bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it Safe to Perform Aggressive Rehabilitation after Distal Biceps Tendon Repair Using the Modified 2-Incision Approach?
Authors: Bisson Leslie J. , Gurske de Perio Jennifer , Weber Alexander E. , Ehrensberger Mark T. , Buyea Cathy
Published: August 2007

Background

Despite improved methods of fixation, there is still a delay in early active motion after distal biceps repair.

Hypothesis

Distal biceps repairs using the modified 2-incision technique can be treated with early motion, and there is no difference in the cyclic performance of Ethibond and Fiberwire when used for the repair.

Study Design

Controlled laboratory study.

Methods

Nine matched pairs of cadaveric elbows had release of the distal biceps followed by repair with either No. 5 Ethibond or Fiberwire through a bone tunnel. The repairs were cyclically loaded for 3000 cycles (1000 cycles from 10-50 N, 1000 cycles from 10-75 N, 1000 cycles from 10-100 N) followed by single-load displacement to failure in surviving specimens.

Results

There was no difference in the displacement or stiffness between surviving repairs at any point measured. Ethibond repairs survived significantly more cycles than did Fiberwire repairs, particularly at higher loads.

Conclusion

Distal biceps repair using the 2-incision technique with Ethibond should allow early active motion, but early active motion may not be possible with Fiberwire.
Clinical Outcomes of the DANE TJ Technique to Treat Ulnar Collateral Ligament Insufficiency of the Elbow
Authors: Dines Joshua S. , ElAttrache Neal S. , Conway John E. , Smith Wade , Ahmad Christopher S.
Published: August 2007

Background

Many improvements in ulnar collateral ligament reconstruction have been made since Jobe et al first described the procedure. A novel elbow ulnar collateral ligament reconstruction technique that combines interference screw fixation on the ulna with docking of the graft on the humeral side (DANE TJ) has been reported.

Hypothesis

Outcomes of ulnar collateral ligament reconstructions performed with the DANE TJ technique are as good as other recently published results of ulnar collateral ligament reconstruction, particularly in cases of insufficient bone stock on the sublime tubercle and revision reconstructions.

Study Design

Case series; Level of evidence, 4.

Methods

During a 3-year period, 22 athletes were treated with surgical reconstruction of the ulnar collateral ligament using proximal docking and distal interference screw fixation of the ligament (DANE TJ technique). All patients had a history, physical examination findings, and magnetic resonance imaging results consistent with ulnar collateral ligament injury. Patients were evaluated at a mean of 36 months postoperatively. Outcomes were classified using a modified Conway Scale.

Results

At the most recent follow-up, 19 of 22 patients had excellent results. There were 2 fair results and 1 poor result. The poor result was in a revision case. The 2 other revision ulnar collateral ligament reconstructions had excellent outcomes. When used in 2 cases of sublime tubercle avulsions, the results were excellent. Postoperative complications occurred in 4 patients: 2 developed ulnar neuritis, and 2 required second surgeries for lysis of adhesions. Three of these 4 patients went on to have excellent outcomes.

Conclusion

Clinically, the initial results compare favorably with other published techniques of elbow ulnar collateral ligament reconstruction. These early data support the use of the DANE TJ technique for revision cases and cases of sublime tubercle insufficiency.
Extensor Retinaculum Impingement in the Athlete
Authors: VanHeest Ann E. , Luger Nancy M. , House James H. , Vener Michael
Published: August 2007

Background

Athletes with repetitive weightbearing hyperextension activities are predisposed to wrist pain.

Purpose

To describe extensor retinaculum impingement of the extensor tendons as a new diagnosis for wrist pain for the athlete performing repetitive wrist hyperextension, to present cadaveric dissections to further understand the anatomical basis for extensor retinaculum impingement, and to report treatment outcomes of extensor retinaculum impingement.

Study Design

Case series; Level of evidence, 4.

Methods

A retrospective chart review was performed for athletes treated from 1987 to 2006 for wrist pain due to extensor retinaculum impingement. Eight wrists in 7 athletes were reviewed with a mean presenting age of 19.6 years. The hallmark symptom was dorsal wrist pain, and signs were extensor tendon synovitis and tenderness at the distal border of the extensor retinaculum, provoked by wrist hyperextension. Ten cadaveric wrists were dissected and examined to evaluate anatomical factors that may contribute to extensor retinaculum impingement.

Results

Two athletes (2 wrists) were treated with corticosteroid injections. Five patients (6 wrists) were treated operatively, with pathologic findings of thickening of the distal border of the extensor retinaculum and concomitant extensor tendon synovial thickening or, in 1 patient, tendon rupture. Partial distal resection of the extensor retinaculum was performed to eliminate impingement. All patients had complete relief of pain and full return to sport.

