tbuckley/cabot-search huggingface dataset:
Insulin Detemir Reduces Weight Gain as a Result of Reduced Food Intake in Patients With Type 1 Diabetes
Authors: Sunil Zachariah, Ben Sheldon, Fariba Shojaee-Moradie, Nicola C. Jackson, Katharine Backhouse, Sigurd Johnsen, Richard H. Jones, A. Margot Umpleby, David L. Russell-Jones
Journal: Diabetes Care (2011)

Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure.A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured.After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir.The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.
Silence Is Not Golden: Communicating With Children Dying From Cancer
Authors: Estela A. Beale, Walter F. Baile, Joann Aaron
Journal: Journal of Clinical Oncology (2005)

Oscar, a 9-year-old boy, was first diagnosed and treated for medulloblastoma at the age of 1 year.Eight years later, all anticancer treatment options for him had been exhausted.Although Oscar knew that he was dying, his parents could not accept the inevitable.Oscar's parents would not allow anyone else to discuss the end of his life with him either.He reacted by becoming despondent and withdrawn and sometimes very obstinate.He stopped eating, was hyperalert much of the time, and for the most part, would not talk. CASE HISTORY: PART 2Oscar's parents were quite disturbed by his depression and withdrawal.A child psychiatrist was called in as a consultant and interviewed them and Oscar.She helped them
Molecular Pathways: A Novel Approach to Targeting Hypoxia and Improving Radiotherapy Efficacy via Reduction in Oxygen Demand
Authors: Alexander Lin, Amit Maity
Journal: Clinical Cancer Research (2015)

Abstract Tumor hypoxia presents a unique therapeutic challenge in the treatment of solid malignancies. Its presence has been established to be a poor prognostic factor in multiple cancer types, and past hypoxia-directed approaches have yielded generally disappointing results. Previous approaches have centered on either increasing oxygen delivery or administering agents that preferentially radiosensitize or kill hypoxic cells. However, a novel and potentially more effective method may be to increase therapeutic benefit by decreasing tumor oxygen consumption via agents such as metformin or nelfinavir in a patient population that is enriched for tumor hypoxia. This promising approach is currently being investigated in clinical trials and the subject of this article. Clin Cancer Res; 21(9); 1995–2000. ©2015 AACR.
Livin Contributes to Tumor Hypoxia–Induced Resistance to Cytotoxic Therapies in Glioblastoma Multiforme
Authors: Chia-Hung Hsieh, Yu-Jung Lin, Chung-Pu Wu, Hsu-Tung Lee, Woei-Cherng Shyu, Chi-Chung Wang
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Tumor hypoxia is one of the crucial microenvironments to promote therapy resistance (TR) in glioblastoma multiforme (GBM). Livin, a member of the family of inhibitor of apoptosis proteins, contributes antiapoptosis. However, the role of tumor hypoxia in Livin regulation and its impact on TR are unclear. Experimental Design: Livin expression and apoptosis for tumor hypoxic cells derived from human glioblastoma xenografts or in vitro hypoxic stress-treated glioblastoma cells were determined by Western blotting, immunofluorescence imaging, and annexin V staining assay. The mechanism of hypoxia-induced Livin induction was investigated by chromatin immunoprecipitation assay and reporter assay. Genetic and pharmacologic manipulation of Livin was utilized to investigate the role of Livin on tumor hypoxia–induced TR in vitro or in vivo. Results: The upregulation of Livin expression and downregulation of caspase activity were observed under cycling and chronic hypoxia in glioblastoma cells and xenografts, concomitant with increased TR to ionizing radiation and temozolomide. However, knockdown of Livin inhibited these effects. Moreover, hypoxia activated Livin transcription through the binding of hypoxia-inducible factor-1α to the Livin promoter. The targeted inhibition of Livin by the cell-permeable peptide (TAT-Lp15) in intracerebral glioblastoma-bearing mice demonstrated a synergistic suppression of tumor growth and increased the survival rate in standard-of-care treatment with radiation plus temozolomide. Conclusions: These findings indicate a novel pathway that links upregulation of Livin to tumor hypoxia–induced TR in GBM and suggest that targeting Livin using cell-permeable peptide may be an effective therapeutic strategy for tumor microenvironment–induced TR. Clin Cancer Res; 21(2); 460–70. ©2014 AACR.
Can psychological factors help us to determine adherence to CPAP? A prospective study
Authors: M.R. Wild, H.M. Engleman, N.J. Douglas, C.A. Espie
Journal: European Respiratory Journal (2004)

