tbuckley/cabot-search huggingface dataset:
Effect of digoxin on global respiratory muscle strength after cholecystectomy: a double blind study
Authors: N M Siafakas
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Upper abdominal surgery has been shown to impair the function of the respiratory muscles. In addition, controversial results have been reported concerning the effect of digoxin on the diaphragm. The aim of this study was to investigate further the mechanism(s) of respiratory muscle dysfunction after cholecystectomy and the effect of digoxin on the impaired respiratory muscle function. <h3>METHODS</h3> Twenty three patients (four men) were studied before and 48 hours after surgery. Eleven received digoxin and 12 placebo. Respiratory muscle strength was assessed 48 hours after surgery by measuring mouth pressure during maximum static inspiratory (Pimax) and expiratory (Pemax) efforts before and after 90 minutes of intravenous administration of 0.25 mg digoxin in a double blind, placebo controlled fashion. In addition, spirometric and pain measurements were performed. <h3>RESULTS</h3> Postoperatively (+48 h) Pimax and Pemax decreased significantly (p&lt;0.01) from their preoperative values in both groups by a similar degree. After administration of digoxin or placebo only the digoxin group showed a significant increase in both Pimax (p&lt;0.02) and Pemax (p&lt;0.05) with a mean increase of 15% for Pimax and 12.3% for Pemax. The mean difference in PImax (ΔPimax) and Pemax (ΔPemax) between the digoxin and placebo groups was 1.01 (95% CI 0.28 to 2.2) and 1.05 (95% CI 0.04 to 2.4), respectively. Estimates of postoperative pain did not differ between the two groups. Spirometric indices showed a similar restrictive defect postoperatively in both groups but did not change after digoxin or placebo. <h3>CONCLUSION</h3> Digoxin improves the impaired global strength of the inspiratory and expiratory muscles after cholecystectomy and this may be clinically relevant. Muscle contractility could play a part in this impairment.
What helps children to move more at school recess and lunchtime? Mid-intervention results from Transform-Us! cluster-randomised controlled trial
Authors: Mine Yıldırım, Lauren Arundell, Ester Cerin, Valerie Carson, Helen Brown, David Crawford, Kylie D Hesketh, Nicola D Ridgers, Saskia J Te Velde, Mai J M Chinapaw, Jo Salmon
Journal: British Journal of Sports Medicine (2013)

Background To investigate the interpersonal and physical environment mediators of the Transform-Us! mid-intervention effects on physical activity (PA) during recess and lunchtime. Methods Transform-Us! is a clustered randomised school-based intervention with four groups: sedentary behaviour intervention (SB-I), PA intervention (PA-I), combined PA+SB-I and control group. All children in grade 3 from 20 participating primary schools in Melbourne, Australia were eligible to complete annual evaluation assessments. The outcomes were the proportion of time spent in moderate-to-vigorous PA (MVPA) and light PA (LPA) during recess and lunchtime assessed by accelerometers. Potential mediators included: perceived social support from teachers; perceived availability of line markings; perceived accessibility of sports equipment; and perceived school play environment. Generalised linear models were used and mediation effects were estimated by product-of-coefficients (a·b) approach. Results 268 children (8.2 years, 57% girls at baseline) provided complete data at both time points. A significant intervention effect on MVPA during recess in the SB-I and PA-I groups compared with the control group (proportional difference in MVPA time; 38% (95% CI 21% to 57%) and 40% (95% CI 20% to 62%), respectively) was found. The perceived school play environment was significantly positively associated with MVPA at recess among girls. An increase in perceived social support from teachers suppressed the PA+SB-I effect on light PA during recess (a·b= −0.03, 95% CI −0.06 to −0.00). No significant mediating effects on PA during recess and lunchtime were observed. Conclusions A positive perception of the school play environment was associated with higher MVPA during recess among girls. Future studies should conduct mediation analyses to explore underlying mechanisms of PA interventions.
<i>Clostridium perfringens</i> Within Intracardiac Thrombus
Authors: Pertha S. Chowdhury, Steven B. H. Timmis, Pamela A. Marcovitz
Journal: Circulation (1999)

