tbuckley/cabot-search huggingface dataset:
Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension
Authors: F. Reichenberger, R. Voswinckel, B. Enke, M. Rutsch, E. El Fechtali, T. Schmehl, H. Olschewski, R. Schermuly, N. Weissmann, H. A. Ghofrani, F. Grimminger, E. Mayer, W. Seeger
Journal: European Respiratory Journal (2007)

For chronic thromboembolic pulmonary hypertension not amenable to pulmonary endarterectomy, effective medical therapy is desired. In an open-label uncontrolled clinical trial, 104 patients (mean +/- sem age 62 +/- 11 yrs) with inoperable chronic thromboembolic pulmonary hypertension were treated with 50 mg sildenafil t.i.d. At baseline, patients had severe pulmonary hypertension (pulmonary vascular resistance 863 +/- 38 dyn.s.cm(-5)) and a 6-min walking distance of 310 +/- 11 m. Eight patients were in World Health Organization functional class II, 76 in class III and 20 in class IV. After 3 months' treatment, there was significant haemodynamic improvement, with reduction of pulmonary vascular resistance to 759 +/- 62 dyn.s.cm(-5). The 6-min walking distance increased significantly to 361 +/- 15 m after 3 months' treatment, and to 366 +/- 18 m after 12 months' treatment. A subset of 67 patients received a single dose of 50 mg sildenafil during initial right heart catheterisation. The acute haemodynamic effect of this was not predictive of long-term outcome. In this large series of patients with inoperable chronic thromboembolic pulmonary hypertension, open-label treatment with sildenafil led to significant long-term functional improvement. The acute effect of sildenafil may not predict the long-term outcome of therapy.
Decrease of body fat during an ultra-endurance triathlon is associated with race intensity
Authors: Beat Knechtle, Maike Schwanke, Patrizia Knechtle, Goetz Kohler
Journal: British Journal of Sports Medicine (2007)

OBJECTIVE: We investigated in a non-stop ultra-endurance triathlon, whether adipose subcutaneous tissue or skeletal muscle mass decreased. DESIGN: Descriptive field study. SETTING: The Triple Iron Triathlon Germany 2006 in Lensahn over 11.6 km swimming, 540 km cycling and 126.6 km running. SUBJECTS: 17 male Caucasian triathletes (mean ± SD, age 39.2 ± 7.5 years, body mass 80.7 ± 8.9 kg, body height 178 ± 5 cm, BMI 25.4 ± 2.4 kg/m2). INTERVENTIONS: None. MAIN OUTCOME MEASUREMENTS: Determination of body mass, skin fold thicknesses, circumferences of extremities as well as calculation of body mass index (BMI), skeletal muscle mass and percent body fat in order to show changes after the race. RESULTS: A statistically significant decrease was shown for body mass (p&lt;0.001), BMI (p&lt;0.001) and calculated percent body fat (p&lt;0.001) whereas skeletal muscle mass did not change statistically significantly (p&gt;0.05). Circumferences of thigh, upper arm and calf did not decrease statistically significantly (p&gt;0.05) whereas all skin fold thickness decreased statistically significantly (p&lt;0.05) with exception of chest and thigh. A statistically significant correlation was found between the loss of percent body fat and the loss of body mass (p&lt;0.01, r2=0.55) as well as ∆ percent body fat with race performance (p&lt;0.05, r2=0.24). CONCLUSIONS: Ultra-triathletes at the Triple Iron Triathlon Germany 2006 showed a statistically significant decrease of body mass and percent body fat, where decrease of percent body fat was associated with race intensity.
Effect of two types of spectators on the performance of motor tasks
Authors: Mahesh Singh Dhapola, Bhagwati P D Pant, Vivek Pandey, Gaurav Pant
Journal: British Journal of Sports Medicine (2010)

