bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose escalation study of an anti-thrombocytopenic agent in patients with chemotherapy induced thrombocytopenia
Authors: Levin Robert D , Daehler MaryAnn , Grutsch James F , Hall John L , Gupta Digant , Lis Christopher G
Published: October 2010

Background

Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy-Induced Thrombocytopenia (CIT).

Methods

Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects self-administered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.

Results

Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia.

Conclusions

Patients receiving myelosuppressive chemotherapy experienced an improvement in the platelet nadir and shorter recovery time when receiving concurrent E coli RNA fragments, when compared to patients who received yeast RNA fragments. These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery. Further clinical investigations are planned to quantify the clinical benefits of the E. coli RNA at the 80 mg dose in patients with chemotherapy induced thrombocytopenia.

Trial Registration

Clinical Trials.gov Identifier: NCT01163110
Health literacy, health status, and healthcare utilization of Taiwanese adults: results from a national survey
Authors: Lee Shoou-Yih D , Tsai Tzu-I , Tsai Yi-Wen , Kuo Ken N
Published: October 2010

Background

Low health literacy is considered a worldwide health threat. The purpose of this study is to assess the prevalence and socio-demographic covariates of low health literacy in Taiwanese adults and to investigate the relationships between health literacy and health status and health care utilization.

Methods

A national survey of 1493 adults was conducted in 2008. Health literacy was measured using the Mandarin Health Literacy Scale. Health status was measured based on self-rated physical and mental health. Health care utilization was measured based on self-reported outpatient clinic visits, emergency room visits, and hospitalizations.

Results

Approximately thirty percent of adults were found to have low (inadequate or marginal) health literacy. They tended to be older, have fewer years of schooling, lower household income, and reside in less populated areas. Inadequate health literacy was associated with poorer mental health (OR, 0.57; 95% CI, 0.35-0.91). No association was found between health literacy and health care utilization even after adjusting for other covariates.

Conclusions

Low (inadequate and marginal) health literacy is prevalent in Taiwan. High prevalence of low health literacy is not necessarily indicative of the need for interventions. Systematic efforts to evaluate the impact of low health literacy on health outcomes in other countries would help to illuminate features of health care delivery and financing systems that may mitigate the adverse health effects of low health literacy.
Investigation and improvement of DNA cleavage models of polyamide + Cu(II) nuclease + OOH- ligands bound to DNA
Authors: Yue Hongwei , Zhu Yanyan , Wang Yan , Chen Guangju
Published: October 2010

Background

Copper nucleases as a famous class of artificial metallonucleases have attracted considerable interest in relation to their diverse potentials not only as therapeutic agents but also in genomic researches. Copper nucleases present high efficient oxidative cleavage of DNA, in which DNA strand scission occurs generally after hydrogen atom abstracted from a sugar moiety. In order to achieve the selective cleavage of DNA sequences by copper nucleases, the DNA specific recognition agents of the Dervan-type hairpin and cyclic polyamides can be considered as proper carriers of copper nucleases. Investigation of the DNA cleavage selectivity of copper nucleases assisted by the hairpin and cyclic polyamides at the molecular level has not yet been elucidated.

Results

We carried out a series of molecular dynamics simulations for the nuclease [Cu(BPA)]2+ or [Cu(IDB)]2+ bound to the hairpin/cyclic polyamide and associated with DNA to investigate the selective DNA cleavage properties of Cu(II)-based artificial nucleases. The simulated results demonstrate that the DNA cleavage selectivity of the two nucleases assisted by the hairpin polyamide is improved efficiently. The [Cu(BPA)]2+ or [Cu(IDB)]2+ nuclease with a substrate OOH- bound to the hairpin polyamide can be stably located at the minor groove of DNA, and possibly abstracts H atom from the sugar of DNA. However, the DNA cleavage properties of the two nucleases assisted by the cyclic polyamide are significantly poor due to the rigidity of linking region between the cyclic polyamide and nuclease. With introduction of the flexible linker -CH2CH2CH2NH2, the modified cyclic polyamide can assist the two copper nucleases to improve the selective DNA cleavage properties efficiently.

Conclusion

A flexible linker and a proper binding site of the polyamide-type recognition agents play an important role in improving the DNA cleavage selectivity of copper nucleases. Current investigations provide an insight into the DNA cleavage specificities of chemical nucleases assisted by an appropriate nucleic acid recognition agent.
Saudi views on consenting for research on medical records and leftover tissue samples
Authors: Al-Qadire Mohammad M , Hammami Muhammad M , Abdulhameed Hunida M , Al Gaai Eman A
Published: October 2010

Background

Consenting for retrospective medical records-based research (MR) and leftover tissue-based research (TR) continues to be controversial. Our objective was to survey Saudis attending outpatient clinics at a tertiary care hospital on their personal preference and perceptions of norm and current practice in relation to consenting for MR and TR.

Methods

We surveyed 528 Saudis attending clinics at a tertiary care hospital in Saudi Arabia to explore their preferences and perceptions of norm and current practice. The respondents selected one of 7 options from each of 6 questionnaires.

