bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpersonal Callousness Trajectories Across Adolescence
Authors: Pardini Dustin A. , Loeber Rolf
Published: January 2008

The current study examined the relation between interpersonal callousness trajectories during adolescence (ages 14 to 18) and characteristics of antisocial personality and internalizing problems in young adulthood (age 26), using a community sample of 506 boys. The influence of several parent and peer factors on callousness trajectories during adolescence was also explored. Although the mean interpersonal callousness trajectory for the entire sample was relatively flat, there was substantial individual variability in both the initial status and rate of change of interpersonal callousness over time. Trajectories of interpersonal callousness were associated with higher levels of antisocial personality features in early adulthood but were unrelated to adult internalizing problems. Conduct problems and parent—child communication difficulties were the best predictors of elevated levels of interpersonal callousness throughout adolescence. However, none of the parenting and peer factors examined predicted substantive changes in interpersonal callousness over time.
The Peer Relationships of Youths With Psychopathic Personality Traits
Authors: Muñoz Luna C. , Kerr Margaret , Besic Nejra
Published: January 2008

Because a callous use of others in many short-term relationships is one criterion for diagnosing psychopathy in adults, one would expect adolescents who are high on psychopathic personality traits to have unstable, conflict-ridden peer relationships. Little is known about this, however, or about the peer activities of youths who are high in psychopathic traits. The authors examined relationship quality and delinquency with peers in a community sample of 12- to 15-year-old adolescents who were stably high or stably low on psychopathic traits during 4 years. Peers also provided data on relationship quality. Youths high on psychopathic traits often engaged in antisocial activities with their peers. Although they reported conflict in their peer relationships, their peers did not report low support or high conflict in those relationships. The authors conclude that youths with psychopathic traits have biased perspectives on interactions with close peers, and this might underlie future problems.
Callous—Unemotional Traits and Antisocial Behavior
Authors: Larsson Henrik , Viding Essi , Plomin Robert
Published: January 2008

This study compared early parenting characteristics in children with different levels of callous—unemotional (CU) traits and antisocial behavior (AB). Four groups were formed on the basis of teacher assessments: high CU and low AB (CU+; N = 378), high CU and high AB (AB/CU+; N = 234), low CU and high AB (AB+; N = 210), and controls ( N = 3,608). In addition, genetic and environmental influences on elevated levels of CU traits were specifically investigated in CU+ and AB/CU+ subgroups. Multivariate analysis of variance and DeFries-Fulker extremes analysis yielded three main findings: First, AB/CU+ and AB+ children exhibited higher levels of early negative parenting characteristics than CU+ children and controls. Second, these higher levels of negative parenting characteristics in AB/CU+ and AB+ children were explained by early child effects on parenting. Third, heritability estimates for CU in AB/CU+ and CU+ groups are of similar magnitude.
Stability of Psychopathic Characteristics in Childhood
Authors: Barry Tammy D. , Barry Christopher T. , Deming Annie M. , Lochman John E.
Published: January 2008

The current study is a preliminary longitudinal investigation of the stability of psychopathic characteristics, including social relationships as a moderator, within a group of aggressive children ( N = 80). Data were collected from the children, their parents, teachers, and peers. Results indicated that the psychopathic characteristics (callous—unemotional traits, impulsive conduct problems, and narcissism) were relatively stable across three time points. Social relationship variables (child self-report of social competence, teacher-rated social competence, and peer-rated social preference) were generally correlated with psychopathic characteristics. Self-report of social competence moderated change from Time 1 to Time 2 narcissism based on parent report. Both peer-rated social preference and teacher-rated social competence moderated change from Time 1 to Time 3 impulsive conduct problems. These results provide preliminary support that psychopathic characteristics are generally stable in aggressive children and that social relationships are a potentially valuable point of intervention when children present with these characteristics.
Long-Term Follow-up of Arthroscopic Treatment of Lateral Epicondylitis
Authors: Baker Champ L. , Baker Champ L.
Published: January 2008

Background

In a previously published report of the authors’ arthroscopic technique of operative management of recalcitrant lateral epicondylitis, they demonstrated short-term success with the procedure in their patients.

Hypothesis

Arthroscopic management of patients with lateral epicondylitis can produce clinical improvement and have successful long-term outcomes.

Study Design

Case series; Level of evidence, 4.