A 70-year-old man with ischemic dilated cardiomyopa- thy and a known right atrial mass, presumed to be thrombus, presented to the hospital with 3 weeks of fevers and chills.One year before this admission, transesophageal echocardiography had demonstrated a 3ϫ3-cm mass in the right atrium, extending into the superior vena cava (Figure, panel a).The mass was contiguous with the tip of a Groshong catheter, which was used for home dobutamine infusion.Because of a high operative risk at that time, the patient had declined surgical resection of the right atrial mass.During the present hospital admission, the Groshong catheter was removed after 4 of 6 blood cultures grew Clostridium perfringens.The presumed source of the bacteremia was the patient's oropharynx, because he had
Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations
Authors: Jose A. Martinez-Climent, Ash A. Alizadeh, Richard Segraves, David Blesa, Fanny Rubio-Moscardo, Donna G. Albertson, Javier Garcia-Conde, Martin J. S. Dyer, Ronald Levy, Daniel Pinkel, Izidore S. Lossos
Journal: Blood (2003)
Tyrosine Kinase Inhibitors: Views of Selectivity, Sensitivity, and Clinical Performance
Authors: Alexander Levitzki
Journal: The Annual Review of Pharmacology and Toxicology (2012)

With the manufacture of imatinib, researchers introduced tyrosine kinase inhibitors (TKIs) into the clinical setting in 2000 to treat cancers; approximately fifteen other TKIs soon followed. Imatinib remains the most successful agent, whereas all the others have had modest effects on the cancers that they target. The current challenge is to identify the agents that need to be combined with TKIs to maximize their efficacy. One of the most promising approaches is to combine immune therapy with TKI treatment. In this review, the therapeutic potential of TKIs for treatment is discussed.
Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study
Authors: Marcelo E Bigal, David W Dodick, Alan M Rapoport, Stephen D Silberstein, Yuju Ma, Ronghua Yang, Pippa S Loupe, Rami Burstein, Lawrence C Newman, Richard B Lipton
Journal: The Lancet Neurology (2015)
Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia
Authors: Pierre-Paul Prévot, Alexandru Simion, Adrien Grimont, Marta Colletti, Abed Khalaileh, Géraldine Van den Steen, Christine Sempoux, Xiaobo Xu, Véronique Roelants, Jacob Hald, Luc Bertrand, Harry Heimberg, Stephen F Konieczny, Yuval Dor, Frédéric P Lemaigre, Patrick Jacquemin
Journal: Gut (2012)

<h3>Objective</h3> Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). The transcriptional regulators required to initiate ADM are unknown, but need to be identified to characterise the regulatory networks that drive ADM. In this study, the role of the ductal transcription factors hepatocyte nuclear factor 6 (HNF6, also known as Onecut1) and SRY-related HMG box factor 9 (Sox9) in ADM was investigated. <h3>Design</h3> Expression of HNF6 and Sox9 was measured by immunostaining in normal and diseased human pancreas. The function of the factors was tested in cultured cells and in mouse models of ADM by a combination of gain and loss of function experiments. <h3>Results</h3> Expression of HNF6 and Sox9 was ectopically induced in acinar cells in human ADM as well as in mouse models of ADM. HNF6 and, to a lesser extent, Sox9 were required for repression of acinar genes, for modulation of ADM-associated changes in cell polarity and for activation of ductal genes in metaplastic acinar cells. <h3>Conclusions</h3> HNF6 and Sox9 are new biomarkers of ADM and constitute candidate targets for preventive treatment in cases when ADM may lead to cancer. This work also shows that ectopic activation of transcription factors may underlie metaplastic processes occurring in other organs.
How best to diagnose urinary tract infection in preschool children in primary care?
Authors: A. D. Hay, P. Whiting, C. C. Butler
Journal: BMJ (2011)

