bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urea for treatment of acute SIADH in patients with subarachnoid hemorrhage: a single-center experience
Authors: Pierrakos Charalampos , Taccone Fabio Silvio , Decaux Guy , Vincent Jean-Louis , Brimioulle Serge 
Published: November 2012

Abstract

Background
Hyponatremia occurring as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting syndrome is a common complication in patients with subarachnoid hemorrhage (SAH). The efficacy and safety of urea as treatment for SIADH-induced hyponatremia has not been reported in this population.

Methods
This is a retrospective analysis of all patients admitted to our department for nontraumatic SAH between January 2003 and December 2008 (n = 368). All patients with SIADH-induced hyponatremia (plasma sodium < 135 mEq/L, urine sodium > 20 mEq/L, and osmolality > 200 mOsm/kg; absence of overt dehydration or hypovolemia; no peripheral edema or renal failure; no history of adrenal or thyroid disease) routinely received urea per os when hyponatremia was associated with clinical deterioration or remained less than 130 mEq/L despite saline solution administration.

Results
Forty-two patients developed SIADH and were treated with urea. Urea was started after a median of 7 (IQR, 5–10) days and given orally at doses of 15–30 g tid or qid for a median of 5 (IQR, 3–7) days. The median plasma sodium increase over the first day of treatment was 3 (IQR, 1–6) mEq/L. Hyponatremia was corrected in all patients, with median times to Na+ >130 and >135 mEq/L of 1 (IQR, 1–2) and 3 (IQR, 2–4) days, respectively. Urea was well tolerated, and no adverse effects were reported.

Conclusions
Oral urea is an effective and well-tolerated treatment for SIADH-induced hyponatremia in SAH patients.
Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease
Authors: Viatte Sebastien , Flynn Edward , Lunt Mark , Barnes Joanne , Singwe-Ngandeu Madeleine , Bas Sylvette , Barton Anne , Gabay Cem 
Published: November 2012

Abstract
Introduction
The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans.

Methods
RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts.

Results
After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001.

Conclusions
The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.
Stem cell factor contributes to tumorigenesis of mast cells via an autocrine/paracrine mechanism
Authors: Amagai Y , Tanaka A , Matsuda A , Jung K , Ohmori K , Matsuda H 
Published: November 2012

Abstract
Contribution of SCF auto-production to neoplastic growth of mast cells.
Mastocytosis is a disease accompanied by the abnormal expansion and accumulation of mast cells. Although the D816V mutation is detected in most cases of systemic mastocytosis, the mutation is rarely observed in other forms of mastocytosis, such as cutaneous mastocytosis and mast cell leukemia/sarcoma, for which the mechanism of tumorigenesis remains unknown. In this study, we demonstrated a novel mechanism of mast cell tumorigenesis via SCF autocrine/paracrine release. SCF was highly expressed in a WT KIT-expressing HRMC line, contributing to the phosphorylation of KIT. Neutralization of external SCF using a neutralizing antibody or suppression of SCF production by RNA interference inhibited the growth of HRMC cells, indicating the essential role of SCF in cell proliferation. To the best of our knowledge, this is the first report to determine the significant contribution of SCF autoproduction to neoplastic proliferation of mast cells. These results indicate the possibility that targeting SCF production may become a novel treatment for mast cell malignancies.
Integrin subtype-dependent CD18 cleavage under shear and its influence on leukocyte-platelet binding
Authors: Zhang Xiaoyan , Zhan Dongying , Shin Hainsworth Y 
Published: November 2012

