bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variation in the Serotonin Transporter Gene (5-HTTLPR, Rs25531) Influences the Analgesic Response to the Short Acting Opioid Remifentanil in Humans
Authors: Kosek Eva , Jensen Karin B , Lonsdorf Tina B , Schalling Martin , Ingvar Martin 
Published: July 2009

BackgroundThere is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders.ResultsAt baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SAand SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression.ConclusionThis is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.
Papillary fibroelastoma of the left atrial wall: a case report
Authors: Bicer Murat , Cikirikcioglu Mustafa , Pektok Erman , Müller Hajo , Dettwiler Sarah , Kalangos Afksendiyos 
Published: July 2009

Abstract
Cardiac papillary fibroelastoma is a rare, benign cardiac tumor. It often arises from valvular endocardium, and non-valvular endocardial location is rare. Although transthoracic echocardiography is usually sufficient for the diagnosis of most cardiac tumors, small tumors such as papillary fibroelastoma may be missed. Transesophageal echocardiography is superior to transthoracic echocardiography in diagnosing these tumors. Despite their benign histology, and independent of their size, they should be resected surgically because of their high potential for embolization.
In this report, we present a case of papillary fibroelastoma located on the left atrial wall, presenting with symptoms of cerebral ischemia. The patient was treated surgically for the prevention of further embolic complications. Pertinent literature is also reviewed for this rare and benign cardiac tumor.
Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity
Authors: Toussirot Éric , Saas Philippe , Deschamps Marina , Pouthier Fabienne , Perrot Lucille , Perruche Sylvain , Chabod Jacqueline , Tiberghien Pierre , Wendling Daniel 
Published: July 2009

Abstract
Introduction
Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied.

Methods
Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR).

Results
High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL.

Conclusions
SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA.
Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand bone loss in patients with rheumatoid arthritis of short duration: a longitudinal study
Authors: Bøyesen Pernille , Hoff Mari , Ødegård Sigrid , Haugeberg Glenn , Syversen Silje W , Gaarder Per I , Okkenhaug Cecilie , Kvien Tore K 
Published: July 2009

Abstract
Introduction
Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration.

Methods
163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up.

Results
During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively.

Conclusions
Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.
Serum Interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study
Authors: Liu Kathleen D , Altmann Christopher , Smits Gerard , Krawczeski Catherine D , Edelstein Charles L , Devarajan Prasad , Faubel Sarah 
Published: July 2009

AbstractIntroductionAcute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation.MethodsThis was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA.ResultsIL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI.ConclusionsSerum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.
Rural–urban migration and depression in ageing family members
left behind
Authors: Abas Melanie A. , Punpuing Sureeporn , Jirapramukpitak Tawanchai , Guest Philip , Tangchonlatip Kanchana , Leese Morven , Prince Martin 
Published: July 2009

BackgroundIt has been suggested that rural–urban migration will have adverse
consequences for older parents left behind.AimsTo describe correlates of outmigration and to estimate any association
between outmigration of children and depression in rural-dwelling older
parents.MethodPopulation-based survey of 1147 parents aged 60 and over in rural
Thailand. We randomly oversampled parents living without children. We
defined an outmigrant child as living outside their parent's district,
and measured depression as a continuous outcome with a Thai version of
the EURO–D.ResultsOutmigration of all children, compared with outmigration of some or no
children, was independently associated with less depression in parents.
This association remained after taking account of social support, parent
characteristics, health and wealth. Parents with all children outmigrated
received more economic remittances and they perceived support to be as
good as that of those with children close by.ConclusionsOutmigration of children was not associated with greater depression in
older parents and, after taking account of a range of possible
covariables, was actually associated with less parental depression. This
could be explained by pre-existing advantages in families sending more
migrants and by the economic benefits of migration.
Randomised evaluation of assertive community treatment: 3-year outcomes
Authors: Killaspy Helen , Kingett Stella , Bebbington Paul , Blizard Robert , Johnson Sonia , Nolan Fiona , Pilling Stephen , King Michael 
Published: July 2009

SummaryThe only randomised controlled trial to test high-fidelity assertive community treatment (ACT) in the UK (the Randomised Evaluation of Assertive Community Treatment (REACT) study) found no advantage over usual care from community mental health teams in reducing the need for inpatient care and in other clinical outcomes, but participants found ACT more acceptable and engaged better with it. One possible reason for the lack of efficacy of ACT might be the short period of follow-up (18 months in the REACT study). This paper reports on participants' service contact, in-patient service use and adverse events 36 months after randomisation.
End of the road for treatment-as-usual studies?
Authors: Burns Tom 
Published: July 2009

