tbuckley/cabot-search huggingface dataset:
The cost of medical management of pulmonary nontuberculous mycobacterial disease in Ontario, Canada
Authors: A. Leber, T.K. Marras
Journal: European Respiratory Journal (2010)

Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is complex, requiring multiple antibiotics and a prolonged treatment course. We determined the monthly cost of treating patients with pulmonary NTM infections in our clinic, a tertiary care centre in Toronto, Ontario, Canada. We reviewed records of a single clinic at the University Health Network (Toronto) for all patients with pulmonary NTM isolates. Pharmacological and nonpharmacological treatment costs were calculated using a number of Canadian references. 172 patients were reviewed, 91 of whom were treated pharmacologically. The median total duration and cost per treated patient were 14 months (interquartile range (IQR) 9-23 months) and CAD 4,916 (IQR CAD 2,934-9,063), respectively. Median monthly drug treatment cost was CAD 321 (IQR CAD 254-458) for all patients, CAD 289 (IQR CAD 237-341) for patients receiving exclusively oral antibiotics and CAD 1,161 (IQR CAD 795-1,646) for patients whose treatment included i.v. antibiotics. The most costly oral regiment consisted of a fluroquinolone, macrolide and rifampin. In multivariable analysis, Mycobacterium abscessus infection, i.v. therapy and Mycobacterium xenopi infection were all associated with increased monthly treatment costs. The direct medical costs of NTM infections are substantial. Less expensive alternative therapies might be most helpful for M. abscessus infection and when i.v. antibiotics are deemed necessary.
Effects of 8 weeks of continuous positive airway pressure on abdominal adiposity in obstructive sleep apnoea
Authors: Sheila Sivam, Craig L. Phillips, Michael I. Trenell, Brendon J. Yee, Peter Y. Liu, Keith K. Wong, Ronald R. Grunstein
Journal: European Respiratory Journal (2012)

The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on regional adipose tissue distribution in patients with moderate or severe obstructive sleep apnoea. Patients received both therapeutic and sham CPAP in a random order for 2 months each with an intervening 1-month washout. Abdominal subcutaneous, visceral and liver fat were quantified using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Liver enzymes and plasma glucose were also determined. Measurements were obtained at baseline and at the end of both treatment arms. 38 eligible patients were randomly assigned to a treatment order, with 27 patients having complete MRI/MRS data. No significant difference was observed in subcutaneous (-28.6 cm 3 ; p=0.49) or visceral (-16.8 cm 3 ; p=0.59) adipose tissue, intrahepatic lipid (-0.2%; p=0.21), or fasting glucose measurements (-0.1 mmol·L −1 ; p=0.46) between treatment modalities. Alkaline phosphatase decreased (-3.1 U·L −1 ; p=0.02) while on therapeutic CPAP compared with sham CPAP but other liver enzymes, including aspartate aminotransferase (0.3 U·L −1 ; p=0.82), alanine aminotransferase (1.34 U·L −1 ; p=0.59) and γ-glutamyltransferase (-2.3 U·L −1 ; p=0.33), remained unchanged. In this first randomised, sham-controlled trial, there was no change in adipose tissue distribution after 8 weeks of therapeutic CPAP compared with 8 weeks of sham CPAP. Longer duration of CPAP use may be necessary to demonstrate a difference.
Glomerular filtration response to elevated ureteral pressure in both the hydropenic and the plasma-expanded rat.
Authors: R C Blantz, K S Konnen, B J Tucker
Journal: Circulation Research (1975)

