bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic peptide derived from the parasite Toxoplasma gondii triggers human dendritic cellsˈ migration
Authors: Persat Florence , Mercier Corinne , Ficheux Damien , Colomb Evelyne , Trouillet Sophie , Bendridi Nadia , Musset Karine , Loeuillet Corinne , Cesbron-Delauw Marie-France , Vincent Claude 
Published: October 2012

Abstract
Pep29, a peptide derived from the Toxoplasma GRA5 protein, is responsible for human dendritic cellsˈ migration toward the CCR7 ligand.
The migration of DCs is a critical function, enabling information to be carried to where the immunological response occurs. Parasites are known to weaken host immunity by interfering with the functions of DCs and thus, may be a source of molecules with immunomodulatory properties. Here, we demonstrate that the soluble protein, GRA5, specific to Toxoplasma gondii, is able to increase the migration of human CD34-DCs toward CCL19. A synthetic Pep29 derived from the GRA5 hydrophilic NT region (Pep29) was found to be internalized by macropinocytosis and to trigger in vitro migration of CD34-DCs via CCR7 expression without activating DCs. Pep29 also induced a decrease in the number of LCs from human skin epidermis. As local depletion of DCs and migration of immature DCs lead to a disruption of the specific innate response, our results highlight the potential of using pathogen-derived synthetic peptides as novel cell modulators with a therapeutic potential to reduce symptoms in inflammatory disorders.
Levoleucovorin as Replacement for Leucovorin in Cancer Treatment
Authors: Chuang Victor Tuan Giam , Suno Manabu 
Published: October 2012

Objective: To comprehensively review the literature regarding the efficacy, safety, and costs associated with the use of levoleucovorin in cancer treatment and to assess whether levoleucovorin would be a reasonable alternative to the use of racemic leucovorin. Data Sources: A MEDLINE search was conducted for English-language human studies published between January 1980 and April 2012 using the terms I-LV. levoleucovorin, d,I-LV, leucovorin, folinic acid, tolinate, 5-formyltetrahydrofolate, folic acid, folates, methotrexate, 5-fluorouracil, and clinical trials. Study Selection and Data Extraction: Articles pertinent to clinical trials (Phase 1, 2, 3) related to evaluating the efficacy, interchangeability, and safety of levoleucovorin were collected and their contents reviewed. Data Synthesis: From these pharmacokinetics and clinical studies, information on the use of levoleucovorin as a modulator of fluorouracil as well as when combined with other antitumor agents were scrutinized and extracted for comparison with leucovorin whenever possible. Two randomized Phase 3 clinical studies comparing the efficacy and adverse effect profiles of leucovorin and levoleucovorin demonstrated that levoleucovorin is as effective as leucovorin in terms of response, toxicity, and survival. Six randomized Phase 3 clinical studies demonstrated the safety and efficacy of levoleucovorin as a modulator of fluorouracil in combination with/without other antitumor agents in colorectal cancer patients. Levoleucovorin has been studied in other cancers. These clinical Phase 1/2/3 studies demonstrated efficacy and safety of levoleucovorin in combination chemotherapeutic regimens comprising fluorouracil and other antitumor agents. Conclusions: The results of the clinical studies suggest that levoleucovorin is efficacious and can be used safely in combination with fluorouracil and other antitumor agents. Levoleucovorin can be used interchangeably with leucovorin for modulating fluorouracil. The current shortage of the supply of leucovorin centered in North America renders levoleucovorin a reasonable alternative in terms of efficacy and toxicity profile, but from the perspective of cost, leucovorin remains the drug of choice.
Examination of the Relationship Between Antimicrobials and Thrombocytosis
Authors: Forehand Christy C , Cribb Jennifer , May J Russell 
Published: October 2012

