bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological treatment of disruptive behavior in Smith–Magenis syndrome
Authors: Laje Gonzalo , Bernert Rebecca , Morse Rebecca , Pao Maryland , Smith Ann C.M. 
Published: October 2010

AbstractSmith–Magenis syndrome (SMS) is a complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2. Children and adults with SMS appear to have unique neurobehavioral problems that include: sleep disturbance, self‐injurious and maladaptive behaviors, stereotypies, and sensory integration disorders. We gathered retrospective psychotropic use information from parents or other caregivers of 62 individuals with SMS who were asked about use of psychotropic medication from a list of commonly used psychiatric medications. For those drugs identified, respondents were asked to rate the experience with the particular medication using a likert‐type scale. Drugs were grouped into seven main categories: (1) stimulants; (2) antidepressants; (3) antipsychotics; (4) sleep aides; (5) mood stabilizers; (6) alpha 2 agonists; and (7) benzodiazepines. Relative frequencies, means and standard deviations pertaining to age and medication effect were derived for each medication category. Six of the seven medication categories examined showed no meaningful deviations from the “no change” score. The benzodiazepine group showed a mild detrimental effect. There were no gender differences in efficacy. Use of psychotropic medication started early in life (mean age 5 years), particularly with sleep aides. Although no medication category was identified as efficacious in SMS, all the categories reported herein may be considered as an option for brief symptomatic relief. Published 2010 Wiley‐Liss, Inc.
The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment
Authors: Morris Colleen A. 
Published: October 2010

AbstractWilliams syndrome (WS), caused by hemizygous deletion of 1.55–1.8 Mb of chromosome 7q11.23, has a recognizable behavior phenotype that is an important diagnostic sign. Individuals with WS are overly friendly, gregarious, empathetic, and loquacious, but have difficulty interpreting social cues and in making and keeping friends. The neurodevelopmental profile is characterized by overall intellectual disability, strength in concrete language, weakness in visuospatial construction, difficulties with sensory modulation, balance, and tool use, and problems with attention and anxiety. Structural and functional MRI studies demonstrate that gray matter deficiency in the intraparietal sulcus alters processing of spatial information in the dorsal stream (spatial) visual pathway, likely contributing to the visuospatial construction disability. Deficient regulation of the amygdala by the oribitofrontal cortex appears to underlie both the social disinhibition and the specific phobia common in WS. Continued study of cognition, behavior, neuroanatomy, and function in WS will continue to elucidate the neurogenetic underpinnings of human behavior. © 2010 Wiley‐Liss, Inc.
Ciprofloxacin prevents myelination delay in neonatal rats subjected to E. coli sepsis
Authors: Loron Gauthier , Olivier Paul , See Hélène , Le Saché Nolwenn , Angulo Leslie , Biran Valérie , Brunelle Nadège , Besson‐Lescure Bernadette , Kitzis Marie‐Dominique , Pansiot Julien , Bingen Edouard , Gressens Pierre , Bonacorsi Stéphane , Baud Olivier 
Published: October 2010

AbstractObjectivePerinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti‐inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis.MethodsWe adapted an Escherichia coli sepsis model to 5‐day‐old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory‐induced brain damage compared with cefotaxime (CTX) (treatment of reference).ResultsCompared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX.InterpretationThese data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis‐induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation. ANN NEUROL 2011
HLA–DRB1*0407 and *1304 are risk factors for scleroderma renal crisis
Authors: Nguyen Binh , Mayes Maureen D. , Arnett Frank C. , del Junco Deborah , Reveille John D. , Gonzalez Emilio B. , Draeger Hilda T. , Perry Marilyn , Hendiani Amir , Anand Kiran K. , Assassi Shervin 
Published: October 2010

AbstractObjectiveTo examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc).MethodsSSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA.ResultsOverall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti–RNA polymerase III (anti–RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti–RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA–DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27–8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30–15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti–RNAP III, and ACAs, remained significantly associated with SRC in the final model.ConclusionThe results of this study suggest that DRB1*0407 and *1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.
Role of innate immunity in a murine model of histidyl–transfer RNA synthetase (Jo‐1)–mediated myositis
Authors: Soejima Makoto , Kang Eun Ha , Gu Xinyan , Katsumata Yasuhiro , Clemens Paula R. , Ascherman Dana P. 
Published: October 2010