The factors affecting glomerular ultrafiltration with elevated ureteral pressure were examined in both plasma-expanded (2.5% body weight) and hydropenic Munich-Wistar rats. Elevated ureteral pressure (20 mm Hg) alternated as the initial condition in both groups. Glomerular capillary hydrostatic pressure (PG) and Bowman's space pressure (Pt) were measured directly in surface glomeruli with a servonulling device (deltaP = PG - PT), systemic (piA) and efferent (piE) peritubular capillary oncotic pressures were estimated by microprotein methods, and single-nephron glomerular filtration rates (sngfr) were determined by micropuncture techniques under control ureteral pressure and after increased ureteral pressure in both experimental groups. All data were then applied to equations describing the process of glomerular ultrafiltration to define the profile of effective filtration pressure (EFP = deltaP - pi) and the glomerular permeability coefficient (LpA), where sngfr = LpA-EFP. In plasma-expanded rats, sngfr fell from 44.8 +/- 2.2 to 38.5 +/- 1.5 nilters/min g-1 kidney weight (P less than 0.025) with elevated ureteral pressure entirely as a result of a decrease in the hydrostatic pressure gradient (deltaP), since PG did not rise and nephron plasma flow remained constant. In hydropenic rats, sngfr fell from 34.7 +/- 1.6 to 27.3 +/- 1.6 nliters/min g-1 kidney weight with increased ureteral pressure. PG rose 8.7 mm Hg (P less than 0.001) due to an increase in vascular resistance between the peritubular capillaries and the renal vein which prevented the reduction in deltaP. The reduction in sngfr appeared to result from a reduction in LpA resulting in disequilibration of EFP. Nephron plasma flow was not changed. The filtration response to elevated ureteral pressure was modified by the prior state of volume expansion and was not associated with changes in either nephron blood flow or afferent arteriolar resistance.
In Vivo Pathology: Seeing with Molecular Specificity and Cellular Resolution in the Living Body
Authors: Christopher H. Contag
Journal: Annual Review of Pathology Mechanisms of Disease (2007)

The emerging tools of in vivo molecular imaging are enabling dynamic cellular and molecular analyses of disease mechanisms in living animal models and humans. These advances have the potential to dramatically change a number of fields of study, including pathology, and to contribute to the development of regenerative medicine and stem cell therapies. The new tools of molecular imaging, which have already had a tremendous impact on preclinical studies, hold great promise for bringing important and novel information to the clinician and the patient. These approaches are likely to enable early diagnosis, rapid typing of molecular markers, immediate assessment of therapeutic outcome, and ready measures of the extent of tissue regeneration after damage. However, the full impact of these new techniques will be determined by our ability to translate them to the clinic and to develop a general strategy that integrates them with other advances in molecular diagnostics and molecular medicine.
Stability of phenotypes defined by physiological variables and biomarkers in adults with asthma
Authors: M. Kupczyk, B. Dahlén, P. J. Sterk, E. Nizankowska‐Mogilnicka, A. Papi, E. H. Bel, P. Chanez, P. H. Howarth, S. T. Holgate, G. Brusselle, N. M. Siafakas, M. Gjomarkaj, S.‐E. Dahlén
Journal: Allergy (2014)

Abstract Background Although asthma is characterized by variable airways obstruction, most studies of asthma phenotypes are cross‐sectional. The stability of phenotypes defined either by biomarkers or by physiological variables was assessed by repeated measures over 1 year in the Pan‐European BIOAIR cohort of adult asthmatics. Methods A total of 169 patients, 93 with severe asthma ( SA ) and 76 with mild‐to‐moderate asthma ( MA ), were examined at six or more visits during 1 year. Asthma phenotype clusters were defined by physiological variables (lung function, reversibility and age of onset of the disease) or by biomarkers (eosinophils and neutrophils in induced sputum). Results After 1 year of follow‐up, the allocation to clusters was changed in 23.6% of all asthma patients when defined by physiological phenotypes and, remarkably, in 42.3% of the patients when stratified according to sputum cellularity ( P = 0.034). In the SA cohort, 30% and 48.6% of the patients changed allocation according to physiological and biomarker clustering, respectively. Variability of phenotypes was not influenced by change in oral or inhaled corticosteroid dose, nor by the number of exacerbations. Lower stability of single and repeated measure was found for all evaluated biomarkers (eosinophils, neutrophils and Fe NO ) in contrast to good stability of physiological variables ( FEV 1 ), quality of life and asthma control. Conclusion Phenotypes determined by biomarkers are less stable than those defined by physiological variables, especially in severe asthmatics. The data also imply that definition of asthma phenotypes is improved by repeated measures to account for fluctuations in lung function, biomarkers and asthma control.
Identification of IEX-1 as a Biomechanically Controlled Nuclear Factor-κB Target Gene That Inhibits Cardiomyocyte Hypertrophy
Authors: Gilles W. De Keulenaer, Yanlin Wang, Yajun Feng, Suphi Muangman, Keiji Yamamoto, John F. Thompson, Thomas G. Turi, Katherine Landschutz, Richard T. Lee
Journal: Circulation Research (2002)

