bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the Src kinase inhibitor saracatinib (AZD0530) on bone turnover in healthy men: A randomized, double-blind, placebo-controlled, multiple-ascending-dose phase I trial
Authors: Hannon Rosemary A , Clack Glen , Rimmer Martin , Swaisland Alan , Lockton J Andrew , Finkelman Richard D , Eastell Richard 
Published: September 2009

Abstract
Src is a nonreceptor tyrosine kinase thought to be essential for osteoclast function and bone resorption. We investigated the effect of the orally available Src inhibitor saracatinib (AZD0530) on bone turnover in healthy men. The study was part of a randomized, double-blind, placebo-controlled multiple-ascending-dose phase I trial of saracatinib. Fifty-nine healthy men (mean age 34.6 years) were divided into five cohorts; four with 12 subjects and one with 11 subjects, and randomized within each cohort in the ratio 3:1 to receive a single dose of saracatinib or placebo, respectively, followed 7 to 10 days later with daily doses for a further 10 to 14 days. Dosing levels of saracatinib ascended by cohort (60 to 250 mg). Markers of bone turnover were measured predose and 24 and 48 hours after the initial single dose and immediately before and 24 and 48 hours and 10 to 14 days after the final dose. Data from 44 subjects were included in the analysis. There was a dose-dependent decrease in bone resorption markers [serum cross-linked C-telopeptide of type I collagen (sCTX) and urinary cross-linked N-telopeptide of type I collagen normalized to creatinine (uNTX/Cr)]. At a dose of 250 mg (maximum tolerated dose), sCTX decreased by 88% [95% confidence interval (CI) 84–91%] and uNTX/Cr decreased by 67% (95% CI 53–77%) from baseline 24 hours after the final dose. There was no significant effect on bone formation markers. There were no significant adverse events. We conclude that inhibition of Src reduces osteoclastic bone resorption in humans. Saracatinib is a potentially useful treatment for diseases characterized by increased bone resorption, such as metastatic bone disease and osteoporosis. © 2010 American Society for Bone and Mineral Research
Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage
Authors: Addison William N , Masica David L , Gray Jeffrey J , McKee Marc D 
Published: September 2009

Abstract
The SIBLING family (small integrin-binding ligand N-linked glycoproteins) of mineral-regulating proteins, which includes matrix extracellular phosphoglycoprotein (MEPE) and osteopontin (OPN), contains an acidic serine- and aspartate-rich motif (ASARM). X-linked hypophosphatemia caused by inactivating mutations of the PHEX gene results in elevated mineralization-inhibiting MEPE-derived ASARM peptides. Although the OPN ASARM motif shares 60% homology with MEPE ASARM, it is still unknown whether OPN ASARM similarly inhibits mineralization. In this study we have examined the role of OPN ASARM and its interaction with PHEX enzyme using an osteoblast cell culture model, mass spectrometry, mineral-binding assays, and computational modeling. MC3T3-E1 osteoblast cultures were treated with differently phosphorylated OPN ASARM peptides [with 5 phosphoserines (OpnAs5) or 3 phosphoserines (OpnAs3)] or with control nonphosphorylated peptide (OpnAs0). Phosphorylated peptides dose-dependently inhibited mineralization, and binding of phosphorylated peptides to mineral was confirmed by a hydroxyapatite-binding assay. OpnAs0 showed no binding to hydroxyapatite and did not inhibit culture mineralization. Computational modeling of peptide-mineral interactions indicated a favorable change in binding energy with increasing phosphorylation consistent with hydroxyapatite-binding experiments and inhibition of culture mineralization. Addition of PHEX rescued inhibition of mineralization by OpnAs3. Mass spectrometry of cleaved peptides after ASARM-PHEX incubations identified OpnAs3 as a PHEX substrate. We conclude that OPN ASARM inhibits mineralization by binding to hydroxyapatite in a phosphorylation-dependent manner and that this inhibitor can be cleaved by PHEX, thus providing a mechanistic explanation for how loss of PHEX activity in X-linked hyposphosphatemia can lead to extracellular matrix accumulation of ASARM resulting in the osteomalacia. © 2010 American Society for Bone and Mineral Research
Description of anisotropically microstrain-broadened line profiles by Edgeworth series
Authors: Leineweber Andreas 
Published: September 2009

