres and assessed according to usual clinical standards. The HKD children were rated by parents and teachers at baseline and at follow‐up 3 months later.

Results: Internal validity of ADHD‐RS was high and the factor structure supported the diagnostic classification system ICD‐10. The questionnaire discriminated HKD patients in a mixed clinical sample, and was sensitive to change in symptom load as measured before and after commencing of the treatment.

Conclusion: The Danish version of ADHD‐RS is valid and clinically feasible when measuring HKD symptom load in a CAMH‐setting. The questionnaire provides useful data in patient management, quality improvement and service planning as well as in effectiveness studies of different interventions for patients with HKD and related disorders in routine clinical settings.
Soothing methods used to calm a baby in an Arab country
Authors: Abdulrazzaq Yousef Mohamed , Kendi Asma Al , Nagelkerke Nicolaas
Published: September 2008

This study was undertaken to determine how mothers soothed their crying infants. A total of 1137 mothers of different cultural backgrounds were approached, 998 agreed to participate in the study, but only 716 completed the questionnaire through a telephone interview. Analysis was restricted to 702 mothers from the UAE nationality, other Arabs, other Muslims, Indians and Philippinos. The questionnaire contained 23 questions on different soothing methods. The most common soothing method was breast‐feeding (99.1%), followed by holding and carrying the infant (96.9%), letting infant suck on his thumb or finger (87.3%), herbal tea (65%), night bottle (42.1%) and swaddling infant (19.5%). Over 90% of mothers of all nationalities, preferred not to use pacifiers. Soothing herbs were often used, with the commonest being anise (165 mothers used anise). Fennel tea was also used by a substantial number of mothers (75), with gripe water (64), cumin (33), chamomile (32), mint (22) and fenugreek (16) making up most of the rest.

Conclusion: Mothers' ethnicity and nationality strongly impacted on the soothing methods used, with Arabs more often using herbal tea, prone positioning and swaddling to calm infants and illustrate the importance of culture in the upbringing of children from a very early age.
GROUP DIFFERENCES IN PERSONALITY: META‐ANALYSES COMPARING FIVE U.S. RACIAL GROUPS
Authors: FOLDES HANNAH J. , DUEHR EMILY E. , ONES DENIZ S.
Published: September 2008

This research poses 2 applied questions: How large are racial group differences on personality scales and are these differences likely to cause adverse impact in personnel selection? We examined the extent to which racial groups differ across Big 5 personality factors and facets. Large‐scale, quantitative estimates based on over 700 effect sizes were meta‐analytically summarized. Multiple personality instruments and understudied racial groups, particularly Asian Americans and American Indians, were included in the meta‐analyses. Most group comparisons and personality scales yielded negligible differences and are not likely to cause adverse impact in selection. However, facet‐level analyses produced different d‐values, with some group comparisons showing moderate differences, suggesting that the use of personality measures in selection does not uniformly circumvent adverse impact concerns. The veracity of this conclusion depends on (a) the particular trait in question, (b) the composition of the applicant pool (i.e., which groups are to be compared with one another), (c) the effect size (i.e., d‐value), and (d) the selection ratio. For practitioners, we present a quantitatively informed summary of when and where to expect adverse impact to result from personality measures used in personnel selection.
AN ALTERNATIVE EXPLANATION FOR THE ASYMMETRICAL EFFECTS IN RELATIONAL DEMOGRAPHY RESEARCH
Authors: TONIDANDEL SCOTT , AVERY DEREK , BUCHOLTZ BROOKE , McKAY PATRICK
Published: September 2008

Several relational demography studies have demonstrated asymmetrical effects of dissimilarity across different groups of employees. Some groups of employees appear to be more influenced by differences from fellow employees, whereas other groups of employees appear indifferent. Although numerous theoretical explanations have been developed to account for these asymmetrical effects, this paper argues that such effects are actually methodological artifacts resulting from an imbalance in the proportion of group members and deficiencies in the most commonly used measure of dissimilarity, Euclidean distance. This paper illustrates how such asymmetrical effects can be observed even when none exist in the population. Suggestions for methodological improvements in future diversity research are discussed along with recommendations for managing diversity in organizations.
THE IMPACT OF HUMAN RESOURCE AND OPERATIONAL MANAGEMENT PRACTICES ON COMPANY PRODUCTIVITY: A LONGITUDINAL STUDY
Authors: BIRDI KAMAL , CLEGG CHRIS , PATTERSON MALCOLM , ROBINSON ANDREW , STRIDE CHRIS B. , WALL TOBY D. , WOOD STEPHEN J.
Published: September 2008

Within the strategic human resource management (SHRM) perspective, psychology‐based practices, especially empowerment, extensive training, and teamwork, are seen as vital to sustained competitive advantage. Other approaches, such as those of integrated manufacturing and lean production, place greater emphasis on operational initiatives such as total quality management, just‐in‐time, advanced manufacturing technology, and supply‐chain partnering as determinants of organizational performance. We investigated the relative merits of these practices through a study of the productivity of 308 companies over 22 years, during which time they implemented some or all of these 7 practices. Consistent with SHRM theory we found performance benefits from empowerment and extensive training, with the adoption of teamwork serving to enhance both. In contrast, none of the operational practices were directly related to productivity nor did they interact with other practices in ways fully consistent with the notions of integrated manufacturing or lean production.