Abstract— Biomechanical strain is a stimulus for cardiomyocyte hypertrophy and heart failure, but the underlying molecular mechanisms remain incompletely understood. Using an in vivo murine model of pressure overload and an in vitro model of mechanical stimulation of primary cardiomyocytes, we identified iex-1 as a gene activated during the early response of cardiomyocytes to hypertrophic stimuli and as a gene product that inhibits hypertrophy without affecting cardiomyocyte viability. On stimulation of cardiomyocytes, iex-1 mRNA and protein expression increased and translocation of the gene product to the cardiomyocyte nucleus occurred. iex-1 has previously been proposed as a mediator of NF-κB-dependent cell survival and growth in tumor cells. Here, we demonstrate that the biomechanical induction of iex-1 in cardiomyocytes was NF-κB-dependent, as overexpression of the NF-κB inhibitor IκBα completely inhibited strain-mediated iex-1 mRNA accumulation. The functional role of iex-1 was investigated by overexpressing wild-type iex-1 with replication-defective adenoviral gene transfer. Overexpression of iex-1 abolished cardiomyocyte hypertrophy by mechanical strain, phenylephrine, or endothelin-1 at levels that did not affect cell viability. These studies identify iex-1 as a biomechanical stress-inducible and NF-κB-dependent gene in cardiac muscle cells during the acute phase of hypertrophy with negative growth regulatory effects that may counterbalance early hypertrophic responses in activated cardiomyocytes.
Lymphocytes in Patients with Variable Immunodeficiency and Panhypogammaglobulinemia
Authors: H. B. Dickler, N. F. Adkinson, R. I. Fisher, W. D. Terry
Journal: Journal of Clinical Investigation (1974)

Peripheral blood lymphocytes from 15 patients with variable immunodeficiency and severe panhypogammaglobulinemia were evaluated for B and T cell surface markers. B cells were enumerated by immunofluorescent detection of both surface immunoglobulin (Ig) and the ability to bind aggregated Ig complexes. T cells were identified by their ability to form nonimmune rosettes with sheep red blood cells. Four distinct patterns were observed which were designated types I-IV. Type I: six patients had normal percentages (8.5-19.0%) of Ig-bearing B lymphocytes. Type II: four patients were observed to have B lymphocytes (4.5-15.0%) which lacked fluorescence-detectable surface Ig. Type III: the peripheral blood of these four patients contained a subpopulation (11.3-20.0%) of lymphocytes which apparently lacked both B and T cell markers ("null" cells). Type IV: one patient's blood was characterized by a subpopulation (18.0-22.0%) of lymphocytes which bore both B and T cell markers. Patients of each type had some clinical features in common. It is concluded that evaluation of lymphocyte surface markers provides a means of separating patients with variable immunodeficiency and panhypogammaglobulinemia into distinct groups which appear to differ in the nature of their fundamental defect.
Return-to-play guidelines following facial fractures
Authors: Christopher John Fowell, Philip Earl
Journal: British Journal of Sports Medicine (2013)

Despite bone healing and the management options of facial fractures being reported at length, there is a lack of evidence-based return-to-play criteria for sportspeople who have sustained these fractures. This shortage of evidence has resulted in a lack of consensus among health professionals. A prospective study of 20 cases of sportsmen who have returned to competitive play 3 weeks after injury or treatment for facial fractures is reported. The risks and benefits of early return-to-play are discussed and return-to-play guidelines for these patients are proposed.
Time relation of the amount of macrophages in the plaque during the chronic phase of in-stent restenosis
Authors: Lodewijk J. Wagenaar, Ad J. van Boven, Allard C. van der Wal, Chris M. van der Loos, RenéA. Tio, Anton E. Becker, Wiek H. van Glist
Journal: Journal of the American College of Cardiology (2003)
RAPID RESPONSE FROM BMJ.COM
Authors: Patrick W Sullivan
Journal: BMJ (2005)

Following is an edited excerpt from one of the Rapid Responses generated by this article, all of which can be read in their entirety athttp://bmj.bmjjournals.com/cgi/eletters/330/7481/39.—Editor 

