tbuckley/cabot-search huggingface dataset:
Outcomes and markers in the assessment of chronic obstructive pulmonary disease
Authors: P. W. Jones, A. G. N. Agusti
Journal: European Respiratory Journal (2006)

The clinical presentation of chronic obstructive pulmonary disease (COPD) is highly variable, reflecting the interaction of a complex range of pathological changes including both pulmonary and systemic effects. The consequences of COPD experienced by the patient ( i.e. its outcomes) include: symptoms, weight loss, exercise intolerance, exacerbations, health-related quality of life, health resource use and death. No single measure can reflect the variety of pathological effects or adequately describe the nature or severity of COPD. Currently, there are few validated markers for assessing COPD and evaluating the effectiveness of treatment. The forced expiratory volume in one second has been used as a global marker of COPD, but it does not fully reflect the burden of COPD on patients. New markers are needed to better characterise the full clinical spectrum of the disease and to guide the development and assessment of new and more effective therapies. This article considers the distinction between outcomes and markers, the various ways in which markers are used and the need for new markers in the management of chronic obstructive pulmonary disease. The process of marker selection and validation is reviewed and potential new biological, physiological and symptomatic markers for chronic obstructive pulmonary disease are assessed.
Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents
Authors: Tanja C. Adam, Claudia Toledo-Corral, Christianne J. Lane, Marc J. Weigensberg, Donna Spruijt-Metz, Jaimie N. Davies, Michael I. Goran
Journal: Diabetes Care (2009)

The purpose of this study was to examine the relationship between changes in insulin sensitivity and subsequent changes in fat mass in obese Hispanic children over 3 consecutive years.In a longitudinal research design, insulin sensitivity (S(i)) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments.The change in S(i) during the first year of the study was a significant predictor of further fat mass development (P < 0.05). Considering different directions of S(i) change, S(i) was a strong predictor for further fat mass development only in the group that decreased their S(i) (P < 0.05).The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.
Spontaneous dietary protein intake during progression of chronic renal failure.
Authors: T A Ikizler, J H Greene, R L Wingard, R A Parker, R M Hakim
Journal: Journal of the American Society of Nephrology (1995)

Malnutrition at the initiation of dialysis is a strong predictor of subsequent increased mortality on dialysis. Few studies have documented the relationship between the progression of renal failure and spontaneous dietary protein intake (DPI) and other indices of malnutrition. In this prospective study, renal function was sequentially measured by creatinine clearance (CrCl) and DPI by 24-h urine collection; simultaneously, multiple sequential biochemical nutritional indices, including serum albumin, transferrin, prealbumin, and insulin-like growth factor-I (IGF-I) concentrations, were measured. The study involved 90 patients (46 men and 44 women) with chronic renal failure (CRF) of various causes monitored in an outpatient clinic. Dietary interventions were minimal. The mean duration of follow-up was 16.5 +/- 11.8 months. The results show that the mean (+/- SD) DPI was 1.01 +/- 0.21 g/kg per day for patients with CrCl over 50 mL/min and decreased to 0.85 +/- 0.23 g/kg per day for patients with CrCl between 25 and 50 mL/min. The DPI further decreased to a level of 0.70 +/- 0.17 g/kg per day for patients with CrCl between 10 and 25 mL/min and was 0.54 +/- 0.16 g/kg per day for patients with CrCl below 10 mL/min. This trend was statistically significant (P < 0.001). A similar statistically significant trend was observed for serum cholesterol, transferrin, and total creatinine excretion (all P < 0.01). A mixed model analysis indicated that for each 10 mL/min decrease in CrCl, DPI decreased by 0.064 +/- 0.007 g/kg per day, transferrin decreased by 16.7 +/- 4.1 mg/dL, weight decreased by 0.38 +/- 0.13% of initial weight, and IGF-I decreased by 6.2 +/- 1.9 ng/mL. It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease. Dietary protein restriction should be used cautiously in CRF patients when CrCl falls below 25 mL/min.
Apoptosis Suppression by Somatic Cell Transfer of Bcl-2 Promotes Sonic Hedgehog–Dependent Medulloblastoma Formation in Mice
Authors: Todd D. McCall, Carolyn A. Pedone, Daniel W. Fults
Journal: Cancer Research (2007)