The present study objective was to establish whether pretreatment social cognitive variables may contribute to the explanation of variance in adherence to continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). A total of 119 of 180 consecutive OSAHS patients were recruited to the study prior to initial CPAP titration. Patients completed psychological measures of health value, health locus of control (incorporating internality, chance, powerful others) and self-efficacy prior to CPAP titration. Objective adherence data were measured by CPAP unit time clocks and collected at 3-month follow-up. Average nightly use was calculated over this period. Logistic regression of prospective predictors of adherence produced a model comprising psychological (health value, internality, powerful others), as well as clinical variables (Epworth score, body mass index, apnoea/hypopnoea index, CPAP pressure). This model explained 24% of the variance in CPAP use, and correctly identified 75% of adherers and 53% of nonadherers. Although the psychological variables explained only a small amount of the overall variance in adherence behaviour, this result provides further support for the hypothesis that psychological variables contribute, in part, to continuous positive airway pressure adherence. Future research should focus on highlighting discrete variables, which may helpfully inform psychologically based interventions aimed at improving the use of continuous positive airway pressure by patients with obstructive sleep apnoea/hypopnoea syndrome at risk of discontinuance.
The rs1800716 variant in CYP2D6 is associated with an increased double endometrial thickness in postmenopausal women on tamoxifen
Authors: A.-S. Dieudonné, D. Lambrechts, D. Smeets, A. Belmans, H. Wildiers, R. Paridaens, C. Hyonil, D. Timmerman, M.-R. Christiaens, I. Vergote, P. Neven
Journal: Annals of Oncology (2013)
Adalimumab use in pregnancy
Authors: L Vesga
Journal: Gut (2005)

Infliximab, a chimeric antibody to tumour necrosis factor alpha (TNF-α), has demonstrated efficacy for the induction and maintenance of remission in patients with Crohn’s disease.1,2 Antibodies to the chimeric component of infliximab can lead to infusion reactions and possible loss of response.3 A human recombinant monoclonal antibody to TNF-α, adalimumab, has recently demonstrated safety and efficacy for induction of remission in Crohn’s disease.4 It has also been effective in patients who have lost response to infliximab.5 Currently, this drug is FDA approved for the treatment of rheumatoid arthritis but it is being administered off label to patients with Crohn’s disease who …
A Phase II Study of Halichondrin B Analog Eribulin Mesylate (E7389) in Patients with Advanced Non-small Cell Lung Cancer Previously Treated with a Taxane: A California Cancer Consortium Trial
Authors: Barbara J. Gitlitz, Denice D. Tsao-Wei, Susan Groshen, Angela Davies, Marianna Koczywas, Chandra P. Belani, Athanassios Argiris, Suresh Ramalingam, Everett E. Vokes, Martin Edelman, Philip Hoffman, Marc S. Ballas, Stephen V. Liu, David R. Gandara
Journal: Journal of Thoracic Oncology (2011)
Country actions to meet UN commitments on non-communicable diseases: a stepwise approach
Authors: Ruth Bonita, Roger Magnusson, Pascal Bovet, Dong Zhao, Deborah C Malta, Robert Geneau, Il Suh, Kavumpurathu Raman Thankappan, Martin McKee, James Hospedales, Maximilian de Courten, Simon Capewell, Robert Beaglehole
Journal: The Lancet (2013)
TCT-179 Procedural and Clinical Outcomes After Endovascular Intervention for Femoral-Tibial Graft Stenosis
Authors: Usman Javed, Christopher Balwanz, Ehrin Armstrong, Satinder Singh, Caroline McCoach, David Anderson, Greg Westin, Khung Keong Yeo, John Laird
Journal: Journal of the American College of Cardiology (2012)
Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury.
Authors: A Kribben, E D Wieder, J F Wetzels, L Yu, P E Gengaro, T J Burke, R W Schrier
Journal: Journal of Clinical Investigation (1994)