Cohen et al state that switching drugs to over the counter availability increases costs for most insured patients in the United States, but we have shown that the Rx-to-OTC switch …
Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study
Authors: Nita G Forouhi, Albert Koulman, Stephen J Sharp, Fumiaki Imamura, Janine Kröger, Matthias B Schulze, Francesca L Crowe, José María Huerta, Marcela Guevara, Joline WJ Beulens, Geertruida J van Woudenbergh, Laura Wang, Keith Summerhill, Julian L Griffin, Edith JM Feskens, Pilar Amiano, Heiner Boeing, Françoise Clavel-Chapelon, Laureen Dartois, Guy Fagherazzi, Paul W Franks, Carlos Gonzalez, Marianne Uhre Jakobsen, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Tilman Kühn, Amalia Mattiello, Peter M Nilsson, Kim Overvad, Valeria Pala, Domenico Palli, J Ramón Quirós, Olov Rolandsson, Nina Roswall, Carlotta Sacerdote, María-José Sánchez, Nadia Slimani, Annemieke MW Spijkerman, Anne Tjonneland, Maria-José Tormo, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, Nicholas J Wareham
Journal: The Lancet Diabetes & Endocrinology (2014)
A novel non-invasive technique for measuring the residual lung volume by nitrogen washout with rapid thoracoabdominal compression in infants
Authors: M. G Morris
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The functional residual capacity (FRC), the only lung volume to be routinely measured in infants, is an unreliable volume landmark. In addition to FRC, the residual volume (RV) was measured by nitrogen washout using rapid thoracoabdominal compression (RTC) in nine infants with cystic fibrosis aged 5–31 months. <h3>METHODS</h3> A commercial system for nitrogen washout to measure lung volumes and a custom made system to perform RTC were used. Lung volume was raised to an airway opening pressure of 30 cm H<sub>2</sub>O (V<sub>30</sub>). RTC was performed from V<sub>30</sub>. The jacket pressure (Pj; 65–92 cm H<sub>2</sub>O) which generated the highest forced expiratory volume (mean 40.2 ml/kg; 95% confidence interval (CI) 33.03 to 47.33) was used during the RV manoeuvre. The infants were manually hyperventilated to inhibit the respiratory drive briefly. RTC was initiated during the last passive expiration. RV was estimated by measuring the volume of nitrogen expired after end forced expiratory switching of the inspired gas from room air to 100% oxygen while jacket inflation was maintained at the time of switching into oxygen during the post-expiratory pause. <h3>RESULTS</h3> In each infant RV and FRC measurements were reproducible and did not overlap; the difference between mean values, which is the expiratory reserve volume, was statistically significant (p&lt;0.05). Mean RV was 21.3 (95% CI 18.7 to 24.0), FRC was 25.5 (95% CI 22.8 to 28.1), and TLC<sub>30</sub>(total lung capacity at V<sub>30</sub>) was 61.5 (95% CI 54.4 to 68.7) ml/kg. These values were dependent on body length, weight and age. When measuring RV the period between switching to oxygen and the end of the Pj plateau was 0.301 (95% CI 0.211 to 0.391) s. The washout duration was longer for RV than for FRC measurement (80.9 s (95% CI 71.3 to 90.4) versus 72.4 s (95% CI 64.9 to 79.8)) (p&lt;0.001). <h3>CONCLUSIONS</h3> A new non-invasive and reliable technique for routine measurement of RV in infants is presented.
Controlled colonic insufflation by a remotely triggered capsule for improved mucosal visualization
Authors: Trisha Pasricha, Byron Smith, Victoria Mitchell, Brian Fang, Erik Brooks, Jason Gerding, Mary Washington, Pietro Valdastri, Keith Obstein
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Capsule endoscopy is an attractive alternative to colorectal cancer screening by conventional colonoscopy, but is currently limited by compromised mucosal visibility because of the lack of safe, controlled colonic insufflation. We have therefore developed a novel system of untethered, wireless-controlled carbon dioxide (CO<sub>2</sub>) insufflation for use in colonic capsule endoscopy, which this study aims to assess in vivo. <b>Material and methods:</b> This observational, nonsurvival, in vivo study used five Yorkshire-Landrace cross swine. A novel insufflation capsule was placed in the porcine colons, and we recorded volume of insufflation, time, force, visualization, and a pathologic assessment of the colon. <b>Results: </b>The mean (standard deviation [SD]) diameter of insufflation was 32.1 (3.9) mm. The volume of CO<sub>2</sub> produced successfully allowed complete endoscopic visualization of the mucosa and safe proximal passage of the endoscope. Pathologic examination demonstrated no evidence of trauma caused by the capsule. <b>Conclusions: </b>These results demonstrate the feasibility of a novel method of controlled colonic insufflation via an untethered capsule in vivo. This technological innovation addresses a critical need in colon capsule endoscopy.
Involvement of Phosphoinositide 3-Kinase γ in Angiogenesis and Healing of Experimental Myocardial Infarction in Mice
Authors: Mauro Siragusa, Rajesh Katare, Marco Meloni, Federico Damilano, Emilio Hirsch, Costanza Emanueli, Paolo Madeddu
Journal: Circulation Research (2010)