Abstract Medulloblastomas are malignant brain tumors that arise in the cerebellum in children. Aberrant activation of the Sonic hedgehog (Shh) signaling pathway, which normally stimulates proliferation of granule neuron precursors (GNP) during cerebellar development, induces tumors in mice that closely mimic human medulloblastomas. Shh-dependent medulloblastoma formation is enhanced by hyperactive insulin-like growth factor (IGF) signaling and ectopic expression of Myc oncogenes. This enhanced tumorigenesis stems from the sensitivity of GNPs to IGF and Myc levels in regulating proliferation. An emerging theme in cancer research is that oncogene-induced cell proliferation cannot initiate neoplastic transformation unless cellular programs that mediate apoptosis are disabled. Here, we report a high frequency of medulloblastoma formation in mice after postnatal overexpression of the antiapoptotic protein Bcl-2 in cooperation with Shh. Ectopic expression of Bcl-2 alone or in combination with N-Myc did not induce tumors, indicating that Shh has essential transforming functions in GNPs not supplied by the mitogenic stimulus of N-Myc combined with a strong antiapoptotic signal provided by Bcl-2. Expression of endogenous Bcl-2 was not up-regulated in Shh-induced tumors. Instead, elevated levels of phosphorylated Akt were found, suggesting that activated phosphatidylinositol 3-kinase signaling is one intrinsic mechanism for suppressing apoptosis in Shh-dependent medulloblastomas. Thus, blockade of apoptosis cooperates with Shh-stimulated proliferation to transform GNPs and induce aggressive medulloblastomas. These findings provide insights into the molecular signals that initiate medulloblastoma formation and they support the importance of blocking apoptosis in carcinogenesis. [Cancer Res 2007;67(11):5179–85]
Cardiovascular Conditioning in Individuals With Diabetic Retinopathy
Authors: Maria Bernbaum, Stewart G Albert, Jerome D Cohen, Ami Drimmer
Journal: Diabetes Care (1989)

The benefit of exercise for individuals with diabetes mellitus and high-risk complications of retinopathy has been questioned. Thirty-nine individuals with diabetes and visual impairment completed a 12-wk rehabilitation program that included cardiovascular conditioning. Pre- and postprogram assessment of exercise training in 30 subjects included a graded stress test with a bicycle ergometer. There were improvements in exercise tolerance as measured by the work load achieved (from 248 +/- 27 to 303 +/- 31 kilopond meter [kpm], P less than .05). There was a trend toward improvement in METS achieved (from 3.3 +/- 0.2 to 3.8 +/- 0.3, P = .06). There was no correlation of improvement in exercise tolerance with improvements in glycemic control, lipoprotein balance, and change in body weight. Individuals with diabetic retinopathy may be given the option of entering cardiovascular training programs with appropriate modifications to fit specific needs.
The cortical thickness phenotype of individuals with DISC1 translocation resembles schizophrenia
Authors: Orla M. Doyle, Catherine Bois, Pippa Thomson, Liana Romaniuk, Brandon Whitcher, Steven C.R. Williams, Federico E. Turkheimer, Hreinn Stefansson, Andrew M. McIntosh, Mitul A. Mehta, Stephen M. Lawrie
Journal: Journal of Clinical Investigation (2015)

BACKGROUND. The disrupted in schizophrenia 1 (DISC1) gene locus was originally identified in a Scottish pedigree with a high incidence of psychiatric disorders that is associated with a balanced t(1;11)(q42.1;q14.3) chromosomal translocation. Here, we investigated whether members of this family carrying the t(1;11)(q42.1;q14.3) translocation have a common brain-related phenotype and whether this phenotype is similar to that observed in schizophrenia (SCZ), using multivariate pattern recognition techniques.
Ultrasound-guided shoulder girdle injections are more accurate and more effective than landmark-guided injections: a systematic review and meta-analysis
Authors: Abdel-Rahman Aly, Sathish Rajasekaran, Nigel Ashworth
Journal: British Journal of Sports Medicine (2014)

