bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Repair of the Lacertus Fibrosus on Distal Biceps Tendon Repairs
Authors: Landa Joshua , Bhandari Sachin , Strauss Eric J. , Walker Peter S. , Meislin Robert J.
Published: November 2008

Background

To date, repair of the lacertus in distal biceps tendon ruptures, recommended by some, has not been evaluated. The goal of these biomechanical experiments was to evaluate the degree to which its repair increases the strength of a distal biceps tendon repair.

Hypothesis

An intact or repaired lacertus fibrosus will increase the strength of a distal biceps tendon repair.

Study Design

Controlled laboratory study.

Methods

Four matched pairs of fresh-frozen human cadaveric upper extremities were prepared by isolating the lacertus fibrosus and the distal biceps tendon. The extremity was placed in a custom-built rig with the distal biceps brachii clamped and affixed to a stepper motor assembly. The distal biceps tendon was sharply removed directly from the radial tuberosity and repaired through a bony tunnel in all specimens. One side of each pair was randomized to also receive repair of the lacertus. The specimens were pulled at a constant rate until failure.

Results

The mean failure strength, defined as maximal strength to 15 mm of displacement, was higher in specimens with a repaired lacertus (250.2 N vs 158.2 N; P = .012), as was mean maximum strength (256.8 N v. 164.5 N; P = .0058). Mean stiffness was not significantly different (16.36 N/mm vs 13.8 N/mm; P = .58). All specimens failed due to fracture at the bony bridge.

Conclusion

Repair of the lacertus strengthened distal biceps tendon repair in a controlled laboratory setting.

Clinical Relevance

Repair of the lacertus fibrosus as an adjunct to distal biceps tendon repair strengthens the repair in the laboratory setting. Clinical testing is needed to verify that this increased strength improves clinical results. Surgeons should be cautioned to protect the underlying neurovascular structures during repair of the lacertus fibrosus and to avoid an overly tight repair.
Isolated Tears of the Anterior Cruciate Ligament
Authors: Taylor Dean C. , Posner Matthew , Curl Walton W. , Feagin John A.
Published: November 2008

Background

Over 30 years ago, Feagin and Curl reported on the diagnosis and treatment of “isolated” injuries of the anterior cruciate ligament (ACL). The purpose of this study was to evaluate the long-term results of the patients initially diagnosed with tears of the ACL, with special emphasis on those treated with primary repair.

Hypothesis

Long-term results are unsatisfactory for open evaluation and treatment of ACL injuries with or without primary repair.

Study Design

Case series; Level of evidence, 4.

Methods

Follow-up was available on 34 of the original 57 patients (60%) who had ACL tears on evaluation by arthrotomy. The average age at the index procedure was 20 years, and average follow-up was 32 (range, 29-36) years. Twenty-five of the 26 complete ACL tears were treated with primary repair. None of the 8 partial tears was repaired. Evaluations included the subjective and symptom ratings of the International Knee Documentation Committee (IKDC) evaluation form, Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner activity scale, and SANE rating.

Results

For the IKDC subjective score, 18 of 34 patients rated their knees as normal or nearly normal. The Lysholm scores averaged 70.1 (range, 20-100). The average SANE rating at 5 years was 74.8 (range, 49-110), and the current SANE rating averaged 68.9 (range, 10-100). The overall KOOS rating averaged 68.6 (range, 26.4-100). The Tegner activity score was 3.7. There was little difference between patients with unrepaired partial tears and those who had primary repairs.

Conclusion

At more than 30-year follow-up, patients have decreased activity levels and an equal mix of acceptable and unacceptable outcomes. We were unable to identify any predictive factors that correlated with the results; however, subsequent meniscal surgery did correlate with poor results. The results at greater than 30 years reinforce the 5-year results that showed unsatisfactory results after the open evaluation and treatment of ACL injuries with or without repair.
From the Inside
Authors: Applegate Brandon K. , Smith Hayden P. , Sitren Alicia H. , Fariello Springer Nicolette
Published: November 2008

Beyond considerations of relative punitiveness, very little is known about how offenders understand the experience of serving a probation sentence. The current study surveyed offenders currently on probation to assess the extent to which they believed their sentence was rehabilitative, incapacitative, deserved, and a deterrent to future offending. Perceptions that probation served no purpose and that it represented a game of manipulation and impression management were also investigated. The results showed that most probationers believed that their sentence was a deterrent, and it was rehabilitative and deserved. They also felt that probation served multiple purposes, and a minority of respondents perceived that there was no point to being on probation. The implications of these findings are discussed.
Generating Usable Knowledge
Authors: Chafouleas Sandra M. , Riley-Tillman T. Chris , Briesch Amy M. , Chanese Julie A.M.
Published: November 2008