Conclusion

Competitive sports that require repetitive wrist extension with an axial load predispose the athlete to extensor retinaculum impingement. Athletes with dorsal wrist pain and tenosynovial thickening worsened with wrist hyperextension should be considered for the diagnosis of extensor retinaculum impingement. When nonoperative management fails, surgical resection of the distal impinging border of the extensor retinaculum can eliminate pain and can still allow athletes to return to sport without diminishing the opportunity for significant athletic accomplishments.
Memories of Childhood Sexual Abuse
Authors: Crowley M. Sue
Published: August 2007

The study explored types of memory for childhood sexual abuse (CSA) in a clinical sample of 30 women and identified factors that led some women ( n = 24) to report recovered memories. Questionnaires produced three types of memory: always ( n = 6), recovered ( n = 14), both ( n = 10); however, analysis of narrative data also revealed the use of language that could not be categorized into discrete types. Recovered memories were linked to three categories of experience (cumulative reactions, atypical reactions, and atypical experiences). Subcategories identified specific contexts associated with those experiences. Findings suggest that further research is needed on the phenomenology of memory experiences using language derived from CSA survivors and a better understanding of the long-term process of interpretations of key experiences that result in reports of recovered memories.
Females' Reasons for Their Physical Aggression in Dating Relationships
Authors: Hettrich Emma L. , O'Leary K. Daniel
Published: August 2007

Approximately 32% of dating college females reported that they engaged in physical aggression against their partners and that they engaged in acts of physical aggression more often than their male partners engaged in aggression against them. However, the females also reported that their male partners attempted to force them to engage in oral sex more often than the females engaged in such coercive behavior. Based on both open-ended and closed responses, the primary reasons given for engaging in physical aggression were anger at the partner and poor communication. Females who reported physical aggression in their relationships were less satisfied with their relationships, and both psychological and physical aggression were negatively correlated with positive feelings about the partners.
Exploring the Link Between Pet Abuse and Controlling Behaviors in Violent Relationships
Authors: Simmons Catherine A. , Lehmann Peter
Published: August 2007

Domestic violence is not as simple as one partner physically harming another. Instead, it consists of a complex range of controlling behaviors including physical, emotional, sexual, and economic maltreatment as well as isolation, male privilege, blaming, intimidation, threats, and minimizing/denying behaviors. In addition to the controlling behaviors reported by women seeking shelter from violent relationships, a growing body of research indicates some individuals who abuse their intimate partner also abuse their pets. This study explores these connections using reports of 1,283 female pet owners seeking refuge from their male batterer in a domestic violence shelter. Findings indicate that batterers who also abuse their pet (a) use more forms of violence and (b) demonstrate greater use of controlling behaviors than batterers who do not abuse their pets. Likewise, positive correlations are found between specific controlling behaviors and cruelty to pets. Implications for practice and future research are discussed.
Human Memory, Social Process, and the Pragmatist Metamorphosis
Authors: Prus Robert
Published: August 2007

Following (a) an introductory statement on the extremely uneven treatment of memory in the social sciences, this article addresses (b) the pragmatizing foundations of human memory and (c) the highly consequential role that ethnographers have to assume if social scientists are to achieve more adequate and authentic conceptualizations of memory as a social process. Subsequent attention is given to (d) memory as a socially accomplished realm of activity, (e) memories as instances of collective ventures, (f) remembering as a generic social process, and (g) the conceptual challenges that ethnographers face if they are to make more substantive contributions to academic memory in the human sciences.
Friends Don't Let Friends Listen to Corporate Rock
Authors: Moore Ryan
Published: August 2007

This article examines punk subculture's methods of commercially independent cultural production. While previous scholarship on punk and other youth cultures concludes that resistance is to be found in fashion, style, and symbolic gestures, the author locates dissent in the act of producing music and media that are relatively autonomous from the corporate culture industry, which in punk subcultures is known as the “do-it-yourself ethic.” Pierre Bourdieu's theory of “the field of cultural production” is used to explain how cultural producers are motivated to create and perform independently of the commercial marketplace. The findings are based on years of participant-observation and in-depth interviewing within punk subcultures in the Southern California region.
Attitudes Toward Women and Tolerance for Sexual Harassment Among Reservists
Authors: Vogt Dawne , Bruce Tamara A. , Street Amy E. , Stafford Jane
Published: August 2007

Women are more likely to experience sexual harassment in some work settings than others; specifically, work settings that have a large proportion of male workers, include a predominance of male supervisors, and represent traditional male occupations may be places in which there is greater tolerance for sexual harassment. The focus of the study was to document attitudes toward women among military personnel, to identify demographic and military characteristics associated with more positive attitudes toward women, and to examine associations between attitudes toward women and tolerance for sexual harassment. The study was based on data from 2,037 male and female former Reservists who reported minimal or no experiences of sexual harassment and no sexual assault in the military. Results suggest that attitudes toward women vary across content domains, are associated with several key demographic and military characteristics, and predict tolerance for sexual harassment. Implications of the findings and future directions are discussed.
Modern-Day Comfort Women
Authors: Hughes Donna M. , Chon Katherine Y. , Ellerman Derek P.
Published: August 2007