Abstract
Fluid shear stress induces differential cleavage of CD18 integrins on leukocyte subpopulations with involvement of cell typespecific proteases and potential effects on platelet binding.
Previous studies showed that exposure of neutrophils to shear stress induces cysteine protease-mediated shedding of surface CD18 integrins involved in leukocyte-platelet interactions. Based on this, we hypothesized that, under noninflamed conditions, shear-induced CD18 cleavage is a control mechanism to minimize spontaneous leukocyte-platelet binding. For this purpose, we characterized the influence of shear on CD18 surface expression and platelet binding by the different leukocyte subsets. Shear stress elicited magnitude- (between 0 and 5 dyn/cm2) and time-dependent reductions in CD18 surface expression. This response was integrin- and cell type-specific, with neutrophils and monocytes exhibiting Mac-1 proteolysis but lymphocytes displaying LFA-1 shedding. Correspondingly, platelet binding, through CD18-fibrinogen interactions, was also influenced by shear exposure in a leukocyte-dependent manner. After treatment with cysteine protease inhibitor E64, neutrophils, but neither monocytes nor lymphocytes, exhibited significantly (P&lt;0.05) enhanced platelet binding and CD18 surface expression under shear. Furthermore, shear exposure significantly (P&lt;0.05) inhibited binding of naïve but not E64-treated neutrophils to fibrinogen. Combined, we provide first evidence that the CD18-cleavage responses of neutrophils to shear interfere with fibrinogen binding and platelet adhesion. These findings have implications as it relates to the efficiency of leukocyte passage through the microcirculation.
Wnt/β-catenin signaling cell-autonomously converts non-hepatic endodermal cells to a liver fate
Authors: So Juhoon , Martin Benjamin L. , Kimelman David , Shin Donghun 
Published: November 2012

Summary
Wnt/β-catenin signaling plays multiple roles in liver development including hepatoblast proliferation and differentiation, hepatocyte differentiation, and liver zonation. A positive role for Wnt/β-catenin signaling in liver specification was recently identified in zebrafish; however, its underlying cellular mechanisms are unknown. Here, we present two cellular mechanisms by which Wnt/β-catenin signaling regulates liver specification. First, using lineage tracing we show that ectopic hepatoblasts, which form in the endoderm posterior to the liver upon activation of Wnt/β-catenin signaling, are derived from the direct conversion of non-hepatic endodermal cells, but not from the posterior migration of hepatoblasts. We found that endodermal cells at the 4–6th somite levels, which normally give rise to the intestinal bulb or intestine, gave rise to hepatoblasts in Wnt8a-overexpressing embryos, and that the distribution of traced endodermal cells in Wnt8a-overexpressing embryos was similar to that in controls. Second, by using an endoderm-restricted cell-transplantation technique and mosaic analysis with transgenic lines that cell-autonomously suppress or activate Wnt/β-catenin signaling upon heat-shock, we show that Wnt/β-catenin signaling acts cell-autonomously in endodermal cells to induce hepatic conversion. Altogether, these data demonstrate that Wnt/β-catenin signaling can induce the fate-change of non-hepatic endodermal cells into a liver fate in a cell-autonomous manner. These findings have potential application to hepatocyte differentiation protocols for the generation of mature hepatocytes from induced pluripotent stem cells, supplying a sufficient amount of hepatocytes for cell-based therapies to treat patients with severe liver diseases.
The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway
Authors: Organista María F. , De Celis Jose F. 
Published: November 2012