Objective: To evaluate whether there is a relationship between antimicrobial therapy and the development of thrombocytosis. Data Sources: Literature was accessed through EMBASE (1977-June 2012) and MEDLINE (1977-June 2012) using the terms thrombocytosis and antimicrobial. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction: All English-language publications identified were evaluated. For case reports, the Naranjo probability scale was used to calculate the likelihood of the drug causing the reaction. Data Synthesis: Thrombocytosis occurring during antimicrobial therapy is well documented, with several case reports and clinical trial observations. However, a direct causal relationship is not yet supported by the available literature. Platelets are welt known to be an acute phase reactant, with an elevated count occurring after acute conditions such as blood loss, inflammation, or infection. Thrombocytosis during antimicrobial therapy may be the result of an infectious process and not an adverse drug event. Conclusions: Based on the current available literature, a definitive link cannot be established between antimicrobial therapy and occurrence of thrombocytosis.
Paradoxical Reaction of Raynaud Phenomenon following the Repeated Administration of Lloprost in a Patient with Diffuse Cutaneous Systemic Sclerosis
Authors: Barreira Rebeca Iglesias , García Belén Bardán , López Mónica Granero , Legazpi Iria Rodríguez , Díaz Hortensia Álvarez , Penín Isaura Rodríguez 
Published: October 2012

Objective TO report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. Case Summary In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5–1 ng/kg/min (6 hours per day, for 5 days every 6–8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Discussion Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. Conclusions This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.
Drug-Related Problems and Hospital Admissions in Cardiac Transplant Recipients
Authors: Repp Kristin L , Hayes Charles , Woods T Mark , Allen Keith B , Kennedy Kevin , Borkon Michael A 
Published: October 2012

Background: Drug-related problems (DRPs) in the general population account for 15% of all hospital admissions, of which approximately 30% are preventable. Cardiac transplant patients may be at increased risk for DRPs because of their complicated medication regimens that include drugs with a narrow therapeutic index. Objective: To determine the incidence and praventability of DRPs causing hospital admission in cardiac transplant patients at a single institution. Methods: Between November 2009 and January 2010, a prospective longitudinal study investigated the incidence and preventability of DRPs in a single cardiac transplant center. Three independent reviewers used validated scoring systems to determine the incidence and preventability of drug-related hospital admissions. DRPs were classified by type, pharmacologic class, and impact on length of stay. Results: During the 3-month study period, 48 cardiac transplant patients were hospitalized. DRPs accounted for 40% (19/48) of these admissions and 58% (11/19) were adjudicated to be preventable. Common DRPs included supratherapeutic (32%) and subtherapeutic (16%) dosage, adverse drug reaction (32%), drug interaction (5%), and nonadherence (5%). Pharmacologic classes implicated included immunosuppressant (63%), antimicrobial (11%), electrolyte/fluid (11%). and anticoagulant (5%). Average length of stay in drug-related compared to non-drug-related admissions was 11.4 versus 8.5 days (p = 0.458). When annualized, 44 hospitalizations or 500 hospital days may have been prevented. Conclusions: Hospital admissions following cardiac transplantation are often drug related (40%) and preventable (58%). Incorporating this insight into the multidisciplinary transplant team may improve outcomes, assist in meeting national quality mandates by the United Network for Organ Sharing and Centers for Medicare Services, and lead to new benchmarks for transplant centers.
Teratogenic Risk of Statins in Pregnancy
Authors: Godfrey Laura M , Erramouspe John , Cleveland Kevin W 
Published: October 2012