Methods

Forty patients (42 elbows) with lateral epicondylitis who had not responded to nonoperative management were treated with arthroscopic resection of pathologic tissue. Thirty of these patients (30 elbows) were located for extended follow-up. At a mean follow-up of 130 months (range, 106–173 months), patients were asked to use a numeric scale to rate their elbow pain from 0 (no pain) to 10 (severe pain). Patients were also asked to rate their elbows according to the functional portion of the Mayo Clinic Elbow Performance Index.

Results

The mean pain score at rest was 0; with activities of daily living, 1.0; and with work or sports, 1.9. The mean functional score was 11.7 out of a possible 12 points. No patient required further surgery or repeat injections after surgery. One patient continued to wear a counterforce brace with heavy activities. Twenty-three patients (77%) stated they were “much better,” 6 patients (20%) stated they were “better,” and 1 patient (3%) stated he was the same. Twenty-six patients (87%) were satisfied, and 28 patients (93%) stated they would have the surgery again if needed.

Conclusion

Arthroscopic removal of pathologic tendinosis tissue is a reliable treatment for recalcitrant lateral epicondylitis. The early high rate of success in patients was maintained at long-term follow-up.
Exercise-Induced Scalenus Syndrome
Authors: Baltopoulos Panagiotis , Tsintzos Charalampos , Prionas George , Tsironi Maria
Published: January 2008

Background

Thoracic outlet syndrome is described as a group of distinct disorders producing signs and symptoms attributed to compression of nerves and blood vessels in the thoracic outlet region.

Purpose

To describe the exercise-induced scalenus anticus syndrome attributed to the anterior scalenus hypertrophy as a thoracic outlet syndrome underlying mechanism and to give recommendations for a safe and effective surgical treatment.

Study Design

Case series; Level of evidence, 4.

Methods

Twelve young professional athletes admitted for thoracic outlet syndrome (8 cases of neurologic thoracic outlet syndrome, 4 cases of mixed neurologic and vascular thoracic outlet syndrome) who reported numbness, tingling, early fatigue, muscle weakness, and pain were enrolled in the study. Scalenus hypertrophy was suspected to be the causative factor. Scalenectomy was performed in all cases.

Results

All patients had moderate to severe hypertrophy of the anterior scalenus muscle. Scalenectomy was performed, and there were no intraoperative or postoperative complications. Full activity was quickly achieved, and no recurrence of symptoms was documented.

Conclusion

Surgical intervention for scalenus anticus syndrome can allow an athlete to return to full activity and improve quality of life. Surgical intervention seems to be the treatment of choice in terms of restoring quality of life and physical activity.
An Orchestration of Electronic Surveillance
Authors: Botello Nelson Arteaga
Published: January 2008

Electronic surveillance has significantly expanded in Mexico over the past 10 years. This represents a change in the form of social organization, where electronic surveillance presents two faces: care and control. On the one hand, surveillance is used to reduce risks; but on the other, for administration of the population. This article examines, in the case of an urban municipality in Mexico, how local authorities and members of society define the problem of violence and delinquency, and how this definition constitutes an orchestration of the relationship of different powers in determining the organization of electronic surveillance, and institutionalizes a certain logic of cultural and social exclusion.
Video Surveillance and Everyday Life
Authors: Zurawski Nils
Published: January 2008

Closed-circuit television (CCTV) has become the icon of surveillance, both in popular culture as well as in actual politics. Its prosthetic forms penetrate the public sphere and spaces. This article discusses results from a study for a more differentiated view on CCTV in everyday life. Interested in the knowledge and assessments of CCTV, the author conducted a two-layered study in Hamburg. Combining a qualitative study, to explore the field and formulate hypotheses, and a quantitative survey, to test some of these assumptions, provided a rich set of data for the analysis of CCTV in everyday life. Mapping methods were used to gather material on issues such as in/security, spatial mobility, and social stereotypes. The analysis shows how spatial perceptions and socio-spatial imaginations influence the assessments of CCTV in the different research areas. With these results, the author discusses aspects of surveillance measures such as social sorting and its spatial dependencies.
Public Perceptions of CCTV in Residential Areas
Authors: Gill Martin , Bryan Jane , Allen Jenna
Published: January 2008