Summary
The expression of the spalt genes is regulated by the Decapentaplegic signalling pathway in the Drosophila wing. These genes participate in the patterning of the longitudinal wing veins by regulating the expression of vein-specific genes, and in the establishment of cellular affinities in the central region of the wing blade epithelium. The Spalt proteins act as transcription factors, most likely regulating gene expression by repression, but the identity of their target genes in the wing is still unknown. As a preliminary step to unravel the genetic hierarchy controlled by the Spalt proteins, we have analysed their requirements during wing development, and addressed to what extent they mediate all the functions of the Decapentaplegic pathway in this developmental system. We identify additional functions for Spalt in cell division, survival, and maintenance of epithelial integrity. Thus, Spalt activity is required to promote cell proliferation, acting in the G2/M transition of the cell cycle. The contribution of Spalt to cell division is limited to the central region of the wing blade, as they do not mediate the extra growth triggered by Decapentaplegic signalling in the peripheral regions of the wing disc. In addition, Spalt function is required to maintain cell viability in cells exposed to high levels of Decapentaplegic signalling. This aspect of Spalt function is related to the repression of JNK signalling in the spalt domain of expression. Finally, we further characterise the requirements of Spalt to maintain epithelial integrity by regulating cellular affinities between cells located in the central wing region. Our results indicate that Spalt function mediates most of the requirements identified for Decapentaplegic signalling, contributing to establish the cellular qualities that differentiate central versus peripheral territories in the wing blade.
Prevalence of thyroid dysfunction and effect of contrast medium on thyroid metabolism in cardiac patients undergoing coronary angiography
Authors: Marraccini Paolo , Bianchi Massimiliano , Bottoni Antonio , Mazzarisi Alessandro , Coceani Michele , Molinaro Sabrina , Lorenzoni Valentina , Landi Patrizia , Iervasi Giorgio 
Published: November 2012

Background Iodinated contrast media (CM) may influence thyroid function. Precautions are generally taken in patients with hyperthyroidism, even if subclinical, whereas the risks in patients with hypothyroidism or low triiodothyronine (T3) syndrome are not considered as appreciable. Purpose To assess the presence and type of thyroid dysfunction in patients admitted for coronary angiography (CA), to assess the concentration of free-iodide in five non-ionic CM, and to evaluate changes in thyroid function after CA in patients with low T3 syndrome. Material and Methods We measured free T3, free thyroxine (T4), and thyroid-stimulating hormone (TSH) in 1752 consecutive patients prior to CA and free-iodide in five non-ionic CM. Urinary free-iodide before and 24 h after CA, and thyroid hormone profile 48 h after CA were also made in 17 patients with low T3 syndrome. Patients were followed up for an average duration of 63.5 months. Results The patients were divided into four groups: euthyroidism (60%), low T3 syndrome (28%), hypothyroidism (10%), and hyperthyroidism (2%). The free-iodide resulted far below the recommended limit of 50 μg/mL in all tested CM. In low T3 syndrome, 24-h free-iodide increased after CA from 99.9± 63 ug to 12276±9285 ug (P< 0.0001). A reduction in TSH (4.97±1.1 vs. 4.17±1.1 mUI/mL, P < 0.01) and free T3 (1.44±0.2 vs. 1.25±0.3 pg/mL, P < 0.01), with an increase in free T4 (11.3±2.9 vs. 12.5±3.4 pg/dL, P < 0.001), was found. Patients with functional thyroid disease in the follow-up had a significant lower rate survival compared to euthyroid patients (90.7 vs. 82.2%, P < 0.00001). Conclusion Thyroid dysfunction is frequent in patients who perform a CA, and low T3 syndrome is the predominant feature. The administration of contrast medium may further compromise the thyroid function.
Three-dimensional Look-Locker MRI for evaluation of postcontrast myocardial and blood T1 values: Comparison with two-dimensional Look-Locker and late gadolinium enhancement MRI
Authors: Amano Yasuo , Tachi Masaki , Kumita Shinichiro 
Published: November 2012