Objective: To evaluate the teratogenic potential of statins in women of child-bearing age. Data Sources: A PubMed search (1980-September 2012) was performed using the search terms statin and pregnancy, then repealed using statin and teratogenicity. Results were limited to articles published in English reporting on use of statins in humans. Study Selection and Data Extraction: All articles presenting data on pregnancy outcomes after statin use during any trimester of pregnancy were included. Three case reports, 2 case series, 2 systematic reviews, 2 registry-based studies, and 1 prospective observational cohort study were reviewed. Data Synthesis: Since initial premarketing studies of lovastatin in animals, terato-genesis has been assumed to be a classwide function of statins' mechanism of action. Data from human exposure during pregnancy have been gathered and analyzed in a variety of study formats to formulate useable conclusions on statins' actual teratogenic risk and pattern of associated birth defects. Although the current trend is that actual risk is lower than once thought, the available literature is limited by potential reporting bias, contains overlap in the data, and frequently lacks numbers of total exposures to statins during pregnancy with reported malformations. Additionally, no human studies included data on the 2 newest statins (rosuvastatin, pitavastatin); the more lipophilic statins (lovastatin, simvastatin) have the most experience and thus have more evidence related to teratogenic potential. Conclusions: Human teratogenic risk has not been proven nor has it been ruled out by the available data on statin use in pregnancy. Possible differences in risk between individual statins require further evaluation. Additional data, including prospective observational cohorts with inadvertent maternal exposure to statins during early weeks of gestation, should further help to clarify appropriate recommendations for statin use in this population.
Readministration of Calcineurin Inhibitors for Ulcerative Colitis
Authors: Hiraoka Sakiko , Kato Jun , Suzuki Hideyuki , Yamamoto Kazuhide 
Published: October 2012

Background: Calcineurin inhibitors (CNIs) such as cyclosporins and tacrolimus have been shown to be effective for treatment of patients with steroid-dependent or steroid-refractory ulcerative colitis (UC) with moderate to severe activity. However, it has not been determined whether readministration of CNIs is effective in patients who experience relapse after remission induced by CNIs. Objective: To determine the effect of readministration of CNIs in patients who had initially responded to CNIs. Methods: A review of the medical records of 46 patients with moderate to severe UC who were treated with a CNI at a single tertiary teaching hospital with 840 beds was conducted. Remission was defined as a clinical activity index (CAI) score of 3 or less within 2 months of starting CNI therapy. Response was defined as a CAI score of 4 or higher but had decreased by half from the start of CNI therapy. Relapse was defined as flare-up of symptoms that required an additional treatment or colectomy. Results: Of the 46 patients, 37 (80%) achieved clinical remission or response with the initial CNI treatment. Among those 37 patients, 19 experienced relapse (median duration to relapse, 6.4 months), 12 of whom were readministered a CNI. Of the 12 patients, 2 achieved clinical remission, 2 had a response, and the remaining 8 had no response to the CNI. In addition, all patients who responded to CNI readministration experienced relapse within 6 months. CNI readministration was significantly less effective than the initial administration (or treatment of UC (80% vs 33%; p = 0.0014). Conclusions: Readministration of CNIs for relapse after remission with CNI treatment does not seem to be successful. Alternative therapies such as anti-tumor necrosis factor antibody should be used or colectomy should be considered.
Continuous Infusion Vancomycin for Treatment of Methicillin-Resistant Staphylococcus aureus in Cystic Fibrosis Patients
Authors: Fung Lela 
Published: October 2012

Objective To report 3 cases of methiciIlin-resistant Staphylococcus aureus (MRSA) in pediatric patients with cystic fibrosis (CF), all of whom had inadequate serum concentrations of vancomycin with conventional intermittent dosing and who achieved therapeutic serum concentrations with continuous infusions of vancomycin. Case Summary In the first case, a 3-year-old patient failed to achieve therapeutic vancomycin trough concentrations despite 2 dose adjustments up to 19 mg/kg every 6 hours. A continuous infusion was initiated and a therapeutic steady-state level was obtained. The remaining case reports describe 2 patients who were readmitted to the hospital after having received intermittent dosing as outpatients. Continuous infusions were started upon readmission, and therapeutic serum concentrations were achieved in both patients. Discussion MRSA is a common pathogen in patients with CR. Intravenous vancomycin, a time-dependent antibiotic that is extensively eliminated by the kidneys, is frequently used to treat MRSA infections. Serum trough concentrations of 15–20 mg/L are considered therapeutic, but these levels are difficult to achieve in patients with CF because of increased renal clearance. Continuous infusions of vancomycin were successfully used in the patients described here and resulted in decreased total daily doses of vancomycin, clinical improvement, and no evidence of nephrotoxicity. Conclusions Although more extensive studies are necessary, the cases presented here suggest that continuous infusion vancomycin is a safe and convenient therapy for MRSA infections.
Associations Between Patterns of Emerging Sexual Behavior and Young Adult Reproductive Health
Authors: Haydon Abigail A. , Herring Amy H. , Halpern Carolyn Tucker 
Published: October 2012