In this study, a self-report measure of intervention usage, the Usage Rating Profile for Interventions (URP-I) is developed and empirically examined with regard to factor structure and internal consistency. Results supported that intervention usage is associated with at least 4 different constructs, and that a measure consisting of 25 items may provide a reliable index of the 4 factors. The 4 factors identified included Acceptability, Knowledge, Feasibility, and Integrity. Findings extend and integrate existing work-related items to acceptability research aimed at predicting usage. Implications, limitations, and future directions are discussed.
Nutrition Considerations in Traumatic Brain Injury
Authors: Cook Aaron M. , Peppard Amy , Magnuson Barbara
Published: November 2008

The provision of adequate nutrition support for patients with traumatic brain injury (TBI) has been a clinical challenge for decades. The primary and secondary injuries create unique metabolic derangements along with accompanying issues such as optimal timing and route of nutrition, appropriate fluid and electrolytes, drug administration, rehabilitation, and dysphagia. Enteral nutrition is clearly established as the preferential route of nutrition support for this population vs parenteral nutrition. There appears to be a consensus on early initiation of enteral nutrition, but less definitive are recommendations on advancement timing and formula components. Nutrition therapies should include exact fluid resuscitation goals specific for TBI and strict electrolyte monitoring to avoid extreme fluid, electrolyte, or glucose shifts that could be detrimental to the patient. While the critical care patient often tolerates small bowel feeding, the long‐term rehabilitation patient should transition to and tolerate gastric feeding. Drug‐nutrient and adverse drug reactions such as diarrhea should be routinely evaluated in patients receiving enteral nutrition. Monitoring for dysphagia is critical to avoid the costly negative aspects associated with aspiration and to capitalize on quality of life and appropriate oral nutrition. Emphasizing the priority of early nutrition support within a multi‐disciplinary team may be the critical key for successful provision and tolerance of nutrition support in the TBI population.
The Gluten‐Free, Casein‐Free Diet in Autism: An Overview With Clinical Implications
Authors: Elder Jennifer Harrison
Published: November 2008

The prevalence of classic autism and autism spectrum disorder (ASD) appears to be on the rise, and to date, there remains no clear etiology or cure. Out of desperation, many families are turning to new therapies and interventions discovered through various media sources and anecdotal reports from other parents. Unfortunately, many of these newer, well‐publicized interventions have little empirical support. One of the most popular yet currently scientifically unproven interventions for ASD is the gluten‐free, casein‐free (GFCF) diet. Clinicians working with families of individuals with ASD are often asked for advice and find themselves unable to offer the most up‐to‐date and scientifically credible information. This article provides an overview of ASD and the GFCF diet, a summary and critique of current research findings, recommendations for future research, and practical advice for families to use in deciding if a trial of the GFCF diet is in the best interest of their child and family.
Implementation of a Multidisciplinary Team That Includes a Registered Dietitian in a Neonatal Intensive Care Unit Improved Nutrition Outcomes
Authors: Sneve Jennifer , Kattelmann Kendra , Ren Cuirong , Stevens Dennis C.
Published: November 2008

This study determined whether nutrition outcomes of neonates who were receiving neonatal intensive care were improved with the implementation of a fully functioning multidisciplinary team that included a registered dietitian. A medical record review was conducted of neonates with birth weights of 1500 g or less who were cared for in Sanford Children's Hospital neonatal intensive care unit from January 1 to December 31, 2001 (prior to functioning multidisciplinary team establishment) and January 1 to December 31, 2004 (subsequent to establishment of a multidisciplinary team). Data from charts in the 2 time periods were examined for differences in nutrition outcomes. Outcome variables included length of stay, birth weight, discharge weight, weight gained for specified time periods, weight at full feeds, weight gain per day, length, head circumference, and number of days to start enteral feeding. Analysis of covariance, controlling for the effect of birth weight, was used to determine differences and was considered significant at P< .05. The mean length of stay (65 days, 95% confidence interval [CI]: 48‐68 vs 72 days, 95% CI: 53‐73) was not different for the 2 periods. The mean weight at the beginning of enteral feeding was significantly less in the period prior to the establishment of the multidisciplinary team (1099 g, 95% CI: 955‐1165 vs 1164 g, 95% CI: 1067‐1211, respectively). Weight at discharge, total weight gained, total daily weight gained, daily weight gain from birth to the initiation of enteral feeds, daily weight gain from birth to full feeds, and head circumference growth were significantly greater for neonates in the postgroup than in the pre‐multidisciplinary team group. Implementation of a multidisciplinary team that included a registered dietitian improved the nutrition outcomes of low birth weight infants in a neonatal intensive care unit.
Outpatient Nutrition Management of the Neurologically Impaired Child
Authors: Mascarenhas Maria R. , Meyers Robin , Konek Susan
Published: November 2008

