tbuckley/cabot-search huggingface dataset:
Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD
Authors: Claus Vogelmeier, Bettina Hederer, Thomas Glaab, Hendrik Schmidt, Maureen P.M.H. Rutten-van Mölken, Kai M. Beeh, Klaus F. Rabe, Leonardo M. Fabbri
Journal: New England Journal of Medicine (2011)

Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD.In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year.A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group.These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).
The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis
Authors: J.K. Bosdou, C.A. Venetis, E.M. Kolibianakis, K.A. Toulis, D.G. Goulis, L. Zepiridis, B.C. Tarlatzis
Journal: Human Reproduction Update (2012)

The aim of this meta-analysis was to evaluate the role of androgens or androgen-modulating agents on the probability of pregnancy achievement in poor responders undergoing IVF. Medline, EMBASE, CENTRAL, Scopus and Web of Science databases were searched for the identification of randomized controlled trials evaluating the administration of testosterone, dehydroepiandrosterone (DHEA), aromatase inhibitors, recombinant luteinizing hormone (rLH) and recombinant human chorionic gonadotrophin (rhCG) before or during ovarian stimulation of poor responders. In two trials involving 163 patients, pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy [risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%] and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. No significant differences in clinical pregnancy and live birth rates were observed between patients who received DHEA and those who did not. Similarly, (i) the use of aromatase inhibitors, (ii) addition of rLH and (iii) addition of rhCG in poor responders stimulated with rFSH for IVF were not associated with increased clinical pregnancy rates. In the only eligible study that provided data, live birth rate was increased in patients who received rLH when compared with those who did not (RD: +19%, 95% CI:+1 to +36%). Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.
Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme
Authors: Helen Athanassiou, Maria Synodinou, Evagelos Maragoudakis, Mihalis Paraskevaidis, Cosmas Verigos, Despina Misailidou, Dosia Antonadou, George Saris, Konstantinos Beroukas, Pantelis Karageorgis
Journal: Journal of Clinical Oncology (2005)

Purpose Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. Patients and Methods One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m 2 /d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m 2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). Results Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P &lt; .0001), as was the 1-year OS at 56.3% v 15.7% (P &lt; .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. Conclusion TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.
Glycine-C-14 incorporation into nucleic acid purine by leucocytes obtained from normal and gouty subjects.
Authors: H S Diamond, M Friedland, D Halberstam, D Kaplan
Journal: Annals of the Rheumatic Diseases (1969)

Attempts to characterize the biochemical defect or defects responsible for overproduction of uric acid in primary gout have been hampered by the lack of a suitable experimental model and the necessary limitations of research in vivo in man.The purpose of the present study was to investigate metabolic abnormalities in purine metabolism in vitro using an intact human cell system.Leuco- cytes were chosen for study because of the ease with which they can be obtained and their relative resistance to non-physiological conditions (Fallon, Frei, Davidson, Trier, and Burk, 1962).The rate of incorporation of C-14 tagged purine precursors into nucleic acid adenine and guanine by isolated human leucocytes was measured in leuco- cytes obtained from hyperuricaemic subjects and normouricaemic controls.Increased incorporation of glycine C-14 by white cells from hyperuricaemic subjects was found. Material and MethodsUniformly labelled glycine-C-14 was used.**Phos- phate buffer (Munroe and Shipp, 1965) pH 7*4 was prepared by diluting 10 ml. of Solution A (75 0 g.NaCl, 7*5 g.KCI, lO0 g.Na2HPO4, 1 * 7 g.KH2PO4, and 0 -5 g.K2HPO4 per litre) and 7 ml. of Solution B (10 0 g.NA2HPO4 per litre) to 100 ml. with water.Pertinent clinical features of leucocyte donors are shown in Table I (see p. 277).All medications were discontinued 72 hours before blood was drawn.Subjects with blood urea nitrogen above 20 mg. per cent.or other evidence of impaired renal function were excluded.No patients with secondary hyperuricaemia were studied.All donors were ambulatory and not ill at the time blood was drawn.Uric acid was measured by the uricase method (Praetorius, 1949).Normouricaemic donors had
The pattern of vasopressin-induced reduction in biliary output of cholephilic probes in the rat can be mimicked by dialysis
Authors: Yashushi Yamaguchi, William G. M. Hardison
Journal: Hepatology (1991)