AbstractObjectivePrevious studies in humans and in animal models support a key role of histidyl–transfer RNA synthetase (HisRS; also known as Jo‐1) in the pathogenesis of idiopathic inflammatory myopathy. While most investigations have focused on the ability of HisRS to trigger adaptive immune responses, in vitro studies clearly indicate that HisRS possesses intrinsic chemokine‐like properties capable of activating the innate immune system. The purpose of this study was therefore to examine the ability of HisRS to direct innate immune responses in a murine model of myositis.MethodsFollowing intramuscular immunization with soluble HisRS in the absence of exogenous adjuvant, selected strains of mice were evaluated at different time points for histopathologic evidence of myositis. Enzyme‐linked immunosorbent assay–based assessment of autoantibody formation and carboxyfluorescein succinimidyl ester proliferation studies provided complementary measures of B cell and T cell responses triggered by HisRS immunization.ResultsCompared to appropriate control proteins, a murine HisRS fusion protein induced robust, statistically significant muscle inflammation in multiple congenic strains of C57BL/6 and NOD mice. Time course experiments revealed that this inflammatory response occurred as early as 7 days postimmunization and persisted for up to 7 weeks. Parallel immunization strategies in DO11.10/RAG‐2–/– and C3H/HeJ (TLR‐4–/–) mice indicated that the ability of murine HisRS to drive muscle inflammation was not dependent on B cell receptor or T cell receptor recognition and did not require Toll‐like receptor 4 signaling.ConclusionCollectively, the findings of these experiments support a model in which HisRS can trigger both innate and adaptive immune responses that culminate in severe muscle inflammation that is the hallmark of idiopathic inflammatory myopathy.
An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: A three‐month randomized, placebo‐controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents
Authors: Genovese Mark C. , Kavanaugh Arthur , Weinblatt Michael E. , Peterfy Charles , DiCarlo Julie , White Michael L. , O'Brien Maryann , Grossbard Elliott B. , Magilavy Daniel B. 
Published: October 2010

AbstractObjectiveTo assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies.MethodsA total of 219 patients with active RA in whom treatment with biologic agents had failed were enrolled in a 3‐month multicenter, randomized, double‐blind, placebo‐controlled trial of R788. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at month 3. Secondary end points included changes in inflammation and damage, as assessed by magnetic resonance imaging (MRI), and changes in the Disease Activity Score.ResultsThe ACR20 response in the R788 100 mg twice daily group was 38%, versus 37% in the placebo group, at month 3. No significant differences were achieved in the ACR20, ACR50, or ACR70 response levels at 3 months. There were differences between the groups from baseline to month 3 in the secondary end points C‐reactive protein (CRP) level and synovitis score on MRI. There were baseline differences in steroid use, prior biologic use, and synovitis score on MRI between the R788 group and the placebo group that may have affected the outcomes. A high placebo response rate was seen in this trial, and exploratory analysis suggested that this may in part have been driven by patients who entered the trial with an elevated erythrocyte sedimentation rate but normal CRP level.ConclusionOur findings indicate that there were no differences in the primary end point between the R788 and placebo groups. Differences were observed between the R788 and placebo groups in secondary end points, particularly in those patients who entered the study with an elevated CRP level.
Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment
Authors: Stamp Lisa K. , O'Donnell John L. , Zhang Mei , James Jill , Frampton Christopher , Barclay Murray L. , Chapman Peter T. 
Published: October 2010

AbstractObjectiveTo determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance–based dose in patients with gout.MethodsPatients with gout who had been receiving a stable dose of allopurinol for ≥1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.ResultsNinety patients were enrolled. The mean age of the patients was 58.7 years (range 27–83 years), 87.9% were male, and 81.9% were of European ancestry. Forty‐five patients had a serum urate concentration of ≥0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level ≥0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/liter (72% versus 88.5%; P = 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.ConclusionIncreasing the dose of allopurinol above the proposed creatinine clearance–based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.
Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum
Authors: Shimada K , Nara S , Esaki M , Sakamoto Y , Kosuge T , Hiraoka N 
Published: October 2010