The nutrition care of children who are neurologically impaired is a challenge for the nutrition care team. Many factors should be considered in the assessment and development of a nutrition plan. That these children can have significant abnormalities in nutrition status, growth, and body composition should be kept in mind. Energy needs are often hard to assess. For this reason, monitoring of weight status over time provides the best indicator of energy requirements. Protein needs are not increased for the healthy child who is neurologically impaired. Nutrition rehabilitation usually corrects micronutrient deficiencies when they are found. Nutrition assessment is a key component of the care of these children. Height assessment can be difficult, and alternative measures of height should be used in the evaluation of growth. For optimal care, management should be done by a multidisciplinary team including a registered dietitian. Improved nutrition status results in improved health outcomes.
Enteral Feeding Misconnections: A Consortium Position Statement
Authors: Miller Sarah J.
Published: November 2008

An invitation from the American Hospital Association (AHA) brought together a number of representatives from various organizations in Washington, D.C., on October 11, 2006, to (1) discuss the current state of practice pertaining to enteral feedings and (2) patient safety risks associated with medical misconnections involving enteral feeding systems. Although the initial focus was on Luer fittings, the scope of the discussion was expanded to the entire enteral feeding system to identify areas where misconnections could occur. This article presents the issues associated with enteral feeding misconnections and proposes a set of solutions. (The Joint Commission Journal on Quality and Patient Safety. 2008;34:285‐292)

P Guenter, RW Hicks, D Simmons, et al
Children's Pain Assessment in Northeastern Thailand: Perspectives of Health Professionals
Authors: Forgeron Paula A. , Jongudomkarn Darunee , Evans Joan , Finley G. Allen , Thienthong Somboon , Siripul Pulsuk , Pairojkul Srivieng , Sriraj Wimonrat , Boonyawatanangkool Kesanee
Published: November 2008

Deficiencies in pain care within the developing world are starting to be realized. Children, in particular, are vulnerable, as preliminary studies suggest that these children receive less pain treatment because of health professionals' attitudes and beliefs. This article reports on some of the findings of the first study in a larger program of research aimed at improving pediatric pain care in Thailand. Improvements in practice are not simply the result of providing evidenced-based knowledge, but a complex process that includes the context of care. Given that little is known about the pain management experiences of Thai health professionals, including the challenges they face, we used focus groups to capture their stories. Data revealed a need for both updating pain knowledge and for supporting an increased use of appropriate practices. In this article, we focus on the issues concerning the assessment of pain resulting from underrecognizing children's pain and complex issues in communicating findings of children's pain.
Being in the Script of Menopause: Mapping the Complexities of Coping Strategies
Authors: Vicki Kafanelis Betty , Kostanski Marion , Komesaroff Paul A. , Stojanovska Lily
Published: November 2008

In this article we explore the discourses of menopause, aging, and the complexities of coping with both menopause and aging among 30 women between the ages of 43 and 61 years living in Melbourne, Australia. Employing a qualitative design with thematic analysis, we uncover the complexity and heterogeneity of coping styles. Three major coping strategies are identified: inventive, troubled, and reactive. Recognition of the variety of coping strategies creatively negotiated within the dynamic, complex processes of aging and menopause might assist women in developing effective responses to these sometimes challenging life experiences.
Development and Standardization of a Test to Measure the Emotional and Behavioral Strengths of Preschool Children
Authors: Epstein Michael H. , Synhorst Lori L. , Cress Cynthia J. , Allen Elizabeth A.
Published: November 2008