Results

Respondents' mean (SD) age was 33 (11) years, 42% were males, 56% were patients, 84% had ≥ secondary school education, and 10% had previously volunteered for research. Respectively, 40% and 49% perceived that the norm is to conduct MR and TR without consent and 38% and 37% with general or proposal-specific consent; the rest objected to such research. There was significant difference in the distribution of choices according to health status (patients vs. companions) for MR (adjusted Kruskal-Wallis test P = 0.03) but not to age group, gender, education level, or previous participation in research (unadjusted P = 0.02 - 0.59). The distributions of perceptions of current practice and norm were similar (unadjusted Marginal Homogeneity test P = 0.44 for MR and P = 0.89 for TR), whereas the distributions of preferences and perceptions of norm were different (adjusted P = 0.09 for MR and P = 0.02 for TR). The distributions of perceptions of norm, preferences, and perceptions of current practice for MR were significantly different from those of TR (adjusted P < 0.009 for all).

Conclusions

We conclude that: 1) there is a considerable diversity among Saudi views regarding consenting for retrospective research which may be related to health status, 2) the distribution of perceptions of norm was similar to the distribution of perceptions of current practice but different from that of preferences, and 3) MR and TR are perceived differently in regard to consenting.
Development and validation of an ELISA using a protein encoded by ORF2 antigenic domain of porcine circovirus type 2
Authors: Sun Shi-Qi , Guo Hui-Chen , Sun De-Hui , Yin Shuang-Hui , Shang You-Jun , Cai Xue-Peng , Liu Xiang-Tao
Published: October 2010

Background

The capsid protein (ORF2) is a major structural protein of porcine circovirus type 2 (PCV2). A simple and reliable diagnostic method based on ORF2 protein immunoreactivity would serve as a valuable diagnostic method for detecting serum antibodies to PCV2 and monitoring PCV infection. Here, we reported an indirect enzyme-linked immunosorbent assay (I-ELISA) by using an antigenic domain (113-147AA) of ORF2-encoded antigen, expressed in E. coli, for diagnosis of PCV infection.

Results

The ELISA was performed on 288 serum samples collected from different porcine herds and compared with an indirect immunofluorescent assay (IFA). In total, 262 of 288 samples were positive as indicated by both I-ELISA and IFA. The specificity and sensitivity of I-ELISA were 87.7% and 93.57%.

Conclusions

This ELISA is suitable for detection and discrimination of PCV2 infection in both SPF and farm antisera.
Protective effects and potential mechanisms of Pien Tze Huang on cerebral chronic ischemia and hypertensive stroke
Authors: Zhang Lihong , Lam Wai Ping , Lü Lanhai , Wang Chunmei , Wong Yeuk Wa , Lam Lok Hang , Tang Hong Chai , Wai Maria SenMun , Wang Mingwei , Kwong Wing Hang , Ngai Sai Ming , Mak Ying Tat , Yew David TaiWai
Published: October 2010

Background

Stroke caused by brain ischemia is the third leading cause of adult disability. Active prevention and early treatment of stroke targeting the causes and risk factors may decrease its incidence, mortality and subsequent disability. Pien Tze Huang (PZH), a Chinese medicine formula, was found to have anti-edema, anti-inflammatory and anti-thrombotic effects that can prevent brain damage. This study aims to investigate the potential mechanisms of the preventive effects of Pien Tze Huang on brain damage caused by chronic ischemia and hypertensive stroke in rats.

Methods

The effects of Pien Tze Huang on brain protein expression in spontaneously hypertensive rat (SHR) and stroke prone SHR (SHRsp) were studied with 2-D gel electrophoresis and mass spectrometric analysis with a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)/TOF tandem mass spectrometer and on brain cell death with enzyme link immunosorbent assay (ELISA) and immunostaining.

Results

Pien Tze Huang decreased cell death in hippocampus and cerebellum caused by chronic ischemia and hypertensive stroke. Immunostaining of caspase-3 results indicated that Pien Tze Huang prevents brain cells from apoptosis caused by ischemia. Brain protein expression results suggested that Pien Tze Huang downregulated QCR2in the electron transfer chain of mitochondria preventing reactive oxygen species (ROS) damage and possibly subsequent cell death (caspase 3 assay) as caused by chronic ischemia or hypertensive stroke to hippocampus and cerebellum.

Conclusion

Pien Tze Huang showed preventive effects on limiting the damage or injury caused by chronic ischemia and hypertensive stroke in rats. The effect of Pien Tze Huang was possibly related to prevention of cell death from apoptosis or ROS/oxidative damage in mitochondria.
Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation
Authors: Stevens Joshua B , Abdallah Batoul Y , Regan Sarah M , Liu Guo , Bremer Steven W , Ye Christine J , Heng Henry H
Published: October 2010

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost synonymously with PCC, is re-examined. Interestingly, many past reports of chromosome pulverization are identified here as chromosome fragmentation and not PCC. These reports describe broad ranging mechanisms of pulverization induction and agree with recent evidence showing chromosome fragmentation is a cellular response to stress. Finally, biological aspects of chromosome fragmentation are discussed, including its application as one form of non-clonal chromosome aberration (NCCA), the driving force of cancer evolution.
Effects of legal and illegal use of benzodiazepines at acute admission to a psychiatric acute department
Authors: Fløvig John C , Vaaler Arne E , Morken Gunnar
Published: October 2010

Background

In the psychiatric acute and emergency services patients present in severe crisis often complicated by behavioral problems, substance use, and multiple axis 1 diagnoses. In these clinical settings both legal and illegal use of benzodiazepines are difficult to evaluate since benzodiazepines could in some patients be regarded as first line treatment and in other patients as the cause of the acute psychiatric condition. The aims of this study were to evaluate the frequency and clinical effects of both legal and illegal use of benzodiazepines at admittance to a psychiatric acute department.