Objective To compare the accuracy and efficacy of ultrasound (US)-guided injections versus landmark-guided injections of the subacromial space, biceps tendon sheath, acromioclavicular (AC) joint and glenohumeral (GH) joint. Methods PubMed, Medline and Cochrane libraries were searched up to 31 July 2013. Two independent authors selected and evaluated randomised controlled trials comparing the accuracy and/or efficacy of US versus landmark-guided injection of the shoulder girdle. A meta-analysis of accuracy, pain Visual Analog Scale (VAS), function score and reported adverse events were performed. Result Four cadaveric studies (300 cadaveric shoulders) and nine live human studies (514 patients) were reviewed. Based on three studies for AC joint, the accuracy of US versus a landmark-guided injection was 93.6% vs 68.2% (p&lt;0.0001). Based on single studies, the accuracy of US versus a landmark-guided injection was 65% vs 70% for the subacromial space (p&gt;0.05), 86.7% vs 26.7% for the biceps tendon sheath (p&lt;0.05), and 92.5% vs 72.5% for the GH joint (p=0.025). Based on three studies for the subacromial space, the US group had a significantly greater reduction in pain (mean difference (MD)=1.47, 95% CI 1.0 to 1.93), and improvement in function (standardised MD=0.70, 95% CI 0.39 to 1.01) at 6 weeks postinjection. Based on a single study for the biceps tendon sheath, the US group had a significantly greater reduction in pain (MD 1.9, 95% CI 1.2 to 2.6) and improvement in function (MD=10.9, 95% CI 6.57 to 15.23). Conclusions US-guided injections showed greater accuracy for all shoulder girdle injections, with the exception of the subacromial space. There was improved efficacy for the subacromial space and biceps tendon sheath injections.
Early asthma control and maintenance with eformoterol following reduction of inhaled corticosteroid dose
Authors: D Price
Journal: Thorax (2002)

Previous studies have indicated the benefits of adding long acting beta(2) agonists to inhaled corticosteroids in the maintenance treatment of moderate to severe asthma. The effects of adding eformoterol to corticosteroids on asthma control and exacerbations in patients with mild to moderate asthma were studied.After a run in period of 7-14 days on existing medication, 663 symptomatic patients were randomised to receive budesonide Turbohaler 400 microg twice daily together with either eformoterol Turbohaler 9 micro g (delivered dose) or placebo twice daily. After 4 weeks patients whose asthma was well controlled (n=505) were re-randomised to receive budesonide 400 microg daily and either eformoterol 9 micro g or placebo twice daily for a further 6 months.Patients receiving eformoterol achieved asthma control 10 days sooner than those receiving budesonide alone, and improvements in lung function, symptoms, quality of life, and relief beta(2) agonist use were significantly greater with eformoterol. During the 6 month follow up the frequency of mild exacerbations was significantly lower in the eformoterol group than in those receiving budesonide alone (7.2 versus 10.5 per patient, 95% confidence interval for ratio 0.49 to 0.96, p=0.03). The time to first day of poorly controlled asthma was 97 days in the eformoterol group compared with 42 days in the placebo group (p=0.003).Adding eformoterol to a low or moderate dose of budesonide in mild asthma resulted in faster and more effective control than treatment with budesonide alone. Eformoterol allowed the corticosteroid dose to be reduced while also decreasing the rate of mild exacerbations compared with budesonide alone. These data suggest a therapeutic advantage of adding eformoterol to inhaled corticosteroids in patients with mild to moderate asthma.
Ribosomal RNA secondary structure: compensatory mutations and implications for phylogenetic analysis.
Authors: Michael T. Dixon, David M. Hillis
Journal: Molecular Biology and Evolution (1993)

Using sequence data from the 28S ribosomal RNA (rRNA) genes of selected vertebrates, we investigated the effects that constraints imposed by secondary structure have on the phylogenetic analysis of rRNA sequence data. Our analysis indicates that characters from both base-pairing regions (stems) and non-base-pairing regions (loops) contain phylogenetic information, as judged by the level of support of the phylogenetic results compared with a well-established tree based on both morphological and molecular data. The best results (the greatest level of support of well-accepted nodes) were obtained when the complete data set was used. However, some previously supported nodes were resolved using either the stem or loop bases alone. Stem bases sustain a greater number of compensatory mutations than would be expected at random, but the number is < 40% of that expected under a hypothesis of perfect compensation to maintain secondary structure. Therefore, we suggest that in phylogenetic analyses, the weighting of stem characters be reduced by no more than 20%, relative to that of loop characters. In contrast to previous suggestions, we do not recommend weighting of stem positions by one-half, compared with that of loop positions, because this overcompensates for the constraints that selection imposes on the secondary structure of rRNA.
Radiotherapy of Carcinoma-In-Situ of the Testis
Authors: Johannes Classen, Klaus-Peter Dieckmann
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.950 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12177118 Radiotherapy of Carcinoma-In-Situ of the Testis Johannes ClassenxJohannes ClassenSearch for articles by this author , Klaus-Peter DieckmannxKlaus-Peter DieckmannSearch for articles by this author Show More University of Tuebingen, Tuebingen, GermanyAlbertinen-Krankenhaus, Hamburg, Germany https://doi.org/10.1200/JCO.2002.99.950 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Increased mortality from infectious pneumonia after occupational exposure to inorganic dust, metal fumes and chemicals
Authors: K. Toren, I. Qvarfordt, I. A. Bergdahl, B. Jarvholm
Journal: Thorax (2011)

