tbuckley/cabot-search huggingface dataset:
Vocal cord dysfunction: what do we know?
Authors: K. Kenn, R. Balkissoon
Journal: European Respiratory Journal (2010)

Vocal cord dysfunction (VCD) is a disorder caused by episodic unintentional paradoxical adduction of the vocal cords, which may induce acute severe dyspnoea attacks not responsive to conventional asthma therapy. The aetiology of VCD is complex and often multifactorial. The essential pathophysiology is that of a hyperfunctional laryngeal reflex to protect the lower airway as a result of any combination of post-nasal drip, gastro-oesophageal reflux, laryngopharyngeal reflux and/or psychological conditions. Laryngoscopic demonstration of the paradoxical motion while wheezing or stridorous is considered the diagnostic gold standard. Speech therapy, including the use of special relaxed-throat breathing patterns is effective for VCD that is purely of the functional nature. Knowledge of the clinical features of VCD and identifying factors that may be contributing to the development of VCD can provide adequate clues to the correct diagnosis and management.
Endothelial Dysfunction in Childhood Infection
Authors: Marietta Charakida, Ann E. Donald, Mari Terese, Sam Leary, Julian P. Halcox, Andy Ness, George Davey Smith, Jean Golding, Peter Friberg, Nigel J. Klein, John E. Deanfield
Journal: Circulation (2005)

Background— Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. Methods and Results— We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3±2.7%, mean±SD) and the convalescent group (8.1±3.1%) than in the control group (9.7±2.5%; P &lt;0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls ( P =0.85) but improved in the AI group ( P &lt;0.001). Conclusions— Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.
Genomic stability and functional activity may be lost in telomerase-transduced human CD8+ T lymphocytes
Authors: Marco W. J. Schreurs, Mario A. J. A. Hermsen, Ramon I. Klein Geltink, Kirsten B. J. Scholten, Antoinette A. T. P. Brink, Esther W. M. Kueter, Marianne Tijssen, Chris J. L. M. Meijer, Bauke Ylstra, Gerrit A. Meijer, Erik Hooijberg
Journal: Blood (2005)
Accuracy of Nasal Cannula Pressure Recordings for Assessment of Ventilation during Sleep
Authors: ROBERT THURNHEER, XIAOBIN XIE, KONRAD E. BLOCH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Nasal prong pressure monitoring (Pnose) is utilized to assess ventilation during sleep. However, it has not been rigorously validated against the gold standard of face-mask pneumotachography (V˙ fm). Therefore, we compared Pnose with V˙ fm in 20 patients with suspected sleep apnea during nocturnal polysomnography, and analyzed factors affecting accuracy of Pnose-derived variables. Patients rated their nasal obstruction on a visual analog scale. Mean ± SE apnea/hypopnea index (AHI) by V˙ fm was 24.0 ± 5.1 h− 1. The bias (mean difference) and limits of agreement ( ± 2 SD) of AHI derived from Pnose, and square root–transformed Pnose, a measure proposed as a surrogate of airflow, were + 3.9 ( ± 4.6), and − 0.9 ( ± 9.0) h− 1. Subjective scores of nasal obstruction before polysomnographies did not herald inaccuracy of AHI from Pnose. Square root–transformed Pnose closely tracked pneumotachographic airflow over 10 breaths (r2 among signals 0.88 to 0.96) but the relationship among these signals was highly variable if comparisons were extended over an entire night. Compared with face-mask pneumotachography, nasal pressure monitoring provides accurate AHI for clinical purposes even in patients perceiving nasal obstruction. Square-root transformation provides near linear nasal pressure/airflow relationships over a short time but is not essential for estimation of AHI.
On the New French Codex
Authors: J. B. Nevins
Journal: BMJ (1867)

onwsal, like a -wedge which distends the wen&~r Iteef, , aud&does so inthe most-advantsous maner, saice it Plugs te .wound in al1l its patsnot allowing it to open anywhere further than is required for its own transit..On the whole, I consider that, by the maeuwe here reeommnended, the operation has become much easer, and an advance has been made towards its more general ;adoption.In principle, I would have uno objection to the first presentation of the margin of the lens beingsqa ed bya gentle-,side-mancuvre, ;asisted by.couterrpreasure with the steadying for- ceps, whereupon the evacuation might be farther iroceedeiv.ithafter the present plan.Since, how- ar, theipressuxe upon the:lower .half, of the cornea is always equal to the occasion, the :complicaoted curse of £a auecesaive resort to both manceuvres does not appear to me ,toimply any material advantage.
Screening for Proteinuria in US Adults
Authors: L. Ebony Boulware, Bernard G. Jaar, Michelle E. Tarver-Carr, Frederick L. Brancati, Neil R. Powe
Journal: JAMA (2003)