The purpose of the present study was to document the development and standardization of the Preschool Behavioral and Emotional Rating Scale and to examine its factor structure, internal consistency, and criterion validity. Data from a nationally representative sample ( N = 1,471) of preschool children with and without disabilities were collected. An exploratory factor analysis identified four factors: Emotional Regulation, School Readiness, Social Confidence, and Family Involvement. The subscales and total instrument appear remarkably stable and consistent (.838 to .983). Age differences across 3-, 4-, and 5-year olds were small in magnitude, although girls were rated as possessing significantly more strengths than boys. Preschool children with disabilities were seen as having less emotional and behavioral strength than their peers without disabilities. The limitations and future research needs are discussed.
Diagnostic Accuracy and Prognostic Value of Core Biopsy in the Management of Breast Cancer: A Series of 542 Patients
Authors: Richter-Ehrenstein Christiane , Müller Sylvia , Noske Aurelia , Schneider Achim
Published: November 2008

Purpose. Core biopsy is considered to be a highly accurate method for gaining preoperative diagnosis of breast cancer. The purpose of this study is to compare the results of core biopsy with those of the surgical excision specimen. Experimental design. A total of 567 core biopsies with subsequent surgical excision were performed. Results. In 488 patients, invasive breast cancer was diagnosed in the preoperative biopsy and in 486 patients (99.6%) the surgical specimen showed identical results. In 160 of the 502 patients (32%) with invasive breast cancer, DCIS was found in the surgical specimen but was not diagnosed in the biopsy. Estrogen and progesterone receptor demonstrated a high rate of agreement, Her2/neu analysis showed a complete concordance in 54% of patients. Conclusions. Core biopsies allow diagnosis of invasive breast cancer with high accuracy. Levels of agreement have to be improved for the detection of DCIS and Her2/neu status.
Beliefs About Science and News Frames in Audience Evaluations of Embryonic and Adult Stem Cell Research
Authors: Stewart Craig O. , Dickerson Daniel L. , Hotchkiss Rose
Published: November 2008

This study investigates the influence of demographic variables, beliefs about science, and news frames on ratings of ethics, credibility, and usefulness of embryonic and adult stem cell research. Framing affected only ratings of ethics, in interaction with type of stem cell, with a large difference between embryonic and adult stem cells in a political conflict frame and no difference in a scientific progress frame. Belief that science is neutral with respect to religion and morality was positively associated with ethics and usefulness ratings for embryonic research; frequency of religious attendance was positively associated with ethics, credibility, and usefulness ratings for adult research only. Humanities and social science majors tended to rate both the embryonic and adult research as more credible, as did participants with higher self-reported science interest and exposure. Quantitative analyses are supplemented with qualitative interview data.
Procedural Justice, Police Legitimacy, and Helping the Police Fight Crime
Authors: Reisig Michael D. , Lloyd Camille
Published: November 2008

Drawing on procedural justice theory and research, this study uses survey data from a sample of Jamaican high school students ( N = 289) to evaluate hypotheses derived from the process-based model of policing. Findings reveal that the correlation between procedural justice judgments and police legitimacy is positive and statistically significant. Students who rate police practices more favorably in terms of procedural justice also report a greater willingness to help the police fight crime (e.g., report suspicious activity to the police) in their community. In combination, the findings show that these two key process-based model hypotheses generalize to the Jamaican context. Although the correlation between police legitimacy and behavioral cooperation is in the expected direction, the relationship is not statistically significant. The findings also show that students from impoverished local communities dominated by “area dons” are less willing to help the police fight crime.
Laser clad Cr3C2–Ni composite coating on titanium alloys
Authors: Sun R. L. , Lei Y. W. , Niu W.
Published: November 2008

Cr3C2–Ni composite coatings were fabricated on Ti–6Al–4V substrate by laser cladding using powder mixture of NiCrBSiC alloy and Cr3C2. Results of the analysis show that the microstructure and microhardness of the coatings depend strongly on the specific laser energy. With a relatively low specific laser energy (133·3 J mm−2), Cr3C2 particles were partially dissolved into melted Ni based alloy, and the coating was formed of undissolved Cr3C2 particles and cannular Cr23C6 uniformly distributed in cellular γ-Ni and eutectic matrix. With a higher specific laser energy (266·7 J mm−2), more Cr3C2 particles were dissolved, and the coating consisted of γ-Ni, TiC dendrites and lamellar CrB. When the specific laser energy is 133·3 and 266·7 J mm−2, the microhardness of the coating is 500–700 HV and 700–1000 HV, respectively.
Nitride coatings on widia substrate for mechanical applications
Authors: Constantinescu S.
Published: November 2008