There are epidemiological studies indicating that exposure to metal fumes is a risk factor for infectious pneumonia. Whether occupational exposure to other agents, such as inorganic dust or chemicals, also increases the risk for infectious pneumonia is not clear. The aim of the present study was to elucidate whether occupational exposure to respiratory pollutants and irritants increases the risk for infectious pneumonia.Prospective cohort study. Setting Swedish male construction workers. Participants 320,143 male construction workers exposed to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, metal fumes and chemicals (organic solvents, diisocyanates and epoxi resins) or unexposed. Main outcome measures The cohort was followed from 1971 to 2003 and the main outcome measures were mortality to infectious pneumonia, lobar pneumonia or pneumococcal pneumonia. RRs were obtained by the person-years method and from Poisson regression models, adjusting for baseline values of age and smoking habits.Among men aged 20-64 years there was increased mortality from infectious pneumonias among construction workers exposed to metal fumes (RR 2.31, 95% CI 1.35 to 3.95), inorganic dust (RR 1.87, 95% CI 1.22 to 2.87) and chemicals (RR 1.91, 95% CI 1.37 to 3.22). The mortality was also increased from both lobar pneumonia and pneumococcal pneumonia. Among men aged 65-84 years the occupational exposure to inorganic dust and chemicals was associated with slightly increased mortality from infectious pneumonia. Among groups with mutually exclusive exposures there was increased mortality from infectious pneumonias among construction workers exposed to inorganic dust, but not among those exposed to wood dust or chemicals. There were no cases among workers exposed only to metal fumes.Our findings indicate that exposure to inorganic dust increases the mortality from infectious pneumonias, especially lobar pneumonia and pneumococcal pneumonia. The mechanism is unclear, but the effect may be mediated through induced airways inflammation.
Systematic Reviews: Synthesis of Best Evidence for Clinical Decisions
Authors: Deborah J. Cook
Journal: Annals of Internal Medicine (1997)

Systematic reviews can help practitioners keep abreast of the medical literature by summarizing large bodies of evidence and helping to explain differences among studies on the same question.A systematic review involves the application of scientific strategies, in ways that limit bias, to the assembly, critical appraisal, and synthesis of all relevant studies that address a specific clinical question. A meta-analysis is a type of systematic review that uses statistical methods to combine and summarize the results of several primary studies. Because the review process itself (like any other type of research) is subject to bias, a useful review requires clear reporting of information obtained using rigorous methods. Used increasingly to inform medical decision making, plan future research agendas, and establish clinical policy, systematic reviews may strengthen the link between best research evidence and optimal health care.
Troxacitabine, an L-Stereoisomeric Nucleoside Analog, on a Five-Times-Daily Schedule: A Phase I and Pharmacokinetic Study in Patients With Advanced Solid Malignancies
Authors: Johann S. De Bono, J Joseph Stephenson, Sharyn D. Baker, Manuel Hidalgo, Amita Patnaik, Lisa A. Hammond, Geoffrey Weiss, Andrew Goetz, Lillian Siu, Cecelia Simmons, Jacques Jolivet, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the feasibility of administering troxacitabine, a unique l-nucleoside that is not a substrate for deoxycytidine deaminase–mediated catabolism, as a 30-minute intravenous (IV) infusion daily for 5 days. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of troxacitabine as a 30-minute IV infusion daily for 5 days. Plasma and urine sampling was performed to characterize the pharmacokinetics and pharmacodynamics of troxacitabine. RESULTS: Thirty-nine patients received 124 courses of troxacitabine at eight dose levels ranging from 0.12 to 1.8 mg/m2/d. Severe neutropenia that was protracted (> 5 days) and/or associated with fever, and skin rashes were consistently experienced by heavily (HP) and minimally pretreated (MP) patients at doses exceeding 1.2 and 1.5 mg/m2/d, respectively. At troxacitabine doses ≥ 1.2 mg/m2/d, treatment was often delayed 1 additional week for complete resolution of hematologic effects, resulting in lengthening of the treatment interval from every 3 to 4 weeks. Skin rash, palmar-plantar erythrodysesthesia, and thrombocytopenia were also observed and were occasionally severe, particularly at the highest doses. A patient with metastatic ocular melanoma experienced a partial response. Pharmacokinetics of troxacitabine were dose-independent; mean (SD) values for the volume of distribution at steady-state and clearance (Cls) were 60 (32) L and 161 (33) mL/min, respectively, on day 1. After treatment on the fifth day, terminal half-life values averaged 39 (63) hours, and Cls was reduced by approximately 20%, averaging 127 (27) mL/min. The principal mode of drug elimination was renal. CONCLUSION: Recommended doses for phase II studies of troxacitabine as a 30-minute infusion daily for 5 days every 4 weeks are 1.5 and 1.2 mg/m2/d for MP and HP patients, respectively. Broad disease-directed evaluations of troxacitabine on this schedule and possibly less frequent schedules are warranted.
Transcriptional regulation of the T cell antigen receptor zeta subunit: identification of a tissue-restricted promoter.
Authors: B L Rellahan, J P Jensen, A M Weissman
Journal: The Journal of Experimental Medicine (1994)

