tbuckley/cabot-search huggingface dataset:
THE EFFECT OF LOCALISED AND GLOBALISED FATIGUE ON MUSCLE LATENCY IN HEALTHY AND FUNCTIONALLY UNSTABLE PARTICIPANTS FOLLOWING A SIMULATED ANKLE SPRAIN
Authors: C Gautrey, T Watson, A Mitchell
Journal: British Journal of Sports Medicine (2014)

Background Anecdotally, most injuries occur during the final third of the second half of a soccer match when fatigue is present. To our knowledge, no studies have evaluated muscular latency times to a simulated ankle sprain mechanism before and immediately after localised and globalised fatigue. Objective To determine whether functional ankle instability (FAI) participants suffer from a neuromuscular deficit compared to healthy controls, as measured by muscle latency following localised and globalised fatigue. Design Non-randomised experimental. Setting University biomechanics laboratory. Participants played at a semi-professional level of soccer. Participants A convenience sample was used to recruit twenty males with unilateral FAI and twenty male healthy controls. Inclusion criteria included males, aged 18–25 years, who participated in semi-professional soccer and who were right leg dominant. Risk factor assessment Two localised fatigue protocols were investigated; isokinetic ankle inversion-eversion exercise and hip abduction-adduction exercise. Maximal repetitions were performed until three consecutive repetitions fell below 50% of participants 1RM. The soccer specific Drust protocol was used to elicit globalised fatigue. Three perturbations on a standing tilt platform simulating the mechanics of an inversion and plantar-flexion ankle sprain were performed before and after fatigue. Subject group and fatigue protocols were the independent variables. Main outcome measure Muscle latency in milliseconds of the peroneus longus, tibialis anterior and gluteus medius to the tilt platform perturbation, before and after localised and globalised fatigue. Results All fatigue conditions when compared to the pre-test showed no significant difference in muscle latency for all muscles tested, in both groups. Conclusion It has been suggested that injuries occur during the latter stages of soccer when fatigue is present. The present study found that localised and globalised fatigue did not lead to increased muscle latencies, and therefore, other factors must be present that lead to this increased injury rate.
Physical activity mediates a healthier body weight in the presence of obesity
Authors: Linda S Pescatello, Jaci L VanHeest
Journal: British Journal of Sports Medicine (2000)

FF is an inhaled corticosteroid (ICS) with higher glucocorticoid receptor affinity, tissue permeability and lung retention than other ICS. We investigated whether these attributes improve the therapeutic index (TI), defined as systemic activity to topical efficacy ratio. In this escalating dose, randomised, incomplete-block, 2-period cross-over study (GSK study 203162, NCT02991859), 54 asthmatic subjects were randomised to one or two of four treatment periods. Each period comprised five dose escalations (µg/d) of 7-days duration: FF (25,100,200,400,800), FP (50, 200,500,1000,2000), BUD (100,400,800,1600,3200) or placebo, with a ≥25-day washout between periods. At the end of each escalation, 12h post-dose adenosine-5’-monophosphate (AMP) challenge PC<sub>20</sub> and 24h plasma cortisol were assessed. Both endpoints showed a dose response (Figure&nbsp;1). The ED<sub>50</sub> µg/d (95% CI) values were: 49 (18,129), 1081 (448,2610), and 1467 (547,3940) for AMP PC<sub>20</sub> and 900 (698,1102), 1986 (1575,2397) and 1927 (1699,2156) for 24h plasma cortisol and TI values (ED<sub>50</sub> 24h cortisol/ED<sub>50</sub> AMP PC<sub>20</sub>) were 18.6, 1.84 and 1.31 for FF, FP and BUD respectively. No on treatment SAEs were reported. Within the approved dose ranges for asthma, FF gave more protection against airway hyperresponsiveness with less systemic activity compared to FP and BUD.
Anemia in chronic respiratory failure
Authors: Florian Kollert, Carolin Müller, Andrea Tippelt, Rudolf A. Joerres, Dominik Heidinger, Corina Probst, Michael Pfeifer, Stephan Budweiser
Journal: European Respiratory Journal (2011)