Methods

All patients acutely admitted to a Norwegian acute psychiatric university department serving a catchment area were asked about use of benzodiazepines, other medications and substances before admission. Patients were asked to give urine samples for analyses of benzodiazepines and substances.

Results

In 227 consecutive admissions there was legal use of benzodiazepines before admission in 39%, illegal use in 13% and no use in 48%. Patients with legal use of benzodiazepines were older, used more often antidepressants and a higher number of prescribed psychotropic medications. Illegal users of benzodiazepines more often used other illegal substances, were evaluated as clinically affected by a substance at admittance and were diagnosed with a substance use disorder. Patients with psychoses or major affective disorders treated with adequate medication (antidepressants, antipsychotics or mood-stabilizers) before admission more often received benzodiazepines than patients without adequate medication.

Conclusions

The patients using benzodiazepines at admittance to psychiatric acute departments could be divided in illegal and legal users. The illegal users were young, used illegal substances and were more often regarded clinically affected by substances at admittance. The legal users were older, did not use other substances and were not regarded as clinically affected by substances at admittance. Benzodiazepines were used as adjuvant therapy to specific pharmacological treatment with antidepressants, antipsychotics or mood stabilizers for major psychiatric disorders.

Trial registration

NCT 00184119/NCT 00184132
Small artery elasticity is decreased in patients with systemic lupus erythematosus without increased intima media thickness
Authors: Nienhuis Hans LA , de Leeuw Karina , Bijzet Johan , van Doormaal Jasper J , van Roon Arie M , Smit Andries J , Graaff Reindert , Kallenberg Cees GM , Bijl Marc
Published: October 2010

Introduction

The objectives of this study were to determine small arterial elasticity (SAE) in systemic lupus erythematosus (SLE) and to investigate its relationship with intima media thickness (IMT), accumulation of advanced glycation end products (AGEs), endothelial activation and inflammation.

Methods

Thirty SLE patients with inactive disease and 30 age- and sex-matched healthy controls were included. Twenty patients with essential hypertension (EH) served as positive control. SAE was assessed by pulse-wave analysis using tonometric recordings of the radial artery. IMT of the carotid arteries was measured by ultrasound. AGE accumulation was assessed with an AGE-reader. Endothelial activation markers and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA).

Results

SAE was decreased in SLE (P = 0.01) and further decreased in EH (P < 0.01) compared to healthy controls. IMT was increased in EH (P < 0.05), but not in SLE. AGE accumulation was increased in SLE (P < 0.05) and further increased in EH (P < 0.01) compared to healthy controls. Endothelial activation markers and CRP were increased in SLE but not in EH. SAE related to AGE accumulation (r = -0.370, P < 0.05), CRP (r = -0.429, P < 0.05) and creatinine clearance (r = 0.440, P < 0.05), but not to IMT and endothelial activation markers. In multivariate analysis SLE was an independent predictor of SAE.

Conclusions

SAE is decreased in SLE patients without increased IMT, independently of traditional cardiovascular risk factors. Longitudinal studies are needed to investigate whether SAE, endothelial activation and AGE accumulation are early markers for cardiovascular disease in SLE.
A phase 2 randomized, double-blind study of AMG 108, a fully human monoclonal antibody to IL-1R, in patients with rheumatoid arthritis
Authors: Cardiel Mario H , Tak Paul P , Bensen William , Burch Francis X , Forejtova Sarka , Badurski Janusz E , Kakkar Tarundeep , Bevirt Terry , Ni Liyun , McCroskery Ellen , Jahreis Angelika , Zack Debra J
Published: October 2010

Introduction

Preclinical work has suggested that IL-1 plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The objective of the present study was to determine the effect of a long-acting IL-1 receptor inhibitor, AMG 108, in a double-blind, placebo-controlled, parallel-dosing study in patients with active RA who were receiving stable methotrexate (15 to 25 mg/week).

Methods

Patients were randomized equally to receive placebo or 50, 125, or 250 mg AMG 108 subcutaneously every 4 weeks for 6 months. The primary efficacy endpoint was a 20% improvement in the American College of Rheumatology response (ACR20) at week 24; other efficacy endpoints included the ACR50, the ACR70, and the RA disease activity score (28-joint count Disease Activity Score) responses, patient-reported outcomes, and pharmacokinetic parameters. Safety endpoints included treatment-emergent adverse events (AEs), infectious AEs, serious AEs, serious infections, injection site reactions, laboratory abnormalities, and antibodies to AMG 108.