The purpose of the study was to find out the effect of hostile and favourable spectators on the performances of motor tasks. For the purpose of this study a total of 50 students of LNUPE were selected and randomly divided into two groups A and B, 25 each (15 male and 10 female). These subjects were tested on the selected variables such as bent knee sit ups, pull-ups (male)/flexed arm hang (female), bass stick test (crosswise), field goal speed test and dribbling test. Total 200 students of LNUPE were selected as spectators and were asked to first act as hostile spectators and then as favourable ones in order to create the two atmospheres for the study. Hostile spectators tried to disturb the subjects while they were performing by whistling, taunting, booing, shouting and hooting them whereas favourable spectators helped in facilitating the performance by clapping, cheering and appreciating the performance efforts in order to create an appropriate atmosphere. These variables were particularly chosen because of their administrative feasibility and they could be conducted very close to the spectators as the size of the spectators was a smaller one. ‘t Test’ was employed at 0.05 level of significance to compare the performance of both the groups under hostile and favourable situations types of spectators on the performance of motor tasks. The statistical findings revealed that the performance of pull ups (male)/flexed arm hang (female), bass stick test (static balance) and field goal speed test showed a significance differences on comparison whereas bent knee sit-ups and dribbling test showed no significant differences on comparison of performances when performed under the presence of hostile and favourable spectators.
Causative allergens of allergic rhinitis in Japan with special reference to silkworm moth allergen
Authors: M. Suzuki, H. Itoh, K. Sugiyama, I. Takagi, J. Nishimura, K. Kato, S. Mamiya, S. Baba, Y. Ohya, H. Itoh, A. Yokota, M. Itoh, N. Ohta
Journal: Allergy (1995)

To determine the importance of silkworm moth allergens, we tested 267 patients with allergic rhinitis with CAP‐RAST®, a new assay system for detecting specific IgE in sera. We used the following allergen sources: house‐dust mite, Candida, Altemaria , cat dander, orchard grass, ragweed, mugwort, Japanese hops, Japanese cedar, Japanese cypress, cotton, silk, larval chironomid midge, adult chironomid midge, and silkworm moth. As expected, the highest positive rate of reaction, as determined by CAP‐RAST, was 73.8% for Japanese cedar, followed by 53.2% for mite and 50.6% for Japanese cypress. Although the positive rate for silkworm moth was not as high as for cedar pollen, one‐third of patients had specific IgE against silkworm moth. The positive rate of reaction to silkworm moth was much higher than that to chironomid. It was interesting to note that the patients reported had not been documented as having frequent contact with silkworm moth allergen. Correlations between silkworm moth and silk, and silkworm moth and chironomid midge were found to be significant ( P &lt;0.001). Silkworm moth allergen showed the third highest reaction rate in patients with severe symptoms. These results suggest that silkworm moth allergen should be considered to be important in patients with allergic rhinitis in Japan.
Endomyocardial gene expression during development of pacing tachycardia-induced heart failure in the dog.
Authors: R E Williams, D A Kass, Y Kawagoe, P Pak, R S Tunin, R Shah, A Hwang, A M Feldman
Journal: Circulation Research (1994)