The trafficking of women has been a lucrative moneymaker for transnational organized crime networks, ranking third, behind drugs and arms, in criminal earnings. The U.S. military bases in South Korea were found to form a hub for the transnational trafficking of women from the Asia Pacific and Eurasia to South Korea and the United States. This study, conducted in 2002, examined three types of trafficking that were connected to U.S. military bases in South Korea: domestic trafficking of Korean women to clubs around the military bases in South Korea, transnational trafficking of women to clubs around military bases in South Korea, and transnational trafficking of women from South Korea to massage parlors in the United States.
Lifetime and Current Sexual Assault and Harassment Victimization Rates of Active-Duty United States Air Force Women
Authors: Bostock Deborah J. , Daley James G.
Published: August 2007

From a stratified random sample, 2,018 active-duty United States Air Force women completed a telephone survey dealing with sexual assault and harassment. The lifetime prevalence of rape among Air Force women (28%) was more than twice as high as the prevalence in a national sample (13%). Nearly half of the military sample had been the victims of rape, molestation, or attempted sexual assault. The majority of both initial rapes (75%) and most recent rapes (56%) involved assault by civilians when the victims were civilians. Family members perpetrated 29% of initial rapes and 33% of most recent rapes. Regarding military status of the perpetrator, 14% of first-time victims were raped by a military member, 26% of multiple-time victims were raped by a military member, 31.8% of military women were sexually harassed by a military supervisor or boss, and 26.7% of military women were sexually harassed by a military coworker.
Rape Rates and Military Personnel in the United States
Authors: Rosen Leora N.
Published: August 2007

This study involves a test of the cultural spillover hypothesis through a state-level analysis of the relationship between rape rates and the proportion of military personnel in the population. A statistically significant correlation not predicted by this hypothesis was found between rape rates and the proportion of Air Force personnel in the population. Further exploration revealed that this was largely because of the high correlation between the Air Force and the Indian population. Multivariate analyses revealed that the proportion of Indian women in the population was the main predictor of rape rates. Per capita alcohol consumption was also found to be positively correlated with both rape rates and Air Force personnel but was not significantly related to rape in the multivariate analysis.
Estimation of Incremental Work Time in Hotel Accounts Department: Envisaging Prospective Hotel Real Estate Investment Trusts in Hong Kong
Authors: Chan Wilco , Wong Kevin
Published: August 2007

The article identifies new features that are different from routine accounting practice by consulting and comparing with an updated consultation paper of the establishment of real estate investment trusts (REITs), existing accounting reports, and the latest version of uniform accounting for hotels. The study identified 28 reporting items that requires additional work time to deal with under the proposed REITs, spreading across 8 items in balance sheet, 12 items in income statement, 7 items in notes to account, and all items in net income reconciliation. An approach investigating the time additions during start-up and routine stages was used. It is estimated that 25 working hours are required to start up the new information set, and 7 additional hours are needed to generate extra information as required by the REIT office on a routine basis, suggesting significant implications for training and development needs that are discussed here.
Propensity To Complain: Effects of Personality and Behavioral Factors
Authors: Gursoy Dogan , McCleary Ken W. , Lepsito Lawrence R.
Published: August 2007

Literature suggests that the antecedents of complaining involve more than dissatisfaction alone; several other factors affect consumers' propensity to complain. This study examined the effects of personality and behavioral factors on consumers' propensity to complain. Findings suggest that consumers' locus of control and their price consciousness have a significant impact on their propensity to complain. Theoretical and managerial implications of these findings are discussed in detail.
Social Capital and HRD: Provocative Insights From Critical Management Studies
Authors: O'Donnell David , Gubbins Claire , McGuire David , Jørgensen Kenneth Mølbjerg , Bo Henriksen Lars , Garavan Thomas N.
Published: August 2007

The problem and the solution. This article initiates a critical management studies evaluation of social capital in an HRD context by drawing on insights from Foucault and Habermas.This article presents alternative interpretations of three seminal social capital concepts—weak ties, structural holes, and social resources. Pragmatic, albeit critical, insights for HRD theory and practice are illustrated to counterbalance the managerialist appropriation of social capital in pursuit of largely economic ends. It is argued here that social well-being is as relevant to HRD practice as economic well-being. Ethical dimensions are noted and avenues of reflexivity for HRD practitioners are suggested.
Knowledge Management and Human Resource Development: An Application in Social Network Analysis Methods
Authors: Parise Salvatore
Published: August 2007