Background:  In patients with severe chronic obstructive pulmonary disease (COPD), anaemia is common and associated with impaired long-term survival and quality of life. Whether anaemia is also prevalent in patients with other severe, non-inflammatory respiratory diseases has not yet been systematically tested.   Methods:  In 595 patients with obstructive (OD, 54.8%) or restrictive disease (RD, 45.2%) and chronic respiratory failure (CRF), anthropometric data, laboratory parameters, lung function, blood gases and co-morbidities were assessed prior to initiation of home mechanical ventilation. Patients were classified as anaemic based on haemoglobin (Hb) levels (Hb    Results:  In patients with CRF the prevalence of anaemia was 13.3% and not different between RD (11.5%) and OD (14.7%) (p=0.276). A sex-related difference occurred only in OD (7.9% (f) versus 17.3% (m); p=0.035). Patients with OD and anaemia presented with higher age (p=0.003), pH (p=0.014) and arterial oxygen pressure (PaO 2 ) (p=0.012), lower body-mass index (BMI) (p=0.011) and total protein (p=0.012), and higher rates of coronary heart disease (p=0.01), cardiac arrhythmia (p=0.014) and diabetes mellitus (p=0.003) in comparison to non-anaemic patients. In patients with RD anaemia was associated with higher age, (p=0.008), pH (p=0.011) and lower leucocytes numbers (p=0.006).   Conclusions:  Anaemia is frequent not only in COPD but also in other severe respiratory diseases combined with CRF. It was associated with advanced age, several co-morbidities, impaired nutritional state and elevations of pH and PaO 2 , probably due to hyperventilation. Its prognostic impact has to be elucidated in future studies.
Epidemiology of Invasive Group B Streptococcal Disease in the United States, 1999-2005
Authors: Christina R Phares, Ruth Lynfield, Monica M Farley, Janet Mohle-Boetani, Lee H Harrison, Susan Petit, Allen S Craig, William Schaffner, Shelley M Zansky, Ken Gershman, Karen R Stefonek, Bernadette A Albanese, Elizabeth R Zell, Anne Schuchat, Stephanie J Schrag
Journal: JAMA (2008)

3][4] Two recommended approaches for identifying chemoprophylaxis candidates were widely adopted in the United States and resulted in substantial declines in disease in infants younger than 7 days (also known as early onset disease). 5,6n 2002, revised guidelines recommended antenatal culture-based screening as the optimal method for identifying chemoprophylaxis candidates. 7sease trends following the release of these guidelines have not yet been well studied.In addition to illness in the first week of life, group B streptococcus also causes invasive disease in older infants, pregnant women, children and young adults with underlying medical conditions, and older adults.Cases outside the perinatal risk period account for nearly 90% of the national burden of disease, 8 and the proportion of patients who die in these age groups, particularly the elderly, are higher than for
Which ultrasound method has the upper hand in the follow-up of the patients with recurrent carpal tunnel syndrome?
Authors: Antonios Kerasnoudis
Journal: Annals of the Rheumatic Diseases (2013)

I read with great interest the study of different diagnostic ultrasound measures of median nerve volume in patients with carpal tunnel syndrome (CTS) by Dejaco et al. 1 It is of great value, in my opinion, that this study succeeded in highlighting the diagnostic value and good reliability of ultrasound determination of median nerve cross-sectional area (CSA) in patients with suspected CTS, and confirmed previously reported results on the value of Doppler ultrasonography in classifying the severity of CTS.2–4

I would like though to draw attention to a subgroup of patients with persistent clinical and electrophysiological signs of CTS and condition after unsuccessful carpal tunnel release (CTR). The aetiology of the persistent neurological semiology is in most of the cases an incomplete release of the retinaculum flexorum. Traction neuropathy, …
Placebo-Controlled Trial of Sertraline in the Treatment of Children With Generalized Anxiety Disorder
Authors: Moira A. Rynn, Lynne Siqueland, Karl Rickels
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The study compared the safety and efficacy of sertraline, a selective serotonin reuptake inhibitor, and placebo in the treatment of generalized anxiety disorder in children and adolescents. METHOD: The study subjects were 22 children and adolescents age 5–17 years who met the DSM-IV criteria for generalized anxiety disorder according to the Anxiety Disorders Interview Schedule for Children—Revised and who had a Hamilton Anxiety Rating Scale score ≥16. The patients underwent a 2–3-week prestudy evaluation period, followed by a 9-week double-blind treatment phase in which they were randomly assigned in blocks of four to receive either sertraline or pill placebo. The maximum dose of sertraline was 50 mg/day. Primary outcome measures were the Hamilton anxiety scale and the Clinical Global Impression scale. RESULTS: The Hamilton anxiety scale total score, psychic factor, and somatic factor and the Clinical Global Impression severity and improvement scales showed significant differences with treatment in favor of sertraline over placebo beginning at week 4. Self-report measures reflected these results at the end of treatment. CONCLUSIONS: The results of this double-blind, placebo-controlled trial suggest that sertraline at the daily dose of 50 mg is safe and efficacious for the treatment of generalized anxiety disorder in children and adolescents.
Loss of α-hemoglobin–stabilizing protein impairs erythropoiesis and exacerbates β-thalassemia
Authors: Yi Kong, Suiping Zhou, Anthony J. Kihm, Anne M. Katein, Xiang Yu, David A. Gell, Joel P. Mackay, Kazuhiko Adachi, Linda Foster-Brown, Calvert S. Louden, Andrew J. Gow, Mitchell J. Weiss
Journal: Journal of Clinical Investigation (2004)