Closed circuit television (CCTV) is commonplace in the United Kingdom and increasingly across the world. It is commonly found in town and city centers, shopping malls, car parks, police stations, and various workplaces. Most of the research that has been conducted so far has concluded that the public is generally supportive. However, the emergence of CCTV in residential areas has been much less commented on. This article reports on a study of residents' views of CCTV, and the findings suggest that although the public are generally positive, it is less so after having experience with cameras. Reduced experience of victimization positively affected residents' perceptions of safety, much more than the introduction of CCTV.
Motivated Information Processing in Group Judgment and Decision Making
Authors: De Dreu Carsten K. W. , Nijstad Bernard A. , van Knippenberg Daan
Published: January 2008

This article expands the view of groups as information processors into a motivated information processing in groups (MIP-G) model by emphasizing, first, the mixed-motive structure of many group tasks and, second, the idea that individuals engage in more or less deliberate information search and processing. The MIP-G model postulates that social motivation drives the kind of information group members attend to, encode, and retrieve and that epistemic motivation drives the degree to which new information is sought and attended to, encoded, and retrieved. Social motivation and epistemic motivation are expected to influence, alone and in combination, generating problem solutions, disseminating information, and negotiating joint decisions. The MIP-G model integrates the influence of many individual and situational differences and combines insight on human thinking with group-level interaction process and decision making.
Television's New Engines
Authors: Keane Michael , Moran Albert
Published: January 2008

Internationalization is a key to the success of television formats. To understand format trade it is necessary to draw out distinctions between formats and genre. Engines— innovations in programming engineered by format devisors—allow formats to regenerate and hybridize across genres. The core principle of formats, however, is the practice of franchising. Causal relations can be established between formats, engines, and the tradability of television culture. The article shows how formats have impacted platforms, markets, labor, audiences, and distribution of TV content.
Racialized Documentary Reception of Ken Burns' Jazz
Authors: Amaya Hector
Published: January 2008

This essay investigates the critical reception of the documentary Jazz: The Story of America's Music , directed by Ken Burns and shown on PBS in 2001. Although studies on reception are now common regarding television, the reception of documentary is an underexplored area. Typically, documentary theory has placed an emphasis on truth and epistemology; only recently have there been inquiries on audiences. Expanding on the latter contributions, the author looks at critics' reception of the documentary and the way identity and truth related to racialized interpretations of the text. The author's analysis suggests that these viewers responded strongly to the documentary's racial arguments. However, the responses were not determined by the viewer's race. To reconcile this finding with an idea of race as determinant of reception, the author proposes that it is not the viewer's racial identity but the function of race in the viewer's life that determines modes of reception.
Basal and angiopoietin-1–mediated endothelial permeability is regulated by sphingosine kinase-1
Authors: Li Xiaochun , Stankovic Milena , Bonder Claudine S. , Hahn Christopher N. , Parsons Michelle , Pitson Stuart M. , Xia Pu , Proia Richard L. , Vadas Mathew A. , Gamble Jennifer R.
Published: January 2008

Endothelial cells (ECs) regulate the barrier function of blood vessels. Here we show that basal and angiopoietin-1 (Ang-1)–regulated control of EC permeability is mediated by 2 different functional states of sphingosine kinase-1 (SK-1). Mice depleted of SK-1 have increased vascular leakiness, whereas mice transgenic for SK-1 in ECs show attenuation of leakiness. Furthermore, Ang-1 rapidly and transiently stimulates SK-1 activity and phosphorylation, and induces an increase in intracellular sphingosine-1-phosphate (S1P) concentration. Overexpression of SK-1 resulted in inhibition of permeability similar to that seen for Ang-1, whereas knockdown of SK-1 by small interfering RNA blocked Ang-1-mediated inhibition of permeability. Transfection with SKS225A, a nonphosphorylatable mutant of SK-1, inhibited basal leakiness, and both SKS225A and a dominant-negative SK-1 mutant removed the capacity of Ang-1 to inhibit permeability. These effects were independent of extracellular S1P as knockdown or inhibition of S1P1, S1P2, or S1P3, did not affect the Ang-1 response. Thus, SK-1 levels in ECs powerfully regulate basal permeability in vitro and in vivo. In addition, the Ang-1–induced inhibition of leakiness is mediated through activation of SK-1, defining a new signaling pathway in the Ang-1 regulation of permeability.
The TNF (−308A) polymorphism is associated with microchimerism in transfused trauma patients
Authors: Gill Ryan M. , Lee Tzong-Hae , Utter Garth H. , Reed William F. , Wen Li , Chafets Dan , Busch Michael P.
Published: January 2008