Selective and specific changes in gene expression characterize the end-stage failing heart. However, the pattern and relation of these changes to evolving systolic and diastolic dysfunction during development of heart failure remains undefined. In the present study, we assessed steady-state levels of mRNAs encoding a group of cardiac proteins during the early development of left ventricular dysfunction in dogs with pacing-induced cardiomyopathy. Corresponding hemodynamic assessments were made in the conscious state in the same animals and at the same time points at baseline, after 1 week of ventricular pacing, and at the onset of clinical heart failure. Systolic dysfunction dominated after 1 week of pacing, whereas diastolic dysfunction was far more pronounced with the onset of heart failure. Atrial natriuretic factor mRNA was undetectable in 7 of 12 hearts at baseline but was expressed in all hearts at 1 week (P &lt; .01 by chi 2 test), and it increased markedly with progression to failure (P = .05). Creatine kinase-B mRNA also rose markedly with heart failure (P &lt; .01). Levels of mRNA encoding beta-myosin heavy chain, mitochondrial creatine kinase, phospholamban, and sarcoplasmic reticulum Ca(2+)-ATPase did not significantly change from baseline, despite development of heart failure. Additional analysis to determine if these mRNA changes were related to the severity of diastolic or systolic dysfunction revealed that phospholamban mRNA decreased in hearts with larger net increases in end-diastolic pressure (+19.2 +/- 1.9 mm Hg) compared with those hearts in which it did not change (+4.0 +/- 4.9, P &lt; .02).(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic bronchiolitis in a 5‐yr-old child after exposure to sulphur mustard gas
Authors: E. Dompeling, Q. Jöbsis, N.M.A. Vandevijver, G. Wesseling, H. Hendriks
Journal: European Respiratory Journal (2004)

Exposure to sulphur mustard (SM) gas may have extensive immediate effects on the respiratory system. However, long-term effects are far less known. This case report describes a Kurdish male child who was exposed to SM gas during a chemical attack in Iraq at 5 yrs of age. In the acute phase, the child developed severe respiratory symptoms with a chemical pneumonia. Extensive burning of the skin occurred. In the course of 10 yrs, lung function deteriorated progressively to a forced expiratory volume in one second of 30% of predicted value. Severe air-trapping occurred. The lung function abnormalities were not reversed by treatment with corticosteroids or bronchodilators. Infectious exacerbations of the child's lung disease occurred. High resolution computed tomography scan showed multiple bronchiectasis. The histological picture of an open lung biopsy was best described as a “chronic bronchiolitis”.
Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice
Authors: Sungjune Kim, Saif Lalani, Vrajesh V. Parekh, Tiffaney L. Vincent, Lan Wu, Luc Van Kaer
Journal: Journal of Clinical Investigation (2008)

Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize glycolipid antigens in the context of the MHC class I–like antigen-presenting molecule CD1d. In vivo activation of mouse iNKT cells with the glycolipid α-galactosylceramide (α-GalCer) results in the acquisition of a hyporesponsive (anergic) phenotype by these cells. Because iNKT cells can become activated in the context of infectious agents, here we evaluated whether iNKT cell activation by microorganisms can influence subsequent responses of these cells to glycolipid antigen stimulation. We found that mouse iNKT cells activated in vivo by multiple bacterial microorganisms, or by bacterial LPS or flagellin, became unresponsive to subsequent activation with α-GalCer. This hyporesponsive phenotype of iNKT cells required IL-12 expression and was associated with changes in the surface phenotype of these cells, reduced severity of concanavalin A–induced hepatitis, and alterations in the therapeutic activities of α-GalCer. These findings may have important implications for the development of iNKT cell–based therapies.
Healthcare workers with tuberculosis infected during work
Authors: G. de Vries, M. M. G. G. Šebek, C. S. B. Lambregts-van Weezenbeek
Journal: European Respiratory Journal (2006)

The risk for healthcare workers (HCWs) of tuberculosis (TB) attributable to occupational exposure is difficult to determine, as are the conditions contributing to this risk. The objective of the present study was to determine which TB cases among HCWs in the Netherlands were infected during work and to analyse factors which contributed to infection and subsequent disease. The total study population consisted of 101 cases over a 5-yr period. In 67 (66%) subjects the route of infection could be determined by epidemiological and microbiological information. Of these cases, 28 out of 67 (42%) were due to infection at work, 19 (28%) were community acquired, and 20 (30%) were infected abroad. The 28 cases infected at work were subject to an in-depth analysis. Delayed diagnosis of the index case, especially in the elderly patient, was the main cause of patient-to-HCW transmission. In some circumstances, inadequate infection-control measures also contributed to transmission. In conclusion, a high suspicion of tuberculosis by the clinician, adequate infection control measures by hospital authorities, and early identification of latent tuberculosis infection by occupational and public-health specialists are necessary to prevent tuberculosis among healthcare workers.
Regulation of Phosphate Homeostasis by PTH, Vitamin D, and FGF23
Authors: Clemens Bergwitz, Harald Jüppner
Journal: Annual Review of Medicine (2010)