Results

Of 813 patients enrolled in the study, 204 patients were randomized to the 50 mg group, 203 to the 125 mg group, 203 to the 250 mg group, and 203 to placebo. At week 24, 40.4% of the 250 mg group, 36% of the 125 mg group, 30.9% of the 50 mg group, and 29.1% of the placebo group achieved an ACR20 (P = 0.022, 250 mg vs. placebo). Of the individual ACR components, numerical dose-dependent improvements were only seen in tender joint counts, pain (visual analog scale), and the acute phase reactants, erythrocyte sedimentation rate and C-reactive protein. No dose-related increase was observed in the incidence of treatment-emergent AEs. No deaths were reported, and the incidence of AEs and infections, serious AEs and infections, and withdrawals from study for safety were similar in the AMG 108 and placebo groups.

Conclusions

This large double-blind randomized trial with a long-acting IL-1 receptor blocker, AMG 108, is consistent with the experience of other IL-1 blockers, represents a definitive experiment showing that IL-1 inhibition provides only moderate symptomatic amelioration of arthritis activity in the majority of RA patients, and provides an answer to a question that has been discussed for many years in the rheumatologic community.

Trial Registration

ClinicalTrials.gov NCT00293826
Opioid-induced chemokine expression requires NF-κB activity: the role of PKCζ
Authors: Happel Christine , Kutzler Michele , Rogers Thomas J
Published: October 2010

Opioid receptor agonists induce broad immunomodulatory activity, which substantially alters host defense and the inflammatory response. Previous studies have shown that the MOR selective agonist DAMGO has the capacity to increase the expression of the proinflammatory chemokines CCL2, CCL5, and CXCL10 in human PBMCs. NF-κB is a transcription factor that plays a pivotal role in innate and adaptive immune responses. We report that NF-κB is a vital player in the DAMGO-induced, MOR-mediated regulation of chemokine expression. Results show that NF-κB inhibitors prevent the induction of CCL2 expression in response to DAMGO administration and that the NF-κB subunit, p65, is phosphorylated at serine residues 311 and 536 in response to MOR activation. Furthermore, we demonstrate that PKCζ is phosphorylated following DAMGO-induced MOR activation, and this kinase is essential for NF-κB activation as well as CCL2 expression and transcriptional activity. Finally, ChIP analysis shows that DAMGO administration induces binding of p65 to the enhancer region of the CCL2 promoter. These data are consistent with the notion that MOR activation promotes a proinflammatory response, which involves NF-κB activation. Our results also suggest a significant and novel role for PKCζ as an essential participant in the MOR-mediated regulation of proinflammatory chemokine expression.
NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease
Authors: Angelini Daniela F , Zambello Renato , Galandrini Ricciarda , Diamantini Adamo , Placido Roberta , Micucci Federica , Poccia Fabrizio , Semenzato Giuseppe , Borsellino Giovanna , Santoni Angela , Battistini Luca
Published: October 2010

The CD94/NKG2 complex is expressed on T and NK lymphocytes. CD94 molecules covalently associate to activating or inhibitory NKG2 molecules, and their expression finely tunes cell responses. Human γδ T cells express several NKRs. Expression of these receptors is confined to the cytolytic Vδ2 subset, which coexpresses the FcγRIII CD16 and CD45RA and has been defined as Vγ9Vδ2 TEMRA cells. We show that the CD94/NKG2C complex, associated with KARAP/DAP12, is fully functional in γδ T cells, as determined by measuring IFN-γ production, T cell proliferation, and cytolytic activity by γδ lymphocytes. In contrast, NKG2A expression was found on all γδ T cell memory subsets, suggesting a crucial role of the inhibitory signal provided by this receptor on γδ T cell responses. Moreover, we found Vγ9Vδ2 TEMRA, NK, and CD8+ αβ T cells coexpressing NKG2A and NKG2C receptors. Functional experiments showed that the inhibitory signal mediated by the NKG2A receptor prevails when double-positive cells are activated. Finally, NKG2A expression on γδ LDGL correlates with asymptomatic pathology, even in the presence of NKG2C coexpression, whereas in symptomatic patients affected by severe disease, the inhibitory NKG2A receptor is absent, and a variety of activatory NKRs was found. We propose that the silent behavior of γδ cells in LDGL patients is a result of effective inhibitory HLA class I receptors.
The biological paths of IL-1 family members IL-18 and IL-33
Authors: Smith Dirk E
Published: October 2010

Cytokines are key mediators of the immune system, and few have been more thoroughly studied than those of the IL-1 family. IL-1α and IL-1β are the founding members and now celebrate 25 years since their cloning. In that time, IL-1-directed research has illuminated many aspects of cytokine biology and innate immunity. The family is now recognized to include 11 total members, including IL-18 and IL-33, which are the topic of this review. These two inflammatory cytokines are expressed broadly, and their actions influence a variety of physiologic responses involved in inflammation and immunity. The purpose of this article is not to provide an exhaustive review of IL-18 and IL-33 but rather, to summarize what is known about their key functions and to provide perspective on their similarities and differences.
Foxp3+IL-17+ T cells promote development of cancer-initiating cells in colorectal cancer
Authors: Yang Shaobo , Wang Binquan , Guan Chunying , Wu Benyan , Cai Changhao , Wang Mengwei , Zhang Binsheng , Liu Tao , Yang Pingchang
Published: October 2010