Chronic kidney disease is a growing public health problem. Screening for early identification could improve health but could also lead to unnecessary harms and excess costs.To assess the value of periodic, population-based dipstick screening for early detection of urine protein in adults with neither hypertension nor diabetes and in adults with hypertension.Cost-effectiveness analysis using a Markov decision analytic model to compare a strategy of annual screening with no screening (usual care) for proteinuria at age 50 years followed by treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II-receptor blocker (ARB).Cost per quality-adjusted life-year (QALY).For persons with neither hypertension nor diabetes, the cost-effectiveness ratio for screening vs no screening (usual care) was unfavorable (282 818 dollars per QALY; incremental cost of 616 dollars and a gain of 0.0022 QALYs per person). However, screening such persons beginning at age 60 years yielded a more favorable ratio (53 372 dollars per QALY). For persons with hypertension, the ratio was highly favorable (18 621 dollars per QALY; incremental cost of 476 dollars and a gain of 0.03 QALYs per person). Cost-effectiveness was mediated by both chronic kidney disease progression and death prevention benefits of ACE inhibitor and ARB therapy. Influential parameters that might make screening for the general population more cost-effective include a greater incidence of proteinuria, age at screening (53 372 dollars per QALY for persons beginning screening at age 60 years), or lower frequency of screening (every 10 years: 80 700 dollars per QALY at age 50 years; 6195 dollars per QALY at age 60 years; and 5486 dollars per QALY at age 70 years).Early detection of urine protein to slow progression of chronic kidney disease and decrease mortality is not cost-effective unless selectively directed toward high-risk groups (older persons and persons with hypertension) or conducted at an infrequent interval of 10 years.
Inpatient Treatment of Children and Adolescents With Severe Obesity in the Netherlands
Authors: Olga van der Baan-Slootweg, Marc A. Benninga, Anita Beelen, Job van der Palen, Christine Tamminga-Smeulders, Jan G. P. Tijssen, Wim M. C. van Aalderen
Journal: JAMA Pediatrics (2014)

Severe childhood obesity has become a major health problem, and effective, evidence-based interventions are needed. The relative effectiveness of inpatient compared with ambulatory treatment remains unknown.To determine whether an inpatient treatment program is more effective than an ambulatory treatment program at achieving a sustained weight loss in children and adolescents with severe obesity.We conducted a randomized clinical trial with a 2-year follow-up at a tertiary referral center for pediatric obesity in the Netherlands. We recruited 90 children and adolescents aged 8 to 18 years with severe obesity (body mass index [BMI] z score, ≥3.0 or >2.3 with obesity-related health problems).Patients were randomly assigned to an inpatient (6 months of hospitalization on working days) or an ambulatory (12 days of hospital visits at increasing intervals during a 6-month period) treatment program. Both treatment programs involved an intensive, family-based, lifestyle intervention, including exercise, nutritional education, and behavior modification for the patients and their caregiver(s).Change in BMI z score. Secondary outcomes included fasting insulin, fasting plasma glucose, 2-hour plasma glucose, and lipid levels, insulin sensitivity, liver function test results, waist circumference, blood pressure, body composition, and aerobic fitness (peak oxygen consumption, Vo₂). Outcomes were analyzed by intention to treat.Immediately after treatment, reductions in the BMI z score were significantly larger for the inpatient than the ambulatory groups (mean [SE] difference, -0.26 [0.12; 95% CI, -0.59 to -0.01]; P = .04). Change from baseline for the BMI z score in the inpatient group was -18.0% (P = .001) immediately after treatment, -8.5% (P = .008) at 18 months, and -6.3% (P = .38) at 30 months; in the ambulatory group, changes from baseline were -10.5% (P = .001), -6.2% (P = .39), and -1.5% (P > .99), respectively. The favorable outcomes of the inpatient group could not be sustained at 12 and 24 months after treatment. In addition, significant differences in favor of the inpatient group immediately after treatment were found for levels of fasting insulin (-6.37 IU/L; P = .02), total cholesterol (-19.51 mg/dL; P = .01), low-density lipoprotein cholesterol (-13.48 mg/dL; P = .03), and triglycerides (-25.39 mg/dL; P = .01), and insulin sensitivity (-1.37; P = .02), fat mass (-3.31%; P = .03), and peak Vo₂ (378.2 mL/min; P = .01).In severely obese children and adolescents, inpatient treatment was superior to ambulatory treatment immediately after treatment, but effects were not sustained at long-term follow-up. These findings stress the need to further study maintenance strategies for sustainable weight loss.trialregister.nl Identifier: NTR1172.
Shrinking pleuritis with atelectasis.
Authors: L Dernevik, P Gatzinsky, E Hultman, K Selin, G William-Olsson, L Zettergren
Journal: Thorax (1982)