Abstract
The diffraction effects within the Stokes-Wilson approximation of a non-Gaussian microstrain distribution in a macroscopically isotropic specimen are described by anisotropic Edgeworth series. This Edgeworth series can for each reflection hkl be quantified by the 3rd, 4th ... N
th cumulants of the microstrain distribution projected on the reflection´s diffraction vector. The diffraction-vector (hkl) dependence of these N
th cumulants can be described by 2N
th-rank tensors which characterise the microstrain distribution in the crystal´s frame of reference. The situation considerably simplifies in the special case of univariateness of the microstrain distribution, leading to equal (or inverted) shapes of the line-broadening contribution due to microstrain for all different hkl reflections. The Edgeworth description of microstrain was applied to X-ray powder diffraction data of two slightly inhomogeneous hexagonal ε-iron-nitride powders, ε-FeN0.433 and ε-FeN0.407. The microstrain-like line-broadening data was evaluated in terms of the probability-density functions described by Edgeworth series for the composition of these two powders.
Structure determinations of three fluorescent organic pigments by powder diffraction and micro-crystal structure analysis
Authors: Brüning Jürgen , Alig Edith , Meents Alke , van de Streek Jacco , Schmidt Martin U. 
Published: September 2009

Abstract
Bisazomethine compounds with 2-hydroxynaphthalene moieties belong to the few organic pigments which show fluorescence in the solid state. The condensation products of hydrazine with 4-formyl-3-hydroxy-2-naphthoic acid-4′-methoxyanilide (C38H30N4O6), as well as the corresponding 4′-chloro and 2′,5′-dichloro derivatives (C36H24Cl2N4O4 and C36H22Cl4N4O4) are almost insoluble in all common solvents, even at temperatures of 200 °C. The 4′-methoxy derivative exists in at least two polymorphs. Small crystals of the a-phase could be obtained from N-methylpyrrolidone at 150 °C. A crystal with a size of just 1 × 2 × 10 μm3 was sufficient to determine the crystal structure by micro-focus synchrotron-X-ray diffraction. The phenyl groups are disordered.
The crystal structure of the β-phase of the 4′-methoxy derivative, as well as the structures of the two other derivatives were determined from X-ray powder diffraction data. The crystal structures were solved by real-space methods using the program DASH, the Rietveld refinement was done with the program TOPAS. The 2′,5′-dichloro derivative crystallises in P-1, Z = 1, all other phases in P21/c with Z = 2. All compounds form intramolecular hydrogen bonds, which explain the solid state fluorescence.
Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome
Authors: Pacifico Lucia , Poggiogalle Eleonora , Costantino Francesco , Anania Caterina , Ferraro Flavia , Chiarelli Francesco , Chiesa Claudio 
Published: September 2009

BackgroundGhrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined.ObjectiveWe investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values.DesignA total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR.ResultsIn the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS.ConclusionsA-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.
Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma
Authors: Hoftijzer Hendrieke , Heemstra Karen A , Morreau Hans , Stokkel Marcel P , Corssmit Eleonora P , Gelderblom Hans , Weijers Karin , Pereira Alberto M , Huijberts Maya , Kapiteijn Ellen , Romijn Johannes A , Smit Johannes W 
Published: September 2009

ObjectiveTreatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression.DesignOpen, single center, single arm 26-week prospective phase II study with open-ended extension.MethodsWe treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases.ResultsAt 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47–68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed.ConclusionsSorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.
The Use of Alteplase for Treatment of Occluded Central Venous Catheters in Home Care
Authors: Moureau Nancy , Mlodzik Lisa , Pool Susan Markel 
Published: September 2009

Abstract
Purpose. The purpose of this trial was to confirm safety and efficacy with thrombolytic use on complete and partially occluded central catheters using alteplase for the home care population. This trial attempts to provide additional evidence for the safe and effective use of a thrombolytic agent for catheter clearance, specifically with home care patients. Method. Patients were eligible for inclusion if (1) blood could not be withdrawn for partial occlusion or (2) blood could not be withdrawn and inability to flush presented with complete occlusion. Through an established Protocol, using the negative-pressure technique, nurses administered alteplase, 1mg/1 cc concentration, to home care patients who met inclusion criteria. Instillations were repeated at 20-minute intervals for up to three repetitions, if needed, with the third instillation remaining overnight. Results. Instillation of alteplase was successful in clearing catheter thrombotic occlusions in 66. 7% of patients studied in this outpatient population without thrombolytic events or drug related adverse effects. Conclusions. The authors confirm that catheter occlusions can be safely resolved in the alternate care/home care setting using established negative-pressure protocols. Although overnight dwell was used successfully and unsuccessfully in this trial without adverse effects, the small sample size does not Provide adequate definitive conclusions.
The Effect of Nursing Interventions on Catheter-related Bloodstream Infections in Patients Receiving Total Parenteral Nutrition Through Peripherally Inserted Central Catheter Lines
Authors: Sucy Sandra C. , Hupka Dennis , Curchoe Ruth 
Published: September 2009