The pathogenesis of CRC remains to be further understood. This study was designed to elucidate the role of Foxp3+IL-17+ T cells in the pathogenesis of CRC. Surgically removed CRC tissue was collected from 12 patients with CRC. The frequency and cytokine profile of Foxp3+IL-17+ T cells in CRC were examined by flow cytometry. Chemokine CXCL11 was examined in CRC tissue by Western blotting. Treg chemotaxis was examined in a transwell system. The effect of Foxp3+IL-17+ T cells on induction of cancer-initiating cells was examined; the latter's Akt and MAPK activities and colony formation were examined afterward. Abundant Foxp3+IL-17+ T cells were detected in CRC tissue that expresses high levels of TGF-β, CXCR3, CCR6, and RORγt. High levels of CXCL11 were detected in CRC tissue-derived CD68+ cells, which had a strong chemotactic effect on Foxp3+ Tregs. Hypoxia induced the expression of IL-17 in Foxp3+ Tregs; Foxp3+IL-17+ T cells were capable of inducing CRC-associated cell markers in BMMo and drove the cells to be cancer-initiating cells. High levels of phosphorylated Akt and MAPK were detected in the induced cancer-initiation cells; the latter has the capability to form a colony. CRC tissue-derived Foxp3+IL-17+ cells have the capacity to induce cancer-initiating cells.
Radiotherapy With Concurrent Carbogen and Nicotinamide in Bladder Carcinoma
Authors: Hoskin Peter J. , Rojas Ana M. , Bentzen Søren M. , Saunders Michele I.
Published: October 2010

Purpose

Phase II clinical studies suggest that hypoxic modification with carbogen and nicotinamide (CON) may increase the efficacy of radiotherapy (RT).

Patients and Methods

Three hundred thirty-three patients with locally advanced bladder carcinoma were randomly assigned to RT alone versus RT with CON. A schedule of either 55 Gy in 20 fractions in 4 weeks or 64 Gy in 32 fractions in 6.5 weeks was used. The primary end point was cystoscopic control at 6 months (CC6m) and secondary end points were overall survival (OS), local relapse-free survival (RFS), urinary and rectal morbidity.

Results

CC6m was 81% for RT + CON and 76% for RT alone (P = .3); however, just more than half of patients underwent cystoscopy at that time. Three-year estimates of OS were 59% and 46% (P = .04) and 3-year estimates of RFS were 54% and 43% (P = .06) for RT + CON versus RT alone. Risk of death was 14% lower with RT + CON (P = .04). In multivariate comparison, RT + CON significantly reduced the risk of relapse (P = .05) and death (P = .03). There was no evidence that differences in late urinary or GI morbidity between treatment groups or between fractionation schedules were significant.

Conclusion

RT + CON produced a small nonsignificant improvement in CC6m. Differences in OS, risk of death, and local relapse were significantly in favor of RT + CON. Late morbidity was similar in both trial arms. Results indicate a benefit of adding CON to radical RT.
Dose Escalation of Lenalidomide in Relapsed or Refractory Acute Leukemias
Authors: Blum William , Klisovic Rebecca B. , Becker Heiko , Yang Xiaoxia , Rozewski Darlene M. , Phelps Mitch A. , Garzon Ramiro , Walker Alison , Chandler Jason C. , Whitman Susan P. , Curfman John , Liu Shujun , Schaaf Larry , Mickle Jon , Kefauver Cheryl , Devine Steven M. , Grever Michael R. , Marcucci, and Guido , Byrd John C.
Published: October 2010

Purpose

Lenalidomide is effective in myeloma and low-risk myelodysplastic syndromes with deletion 5q. We report results of a phase I dose-escalation trial of lenalidomide in relapsed or refractory acute leukemia.

Patients and Methods

Thirty-one adults with acute myeloid leukemia (AML) and four adults with acute lymphoblastic leukemia (ALL) were enrolled. Lenalidomide was given orally at escalating doses of 25 to 75 mg daily on days 1 through 21 of 28-day cycles to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD), as well as to provide pharmacokinetic and preliminary efficacy data.

Results

Patients had a median age of 63 years (range, 22 to 79 years) and a median of two prior therapies (range, one to four therapies). The DLT was fatigue; 50 mg/d was the MTD. Infectious complications were frequent. Plasma lenalidomide concentration increased proportionally with dose. In AML, five (16%) of 31 patients achieved complete remission (CR); three of three patients with cytogenetic abnormalities achieved cytogenetic CR (none with deletion 5q). Response duration ranged from 5.6 to 14 months. All responses occurred in AML with low presenting WBC count. No patient with ALL responded. Two of four patients who received lenalidomide as initial therapy for AML relapse after allogeneic transplantation achieved durable CR after development of cutaneous graft-versus-host disease, without donor leukocyte infusion.