During a 10-year period 28 patients with shrinking pleuritis with atelectasis (SPA) were observed and operated upon. This lesion has been given different names in the literature, for instance rounded atelectasis, pleuroma, pulmonary pseudotumour, and lung folding. All patients except two were operated upon because of a diagnosis of pulmonary tumour. However, at operation no tumour was found. The aetiology and pathogenesis of SPA are discussed on the basis of X-ray, operative, and histopathological findings.
Pentoxifylline in the Treatment of Radiation-Induced Fibrosis
Authors: Paul Okunieff, Elizabeth Augustine, Jeanne E. Hicks, Terri L. Cornelison, Rosemary M. Altemus, Boris G. Naydich, Ivan Ding, Amy K. Huser, Edward H. Abraham, Judith J. Smith, Norman Coleman, Lynn H. Gerber
Journal: Journal of Clinical Oncology (2004)

Fibrotic sequelae remain the most important dose-limiting toxicity of radiation therapy to soft tissue. Functionally, this is reflected in loss of range of motion and muscle strength and the development of limb edema and pain. Tumor necrosis factor alpha and fibroblast growth factor 2 (FGF2), which are abnormally elevated in irradiated tissues, may mediate radiation fibrovascular injury.In an open label drug trial, we studied the effects of pentoxifylline (400 mg orally tid for 8 weeks) on 30 patients who displayed late, radiation-induced fibrosis at 1 to 29 years posttreatment (40 to 84 Gy). The primary outcome measurement was change in physical impairments thought to be secondary to radiation, including active and passive range of motion (AROM and PROM), muscle strength, limb edema, and pain. Plasma levels of cytokines (tumor necrosis factor alpha and FGF2) also were measured. Twenty-seven patients completed baseline and 8-week assessments, and 24 patients completed baseline, 8-week, and 16-week assessments.After 8 weeks of pentoxifylline intervention, 20 of 23 patients with impaired AROM and 19 of 22 with impaired PROM improved; 11 of 19 patients with muscle weakness showed improved motor strength; five of seven patients with edema had decreased limb girth; and nine of 20 patients had decreased pain. Pretreatment FGF2 levels dropped from an average of 44.9 pg/mL to 24.0 pg/mL after 8 weeks of treatment.Patients receiving pentoxifylline demonstrated improved AROM, PROM, and muscle strength and decreased limb edema and pain. Reversal of these delayed radiation effects was associated with a decrease in circulating FGF2.
Cytokeratins mediate epithelial innate defense through their antimicrobial properties
Authors: Connie Tam, James J. Mun, David J. Evans, Suzanne M.J. Fleiszig
Journal: Journal of Clinical Investigation (2012)