Microchimerism (MC), defined as the persistence of allogeneic cells at low concentrations, is well documented in transfused trauma patients. We hypothesized that genetic polymorphisms linked to cytokine production could contribute to trauma-induced immune modulation and development of microchimerism after transfusion of trauma patients. We used high-throughput SYBR-green-based genotyping of single nucleotide polymorphisms (SNPs) to characterize 59 transfused trauma patients, with MC (n = 30) and without MC (n = 29), for 4 functionally significant SNPs: TNF (−308), IL 10 (−1082), IFNG (+874), and TGFB1 (+915). We then compared likelihood for development of MC and the magnitude of immune suppression among subjects with and without these selected immune response SNPs. We identified a significant association between TNF (−308A) SNP and both development of MC and diminished immune responsiveness. Hence predisposing genetic factors may explain, in part, why only a subset of trauma patients develops transfusion-associated microchimerism.
Systematic identification of stem-loop containing sequence families in bacterial genomes
Authors: Cozzuto Luca , Petrillo Mauro , Silvestro Giustina , Di Nocera Pier Paolo , Paolella Giovanni
Published: January 2008

Background

Analysis of non-coding sequences in several bacterial genomes brought to the identification of families of repeated sequences, able to fold as secondary structures. These sequences have often been claimed to be transcribed and fulfill a functional role. A previous systematic analysis of a representative set of 40 bacterial genomes produced a large collection of sequences, potentially able to fold as stem-loop structures (SLS). Computational analysis of these sequences was carried out by searching for families of repetitive nucleic acid elements sharing a common secondary structure.

Results

The initial clustering procedure identified clusters of similar sequences in 29 genomes, corresponding to about 1% of the whole population. Sequences selected in this way have a substantially higher aptitude to fold into a stable secondary structure than the initial set. Removal of redundancies and regrouping of the selected sequences resulted in a final set of 92 families, defined by HMM analysis. 25 of them include all well-known SLS containing repeats and others reported in literature, but not analyzed in detail. The remaining 67 families have not been previously described. Two thirds of the families share a common predicted secondary structure and are located within intergenic regions.

Conclusion

Systematic analysis of 40 bacterial genomes revealed a large number of repeated sequence families, including known and novel ones. Their predicted structure and genomic location suggest that, even in compact bacterial genomes, a relatively large fraction of the genome consists of non-protein-coding sequences, possibly functioning at the RNA level.
Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway
Authors: Jiang Qun , Wei Haiming , Tian Zhigang
Published: January 2008

Background

Toll-like receptor 3 (TLR3) is a critical component of the innate immune response to dsRNA viruses, which was considered to be mainly expressed in immune cells and some endothelial cells. In this study, we investigated the expression and proapoptotic activity of TLR3 in human and murine tumor cell lines.

Methods

RT-PCR and FACS analysis were used to detect expression of TLR3 in various human and murine tumor cell lines. All tumor cell lines were cultured with poly I:C, CHX, or both for 12 h, 24 h, 72 h, and then the cell viability was analyzed with CellTiter 96® AQueous One Solution, the apoptosis was measured by FACS with Annexin V and PI staining. Production of Type I IFN in poly I:C/CHX mediated apoptosis were detected through western blotting. TLR3 antibodies and IFN-β antibodies were used in Blockade and Neutralization Assay.

Results

We show that TLR3 are widely expressed on human and murine tumor cell lines, and activation of TLR3 signaling in cancerous cells by poly I:C made Hela cells (human cervical cancer) and MCA38 cells (murine colon cancer) become dose-dependently sensitive to protein synthesis inhibitor cycloheximide (CHX)-induced apoptosis. Blockade of TLR3 recognition with anti-TLR3 antibody greatly attenuated the proapoptotic effects of poly I:C on tumor cells cultured with CHX. IFN-β production was induced after poly I:C/CHX treatment and neutralization of IFN-β slightly reduced poly I:C/CHX -induced apoptosis.