Abstract
Background: Catheter-related blood-stream infection (CRBSI) is a serious and costly complication associated with central venous catheters. Nursing interventions that focus on decreasing bacterial colonization at the insertion site could decrease infection rates. Method: This retrospective study examined CRBSI in patients requiring peripherally inserted central catheters (PICCs) for total parenteral nutrition. One hundred and ninety-two patients with 235 catheters and an average dwell time of 11.5 days participated. Nursing interventions included a chlorhexidine-impregnated sponge dressing and a double skin scrub prior to insertion. Conclusion: The results of the study show that the interventions did not reduce CRBSI in the target population but the double skin scrub did decrease CRBSI in the general PICC population.
Reduction of Malposition in Peripherally Inserted Central Catheters With Tip Location System
Authors: Naylor Christine L. 
Published: September 2009

Abstract
Catheter malposition is a common occurrence with the insertion of peripherally inserted central catheters (PICCs). Santa Rosa Memorial Hospital (SRMH) in Santa Rosa, California, trialed and implemented a new tip location device to evaluate whether malposition rates could be reduced. This article compares 6 months of data. Three of these months were compiled before using the tip locator device. The right atrial malposition rate remained consistent at 18% with or without the use of the tip locator device. All other malpositions were 13.4% without use of the tip locator. The overall malposition rate was 2.5% with the use of the tip locator device. By using this technology, supply and labor costs were reduced, as were referrals to interventional radiology and delays in treatment. Overall staff satisfaction improved.
Practice, Standards of Care, and Strategies to Prevent Infection: A Review of Flushing Solutions and Injection Caps (Part 3 of a 3-Part Series)
Authors: Richardson Deborah K. 
Published: September 2009

Abstract
This is Part 3 of a 3-part series and will review flushing solutions and injection caps in addition to practice issues, standards, guidelines, and preventive strategies developed to prevent or decrease infections of central venous catheters.
Taking the Leap From PICC Placement to Tip Placement
Authors: Royer Timothy , Earhart Ann 
Published: September 2009

Abstract
Nurses who place peripherally inserted central catheters (PICCs) obtain x-rays after placement to determine tip placement. Radiologists read and interpret the x-ray to verify tip placement. It is then the primary physician or the radiologist who releases the PICC line for use. Until 2002, there were few institutions across the United States that empowered the vascular access nurse to take on this responsibility. This article discusses how to advance practice at the state-board-of-nursing level and discusses strategies to implement the change in scope of practice.
In Vitro Antimicrobial Effectiveness of 5 Catheter Insertion-Site Dressings
Authors: Bhende Shubhangi , Rothenburger Stephen 
Published: September 2009

Abstract
Polyurethane foam dressing impregnated with chlorhexidine gluconate was compared with 4 silver dressings for antimicrobial efficacy. Efficacy of antimicrobial dressings was evaluated using zone of inhibition assay against 7 clinically relevant bacteria and yeast. The test was carried out for up to 7 consecutive days by transferring the dressings daily. Microbiocidal activity exhibited by different dressings within the zone of inhibition was also evaluated as a part of the study. Three silver dressings were similar to each other in performance and had different patterns of efficacy varying from days 1 to 6 than the chlorhexidine dressing. A hydrogel dressing containing silver performed poorly compared to all other dressings. The study results indicated that the antimicrobial dressing impregnated with chlorhexidine gluconate had excellent antimicrobial activity and showed sustained efficacy for a period of 7 days.
Achieving Zero Catheter Related Blood Stream Infections: 15 Months Success in a Community Based Medical Center
Authors: Harnage Sophie A. 
Published: September 2009

Abstract
Achieving Zero Catheter Related Blood Stream Infections: 15 Month Success In A Community Based Medical Center. Background and Purpose: Catheter related blood stream infection (CRBSI) is a major cause of patient morbidity, mortality, and cost. Lower CRBSI rates would decrease inpatient length of stay. Project: An innovative central line bundle was developed to reduce CRBSI. An innovative combination of focused nursing practice and product technologies were selected for the bundle and implemented through a defined educational program. Data was collected from thirty-two critical care beds: 16 medical/surgical ICU and 16 Trauma-Neuro ICU beds. Results: From January 2006 thru March 2007 there were Zero occurrences of CRBSI. Over this 15 month period our PICC insertions increased by 103%, and our interventional radiology referral rate decreased to less than 2%. Implications/Conclusions: A multimodality bundle, combining nursing practice interventions and technology can successfully decrease the incidence of CRBSI. While some of the bundle components have not been widely researched and instead are based on theory or accepted clinical practice, the early outcome provides a basis for additional study and refinement. It also invites research into the various components of the bundle to evaluate the effect each separate practice and product lends to its success.
The Right Mediastinal Border and Central Venous Anatomy on Frontal Chest Radiograph—Direct CT Correlation
Authors: Verhey Peter T. , Gosselin Marc V. , Primack Steven L. , Blackburn Paul L. , Kraemer Alexander C. 
Published: September 2009