AbstractBackgroundMajor hemihepatectomy for advanced gallbladder carcinoma remains controversial as it is associated with serious postoperative complications and poor prognosis.MethodsAll those who underwent extended right hemihepatectomy were identified from a database of patients with gallbladder carcinoma who had surgical resection between 1999 and 2009. The clinicopathological data for these patients were analysed retrospectively.ResultsA total of 126 patients underwent surgical resection, 35 of whom had extended right hemihepatectomy. There were no deaths, but 16 patients had complications. The mean(s.d.) duration of operation and blood loss were 564(206) min and 1472(1268) ml respectively. No blood transfusions were needed in 28 patients. Tumour stage (International Union Against Cancer, sixth edition) was IIA in four, IIB in four, III in 15 and IV in 12 patients. The overall 5-year survival rate was 17 per cent with a median survival of 2·2 years. Three patients survived more than 5 years. The presence of hepatic metastases and gallbladder carcinoma originating from the cystic duct were indicators of poor prognosis.ConclusionExtended right hemihepatectomy for gallbladder cancer is safe and may contribute to long-term survival in selected patients.
Comparison of treatment and outcome information between a clinical trial and the National Cancer Data Repository
Authors:   CLASICC trialists, Morris E J A , Jordan C , Thomas J D , Cooper M , Brown J M , Thorpe H , Cameron D , Forman D , Jayne D , Quirke P 
Published: October 2010

Abstract

Background
Clinical trials are important but many factors limit their success, including the costs of long-term follow-up and participants often not being representative of the general population. The National Cancer Data Repository (NCDR) contains data about patients with cancer in England that may help overcome some of these problems. This study compared treatment and outcome information between the Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASICC) trial and the NCDR.

Methods
Participants in the CLASICC trial were identified in the NCDR, and management and outcome data were compared. Data on all surgically treated English patients with colorectal cancer were extracted from the NCDR and compared with those of CLASICC participants.

Results
Survival and treatment data for those in the CLASICC trial were available in the NCDR for 98·9 and 95·8 per cent of patients respectively. There was agreement in operation type for 86·1 per cent of patients but surgical approach coding was poor, with only 58·4 per cent of laparoscopic procedures coded in the NCDR. There was no significant difference in survival calculated from either data set. Surgical information was available in the NCDR for 19 of 20 trial participants with missing data. The trial population was younger (P &lt; 0·001), of better socioeconomic status (P = 0·001) and with earlier disease (P &lt; 0·001) than the general surgically treated colorectal cancer population. Rectal cancer survival was similar, but 5-year survival after treatment of colonic cancer was significantly better in the trial than in the national data: 57·1 (95 per cent confidence interval 51·5 to 62·3) versus 49·8 (49·3 to 50·2) per cent respectively.

Conclusion
The National Cancer Data Repository demonstrates potential for informing clinical trials, but limitations prevent full intention-to-treat analyses.
Structure and Dynamic Features of an Intramolecular Frustrated Lewis Pair
Authors: Axenov Kirill V. , Mömming Cornelia M. , Kehr Gerald , Fröhlich Roland , Erker Gerhard 
Published: October 2010

AbstractDi(mesityl)cyclohexenylphosphine undergoes hydroboration with Piers' borane [HB(C6F5)2] to yield the cyclohexylene‐anellated frustrated Lewis pair 5. This P/B pair splits H2 with the formation of the product 4 and adds to the CO double bond of phenyl isocyanate to yield 6. In the crystal, compound 5 features a puckered four‐membered heterocyclic core structure with a long PB bond (av. 2.197(5) Å). The activation energy of the PB cleavage of the frustrated Lewis pair 5 was determined by dynamic 19F NMR spectroscopy at ΔG≠(298 K)=12.1±0.3 kcal mol−1.
Pain management in intellectually disabled children: Assessment, treatment, and translational research
Authors: Valkenburg Abraham J. , van Dijk Monique , de Klein Annelies , van den Anker Johannes N. , Tibboel Dick 
Published: October 2010