Conclusion

Our study demonstrated the proapoptotic activity of TLR3 expressed by various tumor cells, which may open a new range of clinical applications for TLR3 agonists as an adjuvant of certain cancer chemotherapy.
Association between the PPP3CC gene, coding for the calcineurin gamma catalytic subunit, and bipolar disorder
Authors: Mathieu Flavie , Miot Stéphanie , Etain Bruno , El Khoury Marie-Anne , Chevalier Fabien , Bellivier Frank , Leboyer Marion , Giros Bruno , Tzavara Eleni T
Published: January 2008

Background

Calcineurin is a neuron-enriched phosphatase that regulates synaptic plasticity and neuronal adaptation. Activation of calcineurin, overall, antagonizes the effects of the cyclic AMP activated protein/kinase A. Thus, kinase/phosphatase dynamic balance seems to be critical for transition to long-term cellular responses in neurons, and disruption of this equilibrium should induce behavioral impairments in animal models. Genetic animal models, as well as post-mortem studies in humans have implicated calcineurin dependent calcium and cyclic AMP regulated phosphorylation/dephosphorylation in both affective responses and psychosis. Recently, genetic association between schizophrenia and genetic variation of the human calcineurin A gamma subunit gene (PPP3CC) has been reported.

Methods

Based on the assumption of the common underlying genetic factor in schizophrenia and bipolar affective disorder (BPAD), we performed association analysis of CC33 and CCS3 polymorphisms of the PPP3CC gene reported to be associated with schizophrenia in a French sample of 115 BPAD patients and 97 healthy controls.

Results

Carrying 'CT' or 'TT' genotypes of the PPP3CC-CC33 polymorphism increased risk to develop BPAD comparing to carry 'CC' genotype (OR = 1.8 [1.01–3.0]; p = 0.05). For the PPP3CC-CCS3 polymorphism, 'AG' or 'GG' carriers have an increased risk to develop BPAD than 'AA' carriers (OR = 2.8 [1.5–5.2]). The CC33 and CCS3 polymorphisms were observed in significant linkage disequilibrium (D' = 0.91, r2 = 0.72). Haplotype frequencies were significantly different in BPAD patients than in controls (p = 0.03), with a significant over-transmission of the 'TG' haplotype in BPAD patients (p = 0.001).

Conclusion:

We suggest that the PPP3CC gene might be a susceptibility gene for BPAD, in accordance with current neurobiological hypotheses that implicate dysregulation of signal-transduction pathways, such as those regulated by calcineurin, in the etiology of affective disorders.
Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes
Authors: Moore R Andrew , Derry Sheena , McQuay Henry J
Published: January 2008

Introduction

Faecal blood loss has been measured using autologous erythrocytes labelled with radioactive chromium for several decades, using generally similar methods. We conducted a systematic review of studies employing this technology to determine the degree of blood loss associated with use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 selective inhibitors (coxibs).

Methods

A systematic search of PubMed and the Cochrane Library (to December 2006) was conducted to identify randomized trials in which treatment with aspirin, NSAIDs, or coxibs was continued for at least 7 days, and with at least 7 days of washout for crossover trials. Rates of faecal blood loss associated with these agents were determined in the randomized trials identified. Comparators were placebo, active, or no treatment. Outcomes of interest were mean daily faecal blood loss, and the number or proportion of individuals recording faecal blood above 5 ml/day and above 10 ml/day.

Results

Forty-five reports of 47 trials were included, including 1,162 individuals, mostly healthy volunteers and predominantly young men. Only 136 patients (as opposed to healthy volunteers; 12%) were included, and these were mostly older people with an arthritic condition. Most NSAIDs and low-dose (325 mg) aspirin resulted in a small average increase in faecal blood loss of 1 to 2 ml/day from about 0.5 ml/day at baseline. Aspirin at full anti-inflammatory doses resulted in much higher average levels of blood loss of about 5 ml/day. Some individuals lost much more blood than average, at least for some of the time, with 5% of those taking NSAIDs having daily blood loss of 5 ml or more and 1% having daily blood loss of 10 ml or more; rates of daily blood loss of 5 ml/day or 10 ml/day were 31% and 10%, respectively, for aspirin at daily doses of 1,800 mg or greater.