During chemical vapour deposition (CVD) process the surface properties of the metallic or non-metallic materials are modified by the generation of a new layer with special chemical and physical properties. This modification in the surface properties is produced by subjecting the substrate materials to a single gas or a combination of gases at elevated temperatures. One type of CVD process is carried out in a heated retort and the chemical reactions that occur are initiated in the space around or on the surface of the substrate. In the present paper, titanium nitride layers on widia substrate have been obtained by an original CVD method, in a heat treatment chamber. Thin layers of 1·5–10 μm using ferrotitanium as raw materials were obtained as a function of exposure time at 1050°C. The microhardness of the coated materials ranges between 25 000 and 25 520 MPa. Although widia is well known as a very good material for cutting devices, cutting experiments on these coated widia plates show that the endurance increases by 3 to 5 times as compared with that of uncoated plates.
Prostaglandin E2 enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells
Authors: Krause Petra , Bruckner Markus , Uermösi Christina , Singer Eva , Groettrup Marcus , Legler Daniel F.
Published: November 2008

Dendritic cell (DC)–based immunotherapy of malignant diseases relies on 2 critical parameters: antigen transport from the periphery to draining lymph nodes and efficient priming of primary and stimulation of secondary immune responses. Prostaglandin E2 (PGE2) signaling has been shown to be pivotal for DC migration toward lymph node–derived chemokines in vitro and in vivo. Here, we demonstrate that PGE2 induced the expression of the costimulatory molecules OX40L, CD70, and 4-1BBL on human DCs. Short triggering by PGE2 early during DC maturation was sufficient to induce the costimulatory molecules. The expression of the costimulatory molecules was independent of the maturation stimulus but strictly dependent on PGE2 on both monocyte-derived (Mo) DCs and peripheral blood myeloid (PB) DCs. PGE2-matured MoDCs showed enhanced costimulatory capacities resulting in augmented antigen-specific CD4+ and CD8+ T-cell proliferation in primary and recall T-cell responses. Blocking OX40/OX40L signaling impaired the enhanced T-cell proliferation induced by PGE2-matured MoDCs. Moreover, MoDCs matured in the presence of PGE2 induced the expression of OX40, OX40L, and CD70 on T cells facilitating T-cell/T-cell interaction that warrant long-lasting costimulation. This newly identified parameter will help to further optimize DC-based immunotherapy.
Processing of hemojuvelin requires retrograde trafficking to the Golgi in HepG2 cells
Authors: Maxson Julia E. , Enns Caroline A. , Zhang An-Sheng
Published: November 2008

Hemojuvelin (HJV) was recently identified as a critical regulator of iron homeostasis. It is either associated with cell membranes through a glycosylphosphatidylinositol anchor or released as a soluble form. Membrane-anchored HJV acts as a coreceptor for bone morphogenetic proteins and activates the transcription of hepcidin, a hormone that regulates iron efflux from cells. Soluble HJV antagonizes bone morphogenetic protein signaling and suppresses hepcidin expression. In this study, we examined the trafficking and processing of HJV. Cellular HJV reached the plasma membrane without obtaining complex oligosaccharides, indicating that HJV avoided Golgi processing. Secreted HJV, in contrast, has complex oligosaccharides and can be derived from HJV with high-mannose oligosaccharides at the plasma membrane. Our results support a model in which retrograde trafficking of HJV before cleavage is the predominant processing pathway. Release of HJV requires it to bind to the transmembrane receptor neogenin. Neogenin does not, however, play a role in HJV trafficking to the cell surface, suggesting that it could be involved either in retrograde trafficking of HJV or in cleavage leading to HJV release.
A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response
Authors: Pratz Keith W. , Cortes Jorge , Roboz Gail J. , Rao Niranjan , Arowojolu Omotayo , Stine Adam , Shiotsu Yukimasa , Shudo Aiko , Akinaga Shiro , Small Donald , Karp Judith E. , Levis Mark
Published: November 2008

Internal tandem duplication mutations of FLT3 (FLT3/ITD mutations) are common in acute myeloid leukemia (AML) and confer a poor prognosis. This would suggest that FLT3 is an ideal therapeutic target, but FLT3 targeted therapy has produced only modest benefits in clinical trials. Due to technical obstacles, the assessment of target inhibition in patients treated with FLT3 inhibitors has been limited and generally only qualitative. KW-2449 is a novel multitargeted kinase inhibitor that induces cytotoxicity in Molm14 cells (which harbor an FLT3/ITD mutation). The cytotoxic effect occurs primarily at concentrations sufficient to inhibit FLT3 autophosphorylation to less than 20% of its baseline. We report here correlative data from a phase 1 trial of KW-2449, a trial in which typical transient reductions in the peripheral blast counts were observed. Using quantitative measurement of FLT3 inhibition over time in these patients, we confirmed that FLT3 was inhibited, but only transiently to less than 20% of baseline. Our results suggest that the failure to fully inhibit FLT3 in sustained fashion may be an underlying reason for the minimal success of FLT3 inhibitors to date, and stress the importance of confirming in vivo target inhibition when taking a targeted agent into the clinical setting. The clinical studies are registered on www.clinicaltrials.gov as NCT00346632.
Diffuse large B-cell lymphoma: reduced CD20 expression is associated with an inferior survival
Authors: Johnson Nathalie A. , Boyle Merrill , Bashashati Ali , Leach Stephen , Brooks-Wilson Angela , Sehn Laurie H. , Chhanabhai Mukesh , Brinkman Ryan R. , Connors Joseph M. , Weng Andrew P. , Gascoyne Randy D.
Published: November 2008