SummaryUsing treatment as usual (TAU) in trials has obscured the repeated finding that assertive outreach has never reduced hospitalisation when compared with treatment by multidisciplinary teams (community mental health teams, CMHTs). Its use has delayed recognising that CMHTs are the more cost-effective, evidence-based approach. The term should be abandoned and trials should compare two equally well-defined services.
Expanding the Spectrum of Mutations in GH1 and GHRHR: Genetic Screening in a Large Cohort of Patients with Congenital Isolated Growth Hormone Deficiency
Authors: Alatzoglou Kyriaki S. , Turton James P. , Kelberman Daniel , Clayton Peter E. , Mehta Ameeta , Buchanan Charles , Aylwin Simon , Crowne Elisabeth C. , Christesen Henrik T. , Hertel Niels T. , Trainer Peter J. , Savage Martin O. , Raza Jamal , Banerjee Kausik , Sinha Sunil K. , Ten Svetlana , Mushtaq Talat , Brauner Raja , Cheetham Timothy D. , Hindmarsh Peter C. , Mullis Primus E. , Dattani Mehul T. 
Published: July 2009

Context: It is estimated that 3–30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics.
Patients and Methods: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR. To explore the possibility of an association of GH1 abnormalities with multiple pituitary hormone deficiencies, we have screened 62 patients with either multiple pituitary hormone deficiencies (42 pedigrees), or IGHD with an ectopic posterior pituitary (21 pedigrees).
Results: Mutations in GH1 and GHRHR were identified in 41 patients from 21 pedigrees (11.1%), with a higher prevalence in familial cases (38.6%). These included previously described and novel mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a&gt;t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, −4.7 ± 1.6 SDS vs. −3.4 ± 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR.
Conclusions: IGHD patients with severe growth failure and a positive family history should be screened for genetic mutations; the evolving endocrinopathy observed in some of these patients suggests the need for long-term follow-up.
Results suggest screening for mutations in GH1 and GHRHR in patients of certain ethnic backgrounds with severe growth failure and a positive family history.
Fatty Acid Metabolism in the Elderly: Effects of Dehydroepiandrosterone and Testosterone Replacement in Hormonally Deficient Men and Women
Authors: Koutsari Christina , Ali Asem H. , Nair K. Sreekumaran , Rizza Robert A. , O'Brien Peter , Khosla Sundeep , Jensen Michael D. 
Published: July 2009

Context: Aging, low dehydroepiandrosterone (DHEA), and testosterone are associated with increased adiposity and metabolic risk. Treatment with these hormones may improve these abnormalities.
Objective: The objective of the study was to determine effects of aging, DHEA, or testosterone replacement on adiposity, meal fat partitioning, and postabsorptive lipolysis.
Design: This was a cross-sectional, 2-yr, double-blind, randomized, placebo-controlled trial.
Setting: The study was conducted in the general community.
Patients: Elderly women and men (≥60 yr) with low DHEA sulfate (women and men) and bioavailable testosterone (men) concentrations and young adults.
Interventions: Thirty elderly women each received 50 mg DHEA or placebo daily for 2 yr. Thirty elderly men received 75 mg DHEA, 29 received 5 mg testosterone (patch), and 32 received placebo daily for 2 yr. Thirty young women and 32 young men served as controls.
Main Outcome Measures: In vivo measures of meal fat storage into sc fat, postabsorptive lipolysis, and regional adiposity at baseline and after treatment.
Results: At baseline, the elderly had more body fat, greater systemic lipolysis (women, P = 0.0003; men, P &lt; 0.0001) adjusted for resting energy expenditure, greater meal fat oxidation (women, P = 0.026; men, P = 0.0025), and less meal fat storage in sc fat (women, P = 0.0139; men, P= 0.0006). Although testosterone treatment increased meal fat storage into upper- vs. lower-body fat in elderly men, neither hormone affected regional adiposity, meal fat oxidation, or systemic lipolysis.
Conclusions: Aging, in the context of low DHEA sulfate (women and men) and bioavailable testosterone (men) concentrations, is associated with changes in meal fat partitioning and postabsorptive lipolysis that are not corrected by DHEA and only partly corrected by testosterone replacement.
DHEA or testosterone treatment of hormone-deficient elderly does not normalize adipose tissue lipolysis, but testosterone restores a “youthful” meal fat storage pattern in elderly men.
Uncoupling Protein-1 and Related Messenger Ribonucleic Acids in Human Epicardial and Other Adipose Tissues: Epicardial Fat Functioning as Brown Fat
Authors: Sacks Harold S. , Fain John N. , Holman Ben , Cheema Paramjeet , Chary Aron , Parks Frank , Karas James , Optican Robert , Bahouth Suleiman W. , Garrett Edward , Wolf Rodney Y. , Carter Russell A. , Robbins Todd , Wolford David , Samaha Joseph 
Published: July 2009