Background Two-dimensional (2D) Look-Locker MRI technique can identify myocardial fibrosis, but cannot cover the whole left ventricle during a single scan. Purpose To develop breath-hold three-dimensional (3D) Look-Locker MRI for the evaluation of postcontrast myocardial and blood T1 values and myocardial scarring in the left ventricle. Material and Methods A phantom and 24 patients with myocardial diseases underwent gadolinium-enhanced 2D and 3D Look-Locker MRI using a 1.5-T unit. We compared the T1 value of the phantom and the values of the myocardium and blood in the patients between the two Look-Locker MRI sequences. In the patient study, the scan ordering of the two Look-Locker MRI was selected randomly. We also assessed the ability of the 3D imaging to detect myocardial scarring that was confirmed by late gadolinium enhancement MRI. Results The phantom study showed a good agreement for the T1 value between 2D and 3D Look-Locker MRI. There were no significant differences in the myocardial T1 values after contrast between 2D and 3D Look-Locker MRI or in the T1 values between the two imaging slices on the 3D Look-Locker MRI (P > 0.10). A better agreement for the myocardial T1 values was found when the 3D Look-Locker imaging was performed first. The T1 values for blood were affected by the scan order (P < 0.05). The 3D Look-Locker MRI showed myocardial scarring with a shorter T1 value (290.4 ± 62.7 ms) than those for unscarred myocardium (360.8±30.3 ms). Conclusion Three-dimensional Look-Locker MRI may precisely estimate the postcontrast myocardial and blood T1 values for the entire left ventricle during a single scan.
A Model for Bidirectional Community-Academic Engagement (CAE): Overview of Partnered Research, Capacity Enhancement, Systems Transformation, and Public Trust in Research
Authors: Baquet Claudia R. 
Published: November 2012

The University of Maryland’s Office of Policy and Planning in collaboration with urban and rural community partners, planned and implemented a model for community-academic engagement (CAE) in partnered research and programs. The model addressed health disparities, cancer and tobacco-related diseases, and public trust in research. Environments have flourished that resulted in bidirectional community-academic interactions, and led to transformation of the academic environment and community capacity to identify and address health issues. This collaborative model produced:
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enhanced public trust in research; and
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enhanced community and Academic Health Center (AHC) capacity to address community health needs as partners.
A unique feature of this model is AHC’s shared grant funding with community partners serving diverse and medically underserved communities for predetermined roles in research, policy and educational programs. Over $18 million in grant funding was provided to community organizations. This paper presents an overview of this model as a case study.
Sorafenib therapy decreases the clearance of thyrotropin
Authors: Verloop Herman , Smit Johannes W A , Dekkers Olaf M 
Published: November 2012

ObjectiveThyroid function abnormalities are common during treatment with tyrosine kinase inhibitors such as sorafenib. Suggested causes are direct effects on thyroid tissue and increased extrathyroidal metabolism of serum thyroxine and 3,5,3-triiodothyronine. We postulated that tyrosine kinase inhibitors may affect the peripheral metabolism of TSH as well. The effect of sorafenib on TSH clearance was studied.DesignIn a study of athyreotic patients on TSH suppression therapy, TSH concentrations were measured after recombinant human TSH (rhTSH) injections before and after 26 weeks of sorafenib therapy.MethodsBefore and after the last week of sorafenib therapy, 20 patients with progressive differentiated thyroid carcinoma received a standard dose regimen of two injections 0.9 mg rhTSH on two consecutive days. TSH concentrations were measured 48 h (TSH48 h) and 96 h (TSH96 h) after the first rhTSH injection. The area under the curve (TSH-AUC), reflecting TSH content between 48 and 96 h following rhTSH administration, was calculated.ResultsTSH48 hlevels (120.5 mU/l before vs 146.3 mU/l after;P=0.029), TSH96 hlevels (22.0 mU/l before vs 35.5 mU/l after;P=0.001), and TSH-AUC (142.7 vs 186.8 mU/l;P=0.001) were significantly higher after sorafenib treatment. Higher sorafenib doses were associated with increased changes in TSH96 hand TSH-AUC. In two patients, TSH levels after sorafenib therapy exceeded 200 mU/l.ConclusionsSorafenib therapy is accompanied by higher rhTSH levels, probably due to a decreased TSH clearance. Further studies are recommended to clarify whether a decreased clearance of TSH is sorafenib specific.
Histometric Analysis of the Effect of Enamel Matrix Derivative on the Healing of Periodontal Defects in Rats With Diabetes
Authors: Corrêa Mônica Grazieli , Gomes Campos Mirella L. , Marques Marcelo R. , Casati Marcio Z. , Nociti Francisco H. , Sallum Enilson A. 
Published: November 2012

