bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic background influences murine prostate gene expression: implications for cancer phenotypes
Authors: Bianchi-Frias Daniella , Pritchard Colin , Mecham Brigham H , Coleman Ilsa M , Nelson Peter S 
Published: June 2007

Abstract
Background
Cancer of the prostate is influenced by both genetic predisposition and environmental factors. The identification of genes capable of modulating cancer development has the potential to unravel disease heterogeneity and aid diagnostic and prevention strategies. To this end, mouse models have been developed to isolate the influences of individual genetic lesions in the context of consistent genotypes and environmental exposures. However, the normal prostatic phenotypic variability dictated by a genetic background that is potentially capable of influencing the process of carcinogenesis has not been established.

Results
In this study we used microarray analysis to quantify transcript levels in the prostates of five commonly studied inbred mouse strains. We applied a multiclass response t-test and determined that approximately 13% (932 genes) exhibited differential expression (range 1.3-190-fold) in any one strain relative to other strains (false discovery rate ≤10%). Expression differences were confirmed by quantitative RT-PCR, or immunohistochemistry for several genes previously shown to influence cancer progression, such as Psca, Mmp7, and Clusterin. Analyses of human prostate transcripts orthologous to variable murine prostate genes identified differences in gene expression in benign epithelium that correlated with the differentiation state of adjacent tumors. For example, the gene encoding apolipoprotein D, which is known to enhance resistance to cell stress, was expressed at significantly greater levels in benign epithelium associated with high-grade versus low-grade cancers.

Conclusion
These studies support the concept that the cellular, tissue, and organismal context contribute to oncogenesis and suggest that a predisposition to a sequence of events leading to pathology may exist prior to cancer initiation.
ABCC transporter inhibition reduces zymosan-induced peritonitis
Authors: Leite Daniela F P , Echevarria-Lima Juliana , Ferreira Samira Cardoso , Calixto João B , Rumjanek Vivian M 
Published: June 2007

AbstractInflammatory mediators are released from injured tissues being responsible for the first steps of inflammatory processes. Multidrug efflux transporters, members of the ATP-binding cassette (ABC) family, are ubiquitously expressed. ABCC molecules transport several endogenous substances, including leukotriene C4 (LTC4) and PGE2, which are involved in zymosan-induced inflammation. The present study investigated the role played by ABCC transporters on zymosan-induced peritonitis in mice. Most of the resident peritoneal cells were macrophages, based on their morphology and membrane-activated complex 3 expression. RT-PCR demonstrated that these cells expressed ABCC, and ABCC activity was analyzed in vivo via the s.c. injection of ABCC inhibitors [probenecid (PROB) 200 mg/kg or MK571 20 mg/kg], followed by an i.v. injection of carboxyfluorescein diacetate (CFDA), an ABCC fluorescent substrate. Both inhibitors increased CFDA accumulation, suggesting ABCC impairment. Moreover, ABCC reversors decreased zymosan-induced plasma exudation by 86.6 ± 7.4 and 97.6 ± 2.3%, a feature related to a diminished secretion of LTC4 (65.1±11 and 47.8±9.9%) and PGE2 (under basal levels). Cell migration was inhibited similarly. Furthermore, PROB and MK571 inhibited IL-1ß by 83.4 ± 13 and 71.2 ± 13.4% and TNF-α content by 47 ± 4.5 and 28.9 ± 0.8%, respectively. NO metabolites and reactive oxygen species production were also reduced. The present results suggest that ABCC molecules have a relevant role in the acute inflammatory response produced by zymosan in mice.
6-Methylprednisolone down-regulates IRAK-M in human and murine osteoclasts and boosts bone-resorbing activity: a putative mechanism for corticoid-induced osteoporosis
Authors: Soares-Schanoski Alessandra , Gómez-Piña Vanesa , De l Fresno Carlos , Rodríguez-Rojas Alexandro , García Felipe , Glaría Alberto , Sánchez Miriam , Vallejo-Cremades María Teresa , Baos Rosa , Fuentes-Prior Pablo , Arnalich Francisco , López-Collazo Eduardo 
Published: June 2007