Context: Uncoupling protein-1 (UCP-1) is the inner mitochondrial membrane protein that is a specific marker for and mediator of nonshivering thermogenesis in brown adipocytes.
Objective: This study was performed to better understand the putative thermogenic function of human epicardial fat.
Design: We measured the expression of UCP-1 and brown adipocyte differentiation transcription factors PR-domain-missing 16 (PRDM16) and peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) in epicardial, substernal, and sc thoracic, abdominal, and leg fat.
Setting: The study was conducted at a tertiary care hospital cardiac center.
Patients: Forty-four patients had coronary artery bypass surgery, and six had heart valve replacement.
Interventions: Fat samples were taken at open heart surgery.
Results: UCP-1 expression was 5-fold higher in epicardial fat than substernal fat and barely detectable in sc fat. Epicardial fat UCP-1 expression decreased with age, increased with body mass index, was similar in women and men and patients on and not on statin therapy, and showed no relationship to epicardial fat volume or waist circumference. UCP-1 expression was similar in patients without and with severe coronary atherosclerosis and metabolic syndrome or type 2 diabetes. PRDM16 and PGC-1α expression was 2-fold greater in epicardial than sc fat. Epicardial fat UCP-1, PRDM16, and PGC1-α mRNAs were similar in diabetics treated with thiazolidinediones compared to diabetics not treated with thiazolidinediones.
Conclusion: Because UCP-1 is expressed at high levels in epicardial fat as compared to other fat depots, the possibility should be considered that epicardial fat functions like brown fat to defend the myocardium and coronary vessels against hypothermia. This process could be blunted in the elderly.
Since uncoupling protein-1 is highly expressed in epicardial fat compared to other fat depots, epicardial fat might function like brown fat, defending the heart against hypothermia.
Management of Altered Hydrocortisone Pharmacokinetics in a Boy with Congenital Adrenal Hyperplasia Using a Continuous Subcutaneous Hydrocortisone Infusion
Authors: Bryan Sinead M. , Honour John W. , Hindmarsh Peter C. 
Published: July 2009

Background: Conventional hydrocortisone dosing schedules do not mimic the normal circadian rhythm of cortisol, making it difficult to optimize treatment in congenital adrenal hyperplasia (CAH).
Case Details: We report a 14.5-year-old boy with CAH who had reduced bioavailability [42% (normal 80% orally and 100% by im route)] and increased clearance [half-life 50 min (normal range, 70–100 min)] of oral doses of hydrocortisone leading to ambient serum 17-hydroxyprogesterone concentrations of 400 nmol/liter (14.5 ng/ml) and androstenedione concentrations of 24.9 nmol/liter (7.1 ng/ml).
Intervention: Using a continuous but variable sc hydrocortisone infusion via an insulin pump, rapid control of his CAH was attained with a normal cortisol circadian profile. Average daily hydrocortisone dose was 17.4–18.6 mg/m2, which produces on average 24-h serum cortisol and 17-hydroxyprogesterone concentrations of 316 nmol/liter (115 ng/ml) and 4.3 nmol/liter (1.4 ng/ml), respectively. Therapy has been maintained over 4 yr with suppression of normal adrenal androgen production and normal progression through puberty.
Conclusions: Continuous sc infusion of hydrocortisone may prove a valuable adjunct to therapy for CAH, particularly in patients requiring high doses of oral hydrocortisone and in those with abnormal hydrocortisone pharmacokinetics.
A boy is described with congenital adrenal hyperplasia and altered hydrocortisone pharmacokinetics managed by continuous subcutaneous hydrocortisone infusion.