tbuckley/cabot-search huggingface dataset:
The use of local anaesthetic injections in professional football
Authors: J Orchard
Journal: British Journal of Sports Medicine (2001)

Local anaesthetic use in professional football is one of the greatest taboos in sports medicine. The subject is not covered comprehensively in any sports medicine textbook or review article. Most of the publications citing local anaesthetic use are legal cases from the National Football League (NFL) in which the procedure has been connected with a career ending injury.1, 2 There are some candid accounts of how commonplace local anaesthetic use is in the NFL,3, 4 and anecdotal evidence suggests that the situation is no different in professional football competitions elsewhere in the world. This includes professional rugby union, in which the practice is officially banned. I have previously published my personal statistics of local anaesthetic injections over a four year period with a professional Australian football team,5, 6 but cannot find any similar documentation from other doctors in the sports medicine literature. The attitude of most professional football doctors may be that this practice is a necessary evil that can be performed on certain occasions, but not mentioned or justified in public.

I contend that we end this hypocrisy. Either sports physicians should cease using local anaesthetics in professional football and recommend that the practice be universally banned, or we should study the procedure, speak and write freely about it, and produce guidelines for its rational use.

The effects of officially banning local anaesthetic use, as the International Rugby Board has done, would include an increase in injury prevalence, which is measured by players missing games. This is because players who could take the field with a painkilling injection would be forced onto the sidelines by team physicians adhering to the law. Anecdotal evidence is that the ban in rugby union has not eliminated the practice from occurring altogether. Most of the desire to …
Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice
Authors: S. Tajima, M. Bando, Y. Ishii, T. Hosono, H. Yamasawa, S. Ohno, T. Takada, E. Suzuki, F. Gejyo, Y. Sugiyama
Journal: European Respiratory Journal (2008)

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg x kg(-1) of BLM. Edaravone (300 mg x kg(-1)) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E(2) concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E(2) production in the present experimental murine system.
Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine
Authors: Anthony Rongvaux, Hitoshi Takizawa, Till Strowig, Tim Willinger, Elizabeth E. Eynon, Richard A. Flavell, Markus G. Manz
Journal: Annual Review of Immunology (2013)

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies.
Analysis of histopathological manifestations of chronic hepatitis C virus infection with respect to virus genotype
Authors: S Mihm, A Fayyazi, H Hartmann, G Ramadori
Journal: Hepatology (1997)

Hepatitis C virus (HCV) causes acute and often chronic hepatitis. On the basis of variations in nucleotide sequence, at least six genotypes and several subtypes have been identified. Histopathologically, chronic HCV infection is characterized by relatively mild hepatic inflammatory activity and a low degree of fibrosis, but hepatic lesions might be accompanied by bile duct damage, intraportal lymphoid aggregates, steatosis, or a combination of these manifestations. The histopathological lesions thus appear quite heterogeneous. To address the question of whether distinct histopathological manifestations are related to particular genotypes of HCV, 90 patients with chronic HCV infection were analyzed regarding histopathological features, biochemical liver parameters, demographic data, and virus genotype. The results revealed a significantly higher prevalence of both steatosis and bile duct lesions among patients infected by HCV type 3a compared to patients infected by types 1a or 1b. Furthermore, the data suggest interrelationships between virus genotype, patient's age, and a history of intravenous drug abuse. However, none of the histopathological manifestations were found to be related to a history of drug abuse. The data further corroborate the relationship of HCV type 1b infection to age, duration of disease, and the degree of fibrosis, respectively. Irrespective of HCV genotype, elevated serum ALT activity was shown to be associated with pronounced inflammatory activity or pronounced steatosis as well. Thus, the current data support the hypothesis that distinct genotypes of HCV appear to be associated with distinct manifestations of disease.
The rise in carboxyhemoglobin and methemoglobin concentration from repeated five second breath-hold maneuvers
Authors: Gerald Zavorsky, Allison Straub, Kaleen Lavin, Kathleen Uhranowsky
Journal: European Respiratory Journal (2012)

