tbuckley/cabot-search huggingface dataset:
Availability of anti-tuberculosis drugs in Europe: Table 1–
Authors: Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Graham Bothamley, Daniela M. Cirillo, Saverio De Lorenzo, Gunar Guenther, Kai Kliiman, Ralf Muetterlein, Victor Spinu, Miguel Villar, Jean-Pierre Zellweger, Andreas Sandgren, Emma Huitric, Christoph Lange, Davide Manissero, Giovanni Battista Migliori
Journal: European Respiratory Journal (2012)

To the Editors:

The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) represents a major threat to TB control globally and, specifically, in Europe [1–3]. MDR-/XDR-TB is at large due to clinical mismanagement of drug-susceptible and drug-resistant TB cases as well as to transmission of resistant strains [1–3]. Continuous availability of quality-controlled drugs is a prerequisite to ensure correct clinical management of TB patients [2, 4].

Comprehensive and updated information on the availability and registration procedures of first-line (FLD) and second-line (SLD) anti-TB drugs is not available, neither in Europe nor elsewhere.

Anecdotal evidence suggested that in most European Union (EU) countries, where TB has a low incidence, procurement procedures are decentralised (not through Global Drug Facility, GDF), and with no specific responsibility for TB drug procurement available at the ministerial level. Despite high costs of SLD, registration procedures are strong enough to potentially prevent marketing and prescription of poor quality drugs. FLD and SLD are usually available (with mechanisms to prevent stock-outs), although the low number of drug doses sold can create challenges in assuring their continuous availability [5].

In EU countries with TB incidence >20 per 100,000 people, high MDR-TB prevalence and intermediate income, drug-procurement procedures are centralised (through GDF), drug costs are lower, and FLD (but not necessarily all SLD) are available. In these countries procurement relies on the Green Light Committee mechanism (GLC, a technical body from the World Health Organization (WHO) and partners providing assistance for developing national …
Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes
Authors: Azra Raza, Peter Meyer, Diya Dutt, Francesca Zorat, Laurie Lisak, Fabiana Nascimben, Morne du Randt, Christopher Kaspar, Cathryn Goldberg, Jerome Loew, Saleem Dar, Sefer Gezer, Parameswaran Venugopal, Jerome Zeldis
Journal: Blood (2001)
Body image and body schema: The shared representation of body image and the role of dynamic body schema in perspective and imitation
Authors: Alessia Tessari, Anna M. Borghi
Journal: Behavioral and Brain Sciences (2007)

Abstract Our commentary addresses two issues that are not developed enough in the target article. First, the model does not clearly address the distinction among external objects, external body parts, and internal bodies. Second, the authors could have discussed further the role of body schema with regard to its dynamic character, and its role in perspective and in imitation.
Lack of Gα<sub>i2</sub>leads to dilative cardiomyopathy and increased mortality in β<sub>1</sub>-adrenoceptor overexpressing mice
Authors: Kirsten Keller, Martina Maass, Sara Dizayee, Veronika Leiss, Suvi Annala, Jessica Köth, Wiebke K. Seemann, Jochen Müller-Ehmsen, Klaus Mohr, Bernd Nürnberg, Stefan Engelhardt, Stefan Herzig, Lutz Birnbaumer, Jan Matthes
Journal: Cardiovascular Research (2015)