Accurate and timely diagnosis of urinary tract infection (UTI) in young children presenting to primary care is important because appropriate treatment may alleviate suffering and help prevent long term sequelae such as renal scarring, poor renal growth, recurrent pyelonephritis, impaired glomerular function, hypertension, end stage renal disease, and pre-eclampsia. 1 2 The prevalence of renal scarring in the general population is unknown, but a systematic review of studies, largely conducted in secondary care, showed 15% of children with an initial episode of UTI had evidence of renal scarring on follow-up dimercaptosuccinic acid (DMSA) scanning, and there was an 8% incidence of UTI recurrence per year. 3Among consultations for illness episodes in children aged under 5 years in the UK, approximately 40% comprise infectious diseases and respiratory episodes, while about 10% of presentations comprise non-specific symptoms.Thus identifying which children have a significant UTI (which often also presents with non-specific symptoms) is a key challenge for primary care clinicians.
Vascular smooth muscle cell phenotypes in primary pulmonary hypertension
Authors: Y. Mitani, M. Ueda, R. Komatsu, K. Maruyama, R. Nagai, M. Matsumura, M. Sakurai
Journal: European Respiratory Journal (2001)

Primary pulmonary hypertension (PPH) is associated with specific structural alterations, including cellular intimal thickening, intimal fibrosis, and plexiform lesions. To determine the phenotypes of smooth muscle cells (SMCs) in such lesions, the authors conducted an immunohistochemical analysis of lung tissues from two patients with PPH, using two antimuscle actin antibodies, HHF35 and CGA7, and two anti-SMC myosin heavy chain markers, anti-SM1 and anti-SM2 antibodies and related antibodies. Cells that stained positive (+) with HHF35, CGA7, anti-SM1, and anti-SM2 were considered to be SMCs of a mature state. Conversely, those that stained positive with HHF35 and anti-SM1, but weakly positive (+/-) or negative (-) with CGA7 and anti-SM2, were considered to be SMCs exhibiting an immature state. Cellular intimal thickening was composed of SMCs of an immature phenotype (HHF35+, CGA7+/-, SM1+, SM2+/-), accompanied by the expression of fibronectin and the presence of macrophages; intimal fibrosis contained mature SMCs (HHF35+, CGA7+, SM1+, SM2+); and plexiform lesion consisted of proliferative endothelial cells (von Willebrand factor-positive cells, proliferating cell nuclear antigen-positive cells) and underlying immature SMCs (HHF35+, CGA7-, SM1+, SM2-) associated with fibronectin expression and macrophage infiltration. These findings suggest that smooth muscle cells with specific phenotypes may contribute to the development of specific vascular lesions in primary pulmonary hypertension.
Commentary: cardiological issues
Authors: Nick Archer
Journal: BMJ (2003)

Nearly all respondents on bmj.com listed Kawasaki disease in the differential diagnosis, even though the duration of illness was only five days. One criterion of Kawasaki disease is fever for 10 days, but intravenous immunoglobulin has been shown to reduce the risk of coronary damage definitely only if administered by day 10.1 Later administration has not been so thoroughly evaluated, and intravenous immunoglobulin may be more effective when given within 5 days than between 5 and 10 days.2 Thus the dilemma when confronted with a febrile child is at what point to acknowledge that Kawasaki disease is likely.

Acute self limiting feverish illnesses are common in young children, and some diagnoses do have specific treatments, particularly streptococcal and other bacterial infections. Streptococcal and staphylococcal sepsis may be linked with Kawasaki disease.3 Treatment with intravenous immunoglobulin is associated with some risks, although they are not well quantified in Kawasaki disease. Thus, there are clinical and practical reasons for not treating every young child with high fever for two or three days with intravenous immunoglobulin. Nevertheless, it is highly desirable to treat before day 10 of Kawasaki disease.
Cognition and performance: anxiety, mood and perceived exertion among Ironman triathletes
Authors: David Parry, Camilla Chinnasamy, Eleni Papadopoulou, Timothy Noakes, Dominic Micklewright
Journal: British Journal of Sports Medicine (2010)