AbstractWe describe a direct and accurate method for defining chest radiographic anatomy and use this method to delineate the anatomic composition of the right mediastinal border in an adult population. Intravenous contrast-enhanced computed tomographic scans of the chest and accompanying scout tomograms from 99 adults without previously known or detected cardiopulmonary disease that could potentially distort mediastinal, cardiac, or pulmonary anatomy were retrospectively evaluated. Transverse CT images through the mediastinum were directly referenced to the respective acquisition location on the scout tomogram via the acquisition reference line. The anatomic composition of the right mediastinal border on the scout tomogram was determined by drawing a vertical line tangential to the most lateral right mediastinal structure in each transverse CT image. The lengths and relationships of these structures were tabulated. These results will help to create a consensus among radiologists and other clinicians regarding radiographic anatomy, allowing improved localization of mediastinal pathology and enabling more optimal positioning of vascular and cardiac support devices.
Low-End Videoconferencing for Vascular Access Device Site Assessment in Homecare
Authors: Astapova Elena V. , Stachura Max E. , Chernecky Cynthia , Rosenkoetter Marlene M. 
Published: September 2009

Abstract
Vascular access devices (VAD) represent high technology and are used frequently in infant, pediatric, adult, and geriatric populations for vascular infusion of chemotherapy, immunotherapy, blood products, biologic response modifiers, nutrition support, analgesics, ionotropics, antibiotics, and other medications, as well as for extraction of pleural fluid from patients with chronic effusions and for treatment with dialysis. Increasingly, these devices are migrating to the home setting as they are used in chronic care and as insurance requirements reduce access to prolonged hospital stays.
Surveillance of infections in high risk patients such as those with cancer, cardiac conditions, or post-trauma convalescence is essential to avoid adverse events and to offer early treatment. VAD site and blood stream infections are common VAD complications, occurring in up to 50% of home care patients, usually during days 4–25 after hospital discharge. Our literature search for reports of remote home monitoring for support of VAD patients and their caregivers found none.
The use of videoconferencing technology to assess VAD sites in the post-discharge environment would significantly enhance patient safety, facilitate continuity of care, and meet the Communicable Disease Center's stated need for the development of surveillance systems to monitor infections in home care settings. Low-cost Internet- or telephone-based videoconferencing technology that could be deployed easily and used during risk periods would be highly beneficial to patients and increase the cost-effective use of homecare nursing personnel.
We report criteria-based protocols for remote assessment of VAD status, for monitoring VAD care procedures employed in the home, and for conducting VAD-care teaching of patients and their caregivers. In addition, we report an initial evaluation of the ability to assess VAD status using low-end videoconferencing technologies.
Improving Safety for Nurses Providing IV Therapy
Authors: Baker Brenda 
Published: September 2009

Abstract
Objectives: The risk nurses face related to exposure to blood borne pathogens associated with IV therapy are daily challenges. Providing a product with the least risk of exposure is the responsibility of the healthcare organization. Where the two meet creates an environment that fosters a safe work environment and raises the awareness that safety is everyone's job.
Project: Following identification of exposure rates from IV catheter stylets the Carilion Clinic undertook a project to improve the practices and provide a higher level of safety for its staff.
Results: Following staff evaluation and selection of a new IV catheter, the exposure rate related to contaminated IV catheter stylets dropped from 13 in 2005 to 2 in 2007. Numerous other practices and products related to IV therapy were reviewed and improved upon following the catheter conversion as well.
Conclusion and Implications for Practice: A higher level of safety can be achieved when nurses are involved in the selection of a product, staff education, and support from leadership.
Difficult Peripheral Venous Access: Recognizing and Managing the Patient at Risk
Authors: Walsh Gabrielle 
Published: September 2009

AbstractNurses commonly face challenges placing peripheral intravenous (IV) lines in adults and children, a situation described as difficult venous access (DVA). Multiple venipuncture attempts can heighten patient anxiety and suffering, delay vital treatment, and increase costs. Numerous factors such as small, fragile or hidden veins can predispose patients to DVA, and collapsed veins due to dehydration are especially problematic. Several techniques can improve venous prominence, but when IV access cannot be achieved promptly, other routes of administration can be valuable. For rehydration fluids and certain drugs, subcutaneous administration may be a safe and effective alternative, providing cost and ease-of-use advantages.