AbstractThe primary focus of pain research in intellectually disabled individuals is still on pain assessment. Several observational pain assessment scales are available, each with its own characteristics, its own target group and its own validated use. Observational studies report differences in the treatment of intra‐ and postoperative pain of intellectually disabled children and almost all children with intellectual disability have comorbidities that need to be addressed. The scope of research has started to broaden. In this review we aim to answer the question: Can we integrate validated ways of pain assessment and postoperative pain treatment in intellectually disabled children to develop specific analgesic algorithms? Regrettably there is little knowledge on possible interaction effects and other relevant pharmacological issues. Possible genotype–phenotype associations related to pain in children with Down syndrome have several promises as six possible candidate genes are located on chromosome 21. In conclusion, the pain assessment tools for intellectually disabled children are there. We should now focus on tailoring the pain treatment. To this aim we need to perform pharmacokinetic and pharmacodynamic studies of analgesics and obtain information about the genotype–phenotype relationships for pain. This can lead to the development of specific analgesic algorithms. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:248–257.
Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature
Authors: Häßler Frank , Reis Olaf 
Published: October 2010

AbstractThe review presented here describes the state of the art of pharmacological treatment of aggression in subjects with mental retardation (MR) summing up results for both, children and adults. In general, psychopharmacological treatment of disruptive behavior in individuals with MR is similar to the treatment in subjects without MR. Compared to individuals without MR medication should “start lower and go slower.” For children and adults results were similar but were obtained by somewhat different medications. There is evidence for the conventional antipsychotic zuclopenthixol having positive effects on disruptive behavior. Most studies described the atypical antipsychotic risperidone to control severe self‐injurious behavior and other behavior problems in a variety of diagnoses. Anticonvulsants, antidepressants, and anxiolytic medications are reported as effective as well for the treatment of individuals with disruptive behavior. Aggression‐related behavior often gets treated with stimulants or with stimulants combined with atypical neuroleptics. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:265–272.
Amino acid‐induced gene expression profiling in clonal β‐cell line INS‐1E cells
Authors: Liu Zhenping , Luo Yonglun , Jeppesen Per Bendix , Gregersen Søren , Hermansen Kjeld 
Published: October 2010

AbstractBackgroundThere is abundant evidence that glucotoxicity and lipotoxicity contribute to impaired β‐cell function in type 2 diabetes. Interestingly, amino acid (AA) derangement is also a characteristic part of the diabetic state. The acute effects of AA on pancreatic β‐cell function have been widely explored; however, to our knowledge, the chronic effects of AA, e.g. proline (Pro), homocysteine (Hcy), and leucine (Leu), on pancreatic β‐cell function and integrity have not yet been studied. We aimed to investigate global alterations in β‐cell gene expression after long‐term exposure of clonal INS‐1E cells to elevated level of specific AA in vitro.MethodsGlobal gene expression profiling was performed to characterize genes differently modified by Pro, Hcy, and Leu, respectively, in INS‐1E cells.ResultsGene expression profiling revealed significant changes in INS‐1E cell mRNAs involved in the control of several aspects of β‐cell function, e.g. epigenetic regulation of gene expression, metabolism, innate and adaptive immune responses, cellular signalling, protein synthesis, apoptosis, and cellular stress response.After 72 h, INS‐1E cells were differentially regulated (≥1.5‐ or ≤ −1.5‐fold) by Pro (295 transcripts), Hcy (301 transcripts), and Leu (701 transcripts). It appears that Hcy effects changes opposite to those induced by Leu and/or Pro.ConclusionsAA appears to participate in and to influence many physiological processes including those involved in cholesterol metabolism, immune responses, and oxidative phosphorylation. Whether such events promote the β‐cell dysfunction and the β‐cell failure in diabetes remains to be elucidated. Our data strongly indicate that AA elevation may take part in the progressive development of type 2 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.