AbstractOsteoclasts are large, multinucleated cells, which originate from the fusion of macrophages. They play a central role in bone development and remodeling via the resorption of bone and are thus important mediators of bone loss, which leads to osteoporosis. IL-1R-associated kinase (IRAK)-M is a pseudokinase, which acts as a negative modulator of innate immune responses mediated by TLRs and IL-1R. Recently, it has been reported that IRAK-M also participates in the control of macrophage differentiation into osteoclasts. In addition, it was shown that IRAK-M knockout mice develop a strong osteoporosis phenotype, suggesting that down-regulation of this molecule activates osteoclast-mediated bone resorption. We studied the effect of the osteoporosis-inducing glucocorticoid, 6-methylprednisolone (6-MP), on IRAK-M expression in osteoclasts. Our results showed that osteoclasts, derived from THP-1 and RAW cells as well as human blood monocytes, differentiated into osteoclasts, express high levels of IRAK-M at mRNA and protein levels. In addition, 6-MP down-regulates IRAK-M expression, which correlates with an increased activation of bone resorption. These findings suggest a mechanism of corticosteroid-induced osteoporosis and open new avenues for treating this endemic disease of Western societies.
Performance of Severity of Illness Scoring Systems in Emergency Department Patients with Infection
Authors: Howell Michael D. , Donnino Michael W. , Talmor Daniel , Clardy Peter , Ngo Long , Shapiro Nathan I. 
Published: June 2007

ObjectivesTo validate the Mortality in Emergency Department Sepsis (MEDS) score, the Confusion, Urea nitrogen, Respiratory rate, Blood pressure, 65 years of age and older (CURB‐65) score, and a modified Rapid Emergency Medicine Score (mREMS) in patients with suspected infection. MethodsThis was a prospective cohort study. Adult patients with clinically suspected infection admitted from December 10, 2003, to September 30, 2004, in an urban emergency department with approximately 50,000 annual visits were eligible. The MEDS and CURB‐65 scores were calculated as originally described, but REMS was modified in neurologic scoring because a full Glasgow Coma Scale score was not uniformly available. Discrimination of each score was assessed with the area under the receiver operating characteristics curve (AUC). ResultsOf 2,132 patients, 3.9% (95% confidence interval [CI] = 3.1% to 4.7%) died. Mortality stratified by the MEDS score was as follows: 0–4 points, 0.4% (95% CI = 0.0 to 0.7%); 5–7 points, 3.3% (95% CI = 1.7% to 4.9%); 8–12 points, 6.6% (95% CI = 4.4% to 8.8%); and ≥13 points, 31.6% (95% CI = 22.4% to 40.8%). Mortality stratified by CURB‐65 was as follows: 0 points, 0% (0 of 457 patients); 1 point, 1.6% (95% CI = 0.6% to 2.6%); 2 points, 4.1% (95% CI = 2.3% to 6.0%); 3 points, 4.9% (95% CI = 2.8% to 6.9%); 4 points, 18.1% (95% CI = 11.9% to 24.3%); and 5 points, 28.0% (95% CI = 10.4% to 45.6%). Mortality stratified by the mREMS was as follows: 0–2 points, 0.6% (95% CI = 0 to 1.2%); 3–5 points, 2.0% (95% CI = 0.8% to 3.1%); 6–8 points, 2.3% (95% CI = 1.1% to 3.5%); 9–11 points, 7.1% (95% CI = 4.2% to 10.1%); 12–14 points, 20.0% (95% CI = 12.5% to 27.5%); and ≥15 points, 40.0% (95% CI = 22.5% to 57.5%). The AUCs were 0.85, 0.80, and 0.79 for MEDS, mREMS, and CURB‐65, respectively. ConclusionsIn this large cohort of patients with clinically suspected infection, MEDS, mREMS, and CURB‐65 all correlated well with 28‐day in‐hospital mortality.
Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model
Authors: Cleveland Nathan R. , Krier Shay , Heard Kennon 
Published: June 2007

BackgroundAcute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective. ObjectivesTo assess whether the combination of these two medications would offer more protection than either treatment alone. MethodsThis was a randomized, blinded, placebo‐controlled trial in CF‐1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded. ResultsAll treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02). ConclusionsThis study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine‐induced seizures.
Impact of Randomized Clinical Trial Results in the National Comprehensive Cancer Network on the Use of Tamoxifen After Breast Surgery for Ductal Carcinoma in Situ
Authors: Yen Tina W.F. , Kuerer Henry M. , Ottesen Rebecca A. , Rouse Layla , Niland Joyce C. , Edge Stephen B. , Theriault Richard L. , Weeks Jane C. 
Published: June 2007