Conclusion

At baseline, or with placebo, faecal blood loss is measured at 1 ml/day or below. With low-dose aspirin and some NSAIDs, average values may be two to four times this, and anti-inflammatory doses of aspirin result in much higher average losses. A small proportion of individuals respond to aspirin or NSAIDs with much higher faecal blood loss of above 5 ml/day or 10 ml/day. There are significant limitations regarding the quality and validity of reporting of these studies, such as limited size and inclusion of inappropriate participants. The potential for blood loss and consequent anaemia requires more study.
Relationship of Breast Magnetic Resonance Imaging to Outcome After Breast-Conservation Treatment With Radiation for Women With Early-Stage Invasive Breast Carcinoma or Ductal Carcinoma in Situ
Authors: Solin Lawrence J. , Orel Susan G. , Hwang Wei-Ting , Harris Eleanor E. , Schnall Mitchell D.
Published: January 2008

Purpose

To determine the relationship of breast magnetic resonance imaging (MRI) to outcome after breast-conservation treatment (BCT) with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ.

Patients and Methods

A total of 756 women with early stage invasive breast carcinoma or ductal carcinoma in situ underwent BCT including definitive breast irradiation during 1992 to 2001. At the time of initial diagnosis and evaluation, routine breast imaging included conventional mammography. Of the 756 women, 215 women (28%) had also undergone a breast MRI study, and 541 women (72%) had not undergone a breast MRI study. The median follow-up after treatment was 4.6 years (range, 0.1 to 13.5 years).

Results

For the women with a breast MRI study compared with the women without a breast MRI study, there were no differences in the 8-year rates of any local failure (3% v 4%, respectively; P = .51) or local-only first failure (3% v 4%, respectively; P = .32). There were also no differences between the two groups for the 8-year rates of overall survival (86% v 87%, respectively; P = .51), cause-specific survival (94% v 95%, respectively; P = .63), freedom from distant metastases (89% v 92%, respectively; P = .16), or contralateral breast cancer (6% v 6%, respectively; P = .39).

Conclusion

The use of a breast MRI study at the time of initial diagnosis and evaluation was not associated with an improvement in outcome after BCT with radiation.
Prevention of Coagulase-Negative Staphylococcal Central Venous Catheter–Related Infection Using Urokinase Rinses: A Randomized Double-Blind Controlled Trial in Patients With Hematologic Malignancies
Authors: van Rooden Cornelis J. , Schippers Emile F. , Guiot Henri F.L. , Barge Renée M. , Hovens Marcel M.C. , van der Meer Felix J.M. , Rosendaal Frits R. , Huisman Menno V.
Published: January 2008

Purpose

Fibrin deposition at the intraluminal surface of the indwelling part of the central venous catheter (CVC) surface increases the risk of CVC-related coagulase-negative staphylococci (CoNS) infection. Therefore, repetitive enzymatic dissolution of fibrin by urokinase might reduce the risk of CVC-related infection. We undertook this study to investigate whether three times weekly urokinase rinsing of CVC reduces the incidence or severity of CVC-related infections by CoNS in patients undergoing intensive cytotoxic treatment for hematologic malignancies.

Patients and Methods

In a double-blind setting, all consecutive patients with a CVC were randomly allocated to receive either urokinase rinses (5 mL of 5,000 U/mL) or placebo (saline), both three times weekly.

Results

The percentage of patients with at least one positive culture with CoNS was lower in patients receiving urokinase compared with patients receiving placebo (26% v 42%, respectively; relative risk [RR] = 0.61; 95% CI, 0.39 to 0.94). Major CVC-related CoNS infection occurred less frequently in patients receiving urokinase versus placebo (1.2% v 14.1%, respectively; RR = 0.09; 95% CI, 0.01 to 0.50). Secondary complications, including CVC-related thrombosis, were observed less frequently in the urokinase group compared with the placebo group (1.3% v 9.0%, respectively; RR = 0.14; 95% CI, 0.02 to 0.82). No severe bleeding complications attributable to urokinase were observed.

Conclusion

Three times weekly urokinase rinsing reduces the incidence of CVC-related CoNS infection in patients treated with intensive cytotoxic therapy for hematologic malignancies, with acceptable safety.
Phase I Trial and Pharmacokinetic Study of Bevacizumab in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study
Authors: Bender Julia L. Glade , Adamson Peter C. , Reid Joel M. , Xu Lu , Baruchel Sylvain , Shaked Yuval , Kerbel Robert S. , Cooney-Qualter Erin M. , Stempak Diana , Chen Helen X. , Nelson Marvin D. , Krailo Mark D. , Ingle Ashish M. , Blaney Susan M. , Kandel Jessica J. , Yamashiro Darrell J.
Published: January 2008

Purpose

We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)–neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer.