During a recent study using isolated perfused rat liver, we concluded that the effects of vasopressin on biliary excretion of several anionic and cationic cholephilic probes could best be explained by passive diffusion of these probes through a paracellular pathway with permeability increased by vasopressin. Replication of the results of that study in an in vitro dialysis system would support the passive nature of the selective efflux of these cholephilic probes from the rat biliary tree and render metabolic events an unlikely explanation for the biliary excretory patterns of the probes. We studied biiary excretion of two bile acids—taurodehydrocholate and taurocholate—and two cholephilic cations—propidium and tributylmethylammonium—perfused single-pass through the isolated rat liver. We collected bile and measured probe output before and during infusion of 10 −8 mol/L vasopressin. We also studied rates of diffusion of these probes in artificial solution and in whole rat bile through a 3,500 mol wt cut-off cellulose dialysis membrane. The relative order of probe efflux rates from the biliary tree with vasopressin administration paralleled their diffusion rates through the dialysis membrane. The only exception was that the biliary tree manifested charge selectivity. The data are compatible with the passive efflux of probe from the biliary tree, and metabolic events need not be invoked to explain their pattern of biliary excretion with vasopressin administration. (HEPATOLOGY 1991;14:175-179.)
Body surface detection of delayed depolarizations in patients with recurrent ventricular tachycardia and left ventricular aneurysm.
Authors: J J Rozanski, D Mortara, R J Myerburg, A Castellanos
Journal: Circulation (1981)

In eight patients with chronic ventricular tachycardia and left ventricular aneurysms, we detected delayed ECG wave forms after the QRS complex from the body surface using a high-resolution ECG recorder, amplification and signal averaging. Delayed wave-form activity (D wave) extended a mean of 70 msec beyond the termination of th QRS complex. This delayed activity frequently extended to the limit of the recording window, and may thus continue throughout much of diastole. Antiarrhythmic agents never abolished the delayed activity; however, it was abolished by aneurysmectomy in four patients. Ventricular tachycardia did not recur after surgery in the four patients during a mean follow-up of 1 year. The D wave was not found in eight control patients who had chronic recurrent ventricular tachycardia nor in 11 of 12 who had aneurysms alone. The surface D wave can be readily and reproducibly detected by high-resolution electrocardiography and appears to be specific for patients with left ventricular aneurysms who also have chronic recurrent ventricular tachycardia. This delayed wave-form activity has been noted during catheter and surgical endocardial and epicardial mapping. It may represent persistence of the cardiac impulse in islands of myocardium and may be a manifestation of the delayed and fractionated activity, noted by previous investigators.
Experts call for research into vCJD test despite only 70% accuracy
Authors: A. O'Dowd
Journal: BMJ (2014)

Experts have said that a test for variant Creutzfeldt-Jakob disease (vCJD) that has a 70% accuracy rate should be studied and possibly used universally.

The House of Commons Science and Technology Committee held an evidence session on 5 February for its inquiry into blood, tissue, and organ screening, in which MPs asked about the value of testing for vCJD.

The degenerative brain disease, sometimes called the human form of bovine spongiform encephalopathy (BSE), emerged after widespread exposure to BSE prions in the late 1980s and early 1990s through contaminated meat products in the food chain.