Conclusion

Lenalidomide was safely escalated to 50 mg daily for 21 days, every 4 weeks, and was active with relatively low toxicity in patients with relapsed/refractory AML. Remissions achieved after transplantation suggest a possible immunomodulatory effect of lenalidomide, and results provide enthusiasm for further studies in AML, either alone or in combination with conventional agents or other immunotherapies.
Feedstock Routing in the ExxonMobil Downstream Sector
Authors: Furman Kevin C. , Song Jin-Hwa , Kocis Gary R. , McDonald Michael K. , Warrick Philip H.
Published: October 2010

ExxonMobil annually transports significant volumes of vacuum gas oil (VGO) from supply points in Europe to refineries in the United States. Optimizing these transportation costs by using modern mathematical programming technology can provide significant cost savings. We developed a mixed-integer programming formulation for VGO routing and inventory management, and we integrated it into a decision support tool to enable experienced traders and schedulers to further improve the performance of ExxonMobil's downstream supply chain.
A mediation analysis of achievement motives, goals, learning strategies, and academic achievement
Authors: Diseth Åge , Kobbeltvedt Therese
Published: October 2010

Background. Previous research is inconclusive regarding antecedents and consequences of achievement goals, and there is a need for more research in order to examine the joint effects of different types of motives and learning strategies as predictors of academic achievement.

Aims. To investigate the relationship between achievement motives, achievement goals, learning strategies (deep, surface, and strategic), and academic achievement in a hierarchical model.

Sample. Participants were 229 undergraduate students (mean age: 21.2 years) of psychology and economics at the University of Bergen, Norway.

Methods. Variables were measured by means of items from the Achievement Motives Scale (AMS), the Approaches and Study Skills Inventory for Students, and an achievement goal scale.

Results. Correlation analysis showed that academic achievement (examination grade) was positively correlated with performance‐approach goal, mastery goal, and strategic learning strategies, and negatively correlated with performance‐avoidance goal and surface learning strategy. A path analysis (structural equation model) showed that achievement goals were mediators between achievement motives and learning strategies, and that strategic learning strategies mediated the relationship between achievement goals and academic achievement.

Conclusions. This study integrated previous findings from several studies and provided new evidence on the direct and indirect effects of different types of motives and learning strategies as predictors of academic achievement.
Intrinsic, identified, and controlled types of motivation for school subjects in young elementary school children
Authors: Guay Frédéric , Chanal Julien , Ratelle Catherine F. , Marsh Herbert W. , Larose Simon , Boivin Michel
Published: October 2010

Background. There are two approaches to the differential examination of school motivation. The first is to examine motivation towards specific school subjects (between school subject differentiation). The second is to examine school motivation as a multidimensional concept that varies in terms of not only intensity but also quality (within school subject differentiation). These two differential approaches have led to important discoveries and provided a better understanding of student motivational dynamics. However, little research has combined these two approaches.

Aims. This study examines young elementary students' motivations across school subjects (writing, reading, and maths) from the stance of self‐determination theory. First, we tested whether children self‐report different levels of intrinsic, identified, and controlled motivation towards specific school subjects. Second, we verified whether children self‐report differentiated types of motivation across school subjects.

Sample. Participants were 425 French‐Canadian children (225 girls, 200 boys) from three elementary schools. Children were in Grades 1 (N=121), 2 (N=126), and 3 (N=178).

Results. Results show that, for a given school subject, young elementary students self‐report different levels of intrinsic, identified, and controlled motivation. Results also indicate that children self‐report different levels of motivation types across school subjects. Our findings also show that most differentiation effects increase across grades. Some gender effects were also observed.

Conclusion. These results highlight the importance of distinguishing among types of school motivation towards specific school subjects in the early elementary years.
Cache pilferage may be prominent in Neotropical forests
Authors: Haugaasen Torbjørn , Tuck Haugaasen Joanne M.
Published: October 2010

No abstract available
Sperm quality assessments for endangered razorback suckers Xyrauchen texanus
Authors: Jenkins Jill A , Eilts Bruce E , Guitreau Amy M , Figiel Chester R , Draugelis-Dale Rassa O , Tiersch Terrence R
Published: October 2010

Flow cytometry (FCM) and computer-assisted sperm motion analysis (CASA) methods were developed and validated for use with endangered razorback suckersXyrauchen texanuscollected (n=64) during the 2006 spawning season. Sperm motility could be activated within osmolality ranges noted during milt collections (here 167–343 mOsm/kg). We hypothesized that sperm quality of milt collected into isoosmotic (302 mOsm/kg) or hyperosmotic (500 mOsm/kg) Hanks' balanced salt solution would not differ. Pre-freeze viabilities were similar between osmolalities (79%±6 (s.e.m.) and 76%±7); however, post-thaw values were greater in hyperosmotic buffer (27%±3 and 12%±2;P=0.0065), as was mitochondrial membrane potential (33%±4 and 13%±2;P=0.0048). Visual estimates of pre-freeze motility correlated with total (r=0.7589; range 23–82%) and progressive motility (r=0.7449) by CASA and were associated with greater viability (r=0.5985;P<0.0001). Count (FCM) was negatively correlated with post-thaw viability (r=−0.83;P=0.0116) and mitochondrial function (r=−0.91;P=0.0016). By FCM-based assessments of DNA integrity, whereby increased fluorochrome binding indicated more fragmentation, higher levels were negatively correlated with count (r=−0.77;P<0.0001) and pre-freeze viabilities (r=−0.66;P=0.0004). Fragmentation was higher in isotonic buffer (P=0.0234). To increase reproductive capacity of natural populations, the strategy and protocols developed can serve as a template for use with other imperiled fish species, biomonitoring, and genome banking.
Racial Differences Among Children With Primary Hypertension
Authors: Brady Tammy M. , Fivush Barbara , Parekh Rulan S. , Flynn Joseph T.
Published: October 2010

OBJECTIVE:

Race is a known risk factor for hypertension and cardiovascular disease in adults and influences blood pressure (BP) in children. We sought to determine if there are differences in clinical, laboratory, or echocardiographic characteristics among children with primary hypertension from different racial groups.