The authors examined the changing patterns of mood before and after an Ironman triathlon, and the relationships between expected performance outcomes, perception of effort and pacing.Twelve participants in the 2008 Ironman Austria triathlon competition were studied before, during and after the event. Each participant completed measures of mood, anxiety and perceived exertion, while pacing was calculated from official race timings at various points on the course.Positive correlations were found between distance covered and rating of perceived exertion (RPE) during each of the individual disciplines, and also between RPE and the percentage of overall race time completed (r=0.826, p<0.001). A negative correlation was found between average speed and distance covered during the run segment (r=-0.911, p<0.005) with pace gradually declining. Differences occurred in the profile of mood states mood subscales of tension and fatigue between the baseline, prerace and postrace trials. Somatic anxiety was higher before the race compared with baseline measures.RPE followed a linear progression of RPE during each discipline followed by a re-setting of the perception of effort at the start of the next discipline. The increase in RPE for the entire event followed a linear increase. The linear decline in run pace is consistent with a recent model in which expected RPE is used to modulate pacing. Anxiety and mood responses of participants in this study indicate that the emotional response of athletes before and after ultra-endurance exercise is closely aligned with their conscious thoughts.
SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages
Authors: Tomomi Ishikawa-Sekigami, Yoriaki Kaneko, Hideki Okazawa, Takeshi Tomizawa, Jun Okajo, Yasuyuki Saito, Chie Okuzawa, Minako Sugawara-Yokoo, Uichi Nishiyama, Hiroshi Ohnishi, Takashi Matozaki, Yoshihisa Nojima
Journal: Blood (2005)
Tumor Vaccines Expressing Flt3 Ligand Synergize with CTLA-4 Blockade to Reject Preimplanted Tumors
Authors: Michael A. Curran, James P. Allison
Journal: Cancer Research (2009)

The transformation of a healthy cell into a malignant neoplasm involves numerous genetic mutations and aberrations in gene expression. As few of these changes are shared between individuals or types of cancer, the best source for eliciting broad-spectrum tumor immunity remains each patient's own tumor. Previously, we have shown that combining blockade of the T-cell-negative costimulatory molecule CTL-associated antigen 4 (CTLA-4) and vaccination with irradiated B16 tumor expressing granulocyte macrophage colony-stimulating factor (GM-CSF; Gvax) promotes rejection of established murine melanomas. Here we show that, like GM-CSF, the cytokine Flt3 ligand (Flt3L) expressed in B16 and coupled with CTLA-4 blockade promotes both prophylactic and therapeutic rejection of B16. When administered at the site of growing tumor, Gvax fails to prevent tumor outgrowth in any mice, whereas the B16-Flt3L vaccine (Fl3vax) induces the rejection of 75% of melanomas implanted 3 days before vaccination. Relative to Gvax, Fl3vax promotes greater infiltration of both the vaccine site and the tumor site by CD8+ T cells and "sentinel" and plasmacytoid dendritic cells. Gvax and Fl3vax did not synergize when used in combination in treating B16 melanoma even in the context of CD25+ regulatory T-cell depletion. Further, we show that a combination of Flt3L expression and CTLA-4 blockade can also promote the rejection of established TRAMP prostate adenocarcinomas, proving that the utility of this treatment extends beyond melanoma. Engineering Flt3L to be constitutively secreted and attaching an IgG2a tail yielded a B16 vaccine that, when combined with CTLA-4 blockade, prevented the outgrowth of significantly more 5-day implanted B16-BL6 tumors than did Gvax.
Global Burden of Tuberculosis
Authors: C Dye, S Scheele, P Dolin, V Pathania, M C Raviglione
Journal: JAMA (1999)