Epithelial cells express antimicrobial proteins in response to invading pathogens, although little is known regarding epithelial defense mechanisms during healthy conditions. Here we report that epithelial cytokeratins have innate defense properties because they constitutively produce cytoprotective antimicrobial peptides. Glycine-rich C-terminal fragments derived from human cytokeratin 6A were identified in bactericidal lysate fractions of human corneal epithelial cells. Structural analysis revealed that these keratin-derived antimicrobial peptides (KDAMPs) exhibited coil structures with low α-helical content. Synthetic analogs of these KDAMPS showed rapid bactericidal activity against multiple pathogens and protected epithelial cells against bacterial virulence mechanisms, while a scrambled peptide showed no bactericidal activity. However, the bactericidal activity of a specific KDAMP was somewhat reduced by glycine-alanine substitutions. KDAMP activity involved bacterial binding and permeabilization, but the activity was unaffected by peptide charge or physiological salt concentration. Knockdown of cytokeratin 6A markedly reduced the bactericidal activity of epithelial cell lysates in vitro and increased the susceptibility of murine corneas to bacterial adherence in vivo. These data suggest that epithelial cytokeratins function as endogenous antimicrobial peptides in the host defense against infection and that keratin-derived antimicrobials may serve as effective therapeutic agents.
High Levels of Gene Expression Explain the Strong Evolutionary Constraint of Mitochondrial Protein-Coding Genes
Authors: B. Nabholz, H. Ellegren, J. B. W. Wolf
Journal: Molecular Biology and Evolution (2012)

The nearly neutral theory of molecular evolution has been widely accepted as the guiding principle for understanding how selection affects gene sequence evolution. One of its central predictions is that the rate at which proteins evolve should negatively scale with effective population size (Ne). In contrast to the expectation of reduced selective constraint in the mitochondrial genome following from its lower Ne, we observe what can be interpreted as the opposite: for a taxonomically diverse set of organisms (birds, mammals, insects, and nematodes), mitochondrially encoded protein-coding genes from the oxidative phosphorylation pathway (mtOXPHOS; n = 12–13) show markedly stronger signatures of purifying selection (illustrated by low dN/dS) than their nuclear counterparts interacting in the same pathway (nuOXPHOS; n: ∼75). To understand these unexpected evolutionary dynamics, we consider a number of structural and functional parameters including gene expression, hydrophobicity, transmembrane position, gene ontology, GC content, substitution rate, proportion of amino acids in transmembrane helices, and protein–protein interaction. Across all taxa, unexpectedly large differences in gene expression levels (RNA-seq) between nuclear and mitochondrially encoded genes, and to a lower extent hydrophobicity, explained most of the variation in dN/dS. Similarly, differences in dN/dS between functional OXPHOS protein complexes could largely be explained by gene expression differences. Overall, by including gene expression and other functional parameters, the unexpected mitochondrial evolutionary dynamics can be understood. Our results not only reaffirm the link between gene expression and protein evolution but also open new questions about the functional role of expression level variation between mitochondrial genes.
Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms.
Authors: M J Janse, F J van Capelle, H Morsink, A G Kléber, F Wilms-Schopman, R Cardinal, C N d'Alnoncourt, D Durrer
Journal: Circulation Research (1980)
Tolerance to the protective effects of salmeterol on methacholine-induced bronchoconstriction: influence of inhaled corticosteroids
Authors: LP Boulet, A Cartier, J Milot, J Cote, JL Malo, M Laviolette
Journal: European Respiratory Journal (1998)

Long-acting beta2-adrenoceptor agonists such as salmeterol reduce airway responsiveness for at least 12 h, but this effect seems to decrease with regular use. We evaluated the time-course of the protective effects of salmeterol on methacholine-induced bronchoconstriction, its modulation by inhaled corticosteroids (ICS) and its influence on asthma control. Thirty two subjects (13 males and 19 females) with mild to moderate stable asthma were divided into two groups according to their medication needs: bronchodilators (BD) alone (n=16) or with ICS (n=16). After a 2 week run-in period, a double-blind crossover study was conducted. Subjects from both groups received salmeterol 50 microg b.i.d. or a placebo for 4 weeks each in random order, separated by a 2 week washout period. The provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) was measured before and after each treatment period, 1 h prior to inhalation of salmeterol or placebo and 1 and 12 h after. Baseline forced expiratory volume in one second (FEV1) increased significantly after salmeterol, both after the first dose and at 4 weeks (BD group: 19 and 17%; ICS: 22 and 13%). On the first day of administration, salmeterol provided significant protection in both groups up to 12 h with a PC20 before and 1 and 12 h postdose of 2.2, 21.7 and 12.4, mg x mL(-1), respectively, in the BD group and 2.1, 11.6 and 55 mg x mL(-1), respectively, in the ICS group. After 4 weeks, this effect was significantly attenuated in both groups with a PC20 before, 1 and 12 h postdose of 3.3, 10.9 and 7.1 mg x mL(-1), respectively, in the BD group and 2.1, 5.0 and 2.3 mg x mL(-1), respectively, in the ICS group. This loss of protective effect was of similar magnitude in both groups. Respiratory symptoms, rescue beta2-agonist use and baseline FEV1 did not change significantly throughout the study in both groups. In conclusion, the bronchoprotective effect of salmeterol decreased with regular use both 1 and 12 h postdose; inhaled corticosteroids did not prevent this reduction. However, the development of tolerance was not associated with loss of asthma control.
Plumbagin, a Medicinal Plant–Derived Naphthoquinone, Is a Novel Inhibitor of the Growth and Invasion of Hormone-Refractory Prostate Cancer
Authors: Moammir H. Aziz, Nancy E. Dreckschmidt, Ajit K. Verma
Journal: Cancer Research (2008)