A study published in the BMJ last October1 estimated that one …
Testicular cancer in Europe and the USA: survival still rising among older patients
Authors: R.H.A. Verhoeven, A. Gondos, M.L.G. Janssen-Heijnen, K.U. Saum, D.H. Brewster, B. Holleczek, E. Crocetti, S. Rosso, T. Hakulinen, T. Aareleid, H. Brenner
Journal: Annals of Oncology (2012)
Primum Non Nocere — The McCain Plan for Health Insecurity
Authors: David Blumenthal
Journal: New England Journal of Medicine (2008)

Dr. David Blumenthal argues that the central purpose of John McCain's health policy is to reduce the role of insurance and make Americans pay a larger part of their health care bills out of pocket. This plan would risk the viability of employer-sponsored insurance and the welfare of chronically ill Americans in pursuit of a radical vision of consumer-driven health care.
Interferon α/β and Interleukin 12 Responses to Viral Infections
Authors: Marc Dalod, Thais P. Salazar-Mather, Lene Malmgaard, Casey Lewis, Carine Asselin-Paturel, Francine Brière, Giorgio Trinchieri, Christine A. Biron
Journal: The Journal of Experimental Medicine (2002)

Interferon (IFN)-α/β and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8α+Ly6G/C+CD11b− phenotype. Another DC subset (CD8α2Ly6G/C−CD11b+) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-α/β functions. Conversely, IFN-α/β production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8α+ DCs resulted in responses limiting IL-12 expression by CD11b+ DCs but enhancing overall IFN-α/β production. Taken together, these data indicate that CD8α+Ly6G/C+CD11b− DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses.
Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism
Authors: Cheryl P. Sanchez, Yu-Zhu He
Journal: Journal of the American Society of Nephrology (2005)

Growth hormone (GH) improves growth in children with chronic renal failure. The response to GH may be affected by the degree of secondary hyperparathyroidism and concurrent treatment with vitamin D. Forty-six rats underwent 5/6 nephrectomy (Nx) and were given a high-phosphorus diet (Nx-Phos) to induce advanced secondary hyperparathyroidism and divided into the following groups: (1) Nx-Phos (n = 10) received saline, (2) GH at 10 IU/kg per d (Nx-Phos+GH; n = 9), (3) GH and daily calcitriol (D) at 50 ng/kg per d (Nx-Phos+GH+daily D; n = 8), (4) GH and intermittent D (three times weekly) at 350 ng/kg per wk (Nx-Phos+GH+int D; n = 9), and (5) intact-control (n = 10). Serum parathyroid hormone (PTH) levels were elevated in Nx-Phos, but IGF-I levels did not change with growth hormone. Body length, tibial length, and growth plate width did not increase with either GH or calcitriol. Proliferating cell nuclear antigen staining, PTH/PTHrP receptor, bone morphogenetic protein-7, and fibroblast growth factor receptor-3 expression increased with GH alone or with intermittent calcitriol but were slightly diminished during daily calcitriol administration. GH enhanced IGF-I, IGF binding receptor-3, and GH receptor but declined with daily and intermittent calcitriol. Overall, there was no improvement in body length, tibial length, and growth plate width at the end of GH therapy, but selected markers of chondrocyte proliferation and chondrocyte differentiation increased, although these changes were attenuated by calcitriol. The combination of GH and calcitriol that is frequently used in children with renal failure and secondary hyperparathyroidism require further studies to evaluate the optimal dose and frequency of administration to increase linear growth and prevent bone disease.
Myotube formation on gelatin nanofibers – Multi-walled carbon nanotubes hybrid scaffolds
Authors: Serge Ostrovidov, Xuetao Shi, Ling Zhang, Xiaobin Liang, Sang Bok Kim, Toshinori Fujie, Murugan Ramalingam, Mingwei Chen, Ken Nakajima, Faten Al-Hazmi, Hojae Bae, Adnan Memic, Ali Khademhosseini
Journal: Biomaterials (2014)
SIMULTANEOUS BILATERAL RUPTURE OF ACHILLES TENDON ASYMPTOMATIC POSTENDINOPATHY
Authors: L Á Martínez, I G Vicente, E A Contreras, C R Jaramillo, T F Jaén
Journal: British Journal of Sports Medicine (2013)