The problem and the solution. This article describes how social network analysis (SNA) can contribute to the knowledge management (KM) efforts of human resource development (HRD) professionals in organizations today.The suggested contributions of SNA are based on primary research conducted across more than 80 organizations. The author first provides an introduction to the people-to-people strategy of today's KM efforts.A detailed look at some common HRD challenges is introduced. Next, an introduction to SNA metrics and techniques is given, and a description of how they can be used to help understand HRD challenges is outlined. The author then provides three cases to illustrate how SNA can aid HRD analysis and interventions involving (a) knowledge creation and innovation, (b) knowledge transfer and retention, and (c) knowledge associated with job succession planning. The author concludes by discussing the implications for HRD of utilizing SNA in the organization.
Hypercoagulable State Due to Alcohol-Paracetamol Syndrome Producing Acute Limb Ischemia
Authors: Moulakakis Konstantinos G. , Sfyroeras Giorgos , Pavlidis Polivios , Besias Nikolaos , Maras Dimitrios , Andrikopoulos Vassilios
Published: August 2007

The authors describe a man with alcohol-paracetamol syndrome and hepatic failure who presented with acute arterial thrombosis of the left limb. The patient has jaundice, increased serum transaminase levels, and significant coagulopathy, with elevated international normalized ratio and prolonged prothrombin time. A transient hypercoagulable state due to liver failure is documented, characterized by acquired deficiencies of antithrombin III, protein C, and protein S. Laboratory and molecular testing for inherited hypercoagulable disorders during the follow-up period is positive for increased levels of factor VIII. The patient undergoes successful thrombectomy and receives intensive symptomatic and causal treatment, resulting in complete recovery. The patient is discharged 20 days after admission on a regimen of acenocoumarol.
Decreased Antioxidant Vitamin Concentration May Be a Risk Factor for Recurrent Carotid Stenosis
Authors: Reid Julie A. , Lau Louis L. , Hannon Raymond J. , Lee Bernard , Young Ian S. , Soong Chee V.
Published: August 2007

Carotid endarterectomy has been found to be associated with a transient increase in systemic oxidative stress, and this has been shown to be a predictor of restenosis. The aim of this study was to determine the incidence of early recurrent stenosis and investigate a possible role of oxidative stress in its development by measuring the concentration of antioxidant vitamins. Patients undergoing carotid endarterectomy between August 2001 and February 2003 were included in the study. A preoperative blood sample was analyzed for antioxidant vitamin concentrations. All patients were followed up by duplex scans 3 and 12 months postoperatively. Ninety-three patients (101 carotid endarterectomies) were recruited. Nine arteries had developed restenosis by 12 months. Those patients who developed recurrent stenosis had significantly lower vitamin C concentrations (19.10 ± 3.69 vs 30.11 ± 19.10, P = .02) than those who did not. This study suggests that low antioxidant vitamin levels may predispose to early restenosis after carotid endarterectomy.
Ureteral Perigraft Fistula
Authors: Deem Samuel , Stone Patrick , Schlarb Chris
Published: August 2007

Ureteral injury following aortic surgery occurs in less than 1% of all cases. Ureteral-arterial fistulae rarely occur in the current literature and only in case reports. This case involves a suspected ureteral aortic graft fistula presenting with acute hematuria with distant history of redo aortic bifemoral graft for aortoenteric fistula. Cystoscopy with retrograde pyelogram was performed and demonstrated what appeared to be a fistula between the left ureter and the aortic graft with a proximal hydroureter and hydronephrosis. After a detailed review of the films, we diagnosed a more benign ureteral perigraft fistula. Multidisciplinary management including urology and vascular surgery suggested conservative management. However, the patient later required more definitive therapy for his illness. This case demonstrates a ureteral perigraft fistula and displays how it appears radiographically. Here we present our experience with this new radiological diagnosis.
Reperfusion Syndrome: Cellular Mechanisms of Microvascular Dysfunction and Potential Therapeutic Strategies
Authors: Hardev Ramandeep Singh Girn  , Ahilathirunayagam Sashi , Mavor Andrew I. D. , Homer-Vanniasinkam Shervanthi
Published: August 2007

Reperfusion injury is the paradoxical and complex phenomenon of exacerbation of cellular dysfunction and increase in cell death after the restoration of blood flow to previously ischemic tissues. It involves biochemical and cellular changes causing oxidant production and complement activation, which culminates in an inflammatory response, mediated by neutrophil and platelet cell interactions with the endothelium and among the cells themselves. The mounted inflammatory response has both local and systemic manifestations. Despite improvements in imaging, interventional techniques, and pharmacological agents, morbidity from reperfusion remains high. Extensive research has furthered the understanding of the various pathophysiological mechanisms involved and the development of potential therapeutic strategies. Preconditioning has emerged as a powerful method of ameliorating ischemia reperfusion injury to the myocardium and in transplant surgery. More recently, postconditioning has been shown to provide a therapeutic counter to vasoocclusive emergencies. More research and well-designed trials are needed to bridge the gap between experimental evidence and clinical implementation.
Geek Chic
Authors: Simon Bart
Published: August 2007