To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997.A panel of 86 TB experts and epidemiologists from more than 40 countries was chosen by the World Health Organization (WHO), with final agreement being reached between country experts and WHO staff.Incidence of TB and mortality in each country was determined by (1) case notification to the WHO, (2) annual risk of infection data from tuberculin surveys, and (3) data on prevalence of smear-positive pulmonary disease from prevalence surveys. Estimates derived from relatively poor data were strongly influenced by panel member opinion. Objective estimates were derived from high-quality data collected recently by approved procedures.Agreement was reached by (1) participants reviewing methods and data and making provisional estimates in closed workshops held at WHO's 6 regional offices, (2) principal authors refining estimates using standard methods and all available data, and (3) country experts reviewing and adjusting these estimates and reaching final agreement with WHO staff.In 1997, new cases of TB totaled an estimated 7.96 million (range, 6.3 million-11.1 million), including 3.52 million (2.8 million-4.9 million) cases (44%) of infectious pulmonary disease (smear-positive), and there were 16.2 million (12.1 million-22.5 million) existing cases of disease. An estimated 1.87 million (1.4 million-2.8 million) people died of TB and the global case fatality rate was 23% but exceeded 50% in some African countries with high HIV rates. Global prevalence of MTB infection was 32% (1.86 billion people). Eighty percent of all incident TB cases were found in 22 countries, with more than half the cases occurring in 5 Southeast Asian countries. Nine of 10 countries with the highest incidence rates per capita were in Africa. Prevalence of MTB/HIV coinfection worldwide was 0.18% and 640000 incident TB cases (8%) had HIV infection. The global burden of tuberculosis remains enormous, mainly because of poor control in Southeast Asia, sub-Saharan Africa, and eastern Europe, and because of high rates of M tuberculosis and HIV coinfection in some African countries.
Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras.
Authors: R E Poelmann, A C Gittenberger-de Groot, M M Mentink, R Bökenkamp, B Hogers
Journal: Circulation Research (1993)

The endothelium of the coronary vascular system has been described in the literature as originating from different sources, varying from aortic endothelium for the main coronary stems, endocardium for the intramyocardial network, and sinus venosus lining for the venous part of the coronary system. Using an antibody against quail endothelial cells (alpha-MB1), we investigated the development of the coronary vascular system in the quail (Hamburger and Hamilton stages 15 to 35) and in a series of 36 quail-chicken chimeras. In the chimeras, pieces of quail epicardial primordium and/or liver tissue were transplanted into the pericardial cavity of a chicken host. The results showed that the coronary vascular endothelial distribution closely followed the formation of the epicardial covering of the heart. However, pure epicardial primordium transplants did not lead to endothelial cell formation, whereas a liver graft with or without an epicardial contribution did have this capacity. The first endothelial cells were seen to reach the heart at the sinus venosus region, subsequently spreading through the inner curvature to the atrioventricular sulcus and the outflow tract and, last of all, over the ventricular surfaces. At these sites, the precursor cells and small vessels were seen to invade the sinus venosus wall, the ventricular and atrial myocardium, and the mesenchymal border of the aortic orifice. Connections with the endocardium of the heart tube were only observed in the right ventricular outflow region. Initially, the connections with the aortic endothelium were multiple, but later in development only two of these connections persisted to form the proximal part of the two main coronary arteries. Connections to the pulmonary orifice were never observed. Our transplantation data showed that the entire coronary endothelial vasculature originated from an extracardiac source. Moreover, using the developing subepicardial layer as a matrix, we showed that the endothelial cells reached the heart from the liver region. Ingrowth into the various cardiac segments was also observed. Implications for the relation to specific congenital cardiac malformations are discussed.
Recurrent tracheal mass
Authors: M. Meysman, M. Noppen, J. De Mey, R. Van Herreweghe, M. Pipeleers-Marichal, W. Vincken
Journal: European Respiratory Journal (2003)

In 1994 a 44-yr-old male was admitted for surgical resection of a hard, not painful, nodule which was believed to originate from the isthmus of the thyroid gland. He was known to have mild asthma, treated with inhaled corticosteroids and short-acting β2-agonists. His medical record revealed a smoking history of 20 pack-yrs. The patient denied any other symptoms, except the presence of the nodule.

On physical examination a hard nodule was felt anteriorly to the trachea. A clear separation with the thyroid gland could not be made.

A preoperative computed tomography (CT) scan of the neck revealed a calcified nodule on the midline, adjacent to the trachea (fig. 1⇓). Laboratory studies demonstrated a euthyroid status.



Fig. 1.— 
Chest computed tomography scan. Internal scale bar=5 cm.



During surgery, the nodule could not be separated from the tracheal cartilaginous ring and a left hemithyroidectomy, with resection of part of the affected cartilaginous ring, was carried out (histology of the nodule in fig. 2a⇓). The tracheal defect was closed with a muscle flap. The patient continued to do well on follow-up examinations ≤5 yrs postoperatively, without complaints. …