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Hormone-refractory invasive PCa is the end stage and accounts for the majority of PCa patient deaths. We present here that plumbagin (PL), a quinoid constituent isolated from the root of the medicinal plant Plumbago zeylanica L., may be a potential novel agent in the control of hormone-refractory PCa. Specific observations are the findings that PL inhibited PCa cell invasion and selectively induced apoptosis in PCa cells but not in immortalized nontumorigenic prostate epithelial RWPE-1 cells. In addition, i.p. administration of PL (2 mg/kg body weight), beginning 3 days after ectopic implantation of hormone-refractory DU145 PCa cells, delayed tumor growth by 3 weeks and reduced both tumor weight and volume by 90%. Discontinuation of PL treatment in PL-treated mice for as long as 4 weeks did not result in progression of tumor growth. PL, at concentrations as low as 5 μmol/L, inhibited in both cultured PCa cells and DU145 xenografts (a) the expression of protein kinase Cε (PKCε), phosphatidylinositol 3-kinase, phosphorylated AKT, phosphorylated Janus-activated kinase-2, and phosphorylated signal transducer and activator of transcription 3 (Stat3); (b) the DNA-binding activity of transcription factors activator protein-1, nuclear factor-κB, and Stat3; and (c) Bcl-xL, cdc25A, and cyclooxygenase-2 expression. The results indicate for the first time, using both in vitro and in vivo preclinical models, that PL inhibits the growth and invasion of PCa. PL inhibits multiple molecular targets including PKCε, a predictive biomarker of PCa aggressiveness. PL may be a novel agent for therapy of hormone-refractory PCa. [Cancer Res 2008;68(21):9024–32]
DRUG-ELUTING BIORESORBABLE STENTS FOR VARIOUS APPLICATIONS
Authors: Meital Zilberman, Robert C. Eberhart
Journal: Annual Review of Biomedical Engineering (2006)

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. Metallic coronary stents were first introduced to prevent arterial dissections and to eliminate vessel recoil and intimal hyperplasia associated with percutaneous transluminal coronary angioplasty. The stent application range has expanded as more experience was gained, and encouraging results have been obtained in the treatment of vascular diseases. Stents are currently used for support of additional body conduits, including the urethra, trachea, and esophagus. The rationale for bioresorbable stents is the support of a body conduit only during its healing process. The stent mass and strength decrease with time, and the mechanical load is gradually transferred to the surrounding tissue. Bioresorbable stents also enable longer term delivery of drugs to the conduit wall from an internal reservoir and abolish the need for a second surgery to remove the device. The present review describes recent advances in bioresorbable stents, focusing on drug-eluting bioresorbable stents for various applications. Controlled release of an active agent from a stent can be used to enhance healing of the surrounding tissues, to increase the implant's biocompatibility, as well as to help cure certain diseases. Because a lot of research in this field has been done by us, examples for these functions are described based mainly on developments in our laboratories.
Association between atopic sensitization and asthma and bronchial hyperresponsiveness in Swedish adults: Pets, and not mites, are the most important allergens☆☆☆★
Authors: Peter Plaschke, Christer Janson, Eva Norrman, Eythor Björnsson, Susanne Ellbjär, Bengt Järvholm
Journal: Journal of Allergy and Clinical Immunology (1999)