This article explores the relationship between computer gamers and their machines in an effort to characterize cultural attitudes toward the materiality of information technology. Whereas dominant culture desires a world in which information technology performs seamlessly within the fabric of everyday life, case-modding gamers prefer to foreground both their computer machinery and their virtuosity in its manipulation. Instead of desiring the disappearance of machines into the background of a world that those machines produce, case modders revel in, and indeed identify with, the material guts of their computer systems. This machine aesthetic is explored further in the context of the LAN party, where the case modders' machines become as much of a spectacle as the games on the screen.
Challenge Everything?
Authors: Lauwaert Maaike
Published: August 2007

This article deals with the popular simulation game SIMCITY by Will Wright. The main question of this article is whether or not the popular notion of SIMCITY as an endless and borderless playground is more than a contaminating marketing strategy. To analyze this question about SIMCITY as a borderless playground, the article will draw historical parallels with construction toys from yesteryear and differentiate between internal and external levels of playing and intended and unintended practices of play. The article claims that unintended practices of play, player “anarchy” through appropriation of the game, are difficult in a game like SIMCITY, thus frustrating the claims and the idea of SIMCITY as a borderless playground.
Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin–mediated human T-cell adhesion
Authors: Ghandour Haifa , Cullere Xavier , Alvarez Angeles , Luscinskas Francis W. , Mayadas Tanya N.
Published: August 2007

Regulated adhesion of T cells by the integrins LFA-1 (lymphocyte function-associated antigen-1) and VLA-4 (very late antigen-4) is essential for T-cell trafficking. The small GTPase Rap1 is a critical activator of both integrins in murine lymphocytes and T-cell lines. Here we examined the contribution of the Rap1 regulatory pathway in integrin activation in primary CD3+ human T cells. We demonstrate that inactivation of Rap1 GTPase in human T cells by expression of SPA1 or Rap1GAP blocked stromal cell-derived factor-1α (SDF-1α)–stimulated LFA-1–ICAM-1 (intercellular adhesion molecule-1) interactions and LFA-1 affinity modulation but unexpectedly did not significantly affect binding of VLA-4 to its ligand VCAM-1 (vascular cell adhesion molecule 1). Importantly, silencing of the Rap1 guanine exchange factor CalDAG-GEFI inhibited SDF-1α- and phorbol 12-myristate 13-acetate (PMA)–induced adhesion to ICAM-1 while having no effect on adhesion to VCAM-1. Pharmacologic inhibition of Phospholipase C (PLC) blocked Rap1 activation and inhibited cell adhesion and polarization on ICAM-1 and VCAM-1. Protein kinase C (PKC) inhibition led to enhanced levels of active Rap1 concomitantly with increased T-cell binding to ICAM-1, whereas adhesion to VCAM-1 was reduced. Thus, PLC/CalDAG-GEFI regulation of Rap1 is selectively required for chemokine- and PMA-induced LFA-1 activation in human T cells, whereas alternate PLC- and PKC-dependent mechanisms are involved in the regulation of VLA-4.
Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis
Authors: Yang Linda , Wang Lei , Kalfa Theodosia A. , Cancelas Jose A. , Shang Xun , Pushkaran Suvarnamala , Mo Jun , Williams David A. , Zheng Yi
Published: August 2007

The Rho GTPase Cdc42 regulates adhesion, migration, and homing, as well as cell cycle progression, of hematopoietic stem cells, but its role in multilineage blood development remains unclear. We report here that inducible deletion of cdc42 in cdc42-floxed mouse bone marrow by the interferon-responsive, Mx1-Cre–mediated excision led to myeloid and erythroid developmental defects. Cdc42 deletion affected the number of early myeloid progenitors while suppressing erythroid differentiation. Cdc42-deficient mice developed a fatal myeloproliferative disorder manifested by significant leukocytosis with neutrophilia, myeloid hyperproliferation, and myeloid cell infiltration into distal organs. Concurrently, Cdc42 deficiency caused anemia and splenomegaly accompanied with decreased bone marrow erythroid burst-forming units (BFU-Es) and colony-forming units-erythroid (CFU-Es) activities and reduced immature erythroid progenitors, suggesting that Cdc42 deficiency causes a block in the early stage of erythropoiesis. Cdc42 activity is responsive to stimulation by SCF, IL3, SDF-1α, and fibronectin. The increased myelopoiesis and decreased erythropoiesis of the knockout mice are associated with an altered gene transcription program in hematopoietic progenitors, including up-regulation of promyeloid genes such as PU.1, C/EBP1α, and Gfi-1 in the common myeloid progenitors and granulocyte-macrophage progenitors and down-regulation of proerythroid gene such as GATA-2 in the megakaryocyte-erythroid progenitors. Thus, Cdc42 is an essential regulator of the balance between myelopoiesis and erythropoiesis.
Efficacy of different protein descriptors in predicting protein functional families
Authors: Ong Serene AK , Lin Hong Huang , Chen Yu Zong , Li Ze Rong , Cao Zhiwei
Published: August 2007

Background

Sequence-derived structural and physicochemical descriptors have frequently been used in machine learning prediction of protein functional families, thus there is a need to comparatively evaluate the effectiveness of these descriptor-sets by using the same method and parameter optimization algorithm, and to examine whether the combined use of these descriptor-sets help to improve predictive performance. Six individual descriptor-sets and four combination-sets were evaluated in support vector machines (SVM) prediction of six protein functional families.