CD19 and CD20 are B cell–specific antigens whose expression is heterogeneous when analyzed by flow cytometry (FCM). We determined the association between CD20 expression and clinical outcome in patients with diffuse large B-cell lymphoma (DLBCL). The mean fluorescence intensity of CD20 and CD19 was determined by FCM, and the cytoplasmic expression of CD20 was determined by immunohistochemistry (IHC) on 272 diagnostic DLBCL samples. Exon 5 of the MS4A1 gene coding for the extracellular component of the CD20 antigen was sequenced in 15 samples. A total of 43 of 272 (16%) samples had reduced CD20 expression by FCM; of these, 35 (13%) had bright CD19 expression. The latter had a markedly inferior survival when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP (R-CHOP; median survival of 1.2 and 3.0 years vs not reached for the others, P < .001 and P = .001), independent of the International Prognostic Index. A total of 41 of 43 samples with reduced CD20 expression by FCM had strong staining for CD20 by IHC. There were no mutations in exon 5 of the MS4A1 gene to explain the discrepancy between FCM and IHC. CD20 and CD19 expression by FCM should be determined on all biopsies of patients with DLBCL because reduced CD20 expression cannot be reliably detected by IHC.
Lipid bilayer composition influences small multidrug transporters
Authors: Charalambous Kalypso , Miller David , Curnow Paul , Booth Paula J
Published: November 2008

Background

Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins.

Results

Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr.

Conclusion

These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.
EMAAS: An extensible grid-based Rich Internet Application for microarray data analysis and management
Authors: Barton G , Abbott J , Chiba N , Huang DW , Huang Y , Krznaric M , Mack-Smith J , Saleem A , Sherman BT , Tiwari B , Tomlinson C , Aitman T , Darlington J , Game L , Sternberg MJE , Butcher SA
Published: November 2008

Background

Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management.

Results

EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms.

Conclusion

EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume.
Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy and side effect attenuation
Authors: Zhu Zhi-feng , Chen Li-juan , Lu Rong , Jia Jing , Liang Yu , Xu Qiong , Zhou Chun-lei , Wang Li , Wang Song , Yao Zhi
Published: November 2008

Background

Tripeptide tyroserleutide (YSL) is a novel small molecule anti-tumor polypeptide that has been shown to inhibit the growth of human liver cancer cells. In this study, we investigated the effects of YSL plus doxorubicin on the growth of human hepatocellular carcinoma BEL-7402 cells that had been transplanted into nude mice.

Methods

Nude mice bearing human hepatocellular carcinoma BEL-7402 tumors were treated with successive intraperitoneal injections of saline; low-, mid-, or high-dose doxorubicin; or low-, mid-, or high-dose doxorubicin plus YSL. Effects on the weight and volume of the tumors were evaluated.

Results

Co-administration of YSL and high-dose doxorubicin (6 mg/kg every other day) prolonged the survival time of tumor-bearing mice as compared to high-dose doxorubicin alone. As well, the anti-tumor effects of mid- and low-dose doxorubicin (2 and 0.7 mg/kg every other day, respectively) were enhanced when supplemented with YSL; the tumor growth inhibition rates for YSL plus doxorubicin were greater than the inhibition rates for the same dosages of doxorubicin alone. The combination of YSL and doxorubicin decreased chemotherapy-associated weight loss, leukocyte depression, and heart, liver, and kidney damage as compared to doxorubicin alone.

Conclusion

The combination of YSL plus doxorubicin enhances the anti-tumor effect and reduces the side effects associated with doxorubicin chemotherapy.
Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores
Authors: Schobesberger Martina , Baltzer Anna , Oberli Andrea , Kappeler Andreas , Gugger Mathias , Burger Hana , Jaggi Rolf
Published: November 2008

Background

Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection.