Patients and Methods

BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors.

Results

Twenty-one patients enrolled, 20 (median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered (median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg (range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data.

Conclusion

BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned.
Phase I Trial of the Novel Mammalian Target of Rapamycin Inhibitor Deforolimus (AP23573; MK-8669) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients With Advanced Malignancies
Authors: Mita Monica M. , Mita Alain C. , Chu Quincy S. , Rowinsky Eric K. , Fetterly Gerald J. , Goldston Michelle , Patnaik Amita , Mathews Lesley , Ricart Alejandro D. , Mays Theresa , Knowles Heather , Rivera Victor M. , Kreisberg Jeff , Bedrosian Camille L. , Tolcher Anthony W.
Published: January 2008

Purpose

This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies.

Patients and Methods

Patients were treated using an accelerated titration design with sequential escalating flat doses of deforolimus administered as a 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QD×5) in a 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, and tumor response assessments were performed.

Results

Thirty-two patients received at least one dose of deforolimus (3 to 28 mg/d). Three dose-limiting toxicity events of grade 3 mouth sores were reported. The maximum-tolerated dose (MTD) was 18.75 mg/d. Common treatment-related adverse events included reversible mouth sores and rash. Whole-blood clearance increased with dose. Pharmacodynamic analyses demonstrated mammalian target of rapamycin inhibition at all dose levels. Four patients (one each with non–small-cell lung cancer, mixed müllerian tumor [carcinosarcoma], renal cell carcinoma, and Ewing sarcoma) experienced confirmed partial responses, and three additional patients had minor tumor regressions.

Conclusion

The MTD of this phase I trial using an accelerated titration design was determined to be 18.75 mg/d. Deforolimus was well tolerated and showed encouraging antitumor activity across a broad range of malignancies when administered intravenously on the QD×5 schedule. On the basis of these overall results, a dose of 12.5 mg/d is being evaluated in phase II trials.
Initial Patient Characteristics Can Predict Pattern and Risk of Relapse in Localized Rhabdomyosarcoma
Authors: Dantonello Tobias M. , Int-Veen Christoph , Winkler Peter , Leuschner Ivo , Schuck Andreas , Schmidt Bernhard F. , Lochbuehler Helmut , Kirsch Sylvia , Hallmen Erika , Veit-Friedrich Iris , Bielack Stefan S. , Niggli Felix , Kazanowska Bernarda , Ladenstein Ruth , Wiebe Thomas , Klingebiel Thomas , Treuner Joern , Koscielniak Ewa
Published: January 2008

Purpose

Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor-directed surveillance program for patients with localized rhabdomyosarcoma (RMS).

Patients and Methods

One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 (median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed.

Results

Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis (range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size.

Conclusion

Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor-directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor-directed guidance for detection of recurrent disease in localized RMS.
Disease Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non–Small-Cell Lung Cancer: Results From Southwest Oncology Group Randomized Trials
Authors: Lara Primo N. , Redman Mary W. , Kelly Karen , Edelman Martin J. , Williamson Stephen K. , Crowley John J. , Gandara David R.
Published: January 2008

Purpose

Tumor shrinkage categorized as complete response (CR) or partial response (PR) is a fundamental efficacy measure for new cancer treatments and often considered a surrogate for overall survival. However, for any given treatment, many more patients typically achieve stable disease (SD) or have progressive disease (PD) than achieve response. We hypothesized that PD (or its converse, disease control rate [DCR], consisting of CR, PR, SD) is a stronger predictor of survival than response alone in advanced non–small-cell lung cancer (NSCLC), and that this determination might be assessable early on during therapy.

Patients and Methods

Data from 984 NSCLC patients entered onto three randomized Southwest Oncology Group trials of platinum-based chemotherapy were pooled and subjected to Landmark survival analysis. Patients were categorized according to proportions alive at weeks 8, 14, and 20 after registration, as well as response status. Elements were fitted into a Cox proportional hazards model.