Results

The performance of these descriptor-sets were ranked by Matthews correlation coefficient (MCC), and categorized into two groups based on their performance. While there is no overwhelmingly favourable choice of descriptor-sets, certain trends were found. The combination-sets tend to give slightly but consistently higher MCC values and thus overall best performance such that three out of four combination-sets show slightly better performance compared to one out of six individual descriptor-sets.

Conclusion

Our study suggests that currently used descriptor-sets are generally useful for classifying proteins and the prediction performance may be enhanced by exploring combinations of descriptors.
Optimization of candidate-gene SNP-genotyping by flexible oligonucleotide microarrays; analyzing variations in immune regulator genes of hay-fever samples
Authors: Pullat Janne , Fleischer Robert , Becker Nikolaus , Beier Markus , Metspalu Andres , Hoheisel Jörg D
Published: August 2007

Background

Genetic variants in immune regulator genes have been associated with numerous diseases, including allergies and cancer. Increasing evidence suggests a substantially elevated disease risk in individuals who carry a combination of disease-relevant single nucleotide polymorphisms (SNPs). For the genotyping of immune regulator genes, such as cytokines, chemokines and transcription factors, an oligonucleotide microarray for the analysis of 99 relevant SNPs was established. Since the microarray design was based on a platform that permits flexible in situ oligonucleotide synthesis, a set of optimally performing probes could be defined by a selection approach that combined computational and experimental aspects.

Results

While the in silico process eliminated 9% of the initial probe set, which had been picked purely on the basis of potential association with disease, the subsequent experimental validation excluded more than twice as many. The performance of the optimized microarray was demonstrated in a pilot study. The genotypes of 19 hay-fever patients (aged 40–44) with high IgE levels against inhalant antigens were compared to the results obtained with 19 age- and sex-matched controls. For several variants, allele-frequency differences of more than 10% were identified.

Conclusion

Based on the ability to improve empirically a chip design, the application of candidate-SNP typing represents a viable approach in the context of molecular epidemiological studies.
Mice Left Out in the Cold: Commentary on the Phenotype of TRPM8-Nulls
Authors: Daniels Richard L , McKemy David D
Published: August 2007

Detection of innocuous temperatures allows an organism to select an appropriate environmental climate, while the ability to recognize noxious temperature extremes warns of impending tissue damage. For temperatures considered cold, the menthol receptor TRPM8 is activated when temperatures drop below ~26°C, thus making it an intriguing candidate as the molecular mediator of cold perception. However, confirmation of this hypothesis in vivo has eluded researchers until recently. Three independent research groups have reported that mice lacking this single gene are severely impaired in their ability to detect cold temperatures. Remarkably, these animals are deficient in many diverse aspects of cold signaling, including cool and noxious cold perception, injury-evoked sensitization to cold, and cooling-induced analgesia. These animals provide a great deal of insight into the molecular signaling pathways that participate in the detection of cold and painful stimuli.
Hand bone loss as an outcome measure in established rheumatoid arthritis: 2-year observational study comparing cortical and total bone loss
Authors: Hoff Mari , Haugeberg Glenn , Kvien Tore K
Published: August 2007

The aim of this 2-year longitudinal observational study was to explore hand bone loss as a disease outcome measure in established rheumatoid arthritis (RA).

A cohort of 215 patients with RA (170 women and 45 men, aged 20–70 years) were recruited from the Oslo RA registry and studied for changes in hand bone mass during a 2-year follow-up. Digital X-ray radiogrammetry (DXR) was used to measure cortical hand bone mineral density (BMD) and metacarpal cortical index, whereas dual-energy X-ray absorptiometry (DXA) was used to assess whole hand BMD, which measures total cortical and trabecular bone. DXA-BMD total hip and spine and informative data for disease and therapy were also collected.

Hand bone loss could be revealed over a 2-year follow-up measured by DXR-BMD (-0.90%, P < 0.01), but not by DXA-BMD (0.00%, P = 0.87). DXA-BMD hand bone loss was only observed in patients with disease duration ≤3 years and not in patients with longer disease duration (-0.96% versus 0.24%, P < 0.01), whereas loss of DXR-BMD was independent of disease duration. Disease activity (measured by the disease activity score including 28 joints) independently predicted loss of DXR-BMD but not changes in the DXA-BMD hand in the multivariate analysis. The change in DXR metacarpal cortical index was highly correlated to DXR-BMD (r = 0.94, P < 0.001).