The measurement of pulmonary diffusing capacity for carbon monoxide (DLCO) raises the carboxyhemoglobin concentration in the blood, \[COHb]. The standard 10 s breath-hold technique increases [COHb] by about 0.7% per test, which results in a 1% decrease in DLCO for every 1% rise in [COHb\] (Respir Physiol, 1990, 81: 303-12). However, few data exist on the rate of increase in [COHb] or methemoglobin [METHb] from the modified Roughton and Forster one-step technique in which 0.28% CO and 40 to 50 ppm NO is inhaled simultaneously for 5 s. The combination of CO and NO inhaled together allows for determination of pulmonary capillary blood volume in a single breath-hold maneuver. Nine healthy subjects [24 (SD 4) yrs, hemoglobin concentration 13.2 (1.7) g/dL] performed repeated DLCO testing on two separate days. The days were randomized to provide either the standard 10 s breath-hold maneuver (0.30% CO), or the 5 s modified Roughton and Forster technique (0.28% CO, 55 ppm NO). Twenty-two 5 s breath-hold maneuvers, each separated by 4 min rest raised [COHb] to 11.1 (1.4)% and minimally raised the [METHb] to 0.8 (0.2)%. After the 22nd test, DLCO was reduced by 3.6 (2.9) mL/min/mmHg. This equates to a 0.44 (SEE 0.08)% increase in [COHb] per 5 s breath-hold maneuver and a concomitant 0.35 (SEE 0.31)% decrease in DLCO. Pulmonary diffusing capacity for nitric oxide (DLNO) was not altered after 22 tests. On another day, the 10 s single breath-hold maneuver increased [COHb] by 0.64 (SEE 0.13)% per test, and reduced DLCO by 0.40 (SEE 0.26)% per test. In conclusion, the 5 s modified one-step technique does not appreciably raise [METHb], and DLCO is only significantly reduced after 10 tests.
Small nucleolar RNA 113–1 suppresses tumorigenesis in hepatocellular carcinoma
Authors: Gang Xu, Fang Yang, Cui-Ling Ding, Lan-Juan Zhao, Hao Ren, Ping Zhao, Wen Wang, Zhong-Tian Qi
Journal: Molecular Cancer (2014)

Emerging evidence suggests that small nucleolar RNAs (snoRNAs) are involved in tumorigenesis. The roles of small nucleolar RNA 113-1 (SNORD113-1) on the development of hepatocellular carcinoma (HCC) remain unknown.The expression of SNORD113-1 was measured in 112 HCC tumor tissues using quantitative RT-PCR and compared with expression levels from with paired non-tumor tissues. The effects of SNORD113-1 on HCC tumorigenesis were investigated in HepG2 and Huh7 cells as well as a xenograft nude mouse model. CpG methylation within the promoter region of the SNORD113-1 gene was identified using Sodium bisulfite sequencing. Cancer pathway reporter investigate the mechanism by which SNORD113-1 suppressed tumorigenesis.SNORD113-1 expression was significantly downregulated in HCC tumors compared with adjacent non-tumor tissues, and downregulation of SNORD113-1 in HCC tumors was significantly associated with worse survival of patients. In addition, CpG methylation at the promoter region of the SNORD113-1 gene was higher in HCC tumors than adjacent non-tumor tissues. Functionally, SNORD113-1 suppressed cancer cell growth in HepG2 and Huh7 cells and in a xenograft nude mouse model. Furthermore, SNORD113-1 inactivated the phosphorylation of ERK1/2 and SMAD2/3 in MAPK/ERK and TGF-β pathways.SNORD113-1 functions as a tumor suppressor role in HCC and may be important as a potential diagnostic and therapeutic target for HCC.
The Transient Receptor Potential Protein Homologue TRP6 Is the Essential Component of Vascular α <sub>1</sub> -Adrenoceptor–Activated Ca <sup>2+</sup> -Permeable Cation Channel
Authors: Ryuji Inoue, Takaharu Okada, Hitoshi Onoue, Yuji Hara, Shunichi Shimizu, Shinji Naitoh, Yushi Ito, Yasuo Mori
Journal: Circulation Research (2001)