Results

Tumor response (CR, PR) was seen in 260 patients (27%). Median time to response, time to progression, and survival time were 2.0, 4.3 and 8.9 months, respectively. Median survival times among patients with CR/PR, SD, or PD were 13.5, 8.4, and 3.1 months, respectively. Of 892 patients alive at week 8, DCR was 62%. Although CR/PR at week 8 was associated with longer survival (hazard ratio [HR] = 0.61; P < .001), DCR was superior in predicting survival (HR = 0.45; P < .0001).

Conclusion

DCR at week 8 is a more powerful predictor of subsequent survival than is the traditional tumor response rate in advanced NSCLC and provides an early assessment of subsequent outcome.
Cardiomyopathy in Children With Down Syndrome Treated for Acute Myeloid Leukemia: A Report From the Children's Oncology Group Study POG 9421
Authors: O'Brien Maureen M. , Taub Jeffrey W. , Chang Myron N. , Massey Gita V. , Stine Kimo C. , Raimondi Susana C. , Becton David , Ravindranath Yaddanapudi , Dahl Gary V.
Published: January 2008

Purpose

To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421.

Patients and Methods

Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m2 and mitoxantrone 80 mg/m2. Outcomes and toxicity were evaluated prospectively and were compared with the non-DS–AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events.

Results

In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS–French-American-British (FAB) M7 (91.7%) and non-DS–non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS–M7 (36.3%) or the non-DS–non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure.

Conclusion

The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.
Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer
Authors: Kaufman Elizabeth L. , Jacobson Judith S. , Hershman Dawn L. , Desai Manisha , Neugut Alfred I.
Published: January 2008

Purpose

Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk.

Methods

We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC ≥ 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC.

Results

Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC.

Conclusion

PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.
Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy
Authors: Kawaguchi Hidetoshi , El-Naggar Adel K. , Papadimitrakopoulou Vali , Ren Hening , Fan You-Hong , Feng Lei , Lee J. Jack , Kim Edward , Hong Waun Ki , Lippman Scott M. , Mao Li
Published: January 2008

Purpose

Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL.

Patients and Methods

Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed.

Results

Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information.

Conclusion

Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.
Anti-Apoptosis Mechanisms in Malignant Gliomas
Authors: Ziegler David S. , Kung Andrew L. , Kieran Mark W.
Published: January 2008

Malignant gliomas are characterized by an intrinsic resistance to apoptosis. Increasing evidence suggests that this is a fundamental mechanism by which gliomas evade elimination when treated with both conventional and targeted therapies. In this review, we describe the multiple anti-apoptotic signals that have been demonstrated to be active in malignant gliomas. We describe the preclinical evidence that suggests that targeting those signaling anomalies can increase tumor responsiveness and enhance the elimination of gliomas in preclinical models. We discuss recent advances in translating pro-apoptotic compounds to clinical trial, and the potential for implementing agents that target the apoptotic pathway as a strategy for improving the outcomes for patients with high-grade gliomas.
Individualized Prediction of Colon Cancer Recurrence Using a Nomogram
Authors: Weiser Martin R. , Landmann Ron G. , Kattan Michael W. , Gonen Mithat , Shia Jinru , Chou Joanne , Paty Philip B. , Guillem José G. , Temple Larissa K. , Schrag Deborah , Saltz Leonard B. , Wong W. Douglas
Published: January 2008

Purpose

Estimates of recurrence after curative colon cancer surgery are integral to patient care, forming the basis of cancer staging and treatment planning. The categoric staging system of the American Joint Committee on Cancer (AJCC) is commonly used to convey risk by grouping patients based on anatomic elements. Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence.

Methods

An institutional database of 1,320 patients with nonmetastatic colon cancer was used to develop a nomogram to estimate recurrence after curative surgery. Prognostic factors were assessed with multivariable analysis using Cox regression, whereas nonlinear continuous variables were modeled with cubic splines. The model was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve.

Results

The colon cancer recurrence nomogram predicted relapse with a concordance index of 0.77, improving on the stratification provided by either the AJCC fifth or sixth staging scheme. Factors in the model included patient age, tumor location, preoperative carcinoembryonic antigen, T stage, numbers of positive and negative lymph nodes, lymphovascular invasion, perineural invasion, and use of postoperative chemotherapy.

Conclusion

Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.