Hemoglobin (Hb) A production during red blood cell development is coordinated to minimize the deleterious effects of free alpha- and beta-Hb subunits, which are unstable and cytotoxic. The alpha-Hb-stabilizing protein (AHSP) is an erythroid protein that specifically binds alpha-Hb and prevents its precipitation in vitro, which suggests that it may function to limit free alpha-Hb toxicities in vivo. We investigated this possibility through gene ablation and biochemical studies. AHSP(-/-) erythrocytes contained hemoglobin precipitates and were short-lived. In hematopoietic tissues, erythroid precursors were elevated in number but exhibited increased apoptosis. Consistent with unstable alpha-Hb, AHSP(-/-) erythrocytes contained increased ROS and evidence of oxidative damage. Moreover, purified recombinant AHSP inhibited ROS production by alpha-Hb in solution. Finally, loss of AHSP worsened the phenotype of beta-thalassemia, a common inherited anemia characterized by excess free alpha-Hb. Together, the data support a model in which AHSP binds alpha-Hb transiently to stabilize its conformation and render it biochemically inert prior to Hb A assembly. This function is essential for normal erythropoiesis and, to a greater extent, in beta-thalassemia. Our findings raise the possibility that altered AHSP expression levels could modulate the severity of beta-thalassemia in humans.
Lumen narrowing after percutaneous transluminal coronary balloon angioplasty follows a near gaussian distribution: A quantitative angiographic study in 1,445 successfully dilated lesions
Authors: Benno J. Rensing, Walter R.M. Hermans, Jaap W. Deckers, Pim J. de Feyter, Jan G.P. Tijssen, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (1992)
Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis
Authors: G Rolla
Journal: Hepatology (1997)

Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo2) to hypoxemia, is commonly present in patients with cirrhosis. Nitric oxide (NO), through pulmonary vasodilatation, may play a major role in the oxygen abnormalities of cirrhosis. Our aim was to study the relationship between NO production and O2 abnormalities in 45 nonsmoking patients with cirrhosis and without major cardiovascular and respiratory diseases. Intrapulmonary shunting was detected by contrast-enhanced (CE) echocardiography. Lung volumes and diffusion, arterial blood gas analysis, serum NO2-/NO3-, NO output in the exhaled air, and cardiac index by the echocardiographic method were determined in all patients. Twenty-seven (60%) patients had an abnormally increased (> 15 mm Hg) AaDo2. The mean values of exhaled NO output and serum NO2-/NO3- were significantly higher in cirrhotic patients than in controls (252 +/- 117 vs. 75.2 +/- 19 nL/min/m2, P < .0001; and 47.5 +/- 29.4 vs. 32.9 +/- 10.1 micromol/L, P < .02, respectively). In all patients, there was a significant correlation between exhaled NO and AaDo2 (r = .78, P < .0001). Twelve patients (26.6%) were found to have CE-echocardiographic evidence of intrapulmonary shunting (positive CE-echo). Nine patients were considered to have hepatopulmonary syndrome (HPS) on the basis of an AaDo2 > 15 mm Hg and positive CE-echo. These 9 patients had a mean value of exhaled NO significantly higher than patients without HPS (331 +/- 73.2 vs. 223 +/- 118.4 nL/min/m2, P < .05). In all patients, cardiac index was positively correlated with exhaled NO (r = .47, P < .001) and with serum NO2-/NO3- (r = .43, P < .01). The results suggest an important role of NO in the oxygenation and circulatory abnormalities of patients with cirrhosis.
β-Tubulin Mutations Are Associated with Resistance to 2-Methoxyestradiol in MDA-MB-435 Cancer Cells
Authors: Yesim Gökmen-Polar, Daniel Escuin, Chad D. Walls, Sharon E. Soule, Yuefang Wang, Kerry L. Sanders, Theresa M. LaVallee, Mu Wang, Brian D. Guenther, Paraskevi Giannakakou, George W. Sledge
Journal: Cancer Research (2005)