These data suggest that DXR-BMD may be a more appropriate technique to identify RA-related bone involvement in hands compared with DXA-BMD measurement, but further studies are needed to explore this hypothesis.
Novel human CD4+ T lymphocyte subpopulations defined by CD300a/c molecule expression
Authors: Clark Georgina J , Rao Min , Ju Xinsheng , Hart Derek N J
Published: August 2007

The CD300c (CMRF-35A) and CD300a (CMRF-35H) molecules are leukocyte surface proteins that are part of a larger family of immunoregulatory molecules encoded by a gene complex on human chromosome 17. The CMRF-35 monoclonal antibody binds to an epitope common to both molecules, expressed on most human leukocyte populations, apart from B lymphocytes and a subpopulation of CD4+ and CD8+ T lymphocytes. We describe the CMRF-35pos and CMRF-35− fractions of CD4+ T lymphocytes. The CMRF-35pos fraction can further be divided into CMRF-35++ and CMRF-35+CD4+ T lymphocyte subpopulations. Resting peripheral CD4+ T lymphocytes express CD300a mRNA and very low amounts of CD300c. Activation results in an initial decrease in CD300a gene expression before an increase in both CD300a and CD300c gene expression. The up-regulated expression of these genes was associated with increased CMRF-35 binding to activated T lymphocytes. The CMRF-35− fraction of CD4+ T lymphocytes proliferated to a greater extent than the CMRF-35pos fraction, in response to mitogens or allogeneic antigen. The poor proliferation of the CMRF-35pos CD4+ in response to mitogens was explained by increased apoptosis within this subpopulation. The recall antigen, tetanus toxoid, stimulated the CMRF-35++CD4+CD45RO+ but not the CMRF-35−CD4+CD45RO+ subpopulation. Resting CMRF-35++ CD4+ lymphocytes express low levels of IFN-γ mRNA. Within 18 h following in vitro activation, CMRF-35++ CD4+ lymphocytes express more IFN-γ mRNA and protein compared with the CMRF-35−CD4+ lymphocytes, however, after 24 h, both the CMRF-35+ and CMRF-35−CD4+ T lymphocytes were able to produce IFN-γ. The CMRF-35++CD4+ T lymphocyte population contains the Th1 memory effector cells.
Stimulatory and costimulatory effects of IL-18 directed to different small intestinal CD43 T cell subsets
Authors: Montufar-Solis Dina , Wang Heuy-Ching , Klein John R
Published: August 2007

This study has examined the stimulatory and costimulatory effects of IL-18 on two subsets of murine small intestinal intraepithelial lymphocytes (IELs) defined by the expression of the CD43 S7 glycoform. Data from gene array studies and real-time PCR indicated that S7+ IELs had significantly higher levels of gene expression for the IL-18 receptor and the IL-18R accessory protein than S7− IELs. IL-18 costimulation of IELs in conjunction with CD3-induced activation resulted in significantly greater proliferation than CD3 stimulation alone. In CFSE dilution experiments, IL-18 costimulation favored the S7+ IEL population. IL-18 costimulation did not affect apoptosis of either S7− or S7+ IELs compared with CD3 stimulation alone. Although IL-18 costimulation did not alter the total number of IFN-γ-producing cells relative to CD3 stimulation alone, twice as many S7+ IELs were IFN-γ -secreting cells than S7− IELs in both CD3-stimulated and IL-18-costimulated cultures. Notably, direct IL-18 stimulation in the absence of CD3 activation induced an IFN-γ response that was predominantly directed to the S7+ population, indicating that IL-18 is itself an IFN-γ activational signal for intestinal T cells. In contrast, direct IL-18 stimulation of IELs did not generate TNF-α-producing cells, indicating a differential response in the activation of proinflammatory cytokines following IL-18 exposure. These findings point to distinctly different activational effects of IL-18 on IELs, both with regard to the type of functional responses elicited and with respect to the IEL subsets affected.
Is Proton Beam Therapy Cost Effective in the Treatment of Adenocarcinoma of the Prostate?
Authors: Konski Andre , Speier William , Hanlon Alexandra , Beck J. Robert , Pollack Alan
Published: August 2007

Purpose

New treatments are introduced routinely into clinical practice without rigorous economic analysis. The specific aim of this study was to examine the cost effectiveness of proton beam radiation compared with current state-of-the art therapy in the treatment of patients with prostate cancer.

Materials and Methods

A Markov model was informed with cost, freedom from biochemical failure (FFBF), and utility data obtained from the literature and from patient interviews to compare the cost effectiveness of 91.8 cobalt gray equivalent (CGE) delivered with proton beam versus 81 CGE delivered with intensity-modulated radiation therapy (IMRT). The length of how many years the model was run, patient's age, probability of FFBF after treatment with proton beam therapy and IMRT, utility of patients treated with salvage hormone therapy, and treatment cost were tested in sensitivity analyses.