Phosphoinositide 3-kinase (PI3K)gamma is expressed in hematopoietic cells, endothelial cells (ECs), and cardiomyocytes and regulates different cellular functions relevant to inflammation, tissue remodeling and cicatrization. Recently, PI3Kgamma inhibitors have been indicated for the treatment of chronic inflammatory/autoimmune diseases and atherosclerosis.We aimed to determine PI3Kgamma contribution to the angiogenic capacity of ECs and the effect of PI3Kgamma inhibition on healing of myocardial infarction (MI).Human umbilical ECs were treated with a selective PI3Kgamma inhibitor, AS605240, or a pan-phosphoinositide 3-kinases inhibitor, LY294002. Both inhibitory treatments and small interfering RNA-mediated PI3Kgamma knockdown strongly impaired ECs angiogenic capacity, because of suppression of the PI3K/Akt and mitogen-activated protein kinase pathways. Constitutive activation of Akt rescued the angiogenic defect. Reparative angiogenesis was studied in vivo in a model of MI. AS605240 did not affect MI-induced PI3Kgamma upregulation, whereas it suppressed Akt activation and downstream signaling. AS605240 strongly reduced inflammation, enhanced cardiomyocyte apoptosis, and impaired survival and proliferation of ECs in peri-infarct zone, which resulted in defective reparative neovascularization. As a consequence, AS605240-treated MI hearts showed increased infarct size and impaired recovery of left ventricular function. Similarly, PI3Kgamma-deficient mice showed impaired reparative neovascularization, enhanced cardiomyocyte apoptosis and marked deterioration of cardiac function following MI. Mice expressing catalytically inactive PI3Kgamma also failed to mount a proper neovascularization, although cardiac dysfunction was similar to wild-type controls.PI3Kgamma expression and catalytic activity are involved at different levels in reparative neovascularization and healing of MI.
Natural and Synthetic Progestins Accelerate 7,12-Dimethylbenz[<i>a</i>]Anthracene-Initiated Mammary Tumors and Increase Angiogenesis in Sprague-Dawley Rats
Authors: Indira Benakanakere, Cynthia Besch-Williford, Jennifer Schnell, Sandra Brandt, Mark R. Ellersieck, Alfredo Molinolo, Salman M. Hyder
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Synthetic progestins are widely used therapeutically; however, there is controversy regarding their proliferative effects. We used a rat 7,12-dimethylbenz[a]anthracene (DMBA)–induced mammary tumor model to test the hypothesis that progestins increase angiogenesis and as a result decrease the latency period and increase the multiplicity of mammary tumors. Experimental Design: Medroxyprogesterone acetate (MPA) pellets were implanted 2, 4, or 6 weeks after DMBA exposure; RU-486 was given 3 days before MPA. Experiments were concluded 70 days after DMBA administration. Results: MPA exposure 4 or 6 weeks after DMBA reduced the latency period for appearance of tumors in a dose-dependent manner and increased tumor incidence. Administration of MPA 2 weeks after DMBA administration reduced tumor incidence and was protective. Progesterone did not reduce the latency period but significantly increased tumor incidence. RU-486 delayed the latency period and decreased tumor incidence in animals exposed to MPA at 4 weeks after DMBA treatment, indicating that the progesterone receptor may be partially responsible for transmission of proliferative signals. RU-486 also delayed the latency period but failed to reduce overall tumor incidence when animals were exposed to MPA at 6 weeks after DMBA treatment, indicating that other factors may also control MPA-induced acceleration. Whereas MPA-accelerated tumors were both intraductal and tubular, progesterone-accelerated and/or DMBA-induced tumors were tubular. Progestin treatment increased vascular endothelial growth factor expression within tumors in a ligand- and cell type–dependent manner and increased angiogenesis in correlation with vascular endothelial growth factor expression. No mammary tumors or progesterone receptor were detected in DMBA-treated ovariectomized rats regardless of progestin administration. Conclusions: We propose that progestins can accelerate the development of mammary tumors and that antiangiogenic agents and/or the use of antiprogestins that can reduce tumor incidence might be a viable therapeutic option for treatment of progestin-accelerated tumors. The model described here is a potentially useful preclinical model for rapidly screening such compounds.