In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal phosphate excretion by reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc in the proximal tubules. Most insights gained into the regulation of phosphate homeostasis by these factors are derived from human genetic disorders and genetically engineered mice, which are reviewed in this paper.
Evaluating the Efficiency of Targeted Designs for Randomized Clinical Trials
Authors: Richard Simon, Aboubakar Maitournam
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Genomic technologies make it increasingly possible to identify patients most likely to benefit from a molecularly targeted drug. This creates the opportunity to conduct targeted clinical trials with eligibility restricted to patients predicted to be responsive to the drug. Experimental Design: We evaluated the relative efficiency of a targeted clinical trial design to an untargeted design for a randomized clinical trial comparing a new treatment to a control. Efficiency was evaluated with regard to number of patients required for randomization and number required for screening. Results: The effectiveness of this design, relative to the more traditional design with broader eligibility, depends on multiple factors, including the proportion of responsive patients, the accuracy of the assay for predicting responsiveness, and the degree to which the mechanism of action of the drug is understood. Explicit formulas were derived for computing the relative efficiency of targeted versus untargeted designs. Conclusions: Targeted clinical trials can dramatically reduce the number of patients required for study in cases where the mechanism of action of the drug is understood and an accurate assay for responsiveness is available.
Successful Transition From Insulin to Sulfonylurea Therapy in a Patient With Monogenic Neonatal Diabetes Owing to a KCNJ11 F333L Mutation
Authors: Katherine Q. Philla, Andrew J. Bauer, Karen S. Vogt, Siri Atma W. Greeley
Journal: Diabetes Care (2013)

Although monogenic neonatal diabetes may be caused by mutations in >20 different genes, the most common are activating heterozygous mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive K+ channel (KATP channel), which is highly expressed in pancreatic β-cells and brain (1). Mutated KATP channels typically have decreased sensitivity to ATP inhibition, hampering insulin secretion even during hyperglycemia. Oral sulfonylureas (SUs) have been demonstrated to be an effective treatment in the majority of cases, given that they close the KATP channels by an ATP-independent mechanism (2). However, the likelihood of success is largely predicted by the particular mutation. Previous reports of the F333L mutation indicated insensitivity to SU therapy. We report a case representing a novel response to SU therapy in this same mutation.

A 13-month …
ROLE OF ABCG2/BCRP IN BIOLOGY AND MEDICINE
Authors: P. Krishnamurthy, J.D. Schuetz
Journal: The Annual Review of Pharmacology and Toxicology (2005)

The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must homodimerize to acquire transport activity. ABCG2 is found in a variety of stem cells and may protect them from exogenous and endogenous toxins. ABCG2 expression is upregulated under low-oxygen conditions, consistent with its high expression in tissues exposed to low-oxygen environments. ABCG2 interacts with heme and other porphyrins and protects cells and/or tissues from protoporphyrin accumulation under hypoxic conditions. Individuals who carry ABCG2 alleles that have impaired function may be more susceptible to porphyrin-induced toxicity. Abcg2 knock-out models have allowed in vivo studies of Abcg2 function in host and cellular defense. In combination with immunohistochemical analyses, these studies have revealed how ABCG2 influences the absorption, distribution, and excretion of drugs and cytotoxins.
A clinic service offering isoniazid preventive therapy to HIV infected adults reduces the incidence of tuberculosis
Authors: A R Khan
Journal: Thorax (2005)

▴ Grant AD, Charalambous S, Fielding KL, et al. Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study. JAMA2005;293:2719–25

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This study followed 1655 HIV infected male employees of a South African gold mining company (median age 37 years) for a median duration of 22.1 months. Isoniazid preventive therapy, 300 mg daily, was offered at clinic enrolment to 679 subjects who attended with no evidence of active tuberculosis (TB).