Results

Analysis at 15 years resulted in an expected mean cost of proton beam therapy and IMRT of $63,511 and $36,808, and $64,989 and $39,355 for a 70-year-old and 60-year-old man respectively, with quality-adjusted survival of 8.54 and 8.12 and 9.91 and 9.45 quality-adjusted life-years (QALY), respectively. The incremental cost effectiveness ratio was calculated to be $63,578/QALY for a 70-year-old man and $55,726/QALY for a 60-year-old man.

Conclusion

Even when based on the unproven assumption that protons will permit a 10-Gy escalation of prostate dose compared with IMRT photons, proton beam therapy is not cost effective for most patients with prostate cancer using the commonly accepted standard of $50,000/QALY. Consideration should be given to limiting the number of proton facilities to allow comprehensive evaluation of this modality.
Disparities in Treatment and Outcome for Renal Cell Cancer Among Older Black and White Patients
Authors: Berndt Sonja I. , Carter H. Ballentine , Schoenberg Mark P. , Newschaffer Craig J.
Published: August 2007

Purpose

Black patients with renal cell cancer have shorter survival compared with their white counterparts, but the causes for this disparity are unclear. To elucidate reasons for this inequality, we examined differences in treatment and survival between black and white patients.

Patients and Methods

A retrospective cohort study was conducted using data from the linked Surveillance, Epidemiology and End Results (SEER) cancer registry and Medicare databases. Participants included 964 black and 10,482 white patients age ≥ 65 years who were enrolled into Medicare and diagnosed with renal cell cancer between 1986 and 1999. Information on surgical treatment was ascertained from both databases, whereas data regarding coexisting illness and survival was obtained from the Medicare database.

Results

The percentage of black patients receiving nephrectomy treatment was significantly lower compared with whites (61.2% v 70.4%; P < .0001). After adjustment for age, sex, median income, cancer stage, tumor size, and comorbidity index, blacks were less likely to undergo nephrectomy treatment compared with whites (risk ratio = 0.93; 95% CI, 0.90 to 0.96). Overall survival was worse for blacks than whites even after adjustment for demographic and cancer prognostic factors (hazard ratio [HR] = 1.16; 95% CI, 1.07 to 1.25); however, additional adjustment for comorbidity index and nephrectomy treatment reduced the disparity substantially (HR = 1.00; 95% CI, 0.93 to 1.09).

Conclusion

This study indicates that the lower survival rate among blacks compared with whites with renal cell cancer can be explained largely by the increased number of comorbid health conditions and the lower rate of surgical treatment among black patients.
A Nomogram Predicting 10-Year Life Expectancy in Candidates for Radical Prostatectomy or Radiotherapy for Prostate Cancer
Authors: Walz Jochen , Gallina Andrea , Saad Fred , Montorsi Francesco , Perrotte Paul , Shariat Shahrokh F. , Jeldres Claudio , Graefen Markus , Bénard Francois , McCormack Michael , Valiquette Luc , Karakiewicz Pierre I.
Published: August 2007

Purpose

Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool.

Patients and Methods

Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram.

Results

Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P < .001), elevated CCI score (P < .001) and treatment type (EBRT v RP, P < .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years.

Conclusion

Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.
Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer
Authors: Kelsen David P. , Winter Katryn A. , Gunderson Leonard L. , Mortimer Joanne , Estes Norman C. , Haller Daniel G. , Ajani Jaffer A. , Kocha Walter , Minsky Bruce D. , Roth Jack A. , Willett Christopher G.
Published: August 2007

Purpose

We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed.

Patients and Methods

The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated.

Results

Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival.

Conclusion

For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.
Assessing Individual Risk for Prostate Cancer
Authors: Nam Robert K. , Toi Ants , Klotz Laurence H. , Trachtenberg John , Jewett Michael A.S. , Appu Sree , Loblaw D. Andrew , Sugar Linda , Narod Steven A. , Kattan Michael W.
Published: August 2007

Purpose

To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC.

Patients and Methods

We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score ≥ 7).

Results

Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio, PSA, and DRE, was 0.74 (95% CI, 0.71 to 0.81) and 0.77 (95% CI, 0.74 to 0.81) for high-grade cancer. This was significantly greater than the AUC that considered using the conventional screening method of PSA and DRE only (0.62; 95% CI, 0.58 to 0.66 for any cancer; 0.69; 95% CI, 0.65 to 0.73 for high-grade cancer). From receiver operating characteristic analysis, risk factors including age, ethnicity, FHPC, symptoms, and free:total PSA ratio contributed significantly more predictive information than PSA and DRE.

Conclusion

In a PC screening program, it is important to consider age, family history of PC, ethnicity, urinary voiding symptoms, and free:total PSA ratio, in addition to PSA and DRE.