PurposeThe National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers.Patients and MethodsTamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses.ResultsOverall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001).ConclusionTamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.
American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects
Authors: Carver Joseph R. , Shapiro Charles L. , Ng Andrea , Jacobs Linda , Schwartz Cindy , Virgo Katherine S. , Hagerty Karen L. , Somerfield Mark R. , Vaughn David J. 
Published: June 2007

PurposeTo review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors.MethodsAn American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006.ResultsFew studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans.ConclusionAn increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.
Primary Treatment of Waldenström Macroglobulinemia With Dexamethasone, Rituximab, and Cyclophosphamide
Authors: Dimopoulos Meletios Athanasios , Anagnostopoulos Athanasios , Kyrtsonis Marie-Christine , Zervas Konstantinos , Tsatalas Constantinos , Kokkinis Garyfallia , Repoussis Panagiotis , Symeonidis Argyris , Delimpasi Souzana , Katodritou Eirini , Vervessou Elina , Michali Evridiki , Pouli Anastasia , Gika Dimitra , Vassou Amalia , Terpos Evangelos , Anagnostopoulos Nikolaos , Economopoulos Theophanis , Pangalis Gerasimos 
Published: June 2007

Purpose Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC). Patients and Methods Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5 (total dose, 1,000 mg/m2). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta2-microglobulin (43%). Results On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab. Conclusion Our large, multicenter trial showed that the non–stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.
Blood gas and patient safety: considerations based on experience developed in accordance with the Risk Management perspective
Authors: Rambaldi Marco , Baranzoni MariaTeresa , Coppolecchia Pasquale , Moschello Jennifer N. , Novaco Francesca 
Published: June 2007

AbstractIt is the responsibility of health organizations to guarantee a high level of healthcare by using adequate methodologies and instruments, creating secure conditions for treatment, and preventing adverse events due to human or system errors. It is necessary to introduce Risk Management programs, and in particular to promote Clinical Risk Management, one of the constituent elements of Clinical Governance, to assure the delivery of high-quality performance and services. In the point-of-care testing (POCT) context, using an analysis of our experiences, we discuss the entire analytical process, including acquisition and usage, while focusing on blood gas analyzers. Our experience confirms that within a Clinical Governance framework, it is necessary to apply, even when choosing instruments, a systematic vision that is not limited to analytical validation, but also includes an in-depth analysis of the impact in a specific context. Assessment of the correlated risks, independent of the analytical methodology used, is indispensable in a clinical environment to identify the most suitable approach for such risks. A study of the latent factors can be proactively performed to identify (and stimulate) what the pre-organizational environment (producer companies) can offer in terms of product orientation to effectively reduce correlated risk during use. Among the different options for possible treatment of risk, one involves the transfer of the assumption of risk to third parties (e.g., maintenance and quality controls). Transferring the responsibility for control operations to the operator of the instrument, which follows the quality controls with total autonomy, is equivalent to transferring the correlated risk for the clinician (in the POCT case) to the producer, who becomes the guarantor. In practice this is equivalent to a specific assurance stipulation with zero cost.Clin Chem Lab Med 2007;45:774–80.
Risk management in laboratory medicine: quality assurance programs and professional competence
Authors: Sciacovelli Laura , Secchiero Sandra , Zardo Lorena , D'Osualdo Alessandra , Plebani Mario 
Published: June 2007