A …

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Poly-<scp>l</scp>-Lysine Compacts DNA, Kills Bacteria, and Improves Protease Inhibition in Cystic Fibrosis Sputum
Authors: Alice V. Dubois, Patrick Midoux, Delphine Gras, Mustapha Si-Tahar, Déborah Bréa, Sylvie Attucci, Mustapha-Kamel Khelloufi, Reuben Ramphal, Patrice Diot, Francis Gauthier, Virginie Hervé
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Neutrophil serine proteases in cystic fibrosis (CF) lung secretions partially resist inhibition by natural and exogenous inhibitors, mostly because DNA impairs their control. Cationic polypeptides display the property of condensing DNA and retain antimicrobial properties. We hypothesized that DNA condensation by cationic polypeptides in CF sputum would result in a better control of CF inflammation and infection.Objectives: We examined whether poly-l-lysine would compact DNA in CF lung secretions and liquefy CF sputum, improve the control of extracellular proteases by exogenous inhibitors, and whether it displays antibacterial properties toward CF-associated bacteria.Methods: We used fluorogenic methods to measure proteolytic activities and inhibition by protease inhibitors in whole sputum homogenates from patients with CF before and after treatment with poly-l-lysine. Antibacterial properties of poly-l-lysine were measured in bacterial cultures and in whole CF sputum. Poly-l-lysine toxicity was evaluated after aerosolization by histologic analysis, flow cytometry, and quantification of proinflammatory cytokines.Measurements and Main Results: Poly-l-lysine compacts CF sputum DNA, generating a liquid phase that improves ciliary beating frequency at the lung epithelial surface, and allows the control of neutrophil elastase and cathepsin G by their natural inhibitors. It retains antimicrobial properties against Pseudomonas aeruginosa and Staphylococcus aureus at doses that induce no inflammation in the mouse lung after aerosol administration.Conclusions: Poly-l-lysine may be an alternative to dornase-α to liquefy sputum with added benefits because it helps natural inhibitors to better control the deleterious effects of extracellularly released neutrophil serine proteases and has the ability to kill bacteria in CF sputum.
Predictive Values of Neurocognition and Negative Symptoms on Functional Outcome in Schizophrenia: A Longitudinal First-Episode Study With 7-Year Follow-Up
Authors: Peter Milev, Beng-Choon Ho, Stephan Arndt, Nancy C Andreasen
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The relationship between cognition and outcome in people with schizophrenia has been established in studies that, for the most part, examined chronic patients and were cross-sectional in design. The purpose of this study was to analyze the relationships between neurocognitive variables assessed at illness onset and functional outcome in a longitudinal design. An additional area of interest was whether the severity of negative symptoms would predict outcome independently from neurocognitive variables or whether there would be an overlap in their predictive power. METHOD: The authors administered a comprehensive cognitive battery and clinical assessments to 99 subjects who were in their first episode of illness and analyzed the relationship of cognition and symptom severity at intake with community outcome after an average follow-up period of 7 years. RESULTS: Verbal memory, processing speed and attention, and the severity of negative symptoms at intake were related to subsequent outcome. Global psychosocial functioning was predicted by negative symptoms and attention. Verbal memory was the significant predictor of the degree of impairment in recreational activities. Impairment in relationships was predicted by negative symptoms and memory, whereas attention and negative symptoms were predictive of work performance. There was an overlap in the variance in outcome explained by cognitive variables and negative symptoms. CONCLUSIONS: Verbal memory and processing speed and attention are potential targets for psychosocial interventions to improve outcome. Results from cross-sectional or chronic patient studies do not necessarily correspond to the findings of this prospective first-episode study in which cognition appears to explain less of the variance in outcome.