The Drosophila transient receptor potential protein (TRP) and its mammalian homologues are thought to be Ca(2+)-permeable cation channels activated by G protein (G(q/11))-coupled receptors and are regarded as an interesting molecular model for the Ca(2+) entry mechanisms associated with stimulated phosphoinositide turnover and store depletion. However, there is little unequivocal evidence linking mammalian TRPs with particular native functions. In this study, we have found that heterologous expression of murine TRP6 in HEK293 cells reproduces almost exactly the essential biophysical and pharmacological properties of alpha(1)-adrenoceptor-activated nonselective cation channels (alpha(1)-AR-NSCC) previously identified in rabbit portal vein smooth muscle. Such properties include activation by diacylglycerol; S-shaped current-voltage relationship; high divalent cation permeability; unitary conductance of 25 to 30 pS and augmentation by flufenamate and Ca(2+); and blockade by Cd(2+), La(3+), Gd(3+), SK&F96365, and amiloride. Reverse transcriptase-polymerase chain reaction and confocal laser scanning microscopy using TRP6-specific primers and antisera revealed that the level of TRP6 mRNA expression was remarkably high in both murine and rabbit portal vein smooth muscles as compared with other TRP subtypes, and the immunoreactivity to TRP6 protein was localized near the sarcolemmal region of single rabbit portal vein myocytes. Furthermore, treatment of primary cultured portal vein myocytes with TRP6 antisense oligonucleotides resulted in marked inhibition of TRP6 protein immunoreactivity as well as selective suppression of alpha(1)-adrenoceptor-activated, store depletion-independent cation current and Ba(2+) influx. These results strongly indicate that TRP6 is the essential component of the alpha(1)-AR-NSCC, which may serve as a store depletion-independent Ca(2+) entry pathway during increased sympathetic activity.
Pathfinding of Corticothalamic Axons Relies on a Rendezvous with Thalamic Projections
Authors: Marie Deck, Ludmilla Lokmane, Sophie Chauvet, Caroline Mailhes, Maryama Keita, Mathieu Niquille, Michio Yoshida, Yutaka Yoshida, Cécile Lebrand, Fanny Mann, Elizabeth A. Grove, Sonia Garel
Journal: Neuron (2013)
Can We Prevent, Delay, or Shorten the Course of Dementia?
Authors: Willem A Van Gool
Journal: PLoS Medicine (2006)

“You already know how it ends when you are born”, my mother said in sorrow after my father died. And she is not even medically qualified. Should we extend this common wisdom on the realities of old age towards the development of dementia? In other words, is dementia a curse that is inescapably linked to old age?
Molecular Clock Mechanisms and Circadian Rhythms Intrinsic to the Heart
Authors: Michael A. Portman
Journal: Circulation Research (2001)

ircadian rhythms are the external expression of an internal clock mechanism that measures daily time. 1 Periodic environmental cues entrain or set the circadian clocks.The daily light-dark cycle represents the most dominant and potent entraining stimulus in mammals.An entrained clock coordinates physiological events to the 24hour day.Normally, cardiovascular or hemodynamic parameters, such as heart rate and blood pressure, exhibit variations
Renal sodium and water handling in hypothyroid patients
Authors: M Allon, A Harrow, C B Pasque, M Rodriguez
Journal: Journal of the American Society of Nephrology (1990)