The role of cytosolic free Ca2+ ([Ca2+]i) in hypoxic injury was investigated in rat proximal tubules. [Ca2+]i was measured using fura-2 and cell injury was estimated with propidium iodide (PI) in individual tubules using video imaging fluorescence microscopy. [Ca2+]i increased from approximately 170 to approximately 390 nM during 5 min of hypoxia. This increase preceded detectable cell injury as assessed by PI and was reversible with reoxygenation. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 100 microM) reduced [Ca2+]i under basal conditions (approximately 80 nM) and during hypoxia (approximately 120 nM) and significantly attenuated hypoxic injury. When [Ca2+]i and hypoxic cell injury were studied concurrently in the same individual tubules, the 10 min [Ca2+]i rise correlated significantly with subsequent cell damage observed at 20 min. 2 mM glycine did not block the rise in [Ca2+]i, yet protected the tubules from hypoxic injury. These results indicate that in rat proximal tubules, hypoxia induces an increase of [Ca2+]i which occurs before cell damage. The protective effect of BAPTA supports a role for [Ca2+]i in the initiation of hypoxic proximal tubule injury. The glycine results, however, implicate calcium-independent mechanisms of injury and/or blockade of calcium-mediated processes of injury such as activation of phospholipases or proteases.
T Cell Costimulatory Blockade
Authors: HREFNA GUDMUNDSDOTTIR, LAURENCE A. TURKA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Optimal T cell responses occur when T cells receive both antigen-specific signals through the T cell receptor and non-antigen-specific costimulatory signals through accessory cell surface molecules. The best understood costimulatory receptor is CD28. Signals through the T cell receptor and CD28 cooperatively induce cytokine gene expression and promote T cell proliferation and survival. Negative signals delivered through a related cell surface receptor, cytotoxic T lymphocyte antigen (CTLA-4), act to terminate immune responses and are required for normal immune homeostasis. This article reviews T cell costimulation, including the CD28/CTLA-4 system and other potential costimulatory pathways (such as CD40/CD154), the role of these pathways in normal immune responses, and the potential for the inhibition of these pathways to induce transplantation tolerance.
Impact of Aortic Valve Replacement on Outcome of Symptomatic Patients With Severe Aortic Stenosis With Low Gradient and Preserved Left Ventricular Ejection Fraction
Authors: Alper Ozkan, Rory Hachamovitch, Samir R. Kapadia, E. Murat Tuzcu, Thomas H. Marwick
Journal: Circulation (2013)

The optimal management of low-gradient "severe" aortic stenosis (mean gradient <40 mm Hg, indexed aortic valve area ≤0.6 cm2/m2) with preserved left ventricular ejection fraction remains controversial because gradients may be similar after aortic valve replacement (AVR). We compared outcomes of low-gradient severe aortic stenosis with AVR or medical therapy.Comprehensive echocardiographic measurements including hemodynamic calculations were completed in 260 prospectively identified patients with symptomatic low-gradient severe aortic stenosis. Patients were followed up for mortality over 28±24 months. AVR was performed in 123 patients (47%). Compared with AVR patients, medically treated patients had a higher prevalence of diabetes mellitus (25% versus 41%, P=0.009), lower stroke volume index (36.4±8.4 versus 34.4±8.7 mL/m2, P=0.02), higher pulmonary artery pressure (38±11 versus 48±21 mm Hg, P=0.001), and higher creatinine level (1.1±0.4 versus 1.22±0.5 mg/dL, P=0.02). These and other clinically relevant variables were entered into a propensity model that reflected likelihood of referral to AVR. This score and other variables were entered into a Cox model to explore the independent effect of AVR on outcome. During follow-up, 105 patients died (40%): 32 (30%) in the AVR group and 73 (70%) in the medical treatment group. AVR (hazard ratio, 0.54; 95% confidence interval, 0.32-0.94; P<0.001) was independently associated with outcome and remained a strong predictor of survival after adjustment for propensity score. Medical therapy was associated with 2-fold greater all-cause mortality than AVR. The protective effect of AVR was similar in 125 patients with normal flow (stroke volume index >35 mL/m2; P=0.22).AVR is associated with better survival than medical therapy in patients with symptomatic low-gradient severe AS and preserved left ventricular ejection fraction.
Tuberculosis in London: the importance of homelessness, problem drug use and prison
Authors: A Story, S Murad, W Roberts, M Verheyen, A C Hayward
Journal: Thorax (2007)