Abstract 2-Methoxyestradiol is an estradiol metabolite with significant antiproliferative and antiangiogenic activity independent of estrogen receptor status. To identify a molecular basis for acquired 2-methoxyestradiol resistance, we generated a stable 2-methoxyestradiol-resistant (2ME2R) MDA-MB-435 human cancer cell line by stepwise exposure to increasing 2-methoxyestradiol concentrations. 2ME2R cells maintained in the presence of the drug and W435 cells maintained in the absence of the drug showed 32.34- to 40.07-fold resistance to 2-methoxyestradiol. Cross-resistance was observed to Vinca alkaloids, including vincristine, vinorelbine, and vinblastine (4.29- to 6.40-fold), but minimal resistance was seen to colchicine-binding agents including colchicine, colcemid, and AVE8062A (1.72- to 2.86-fold). No resistance was observed to paclitaxel and epothilone B, polymerizing agents (0.89- to 1.14-fold). Genomic sequencing identified two different heterozygous point mutations in the class I (M40) isotype of β-tubulin at amino acids 197 (Dβ197N) and 350 (Kβ350N) in 2ME2R cells. Tandem mass spectrometry confirmed the presence of both wild-type and the mutant β-tubulin in 2ME2R cells at the protein level. Consistently, treatment of parental P435 cells with 2-methoxyestradiol resulted in a dose-dependent depolymerization of microtubules, whereas 2ME2R cells remained unaffected. In contrast, paclitaxel affected both cell lines. In the absence of 2-methoxyestradiol, 2ME2R cells were characterized by an elevated level of detyrosination. Upon 2-methoxyestradiol treatment, levels of acetylated and detyrosinated tubulins decreased in P435 cells, while remaining constant in 2ME2R cells. These results, together with our structure-based modeling, show a tight correlation between the antitubulin and antiproliferative effects of 2-methoxyestradiol, consistent with acquired tubulin mutations contributing to 2-methoxyestradiol resistance.
Sexual Misconduct in the Practice of Medicine
Authors: Richard J. McMurray
Journal: JAMA (1991)

The American Medical Association's Council on Ethical and Judicial Affairs recently reviewed the ethical implications of sexual or romantic relationships between physicians and patients. The Council has concluded that (1) sexual contact or a romantic relationship concurrent with the physician-patient relationship is unethical; (2) sexual contact or a romantic relationship with a former patient may be unethical under certain circumstances; (3) education on the ethical issues involved in sexual misconduct should be included throughout all levels of medical training; and (4) in the case of sexual misconduct, reporting offending colleagues is especially important. (<i>JAMA</i>. 1991;266:2741-2745)
Cu, Zn-superoxide dismutase 1 (SOD1) is a novel target of Puromycin-sensitive aminopeptidase (PSA/NPEPPS): PSA/NPEPPS is a possible modifier of amyotrophic lateral sclerosis
Authors: Guijie Ren, Zhongcai Ma, Maria Hui, Lili C Kudo, Koon-Sea Hui, Stanislav L Karsten
Journal: Molecular Neurodegeneration (2011)