Methods

In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR.

Results

Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan® Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient.

Conclusion

We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen.
The complicated management of a patient following transarterial chemoembolization for metastatic carcinoid
Authors: Pearson Andrew C , Steinberg Steven , Shah Manisha H , Bloomston Mark
Published: November 2008

Background

Transarterial Chemoembolization (TACE) has been recognized as a successful way of managing symptomatic and/or progressive hepatic carcinoid metastases not amenable to surgical resection. Although it is a fairly safe procedure, it is not without its complications.

Case presentation

This is a case of a 53 year-old woman with a patent foramen ovale (PFO) and mild pulmonary hypertension who underwent TACE for progressive carcinoid liver metastases. She developed acute heart failure, due to a severe inflammatory response; this resulted in pneumatosis intestinalis due to non-occlusive mesenteric ischemia. We describe the successful non-operative management of her pneumatosis intestinalis and the role of a PFO in this patient's heart failure.

Conclusion

TACE remains an effective and safe treatment for metastatic carcinoid not amenable to resection, this case illustrates the complexity of complications that can arise. A multi-disciplinary approach including ready access to advanced critical care facilities is recommended in managing such complex patients.
Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients
Authors: Yu Jessie Z , Warycha Melanie A , Christos Paul J , Darvishian Farbod , Yee Herman , Kaminio Hideko , Berman Russell S , Shapiro Richard L , Buckley Michael T , Liebes Leonard F , Pavlick Anna C , Polsky David , Brooks Peter C , Osman Iman
Published: November 2008

Background

Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression.

Methods

The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients.

Results

Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients.

Conclusion

Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.
Identification of possible candidate genes regulating Sjögren's syndrome-associated autoimmunity: a potential role for TNFSF4in autoimmune exocrinopathy
Authors: Nguyen Cuong Q , Cornelius Janet G , Cooper Lauren , Neff Jonathan , Tao Joann , Lee Byung Ha , Peck Ammon B
Published: November 2008

Introduction

Sjögren syndrome (SjS) is a systemic autoimmune disease in which an immunological attack primarily against the salivary and lacrimal glands results in the loss of acinar cell tissue and function, leading to stomatitis sicca and keratoconjunctivitis sicca. In recent years, two genetic regions, one on chromosome 1 (designated autoimmune exocrinopathy 2 or Aec2) and the second on chromosome 3 (designated autoimmune exocrinopathy 1 or Aec1) derived from nonobese diabetic (NOD) mice, have been shown to be necessary and sufficient to replicate SjS-like disease in nonsusceptible C57BL/6 mice.

Methods

Starting with the SjS-susceptible C57BL/6-derived mouse, referred to as C57BL/6.NOD-Aec1Aec2, we generated a large set of recombinant inbred (RI) lines containing portions of Aec2 as a means of identifying more precisely the genetic elements of chromosome 1 responsible for disease development.

Results

Disease profiling of these RI lines has revealed that the SjS susceptibility genes of Aec2 lie within a region located at approximately 79 ± 5 cM distal to the centromere, as defined by microsatellite markers. This chromosomal region contains several sets of genes known to correlate with various immunopathological features of SjS as well as disease susceptibility genes for both type 1 diabetes and systemic lupus erythematosus in mice. One gene in particular, tumor necrosis factor (ligand) superfamily member 4 (or Ox40 ligand), encoding a product whose biological functions correlate with both physiological homeostasis and immune regulations, could be a potential candidate SjS susceptibility gene.

Conclusions

These new RI lines represent the first step not only in fine mapping SjS susceptibility loci but also in identifying potential candidate SjS susceptibility genes. Identification of possible candidate genes permits construction of models describing underlying molecular pathogenic mechanisms in this model of SjS and establishes a basis for construction of specific gene knockout mice.
Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma
Authors: Daud Adil I. , DeConti Ronald C. , Andrews Stephanie , Urbas Patricia , Riker Adam I. , Sondak Vernon K. , Munster Pamela N. , Sullivan Daniel M. , Ugen Kenneth E. , Messina Jane L. , Heller Richard
Published: November 2008

Purpose

Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection of DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA.

Patients and Methods

A phase I dose escalation trial of plasmid interleukin (IL)-12 electroporation was carried out in patients with metastatic melanoma. Patients received electroporation on days 1, 5, and 8 during a single 39-day cycle, into metastatic melanoma lesions with six 100-μs pulses at a 1,300-V/cm electric field through a penetrating six-electrode array immediately after DNA injection. Pre- and post-treatment biopsies were obtained at defined time points for detailed histologic evaluation and determination of IL-12 protein levels.