CONTEXTIdentifying young adult outcomes associated with adolescent sexual behavior, including patterns of first oral, vaginal and anal sex, is critical to promoting healthy sexual development.METHODSAssociations between patterns of emerging sexual behavior, defined using latent class analysis, and young adult sexual and reproductive health were examined among 9,441 respondents to Waves 1 (1994–1995), 3 (2001–2002) and 4 (2008) of the National Longitudinal Study of Adolescent Health. Logistic regression analyses examined associations between class membership and young adult outcomes, and tested for interactions by race and ethnicity.RESULTSCompared with respondents who initiated vaginal sex first and reported other sexual behaviors within two years, those who initiated oral and vaginal sex during the same year had similar odds of having had an STD diagnosis ever or in the last year, of having had concurrent sexual partnerships in the last year and of having exchanged sex for money. However, respondents who postponed sexual activity had reduced odds of each outcome (odds ratios, 0.2–0.4); those who initiated vaginal sex and reported only one type of sexual behavior had reduced odds of reporting STD diagnoses and concurrent partnerships (0.4–0.6). Respondents who reported early initiation of sexual activity combined with anal sex experience during adolescence had elevated odds of having had concurrent partnerships (1.6). The data suggest racial and ethnic disparities even when patterns of emerging sexual behavior were the same.CONCLUSIONSPatterns of early sexual behavior considered high‐risk may not predict poor sexual and reproductive health in young adulthood.
Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism
Authors: Fourkiotis Verena , Vonend Oliver , Diederich Sven , Fischer Evelyn , Lang Katharina , Endres Stephan , Beuschlein Felix , Willenberg Holger S , Rump Lars C , Allolio Bruno , Reincke Martin , Quinkler Marcus , _ _ 
Published: October 2012

ObjectivePrimary aldosteronism (PA) has deleterious effects on kidney function independent of blood pressure levels. Up to now, data on effectiveness of different PA therapies regarding renal function are scarce.Design and methodsThis prospective multi-center study included 29 patients with newly diagnosed PA evaluated before and 1 year after treatment initiation, and a second cohort including 119 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Glomerular filtration rate (GFR), spot urine albumin excretion/urinary creatinine (UAE/Ucrea) ratio, biochemical parameters, and 24-h blood pressure were measured. In a larger cross-sectional cohort, renal function was evaluated depending on the type of treatment (adrenalectomy (ADX; n=86); spironolactone (n=65); and eplerenone (n=18)).ResultsGFR and UAE/Ucrea ratio significantly decreased in newly diagnosed PA patients after treatment initiation. In the second cohort, GFR and UAE/Ucrea ratio did not change during study period, and blood pressure was well controlled. In the larger cross-sectional cohort, no differences were seen in GFR and UAE/Ucrea ratio between PA patients on different treatment regimens. However, eplerenone treatment showed lower potassium levels and higher number of required antihypertensive medications.ConclusionsRenal dysfunction with elevated albuminuria was seen in PA patients and was reversible after treatment initiation. Medical therapies with spironolactone or eplerenone seem to be as effective as ADX regarding renal function and blood pressure; however, sufficient daily doses need to be given.
Development of an Analytical Method for the Determination of Arsenic in Urine by Gas Chromatography‐mass Spectrometry for Biological Monitoring of Exposure to Inorganic Arsenic
Authors: Takeuchi Akito , Namera Akira , Kawasumi Yaeko , Imanaka Tsutoshi , Sakui Norihiro , Ota Hirokazu , Endo Yoko , Sumino Kimiaki , Endo Ginji 
Published: October 2012