The control of tuberculosis (TB) is founded on early case detection and complete treatment of disease. In the UK, TB is concentrated in subgroups of the population in large urban centres. The impact of homelessness, imprisonment and problem drug use on TB control in London is reviewed.A cohort study was undertaken of all patients with TB in Greater London to determine the point prevalence of disease in different groups and to examine risk factors for smear positivity, drug resistance, treatment adherence, loss to follow-up and use of directly observed therapy (DOT).Data were collected on 97% (1941/1995) of eligible patients. The overall prevalence of TB was 27 per 100,000. An extremely high prevalence of TB was seen in homeless people (788/100,000), problem drug users (354/100,000) and prisoners (208/100,000). Multivariate analysis showed that problem drug use was associated with smear positive disease (OR 2.2, p<0.001), being part of a known outbreak of drug resistant TB (OR 3.5, p = 0.001) and loss to follow-up (OR 2.7, p<0.001). Imprisonment was associated with being part of the outbreak (OR 10.3, p<0.001) and poor adherence (OR 3.9, p<0.001). Homelessness was associated with infectious TB (OR 1.6, p = 0.05), multidrug resistance (OR 2.1, p = 0.03), poor adherence (OR 2.5, p<0.001) and loss to follow-up (OR 3.8, p<0.001). In London, homeless people, prisoners and problem drug users collectively comprise 17% of TB cases, 44% of smear positive drug resistant cases, 38% of poorly compliant cases and 44% of cases lost to follow-up. 15% of these patients start treatment on DOT but 46% end up on DOT.High levels of infectious and drug resistant disease, poor adherence and loss to follow-up care indicate that TB is not effectively controlled among homeless people, prisoners and problem drug users in London.
Variable Expressivity and High Penetrance of CYP1B1 Mutations Associated with Primary Congenital Glaucoma
Authors: Fatemeh Suri, Shahin Yazdani, Mehrnaz Narooie-Nejhad, Seyed Jalal Zargar, Seyed Hassan Paylakhi, Sirous Zeinali, Mohammad Pakravan, Elahe Elahi
Journal: Ophthalmology (2009)
The isolation and sequence of a novel gene from a human functional T cell line.
Authors: J Jongstra, T J Schall, B J Dyer, C Clayberger, J Jorgensen, M M Davis, A M Krensky
Journal: The Journal of Experimental Medicine (1987)

Using a subtractive hybridization procedure we have constructed a cDNA library enriched for sequences present in functional human T cell lines, but not in human EBV-transformed B cell lines. We have isolated a cDNA clone, AH2-519, representing a novel gene, designated 519. This novel gene is expressed in functional human cytolytic and Th cell lines but not in a variety of other cell lines, including several long-term human T cell tumor lines. The expression of gene 519 is inducible in cultures of normal human PBL using antigenic or mitogenic stimulation. Neither the DNA sequence determined from a full-length cDNA clone overlapping with clone AH2-519 nor the amino acid sequence of its predicted protein product has significant homology to published sequences in the GenBank or NBRF databases. The restricted expression of gene 519 suggests that its gene product is involved in the growth and/or differentiation of normal T cells. The data also show that normal, nontransformed, functional T cells express gene products that can not be readily identified in long-term tumor lines of the same cell lineage.
Medical treatment of pulmonary hypertension in acute lung disease
Authors: R Naeije
Journal: European Respiratory Journal (1993)