Accumulation of misfolded neurotoxic Cu, Zn-superoxide dismutase-1 (SOD1) protein found in both familial and sporadic amyotrophic lateral sclerosis (ALS) is recognized as an important contributing factor of neuronal cell death. However, little is known about the mechanisms controlling the accumulation and turnover of SOD1 protein. Puromycin-sensitive aminopeptidase (PSA/NPEPPS) was recently identified as a major peptidase acting on neurotoxic TAU protein and protecting against TAU-induced neurodegeneration. In addition, recent report implicated PSA/NPEPPS in the direct removal of neurotoxic polyglutamine repeats. These combined data suggest that PSA/NPEPPS might represent a novel degradation pathway targeting pathologically aggregating neurotoxic protein substrates including SOD1. Here, we report that PSA/NPEPPS directly regulates SOD1 protein abundance and clearance via proteolysis. In addition, PSA/NPEPPS expression is significantly decreased in motor neurons of both SODG93A transgenic mice and sporadic ALS patients, suggesting its possible contribution to the disease pathogenesis. These results implicate SOD1 as a new target protein of PSA/NPEPPS and point to the possible neuroprotective role of PSA/NPEPPS in ALS.
Role of Mitochondrial Na+ Concentration, Measured by CoroNa Red, in the Protection of Metabolically Inhibited MDCK Cells
Authors: Szilvia Baron, Adrian Caplanusi, Martin van de Ven, Mihai Radu, Sanda Despa, Ivo Lambrichts, Marcel Ameloot, Paul Steels, Ilse Smets
Journal: Journal of the American Society of Nephrology (2005)

In ischemic or hypoxic tissues, elevated cytosolic calcium levels can induce lethal processes. Mitochondria, besides the endoplasmic reticulum, play a key role in clearing excessive cytosolic Ca2+. In a previous study, it was suggested that the clearance of cytosolic Ca2+, after approximately 18 min of metabolic inhibition (MI) in renal epithelial cells, occurs via the reverse action of the mitochondrial Na+/Ca2+ exchanger (NCX). For further investigating the underlying mechanism, changes in the mitochondrial Na+ concentration ([Na+](m)) were monitored in metabolically inhibited MDCK cells. CoroNa Red, a sodium-sensitive fluorescence probe, was used to monitor [Na+]m. In the first 15 min of MI, a twofold increase of [Na+]m was observed reaching 113 +/- 7 mM, whereas the cytosolic Na+ concentration ([Na+]c) elevated threefold, to a level of 65 +/- 6 mM. In the next 45 min of MI, [Na+]m dropped to 91 +/- 7 mM, whereas [Na+]c further increased to 91 +/- 4 mM. The striking rise in [Na+]m is likely sufficient to sustain the driving force for mitochondrial Ca2+ uptake via the NCX. Furthermore, when CGP-37157, a specific inhibitor of the mitochondrial NCX, was applied during MI, the second-phase drop of [Na+]m was completely abolished. The obtained results support the hypothesis that the mitochondrial NCX reverses after approximately 15 min of MI. Moreover, because the cellular homeostasis can recover after MI, the mitochondria likely protect MDCK cells from injury during MI by the reversal of the mitochondrial NCX. This study is the first to report [Na+]m measurements in nonpermeabilized living cells.
Home assessment of activities of daily living in patients with severe chronic obstructive pulmonary disease on long-term oxygen therapy
Authors: AA Okubadejo, L O'Shea, PW Jones, JA Wedzicha
Journal: European Respiratory Journal (1997)

In patients with severe chronic obstructive pulmonary disease (COPD) using long-term oxygen therapy (LTOT), few studies have investigated activities of daily living (ADL). We examined the relationships between ADL, quality of life, mood state and airways obstruction in patients using long-term oxygen therapy (LTOT) and in patients not requiring LTOT. We studied 23 patients (14 males, 9 females; median age 71, range 60-84 yrs) with COPD who received LTOT using oxygen concentrators (LTOT group). We also studied a control group of 19 patients (14 males, 5 females; median age 72, range 62-75 yrs) with COPD but without severe hypoxaemia (non-LTOT group). We found no significant difference between groups in health status using the St George's Respiratory Questionnaire (SGRQ). Median Nottingham Extended Activities of Daily Living (EADL) total scores were: LTOT group 10, non-LTOT 17; (p=0.01). Significant correlations (p&lt;0.001) with Nottingham EADL score were found for Hospital Anxiety and Depression (HAD) score (rho=0.59), SGRQ Total score (rho=0.65) and percentage predicted forced expiratory volume in one second (FEV1) (rho=0.66). In conclusion, in patients with severe chronic obstructive pulmonary disease and broadly similar health status, those using long-term oxygen therapy were less independent in activities of daily living than those not requiring long-term oxygen therapy. Reduced independence in activities of daily living is, however, associated with the extent of airflow limitation, depression and poor health status, and does not, therefore, appear to be simply a result of restriction in movements imposed by the stationary device.