PATIENTS AND METHODS:

Study participants were 184 children aged 3 to 20 years with a diagnosis of primary hypertension who were examined at 1 of 3 participating centers at the time of initial evaluation of elevated BP. Black children were categorized as African American (AA) and nonblack children as non-AA. Comparisons were made for the entire group and after stratification according to age (<13 or ≥13 years).

RESULTS:

Overall, children categorized as AA had a higher prevalence of overweight/obesity and left ventricular hypertrophy and had higher plasma renin activity than children who were categorized as non-AA. After age stratification, these differences remained only in the children younger than 13 years old; there were no differences in these findings among children aged 13 years or older. AA children who were aged 13 years or older, however, had higher BPs for both casual and ambulatory measurements. Specifically, they had higher casual diastolic BP, higher 24-hour diastolic BP, higher daytime systolic and diastolic BP, and higher BP loads at night and over a 24-hour period compared with non-AA children who were aged 13 years or older.

CONCLUSIONS:

These data indicate that black children with primary hypertension may be at increased cardiovascular risk compared with nonblack children with primary hypertension. However, the high prevalence of overweight/obesity and left ventricular hypertrophy in all youth with primary hypertension demonstrates the need for greater preventive and therapeutic efforts aimed at reducing cardiovascular risk in this vulnerable population.
Peering Into the Future: Pediatrics in a Changing World
Authors: Leslie Laurel K. , Slaw Kenneth M. , Edwards Anne , Starmer Amy J. , Duby John C. ,   Members of the Vision of Pediatrics 2020 Task Force
Published: October 2010

Over the last decade, health care has experienced continuous, capricious, and ever-accelerating change. In response, the American Academy of Pediatrics convened the Vision of Pediatrics (VOP) 2020 Task Force in 2008. This task force was charged with identifying forces that affect child and adolescent health and the implications for the field of pediatrics. It determined that shifts in demographics, socioeconomics, health status, health care delivery, and scientific advances mandate creative responses to these current trends. Eight megatrends were identified as foci for the profession to address over the coming decade. Given the unpredictable speed and direction of change, the VOP 2020 Task Force concluded that our profession needs to adopt an ongoing process to prepare for and lead change. The task force proposed that pediatric clinicians, practices, organizations, and interest groups embark on a continual process of preparing, envisioning, engaging, and reshaping (PEER) change. This PEER cycle involves (1) preparing our capacity to actively participate in change efforts, (2) envisioning possible futures and potential strategies through ongoing conversations, (3) engaging change strategies to lead any prioritized changes, and (4) reshaping our futures on the basis of results of any change strategies and novel trends in the field. By illustrating this process as a cycle of inquiry and action, we deliberately capture the continuous aspects of successful change processes that attempt to peer into a multiplicity of futures to anticipate and lead change.
Pediatrics in the Year 2020 and Beyond: Preparing for Plausible Futures
Authors: Starmer Amy J. , Duby John C. , Slaw Kenneth M. , Edwards Anne , Leslie Laurel K. ,   Members of the Vision of Pediatrics 2020 Task Force
Published: October 2010

Although the future of pediatrics is uncertain, the organizations that lead pediatrics, and the professionals who practice within it, have embraced the notion that the pediatric community must anticipate and lead change to ultimately improve the health of children and adolescents. In an attempt to proactively prepare for a variety of conceivable futures, the board of directors of the American Academy of Pediatrics established the Vision of Pediatrics 2020 Task Force in 2008. This group was charged to think broadly about the future of pediatrics, to gather input on key trends that are influencing the future, to create likely scenarios of the future, and to recommend strategies to best prepare pediatric clinicians and pediatric organizations for a range of potential futures. The work of this task force led to the development of 8 “megatrends” that were identified as highly likely to have a profound influence on the future of pediatrics. A separate list of “wild-card” scenarios was created of trends with the potential to have a substantial influence but are less likely to occur. The process of scenario-planning was used to consider the effects of the 8 megatrends on pediatrics in the year 2020 and beyond. Consideration of these possible scenarios affords the opportunity to determine potential future pediatric needs, to identify potential solutions to address those needs, and, ultimately, to proactively prepare the profession to thrive if these or other future scenarios become realities.
Tremor: adaptação de uma escala clínica
Authors: Nicaretta Denise Hack , Pereira João Santos , Pimentel Maria Lúcia Vellutini
Published: October 2010