AbstractTo guarantee excellent performance and service, the process of identifying and treating error risks must be integrated into the total testing process. Quality Assurance Programs (QAPs) represent an important tool that allows us to identify errors and pinpoint any need for further systematic investigations, and to rectify procedures to improve the inputs and processes by which the service is delivered. The models used by the laboratory to assure quality and manage the risk of errors have been modified in line with an approach in which the identification of quality goals and the redefinition of professionals duties and responsibilities are indispensable. Error risk is currently high in some areas of laboratory activity, and QAP is needed now more than ever.The present paper provides some descriptive examples of an approach that can be followed to manage an External Quality Assessment Scheme (EQAS) and quality indicators (QIs), the main tools used by laboratories to assure the quality of their service, for the prevention of error risk. In particular, we describe the correct approach to choose EQAS, to use information from the EQAS report, to design a QI model, and to analyze any QI data. The examples highlight that any well-designed quality system can be ineffective if it is not managed by highly competent professionals with a deep sense of responsibility.Clin Chem Lab Med 2007;45:756–65.
Does external evaluation of laboratories improve patient safety?
Authors: Noble Michael A. 
Published: June 2007

AbstractLaboratory accreditation and External Quality Assessment (also called proficiency testing) are mainstays of laboratory quality assessment and performance. Both practices are associated with examples of improved laboratory performance. The relationship between laboratory performance and improved patient safety is more difficult to assess because of the many variables that are involved with patient outcome. Despite this difficulty, the argument to continue external evaluation of laboratories is too compelling to consider the alternative.Clin Chem Lab Med 2007;45:753–5.
“Pre-pre” and “post-post” analytical error: high-incidence patient safety hazards involving the clinical laboratory
Authors: Laposata Michael , Dighe Anand 
Published: June 2007

AbstractData from recent studies suggest that the highest incidence of laboratory-related errors occurs in the pre-analytical phase of laboratory testing. However, few studies have examined the frequency of errors in laboratory test selection and interpretation. A survey of physicians who use our clinical laboratory demonstrated that the largest number of test ordering errors appear to involve physicians simply ordering the wrong test. Diagnostic algorithms providing guidance for test selection in specific disorders are also used as the basis for the establishment of reflex protocols in the clinical laboratory. The provision of an expert-driven interpretation by laboratory professionals resulted in improvements both in the time to and the accuracy of diagnosis. A survey of our physician staff has shown that in the absence of such an interpretation, for patients being assessed for a coagulation disorder, approximately 75% of the cases would have involved some level of test result misinterpretation.Clin Chem Lab Med 2007;45:712–9.
Recommendations for detection and management of unsuitable samples in clinical laboratories
Authors: Lippi Giuseppe , Banfi Giuseppe , Buttarello Mauro , Ceriotti Ferruccio , Daves Massimo , Dolci Alberto , Caputo Marco , Giavarina Davide , Montagnana Martina , Miconi Valentino , Milanesi Bruno , Mosca Andrea , Morandini Margherita , Salvagno Gian Luca 
Published: June 2007

AbstractA large body of evidence attests that quality programs developed around the analytical phase of the total testing process would only produce limited improvements, since the large majority of errors encountered in clinical laboratories still prevails within extra-analytical areas of testing, especially in manually intensive preanalytical processes. Most preanalytical errors result from system flaws and insufficient audit of the operators involved in specimen collection and handling responsibilities, leading to an unacceptable number of unsuitable specimens due to misidentification, in vitro hemolysis, clotting, inappropriate volume, wrong container or contamination from infusive routes. Detection and management of unsuitable samples are necessary to overcome this variability. The present document, issued by the Italian Inter-society SIBioC-SIMeL-CISMEL (Society of Clinical Biochemistry and Clinical Molecular Biology-Italian Society of Laboratory Medicine-Italian Committee for Standardization of Hematological and Laboratory Methods) Study Group on Extra-analytical Variability, reviews the major causes of unsuitable specimens in clinical laboratories, providing consensus recommendations for detection and management.Clin Chem Lab Med 2007;45:728–36.
The role of in vitro diagnostic companies in reducing laboratory error
Authors: Stankovic Ana K. , Romeo Peter 
Published: June 2007

AbstractLaboratory errors have a significant impact on patient safety. The manufacturers of in vitro diagnostic (IVD) products play an important role in the reduction of laboratory errors by ensuring the highest possible safety and efficacy of their products. In order to achieve this, the IVD industry has implemented rigorous product development and manufacturing processes. Many IVD companies apply Six Sigma principles in order to minimize variability within the whole product life cycle, starting with customer requirements, through product design and manufacture, as well as management of the potential issues that occur after the products have been released for use. A closer look into this process is presented here, using an evacuated blood collection tube as a model device.Clin Chem Lab Med 2007;45:781–8.