Inhibitory G (Gi) proteins have been proposed to be cardioprotective. We investigated effects of Gαi2 knockout on cardiac function and survival in a murine heart failure model of cardiac β1-adrenoceptor overexpression. β1-transgenic mice lacking Gαi2 (β1-tg/Gαi2−/−) were compared with wild-type mice and littermates either overexpressing cardiac β1-adrenoceptors (β1-tg) or lacking Gαi2 (Gαi2−/−). At 300 days, mortality of mice only lacking Gαi2 was already higher compared with wild-type or β1-tg, but similar to β1-tg/Gαi2−/−, mice. Beyond 300 days, mortality of β1-tg/Gαi2−/− mice was enhanced compared with all other genotypes (mean survival time: 363 ± 21 days). At 300 days of age, echocardiography revealed similar cardiac function of wild-type, β1-tg, and Gαi2−/− mice, but significant impairment for β1-tg/Gαi2−/− mice (e.g. ejection fraction 14 ± 2 vs. 40 ± 4% in wild-type mice). Significantly increased ventricle-to-body weight ratio (0.71 ± 0.06 vs. 0.48 ± 0.02% in wild-type mice), left ventricular size (length 0.82 ± 0.04 vs. 0.66 ± 0.03 cm in wild types), and atrial natriuretic peptide and brain natriuretic peptide expression (mRNA: 2819 and 495% of wild-type mice, respectively) indicated hypertrophy. Gαi3 was significantly up-regulated in Gαi2 knockout mice (protein compared with wild type: 340 ± 90% in Gαi2−/− and 394 ± 80% in β1-tg/Gαi2−/−, respectively). Gαi2 deficiency combined with cardiac β1-adrenoceptor overexpression strongly impaired survival and cardiac function. At 300 days of age, β1-adrenoceptor overexpression alone had not induced cardiac hypertrophy or dysfunction while there was overt cardiomyopathy in mice additionally lacking Gαi2. We propose an enhanced effect of increased β1-adrenergic drive by the lack of protection via Gαi2. Gαi3 up-regulation was not sufficient to compensate for Gαi2 deficiency, suggesting an isoform-specific or a concentration-dependent mechanism.
Predicting Outcome in Follicular Lymphoma by Using Interactive Gene Pairs
Authors: David LeBrun, Tara Baetz, Cheryl Foster, Patricia Farmer, Roger Sidhu, Hong Guo, Karen Harrison, Roland Somogyi, Larry D. Greller, Harriet Feilotter
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Follicular lymphoma is a common lymphoma of adults. Although its course is often indolent, a substantial proportion of patients have a poor prognosis, often due to rapid progression or transformation to a more aggressive lymphoma. Currently available clinical prognostic scores, such as the follicular lymphoma international prognostic index, are not able to optimally predict transformation or poor outcome. Experimental Design: Gene expression profiling was done on primary lymphoma biopsy samples. Results: Using a statistically conservative approach, predictive interaction analysis, we have identified pairs of interacting genes that predict poor outcome, measured as death within 5 years of diagnosis. The best gene pair performs &amp;gt;1,000-fold better than any single gene or the follicular lymphoma international prognostic index in our data set. Many gene pairs achieve outcome prediction accuracies exceeding 85% in extensive cross-validation and noise sensitivity computational analyses. Many genes repeatedly appear in top-ranking pairs, suggesting that they reproducibly provide predictive capability. Conclusions: The evidence reported here may provide the basis for an expression-based, multi-gene test for predicting poor follicular lymphoma outcomes.
Heart failure increases protein expression and enzymatic activity of heme oxygenase-1 in the lung
Authors: C LAM, A CROATT, D RICHARDSON, K NATH, Z KATUSIC
Journal: Cardiovascular Research (2004)

Objective: Heart failure (HF) cell or siderophages are pulmonary macrophages that phagonicytize erythrocytes leaked from the congested capillaries due to HF. Degradation of erythrocytes and hemoglobin increases concentrations of heme in the lung. We hypothesized that the HF-induced increase in the concentration of heme up-regulates the expression and enzymatic activity of heme oxygenase (HO)-1 in the lung.
Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: Results of a pilot randomized controlled clinical trial
Authors: Mariam Conchillo, Robert J. de Knegt, Marina Payeras, Jorge Quiroga, Bruno Sangro, Jose-Ignacio Herrero, Inma Castilla-Cortazar, Jan Frystyk, Allan Flyvbjerg, Carl Yoshizawa, Peter L.M. Jansen, Bruce Scharschmidt, Jesús Prieto
Journal: Journal of Hepatology (2005)
Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study
Authors: Chun-Ying Wu, Yao-Chun Hsu, Hsiu J Ho, Yi-Ju Chen, Teng-Yu Lee, Jaw-Town Lin
Journal: Gut (2015)