Adaptamos a escala clínica para avaliação de tremor de Fahn, Tolosa e Marín para a monitorização em nosso meio dos pacientes com tremor. Aplicamos essa escala em 123 pacientes com esse distúrbio do movimento, sem restrição etiológica ou de faixa etária, selecionados aleatoriamente no Ambulatório de Medicina Integral e no Serviço de Pronto Atendimento do Hospital Universitário Pedro Ernesto da Universidade do Estado do Rio de Janeiro. Embora tenham sido observadas algumas variáveis influenciando nos escores da escala, estas não parecem ser relevantes para alterar a padronização da mesma e sua aplicabilidade clínica.
Somatotrophic and corticotrophic function outcome after transesphenoidal surgery in patients with sellar tumors and pre-operative endocrine deficits
Authors: Pimentel-Filho Fernando R. , Salgado Luis Roberto , Cukiert Arthur , Liberman Bernardo
Published: October 2010

Sixteen patients with sellar tumors that were treated surgically and who had pre-operative somatotrophic and corticotrophic function deficits were submitted to pre- and early post-operative insulin tolerance tests (ITTs). Seven patients had non-functioning adenomas, 5 had prolactinomas, 3 had craniopharyngioma and 1 had cordoma of the clivus. All patients had macro-tumors and none received radiotherapy within the studied period. Seven patients had GH, 4 had Cortisol and 5 had both GH/cortisol function pre-operative deficit. Five patients with isolated GH, 4 with isolated Cortisol and 3 with both GH/cortisol deficiencies showed a postoperative functional recovery. New Cortisol secretion deficits were observed in 2 patients postoperatively and both required long-term steroid replacement. These data suggest that preoperative endocrine deficits may be reversible after surgical decompression of the sellar region and that new endocrine deficits are rarely seen after surgery. All such patients should be tested postoperatively from an endocrinological point of view to reevaluate the need for replacement therapies.
The concept of nemesis in psychoneurosis
Authors: Chapman A. H. , Chapman-Santana Miriam , Vieira e Silva Djalma
Published: October 2010

A patient who has a nemesis fear as the basic process in his psychoneurosis feels that he is destined to repeat the life course of one of his parents to eventual long-term psychosis, or incapacitating physical illness or death by illness or accident. He feels that this will occur at about the same age as that at which his parent suffered his misfortune. The patient during his childhood and adolescence had a traumatic relationship with this parent, and is haunted by guilt feelings about it, and fears that avenging destiny, or nemesis, requires that he pay with a similar misfortune for that which he feels he caused. These patients improve much in psychotherapy, but the underlying nemesis fear, though much reduced in severeity, is not entirely eliminated.
Desmielinização e remielinização após múltiplas injeções intramedulares de brometo de etídio em ratos Wistar
Authors: Fernandes Cristina Gevehr , Graça Dominguita Lühers , Pereira Luis Antônio Violin Dias
Published: October 2010

O modelo de desmielinização do brometo de etídio foi utilizado para estudar a reação do sistema nervoso central frente a múltiplos episódios de desmielinização tóxica. Foram utilizados 27 ratos Wistar, submetidos a 2,3 ou 4 injeções de 1μl de solução 0,1 % de brometo de etídio (19 ratos) ou de solução salina 0,9% (8 ratos) em diferentes pontos da medula espinhal. Os intervalos entre as injeções variaram de 28 a 42 dias. Dez dias após a última injeção os animais foram perfundidos com glutaraldeído 2,5%. As medulas espinhais foram avaliadas pela macroscopia, microscopia óptica de cortes semifinos e microscopia eletrônica de transmissão. As lesões foram caracterizadas por desmielinização primária focal, com preservação das estruturas vasculares, e variavam em tamanho e características histológicas. Remielinização pode ser observada, ou não, de acordo com o tipo de lesão. Como conseqüência das injeções múltiplas e seqüenciais de brometo de etídio, o sistema nervoso central pareceu modificar sua capacidade de responder a um estímulo inflamatório, mas não variou seu padrão de remielinização.
Hemiatrofia facial progressiva (doença de Parry-Romberg): relato de dois casos associados a trigeminalgia e câimbras
Authors: Brito José Correia de Farias , Holanda Maurus Marques de Almeida , Holanda Glerystane , Silva José Alberto Gonçalves da
Published: October 2010

Os autores relatam dois casos de hemiatrofia facial progressiva (HFP), ambos do sexo feminino, associados à hiperexcitabilidade neuromuscular, representada por dores neurálgicas e espasmos musculares (câimbras) numa hemiface. Uma das pacientes (Caso 1), com 41 anos de idade, começou a notar a presença de atrofia no lado esquerdo da face, ao término da primeira década de vida. Nos últimos 3 meses, achando-se a doença estacionaria, a paciente passou a sofrer crises álgicas típicas de neuralgia do trigêmeo, cujo alívio só foi possível através de tratamento neurocirúrgico. A outra paciente (Caso 2), com 33 anos de idade, tem uma história de doença de 8 anos de duração, quando notou o desenvolvimento de atrofia ao nível da bochecha direita. Há cerca de 2 meses observou redução do diâmetro da coxa direita, o que sugere achar-se a doença em plena atividade. Freqüentemente, é acometida de espasmos dolorosos (câimbras) na região submandibular direita, provocados, algumas vezes, pela abertura da boca. Uma possível relação entre os fenômenos de irritação neuromuscular e a HFP é discutida.