Background: Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in impaired periodontal repair. There is a lack of information about the outcomes of regenerative approaches under the influence of DM. Enamel matrix derivatives (EMDs) have been used in periodontal regenerative procedures, resulting in improvement of clinical parameters. Thus, the aim of this histomorphometric study is to evaluate the healing of periodontal defects after treatment with EMD under the influence of DM.Methods: Twenty Wistar rats were randomly assigned to two groups: group 1 (G1): DM was induced with a single intraperitoneal injection of streptozotocin (STZ) (n = 10); group 2 (G2): rats were not exposed to STZ (n = 10). Seven days after DM induction, bilateral fenestration defects were created at the buccal aspect of the first mandibular molar. After the surgeries, the defects of each animal were randomly assigned to two subgroups: non‐treated (control) and treated with EMD. The animals were euthanized 21 days later, and the percentage of defect fill (DF), newly formed bone density (BD), and new cementum formation (NCF) were histometrically assessed. The number of osteoclasts was determined by tartrate‐resistant acid phosphatase. Weight and blood glucose were also analyzed. Mann‐Whitney U test was used for comparison among groups and Wilcoxon test for comparison between the start and end times (weight and blood glucose) and between treatments (NCF and number of osteoclasts). One‐way analysis of variance was used to assess DF and BD. Tukey test was used when the analysis of variance test detected significant differences (α = 5%).Results: G1 (DM) showed less DF and BD compared with G2. EMD provided an increased DF in both groups and enhanced BD and NCF only in G2. The number of TRAP‐positive osteoclasts was significantly higher in EMD‐treated sites of G1.Conclusions: DM may produce a significant detrimental effect on BD. EMD may provide greater DF under diabetic or normal conditions; however, it may not significantly increase NCF in animals with DM.
Thermo‐Reversible Green Tea Catechin Gel for Local Application in Chronic Periodontitis: A 4‐Week Clinical Trial
Authors: Chava Vijay Kumar , Vedula Bhargavi Devi 
Published: November 2012

Background: Green tea extract is a naturally occurring antimicrobial agent, consisting of polyphenols (catechin) with anticariogenic, anti‐inflammatory, anticollagenolytic properties. Hence, in the present study, an attempt was made to develop a thermo‐reversible sustained‐release green tea gel and to study its clinical effects on patients with chronic periodontitis (CP).Methods: Thermo‐reversible sustained‐release green tea catechin gel was prepared and tested for its in vitro release characteristics. An in vivo controlled, randomized, split‐mouth single‐evaluator masked study was conducted. Thirty patients with two sites in the contralateral quadrants having probing depths (PDs) of ≥4 mm were selected. Assessment of gingival index (GI), PD, and relative clinical attachment levels (rCALs) was done at baseline and at 4 weeks. Green tea and placebo gels were placed at test and control sites as an adjunct to Phase 1 periodontal therapy.Results: Comparison of the mean ± SD GI, PD, and rCAL values within the test group at baseline (1.92 ± 0.24, 4.93 ± 0.58, and 9.97 ± 0.72, respectively) and the end of 4 weeks (0.01 ± 0.04, 2.87 ± 0.51, and 7.87 ± 0.51, respectively) showed high statistical significance (P <0.001). Comparison of mean ± SD of GI, PD, and rCAL within the control group at baseline (1.95 ± 0.16, 4.77 ± 0.50, and 9.73 ± 0.45, respectively) and the end of 4 weeks (0.16 ± 0.11, 3.8 ± 0.48, and 8.76 ± 0.43, respectively) showed significance with P <0.001. High significance was observed between the delta of measurements (0 to 4 weeks) of GI, PD, and rCAL between test (1.91 ± 0.20, 2.06 ± 0.07, and 2.1 ± 0.21, respectively) and control (1.79 ± 0.05, 0.97 ± 0.02, and 0.97 ± 0.02, respectively) groups.Conclusion: Adjunctive local drug therapy with thermo‐reversible green tea gel has shown to reduce pockets and inflammation during the 4 weeks of the clinical trial in patients with CP.