Development of an Analytical Method for the Determination of Arsenic in Urine by Gas Chromatography‐mass Spectrometry for Biological Monitoring of Exposure to Inorganic Arsenic: Akito TAKEUCHI, et al. Osaka Occupational Health Service Center, Japan Industrial Safety and Health Association—ObjectivesThe purpose of this study was to develop an analytical method for the simultaneous determination of inorganic arsenic [As(III) and As(V)] and monomethylarsonic acid (MMA) in urine by gas chromatography‐mass spectrometry (GC‐MS) for the biological monitoring of exposure to inorganic arsenic.MethodsArsenic compounds (after reduction of arsenic to the trivalent state) were derivatized with 2,3dimercapto‐1‐propanol and then analyzed using a GC‐MS. The proposed method was validated according to the US Food and Drug Administration guidelines. The accuracy of the proposed method was confirmed by analyzing Standard Reference Material (SRM) 2669 (National Institute of Standards and Technology).ResultsCalibration curves showed linearity in the range 1−100 µg/l for each of the arsenic species, with correlation coefficients of >0.999. For each of the arsenic species, the limits of detection and quantification were 0.2 µg/l and 1 µg/l, respectively. The recoveries were 96−100%, 99−102% and 99−112% for As(III), As(V) and MMA, respectively. Intraday accuracy and precision were 82.7−99.8% and 0.9−7.4%, respectively. Interday accuracy and precision were 81.3−100.0% and 0.8−9.9%, respectively. The analytical values of SRM 2669 obtained by the proposed method were sufficiently accurate.ConclusionsThe proposed method overcame the disadvantages of high‐performance liquid chromatography with inductively coupled plasma mass spectrometry. It was a robust, selective and cost‐effective method suitable for routine analyses and could be useful for the biological monitoring of occupational exposure to inorganic arsenic.
Thin-film Micro-Batteries Based on Metal Nanoparticles
Authors: Peng Shuang , Du Wenjun , Rakesh Leela , Mellinger Axel , Kaya Tolga 
Published: October 2012

ABSTRACTWe proposed the use of Copper (Cu) and Zinc (Zn) nanoparticles as the electrodes for thin-film microbatteries in the applications of micro-scale sensors. Compared to the widely used lithium-based batteries, Cu and Zn nanoparticles are less expensive, less prone to oxidation (thus involving simpler fabrication steps) and flammability, safe to use, and only requires very simple fabrication processes.Even though the voltage output is inherently smaller (∼1V) than conventional lithium-based batteries, it is sufficient for low-voltage Integrated Circuits (IC) technologies such as 130 nm and 90 nm channel length transistor processes.Commercial paper will be used as the separator to demonstrate the battery capacity. Paper that acts as the separator is slurry-casted with nanoparticles (30-40 nm in size) on both sides. The thickness of the metal nanoparticles-coated thin films and the paper separator are 1 μm and 100 μm, respectively.The electrodes were developed to achieve high conductivity (lower than 1 (Ω·cm)-1) with smooth surface, good adhesion, and flexibility. The metal nanoparticles will be formulated to slurry solutions for screen printing or ink-jet printing for the battery fabrication. For fabrication purposes, the slurries viscosity is approximately in the range of 10-12 cPs at the operating temperature, a surface tension between 28-33 dynes/cm. During the fabrication process including printing/coating and sintering, reductive environment is required to minimize the oxidation. AFM (Atomic Force Microscopy) and EDS (Energy Dispersive Spectroscopy) results will be employed to demonstrate the surface morphology as well as the percentages of metal oxides. Batteries will be tested with and without an ionic liquid for comparison. Humidity effects on the battery performance will also be discussed.Different geometries that are designed to make the batteries with higher voltage or charge will be proposed. Characterization results will include the open-circuit voltage, dielectric property, charging and discharging curve, capacitance and capacity, AFM of the surface test, EDS of the electrodes and the SEM (Scanning Electron microscopy) of the particles.Ourresearch suggest that conductive paper can be scalable and could make high-performance energy storage and conversion devices at low cost and would bring new opportunities for advanced applications.