<h3>Objective</h3> Current guidelines recommend screening for hepatocellular carcinoma (HCC) in high-risk populations. However, the effectiveness of screening in reducing mortality has been challenged. In addition, it is unclear which subgroups benefit most from HCC screening. <h3>Design</h3> This nationwide cohort study identified a total of 52 823 newly diagnosed HCC patients between 1 January 2002 and 31 December 2007. These HCC patients were classified into the following cohorts according to the time intervals in which they received ultrasonography screening: 0–6 months (6M), 7–12 months (12M), 13–24 months (24M), 25–36 months (36M) and not screened within 3 years (never screened). The chance to receive curative therapy and 5-year cumulative mortalities were calculated after adjusting for lead-time bias. <h3>Results</h3> Chances to receive curative therapy among the 6M, 12M, 24M, 36M and never screened cohorts were 24.3% (95% CI 23.7% to –24.9%), 26.9% (95% CI 25.7% to 28.2%), 22.9% (95% CI 21.8% to 24.1%), 21.3% (95% CI 19.9% to 22.8%) and 18.3% (95% CI 17.8% to 18.8%), respectively. Compared with the 6M cohort, adjusted HRs of mortality for the 12M, 24M, 36M and never screened cohorts were 1.11 (95% CI 1.07 to 1.15), 1.23 (95% CI 1.19 to 1.28), 1.31 (95% CI 1.26 to 1.37) and 1.47 (95% CI 1.43 to 1.51) (all p&lt;0.001), respectively. On multivariable subgroup analyses, the associations between shorter screening intervals and better survival were observed in nearly all subgroups, especially in younger patients, patients without diabetes and patients with hepatitis B infection. <h3>Conclusions</h3> Shorter ultrasonography screening intervals are associated with reduced overall mortality in HCC patients in a dose-dependent manner.
A Phase I, Multicenter, Open-Label, First-in-Human, Dose-Escalation Study of the Oral Smoothened Inhibitor Sonidegib (LDE225) in Patients with Advanced Solid Tumors
Authors: Jordi Rodon, Hussein A. Tawbi, Anne L. Thomas, Ronald G. Stoller, Christian P. Turtschi, Jose Baselga, John Sarantopoulos, Devalingam Mahalingam, Yaping Shou, Melissa A. Moles, Lin Yang, Camille Granvil, Eunju Hurh, Kristine L. Rose, Dereck D. Amakye, Reinhard Dummer, Alain C. Mita
Journal: Clinical Cancer Research (2014)

Abstract Purpose: This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. Experimental Design: Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period. Dose escalations were guided by a Bayesian logistic regression model. Safety, tolerability, efficacy, pharmacokinetics, and biomarkers in skin and tumor biopsies were assessed. Results: The MTDs of sonidegib were 800 mg daily and 250 mg twice daily. The main DLT of reversible grade 3/4 elevated serum creatine kinase (18% of patients) was observed at doses ≥ the MTD in an exposure-dependent manner. Common grade 1/2 adverse events included muscle spasm, myalgia, gastrointestinal toxicities, increased liver enzymes, fatigue, dysgeusia, and alopecia. Sonidegib exposure increased dose proportionally up to 400 mg daily, and displayed nonlinear pharmacokinetics at higher doses. Sonidegib exhibited exposure-dependent reduction in GLI1 mRNA expression. Tumor responses observed in patients with medulloblastoma and BCC were associated with evidence of hedgehog pathway activation. Conclusions: Sonidegib has an acceptable safety profile in patients with advanced solid tumors and exhibits antitumor activity in advanced BCC and relapsed medulloblastoma, both of which are strongly associated with activated hedgehog pathway, as determined by gene expression. Clin Cancer Res; 20(7); 1900–9. ©2014 AACR.
Bevacizumab Increases Viral Distribution in Human Anaplastic Thyroid Carcinoma Xenografts and Enhances the Effects of E1A-Defective Adenovirus <i>dl</i>922-947
Authors: Silvana Libertini, Irma Iacuzzo, Giuseppe Perruolo, Stefania Scala, Caterina Ieranò, Renato Franco, Gunnel Hallden, Giuseppe Portella
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Anaplastic thyroid carcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms and is refractory to conventional treatments such as chemotherapy and radiotherapy. We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl922-947. Experimental Design: The antitumor efficacies of the E1AΔCR2 (dl922-947) and ΔE1B55K (dl1520) mutants were compared in human thyroid anaplastic carcinoma cells in culture and in xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroid carcinoma tumor xenografts were treated with dl922-947 in combination with bevacizumab. Results: We showed that the efficacy of dl922-947 exceeded that of dl1520 in all tested anaplastic thyroid carcinoma cells in vitro and in vivo. Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improved viral distribution in neoplastic tissues. Conclusions: Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 in anaplastic thyroid carcinoma cell lines and might represent a better option for virotherapy of anaplastic thyroid carcinoma. Moreover, bevacizumab increased the oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.
A Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis
Authors: S. Joanna Cowell, David E. Newby, Robin J. Prescott, Peter Bloomfield, John Reid, David B. Northridge, Nicholas A. Boon
Journal: New England Journal of Medicine (2005)

Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression.In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score.Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050).Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis.
Review of the Literature on Acute Rheumatism During the Years 1939-1945
Authors: C. Bruce Perry
Journal: Annals of the Rheumatic Diseases (1947)

Incidence Glover (1943) has again drawn attention to the decline in the death rate from acute rheumatism and rheumatic heart disease, as shown by the Registrar-General's returns, which has been in progress since the beginning of the century.He shows that this decline was considerably 4ccelerated during the first three years of the war.Glover discusses the possible significance of this, and points out that, while it coincides with a general improvement in the standard of living, it is roughly paralleled by the fall in death rate of streptococcal infections like scarlet fever.Hedley (1939) has shown a similar trend in the United States.He notes the asscvciation with an increased standard of living, and points out that the mortality is appreciably higher amongst young negroes than amongst the whites, who cer- tainly live, on the average, under more favourable conditions.Hedley also suggests that the recent widespread practice of tonsillectomy may have had some influence.It has long been considered that acute rheumatism is a rare occurrence in the tropics.However, Fernando (1939) shows that rheumatic heart disease is respon- sible for 21*5% of all cardiac admissions to hospital in Ceylon and that rheumatic heart disease was found in 3.6% of all nectopsies.He found that the clinical features differed in no material way from those met with in temperate climates, except that chorea was very rare.Reports by Stott (1939).andKutumbiah (1941) indicate that, while the disease is much rarer in India than in northern countries, it is not unknown.Stott found that-about 1% of all hospital admissions in India are due to chronic'rheumatic heart disease with valvular lesions.Pestana (1940) states that the disease is not uncommon in Singapore, and reports an incidence of 1.6% of all necropsies performed in 1938.In a study of the incidence in French colonies Sorel (1939) found a very low incidence in Chine du Nord.From America there have been reports of the incidence from all parts of the United States and from South America.From these it emerges that, broadly speaking, the nearer the equator, the lower the incidence of the disease.For instance, in San Jos6, Costa Rica (latitude 90 N.) Carrillo (1942) found mitral stenosis in 1-0% of 1,000 autopsies, while there were 22 cases in the paediatric wards among 3,771 admissions.In Puerto Rico (latitude 18°-49°N.)Suarez (1945) showed that acute rheumatism is responsible for only 17-4% of all cases of heart disease.How- ever Chavez (1942) reports as many as 41% of all cases of heart disease in Mexico (latitude 190 N.) 162
Dietary Carbohydrate, a Big Mac, and Insulin Requirements in Type I Diabetes
Authors: Frederika V Vlachokosta, Cheryl M Piper, Ray Gleason, Laura Kinzel, C Ronald Kahn
Journal: Diabetes Care (1988)