Results

Twenty-four patients were treated at seven dose levels, with minimal systemic toxicity. Transient pain after electroporation was the major adverse effect. Post-treatment biopsies showed plasmid dose proportional increases in IL-12 protein levels as well as marked tumor necrosis and lymphocytic infiltrate. Two (10%) of 19 patients with nonelectroporated distant lesions and no other systemic therapy showed complete regression of all metastases, whereas eight additional patients (42%) showed disease stabilization or partial response.

Conclusion

This report describes the first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation. The results indicated this modality to be safe, effective, reproducible, and titratable.
Self-Reported Practices and Attitudes of US Oncologists Regarding Off-Protocol Therapy
Authors: Peppercorn Jeffrey , Burstein Harold , Miller Franklin G. , Winer Eric , Joffe Steve
Published: November 2008

Purpose

Investigational cancer therapies being tested in clinical trials may be available outside of trials, or off-protocol (OPRx). We evaluated the practices and attitudes among US oncologists with regard to this controversial practice.

Methods

We mailed an anonymous survey to a random sample of US medical oncologists evaluating frequency and prevalence of OPRx and evaluated the correlation between demographic factors, attitudes, and practice.

Results

One hundred forty-six (31%) of 471 oncologists responded. Ninety-three percent reported ever discussing and 81% ever prescribing OPRx. Academic oncologists were more likely than community oncologists to have ever provided OPRx (89% v 75%; P = .06), to discuss OPRx at least once/month (41% v 19%; P = .0004), and to deny requests for OPRx at least once/month (16% v 2%; P = .004). While 61% of oncologists believed that patients should be discouraged from OPRx, only 31% felt it should not be available. With regard to trial recruitment, 53% felt that informed consent requires discussion of OPRx, 34% disagree, and 26% feel that patients should be provided OPRx on request, while 56% disagree. There was lack of consensus on access to OPRx in scenarios based on open trials at the time of the survey, such as adjuvant trastuzumab, which 41% would provide, 59% would not.

Conclusion

US oncologists report common discussion and use of OPRx, but attitudes and practices may vary substantially. There is need for greater debate regarding OPRx in oncology, further definition of the ethical and clinical issues at stake, and development of guidelines in this area.
The Ricardo Puzzle
Authors: Lopes Francisco L.
Published: November 2008

This paper tackles the puzzle of Ricardo's stubborn commitment to a labor theory of value that he himself saw as no more than an approximation to reality and which was heavily opposed by Malthus, his most respected contemporary. We show it is wrong to think that the theory was just the result of personal stubborness with no analytical benefit. Quite to the contrary, it was the only defense Ricardo could find against Malthus' destructive criticism, which introduced an unacceptable degree of indetermination in his theory of profits. By adopting the labor theory of value, Ricardo drastically simplified the method of proof of his main proposition, which otherwise seemed to present impossible analytical challenges. The irony is that the proposition was correct, quite independently of the labor theory of value, but Ricardo was just unable to prove it.
Arrival at Home
Authors: Morgensen Scott Lauria
Published: November 2008

Radical faerie culture produces modern sexual minorities by mediating their racial and national relationship to histories of colonization. Radical faeries arose in the US by forming itinerant rural gatherings--and, over time, landed rural sanctuaries to host them--where they sought to liberate an authentic gay subjectivity grounded in indigenous cultural roots. I examine the formation of rural sanctuaries and gatherings as sources for gay liberation by investigating how they are structured as spaces of homecoming. Radical faeries who travel to gatherings and sanctuaries arrive at home--despite neither originating nor remaining at these sites--when they find in rural spaces and in tales of indigeneity a self-acceptance and shared nature that grants new belonging to settled land. I narrate key moments when practices of rural mobility and emplacement call gay men home to authentic subjectivity and radical community, by means of loving communion, multigenerational rural ties, indigenous spirituality, and a newly indigenized relationship to settled land. My argument arises from reflexive ethnographic interpretation of the quotidian practices of gatherings and sanctuaries. My ethnographic attention marks the integrity of radical faerie culture as a creative mediation of the racial, national, and colonial conditions of sexuality. My analysis calls queer studies to attend more deeply to the intersectionality and coloniality of sexual minority formations in settler societies, and to let ethnographic interpretation mark both how normative power relations condition sexualities and how sexual subjects creatively engage them.