The mechanism responsible for renal tubular abnormalities in sodium and water excretion in hypothyroid patients is poorly understood. To evaluate the possible contribution of the reduced glomerular filtration rate of hypothyroidism to these abnormalities, tubular function in hypothyroid patients was compared with that in patients with chronic renal failure and in normal subjects. The lithium clearance method and oral water loading were used to evaluate parameters of tubular sodium and water handling, respectively. The hypothyroid and the chronic renal failure patients were selected to have similar reductions in glomerular filtration rate. As compared to the normal subjects, the hypothyroid and chronic renal failure patients had a decrease in proximal sodium reabsorption and an increase in distal sodium reabsorption. The changes in tubular handling of sodium were not different in the hypothyroid and the chronic renal failure patients. Maximal urinary flow rate and free water clearances were similarly reduced in the hypothyroid patients and the chronic renal failure patients. For all subjects studied, proximal sodium reabsorption and maximal urinary volume were directly correlated with the glomerular filtration rate, and distal nephron sodium reabsorption was proportionate to delivery of sodium from the proximal tubule. The results suggest that the abnormalities in tubular sodium and water handling in hypothyroid patients are comparable to those present in other patients with a similar degree of renal insufficiency. Thus, the tubular abnormalities in hypothyroidism may be a consequence of the associated decrease in glomerular filtration rate.
Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial
Authors: Paul P Tak, Andra Balanescu, Vira Tseluyko, Silvia Bojin, Edit Drescher, Dan Dairaghi, Shichang Miao, Vittorio Marchesin, Juan Jaen, Thomas J Schall, Pirow Bekker
Journal: Annals of the Rheumatic Diseases (2012)

CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA).CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score-CRP, individual ACR components, as well as soluble bone turnover markers.CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits.CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.
Prospective Evaluation of Point-of-Care Ultrasonography for the Diagnosis of Pneumonia in Children and Young Adults
Authors: Vaishali P Shah, Michael G Tunik, James W Tsung
Journal: JAMA Pediatrics (2012)

<h3>Objective</h3>To determine the accuracy of point-of-care ultrasonography for the diagnosis of pneumonia in children and young adults by a group of clinicians.<h3>Design</h3>Prospective observational cohort study.<h3>Setting</h3>Two urban emergency departments.<h3>Participants</h3>Patients from birth to age 21 years undergoing chest radiography for suspected community-acquired pneumonia.<h3>Intervention</h3>After documenting clinical examination findings, clinicians with 1 hour of focused training used ultrasonography to diagnose pneumonia in children and young adults.<h3>Main Outcomes Measures</h3>Test performance characteristics for the ability of ultrasonography to diagnose pneumonia were determined using chest radiography as a reference standard. Subgroup analysis was performed in patients having lung consolidation exceeding 1 cm with sonographic air bronchograms detected on ultrasonography; specificity and positive likelihood ratio (LR) were calculated to account for lung consolidation of 1 cm or less with sonographic air bronchograms undetectable by chest radiography.<h3>Results</h3>Two hundred patients were studied (median age, 3 years; interquartile range, 1-8 years); 56.0% were male, and the prevalence of pneumonia by chest radiography was 18.0%. Ultrasonography had an overall sensitivity of 86% (95% CI, 71%-94%), specificity of 89% (95% CI, 83%-93%), positive LR of 7.8 (95% CI, 5.0-12.4), and negative LR of 0.2 (95% CI, 0.1-0.4) for diagnosing pneumonia by visualizing lung consolidation with sonographic air bronchograms. In subgroup analysis of 187 patients having lung consolidation exceeding 1 cm, ultrasonography had a sensitivity of 86% (95% CI, 71%-94%), specificity of 97% (95% CI, 93%-99%), positive LR of 28.2 (95% CI, 11.8-67.6) and negative LR of 0.1 (95% CI, 0.1-0.3) for diagnosing pneumonia.<h3>Conclusion</h3>Clinicians are able to diagnose pneumonia in children and young adults using point-of-care ultrasonography, with high specificity.
Effect of Long-Detection Interval vs Standard-Detection Interval for Implantable Cardioverter-Defibrillators on Antitachycardia Pacing and Shock Delivery
Authors: Maurizio Gasparini, Alessandro Proclemer, Catherine Klersy, Axel Kloppe, Maurizio Lunati, José Bautista Martìnez Ferrer, Ahmad Hersi, Marcin Gulaj, Maurits C. E. F. Wijfels, Elisabetta Santi, Laura Manotta, Angel Arenal
Journal: JAMA (2013)

Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary implantable cardioverter-defibrillator (ICD) therapies.To determine whether using 30 of 40 intervals to detect ventricular arrhythmias (VT) (long detection) during spontaneous fast VT episodes reduces antitachycardia pacing (ATP) and shock delivery more than 18 of 24 intervals (standard detection).Randomized, single-blind, parallel-group trial that enrolled 1902 primary and secondary prevention patients (mean [SD] age, 65 [11] years; 84% men; 75% primary prevention ICD) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers (March 2008-December 2010).Patients were randomized 1:1 to programming with long- (n = 948) or standard-detection (n = 954) intervals.Total number of ATPs and shocks delivered for all episodes (primary outcomes) and inappropriate shocks, mortality, and syncopal rate (secondary outcomes).During a median follow-up of 12 months (interquartile range, 11-13), long-detection group had 346 delivered therapies (42 therapies per 100 person-years, 95% CI, 38-47) vs 557 in the standard-detection group (67 therapies per 100 person-years [95% CI, 62-73]; incident rate ratio [IRR], 0.63 [95% CI, 0.51-0.78]; P < .001). The long- vs the standard-detection group experienced 23 ATPs per 100 person-years (95% CI, 20-27) vs 37 ATPs per 100 person-years (95% CI, 33-41; IRR, 0.58 [95% CI, 0.47-0.72]; P < .001); 19 shocks per 100 person-years (95% CI, 16-22) vs 30 shocks per 100 person-years (95% CI, 26-34; IRR, 0.77 [95% CI, 0.59-1.01]; P = .06), with a significant difference in the probability of therapy occurrence (P < .001); and a reduction in first occurrence of inappropriate shock (5.1 per 100 patient-years [95% CI, 3.7-6.9] vs 11.6 [95% CI, 9.4-14.1]; IRR, 0.55 [95% CI, 0.36-0.85]; P = .008). Mortality (5.5 [95% CI, 4.0-7.2] vs 6.3 [95% CI, 4.8-8.2] per 100 patient-years; HR, 0.87; P = .50) and arrhythmic syncope rates (3.1 [95% CI, 2.6-4.6] vs 1.9 [95% CI, 1.1-3.1] per 100 patient-years; IRR, 1.60 [95% CI, 0.76-3.41]; P = .22) did not differ significantly between groups.Among patients receiving an ICD, the use of a long- vs standard-detection interval resulted in a lower rate of ATP and shocks, and inappropriate shocks. This programming strategy may be an appropriate alternative.clinicaltrials.gov Identifier: NCT00617175.
Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients
Authors: A. Somfay, J. Porszasz, S.M. Lee, R. Casaburi
Journal: European Respiratory Journal (2001)

Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement. Ten severe COPD patients without clinically significant oxygen (O 2 ) desaturation during exercise, and seven healthy subjects, performed five exercise tests at 75% of maximally tolerated work rate. Inspired oxygen fraction ( F I,O 2 ) was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order. Ventilation ( V ' E ) was measured, and end-inspiratory (EILV) and end-expiratory (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres. In the patients, compared to room air, endurance time increased with F I,O 2 =0.3 (mean±sem 92±20%) and increased further with F I,O 2 =0.5 (157±30%). At isotime, compared to room air, there were significant reductions in dyspnoea score, EELV, EILV, V ' E and respiratory frequency ( f R ) with F I,O 2 =0.3. Improved endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and EILV (r=043, p=0.005). The dyspnoea rating decrease correlated with f R decrease. In healthy subjects, smaller V ' E and f R decreases were observed at F I,O 2 =0.5, accompanied by more modestly increased endurance. Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be partly related to decreased hyperinflation and slower breathing pattern. This effect is maximized at an inspired oxygen fraction of 0.5.