Introduction Rupture of Achilles tendon is the most common among those taking place in the lower extremities, being twice as common in men than in women between 30–50 years old and usually caused while doing sport. There are some risk factors such as age or chronic treatments based on corticosteroids or antibiotics when belonging to Quinolones group. Spontaneous bilateral rupture of the Achilles tendon is much more infrequent, being almost exceptional in young and healthy patients without known pathological conditions. Method In relation to a specific clinical case, a medical history review was developed: personal history, diagnosis, treatment and progress. Result Asthmatic 45 year old male occasionally undergoing medical treatment with inhaled corticosteroids. Previously asymptomatic. Training athletics in the morning and handball in the afternoon. After the first 10 min of the match notices a bilateral acute pain when starting to run, showing ruptures of both Achilles tendons confirmed by MRI scan. Treatment: surgical open-to-end suture reinforced with inverted taenia (see figure 1 below). Development: 3 weeks immobilisation without setting foot, 3 weeks Walker boot, partial setting foot and rehabilitation, medical discharge after 6 months without complications. Discussion Simultaneous and spontaneous rupture of bilateral Achilles tendons in patients without pathological factors is really unusual. 25% of the healthy population above 30 years of age has degenerative structural changes in the Achilles tendon that increase the risk of rupture depending on the patient's activity level. Both percutaneous and open surgical treatments on young and active patients provide an appropriate alternative. The open surgical treatment allows the possibility of tendon reinforcement techniques and a more complete visualisation of the damage. The postsurgical rehabilitation management is an important factor for biomechanic tendon recovery alsoallowing the restart of patient's activities as soon as possible. Figure 1 Appearance of Achilles tendon before (left) and after (right) surgical repair.
IMPLEMENTATION OF A NEUROMUSCULAR TRAINING PROGRAMME IN FEMALE ADOLESCENT FOOTBALL: 3-YEAR FOLLOW-UP STUDY AFTER AN RCT
Authors: H Lindblom, M Waldén, S Carlfjord, M Hägglund
Journal: British Journal of Sports Medicine (2014)

Background Neuromuscular training (NMT) has been shown to reduce injury rates in highly structured clinical trials. There is, however, a paucity of studies that evaluate implementation of NMT programmes in sports. Objective To evaluate the spread and implementation of a NMT programme in female adolescent football three years after a randomised controlled trial (RCT). Design Cross-sectional study using web-based questionnaires, based on the RE-AIM SSM (Reach, Effectiveness, Adoption, Implementation and Maintenance Sports Setting Matrix) framework. Setting Female adolescent football in Sweden. Participants Representatives for the Swedish Football Association (FA) and eight district FAs that participated in an RCT in 2009, all coaches (n=303) who participated in the RCT and all currently (season 2012) active coaches for female adolescent teams (n=496) within the same districts were contacted. The response rates were 100% (Swedish and district FAs), 57% (RCT coaches, n=173) and 36% (current coaches, n=179), respectively. Interventions Not applicable. Main outcome measurements Reach, perceived effectiveness, adoption, implementation and maintenance of the NMT programme. Results The reach of the programme was high, 99% of RCT coaches (control group) and 91% of current coaches were familiar with it, and the programme was generally positively perceived. The adoption rate (usage) among current coaches was 74%. Regarding implementation, 75–77% of coaches reported programme modifications. Usage of the programme was fairly well maintained over time among RCT coaches. Formal or informal policies regarding the programme's implementation existed in the Swedish FA and in two district FAs. Among current coaches 87% reported no club routines for programme use. Conclusions Reach and adoption of the NMT programme was high among coaches. However, the follow-up also identified low programme fidelity and lack of formal policies for its implementation and use in clubs and district FAs.
The Human Mutation Rate Is Increasing, Even As It Slows
Authors: Gregg W.C. Thomas, Matthew W. Hahn
Journal: Molecular Biology and Evolution (2013)

Substitution rates vary between species, and many explanations regarding the causes of this variation have been proposed. Here we consider how new genomic data on the per-generation mutation rate impinge on proposed hypotheses for substitution rate variation in primates. We propose that the generation-time effect as it is usually understood cannot explain the observed rate variation, but instead that selection for decreased somatic mutation rates can. By considering the disparate causes underlying mutation rate changes in recent human history, we also show that the per-generation mutation rate is increasing even as the per-cell-division rate is decreasing.