The cell surface expression of T cell antigen receptors (TCR) is regulated in part by the limiting synthesis of the zeta subunit. Utilizing fragments from the 5' region of the human zeta gene, two discrete regions that promote transcription were characterized. Both of these elements are located within 125 bases of the most 3' site of transcription initiation. The more proximal (3') promoter exhibits activity in lymphoid as well as nonlymphoid cells. In contrast, the more distal (5') promoter element functions in a tissue-restricted fashion. The tissue-specific promoter is localized to a 29-base fragment. The sequence of this region is remarkable for a stretch of 11 consecutive purines that are required for activity. This element constitutes the only known tissue-specific promoter for an invariant TCR subunit. Consistent with the unique role served by the zeta subunit in assembly of the TCR, this study demonstrates that the expression of the zeta gene is regulated in a fashion distinct from other TCR components.
Transcatheter Arterial Chemoembolization Therapy for Patients With Hepatocellular Carcinoma: A Case-Controlled Study
Authors: M BISELLI, P ANDREONE, A GRAMENZI, F TREVISANI, C CURSARO, C ROSSI, S RICCAROSELLINI, C CAMMA, S LORENZINI, G STEFANINI
Journal: Clinical Gastroenterology and Hepatology (2005)
Disease-Free Survival (Dfs) in the Lapatinib Alone Arm and Expanded Results of the Phase III Altto Trial (Big 2-06; Ncctg (Alliance) N063D) in the Adjuvant Treatment of Her2-Positive Early Breast Cancer (Ebc)
Authors: E.A. Perez, E. Holmes, E. De Azambuja, A. Dueck, J. Baselga, G. Viale, J.A. Zujewski, A. Goldhirsch, R. Crescenzo, K. Pritchard, A.C. Wolff, C. Jackisch, I. Láng, M. Untch, I. Smith, F. Boyle, B. Xu, H.L. Gomez, R.D. Gelber, M. Piccart
Journal: Annals of Oncology (2014)
Apolipoprotein E in Alzheimer's Disease: An Update
Authors: Jin-Tai Yu, Lan Tan, John Hardy
Journal: Annual Review of Neuroscience (2014)

The vast majority of Alzheimer's disease (AD) cases are late onset (LOAD), which is genetically complex with heritability estimates up to 80%. Apolipoprotein E (APOE) has been irrefutably recognized as the major genetic risk factor, with semidominant inheritance, for LOAD. Although the mechanisms that underlie the pathogenic nature of APOE in AD are still not completely understood, emerging data suggest that APOE contributes to AD pathogenesis through both amyloid-β (Aβ)-dependent and Aβ-independent pathways. Given the central role for APOE in the modulation of AD pathogenesis, many therapeutic strategies have emerged, including converting APOE conformation, regulating APOE expression, mimicking APOE peptides, blocking the APOE/Aβ interaction, modulating APOE lipidation state, and gene therapy. Accumulating evidence also suggests the utility of APOE genotyping in AD diagnosis, risk assessment, prevention, and treatment response.