Using the artificial beta-cell (Biostator), we determined the insulin requirements in five nonobese type I (insulin-dependent) diabetic subjects who received isocaloric 40 and 60% mixed-carbohydrate diets in a crossover randomized fashion for 4 days, each day consisting of four equal meals. This was followed on day 5 by a "Big Mac Attack" lunch consisting of a Big Mac, french fries, and milk shake. Insulin requirements to maintain normoglycemia were calculated for each 24-h period and for the 2 h after each meal. The mean 24-h insulin requirements to maintain normoglycemia was greater for the 60% carbohydrate diet than the 40% diet. Although the four meals were of equal size, in all patients the insulin required to cover breakfast greater than lunch greater than dinner greater than or equal to snack. Expressed as milliunits per kilocalorie, the amount of insulin to cover breakfast was greater for the 60% (P less than .05) than the 40% carbohydrate diet and greater for breakfast than the other meals (P less than .01). Insulin requirements for the Big Mac (43% carbohydrate) were 58% greater than for the 40% carbohydrate diet, even after correction for caloric differences. In summary, 1) increasing dietary carbohydrate from 40 to 60% results in an increased insulin requirement for meals only; 2) insulin requirements are greater in the morning than in the evening, even when meal size is constant; and 3) very large meals with high fat and carbohydrate content result in a major increase in insulin requirement. These data indicate that diet has an important impact on insulin requirements in diabetes.
Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease. The Lung Health Study Research Group.
Authors: D P Tashkin, M D Altose, J E Connett, R E Kanner, W W Lee, R A Wise
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

As part of a clinical trial of early intervention in chronic obstructive pulmonary disease (COPD) (the Lung Health Study), 5,733 smokers with mild to moderate airflow obstruction underwent methacholine challenge tests at baseline. All participants were randomized to receive either usual care (no intervention) or special intervention, consisting of intensive smoking cessation counseling and the prescription of a metered-dose inhaler containing either ipratropium bromide or placebo (two inhalations three times daily). For this report, we analyzed the relationship between baseline methacholine reactivity and subsequent change in lung function. Methacholine reactivity was expressed as a logarithmic function of the two-point slope of percent decline in FEV1 over the concentration of methacholine (LMCR). Using a random effects linear model, LMCR was found to be a strong predictor of change in FEV1% predicted, after controlling for baseline lung function, age, sex, baseline smoking history, and changes in smoking status. Significant interactions were found between reactivity and smoking behavior. In the first year, participants who quit smoking showed improvement in FEV1, whereas continuing smokers showed worsening, and between Years 1 and 5, lung function declined to a greater extent in continuing smokers than in sustained quitters. For both time periods, these quitter/smoker differences increased as a function of airway reactivity. These findings indicate that methacholine reactivity is an important predictor of progression of airway obstruction in continuing smokers with early COPD, independent of the baseline level of obstruct.
Synergistic effects of haemodynamic stabilisation and blockade on ventricular fibrillation threshold in coronary artery ligated pigs
Authors: C. A Muller, A. C Kralios
Journal: Cardiovascular Research (1993)

Journal Article Synergistic effects of haemodynamic stabilisation and β blockade on ventricular fibrillation threshold in coronary artery ligated pigs Get access Cecilia A Muller, Cecilia A Muller MRC Ischaemic Heart Disease Research Unit, Department of Medicine, Medical School, University of Cape Town, Observatory 7925, Cape Town, South Africa: C A Muller; Cardiology Division, Veterans Affairs and University of Utah Medical Centers, Salt Lake City, Utah, USA: A C Kralios. Correspondence to Dr Muller. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alexandros C Kralios Alexandros C Kralios MRC Ischaemic Heart Disease Research Unit, Department of Medicine, Medical School, University of Cape Town, Observatory 7925, Cape Town, South Africa: C A Muller; Cardiology Division, Veterans Affairs and University of Utah Medical Centers, Salt Lake City, Utah, USA: A C Kralios. Correspondence to Dr Muller. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 2, February 1993, Pages 274–278, https://doi.org/10.1093/cvr/27.2.274 Published: 01 February 1993 Article history Received: 17 July 1991 Accepted: 30 June 1992 Published: 01 February 1993