A moderate pulmonary hypertension is a hallmark of experimental, as well as clinical, acute lung injury. Pulmonary hypertension in acute lung injury, appears to be caused primarily by a partially reversible increase in extra-alveolar vascular closing pressure, the latter being modulated by vasodilating products of the cyclooxygenase pathway of arachidonic acid metabolism, as well as by an endogenous release of nitric oxide. Gas exchange in acute lung injury is improved by increased pulmonary vascular tone. However it is also improved by inhaled nitric oxide, which increases perfusion to the better aerated lung areas. Whether pharmacological interventions aimed at the prevention of right ventricular failure in acute lung injury improve right ventriculo-vascular coupling sufficiently to exert a favourable influence on outcome, remains to be shown.
Role of liver scanning in the preoperative evaluation of patients with cancer
Authors: K. P. Poulose, R. C. Reba, F. H. Deland, H. N. Wagner
Journal: BMJ (1969)

Liver scan characteristics and liver function tests of 72 patients with proved hepatic malignancy (54 metastatic, 18 primary) were evaluated. Well-defined focal defects were observed in 83% of patients with metastatic and 77% of patients with primary liver carcinoma. In 10% of the patients with metastatic liver disease the distribution of radioactivity was normal. Four or more biochemical liver function tests were normal in 33% of metastatic and 29% of primary liver cancer patients. Hepatic enlargement was present in the scan in 94% of the patients with liver metastases; however, data obtained from 104 necropsies of patients with hepatic metastases showed that only 46% had hepatomegaly. We recommend, therefore, that a liver scan should be performed before major tumour surgery in every patient with known malignancy regardless of normal liver size or normal liver function tests.
A Case of Tetany with Remarks on the Cause and Pathology of the Disease
Authors: T. F. Tannahill
Journal: BMJ (1885)

subject.She had sufficient good sense to understand the motive for our appeal to her to give up at once all alcoholic liquors, and, as it subsequently proved, sufficient moral control over herself to carry out her resolve.A mixture of bromide of potassium with compound tincture of lavender and aromatic spirit of ammonia was prescribed, to relieve
Global feasibility assessment of interrupting the transmission of soil-transmitted helminths: a statistical modelling study
Authors: Simon J Brooker, Birgit Nikolay, Dina Balabanova, Rachel L Pullan
Journal: The Lancet Infectious Diseases (2015)

BackgroundEmphasis is being given to the control of neglected tropical diseases, including the possibility of interrupting the transmission of soil-transmitted helminths (STH). We evaluated the feasibility by country of achieving interruption of the transmission of STH.MethodsBased on a conceptual framework for the identification of the characteristics of a successful STH control programme, we assembled spatial data for a range of epidemiological, institutional, economic, and political factors. Using four different statistical methods, we developed a composite score of the feasibility of interrupting STH transmission and undertook a sensitivity analysis of the data and methods.FindingsThe most important determining factors in the analysis were underlying intensity of STH transmission, current implementation of control programmes for neglected tropical diseases, and whether countries receive large-scale external funding and have strong health systems. The composite scores suggested that interrupting STH transmission is most feasible in countries in the Americas and parts of Asia (eg, Argentina [range of composite feasibility scores, depending on scoring method, 9·4–10·0], Brazil [8·7– 9·7], Chile [8·84–10·0], and Thailand [9·1–10·0]; there was perfect agreement between the four methods), and least feasible in countries in sub-Saharan Africa (eg, Congo [0·4–2·7] and Guinea [2·0–5·6]; there was full agreement between methods), but there were important exceptions to these trends (eg, Ghana [7·4–10·0]; there was agreement between three methods). Agreement was highest between the scores derived with the expert opinion and principal component analysis weighting schemes (Pearson correlation coefficient, r=0·98). The largest disagreement was between benefit-of-the-doubt-derived and principal-component-analysis-derived weighting schemes (r=0·74).InterpretationThe interruption of STH transmission is feasible, especially in countries with low intensity of transmission, supportive household environments, strong health systems, and the availability of suitable delivery platforms and in-country funds, but to achieve local elimination of STH an intersectoral approach to STH control will be needed.FundingBill & Melinda Gates Foundation and Wellcome Trust.