tbuckley/cabot-search huggingface dataset:
Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation
Authors: Antony J Workman, Kathleen A Kane, Andrew C Rankin
Journal: Cardiovascular Research (2003)

Objective: To assess the contribution of the Na, K pump current (Ip) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether Ip contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF). Methods: Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (>3 months). Results: In cells from patients in SR, the Ip blocker, ouabain (10 μM) significantly depolarised the membrane potential, Vm, from −80±2 (mean±S.E.) to −73±2 mV, and lengthened both the APD (174±17 vs. 197±23 ms at 90% repolarisation) and ERP (198±22 vs. 266±14 ms; P<0.05 for each, Student's t-test, n=7 cells, 5 patients). With an elevated pipette [Na+] of 30 mM, Ip was measured by increasing extracellular [K+] ([K+]o) from 0 to 5.4 mM. This produced an outward shift in holding current at −40 mV, abolished by 10 μM ouabain. K+- and ouabain-sensitive current densities were similar, at 0.99±0.13 and 1.12±0.11 pA/pF, respectively (P>0.05; n=9 cells), confirming the K+-induced current as Ip. Ip increased linearly with increasing Vm between −120 and +60 mV (n=25 cells). Stepwise increments in [K+]o (between 0 and 10 mM) increased Ip in a concentration-dependent manner (maximum response, Emax=1.19±0.09 pA/pF; EC50=1.71±0.15 mM; n=27 cells, 9 patients). In cells from patients in AF, the sensitivity of Ip to both Vm and [K+]o (Emax=1.02±0.05 pA/pF, EC50=1.54±0.11 mM; n=44 cells, 9 patients) was not significantly different from that in cells from patients in SR. Within the group of patients in AF, long-term digoxin therapy (n=5 patients) was associated with a small, but significant, reduction in Emax (0.92±0.07 pA/pF) and EC50 (1.35±0.15 mM) compared with non-treatment (Emax=1.13±0.08 pA/pF, EC50=1.76±0.14 mM; P<0.05 for each, n=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K+]o-sensitivity (Emax and EC50) were similar to those in cells from patients in SR. Conclusions: The Na, K pump current contributes to the human atrial cell Vm, action potential shape and ERP. However, the similarity in Ip sensitivity to both [K+]o and Vm between atrial cells from patients with and without chronic AF indicates that Ip is not involved in AF-induced electrophysiological remodelling in patients.
Relationship between quantitative radiographic assessments of interstitial lung disease and physiological and clinical features of systemic sclerosis
Authors: Donald P Tashkin, Elizabeth R Volkmann, Chi-Hong Tseng, Hyun J Kim, Jonathan Goldin, Philip Clements, Daniel Furst, Dinesh Khanna, Eric Kleerup, Michael D Roth, Robert Elashoff
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Extent of systemic sclerosis (SSc)-related interstitial lung disease (ILD) assessed from thoracic high-resolution CT (HRCT) predicts disease course, mortality and treatment response. While quantitative HRCT analyses of extent of lung fibrosis (QLFib) or total interstitial lung disease (QILD) are more sensitive and reproducible than visual HRCT assessments of SSc-ILD, these analyses are not widely available. This study evaluates the relationship between clinical disease parameters and QLFib and QILD scores to identify potential surrogate measures of radiographic extent of ILD. <h3>Methods</h3> Using baseline data from the Scleroderma Lung Study I (SLS I; N=158), multivariate regression analyses were performed using the best subset selection method to identify one to five variable models that best correlated with QLFib and QILD scores in both whole lung (WL) and the zone of maximal involvement (ZM). These models were subsequently validated using baseline data from SLS II (N=142). Bivariate analyses of the radiographic and clinical variables were also performed using pooled data. SLS I and II did not include patients with clinically significant pulmonary hypertension (PH). <h3>Results</h3> Diffusing capacity for carbon monoxide (DLCO) was the single best predictor of both QLF and QILD in the WL and ZM in all of the best subset models. Adding other disease parameters to the models did not substantially improve model performance. Forced vital capacity (FVC) did not predict QLF or QILD scores in any of the models. <h3>Conclusions</h3> In the absence of PH, DLCO provides the best overall estimate of HRCT-measured lung disease in patients from two large SSc cohorts. FVC, although commonly used, may not be the best surrogate measure of extent of SSc-ILD at any point in time. <h3>Trial registration numbers</h3> SLS I: www.clinicaltrials.gov NCT 00000-4563; SLS II: www.clinicaltrials.gov NCT 00883129.
Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial
Authors: William W Busse, Eugene R Bleecker, Eric D Bateman, Jan Lötvall, Richard Forth, Angela M Davis, Loretta Jacques, Brett Haumann, Ashley Woodcock
Journal: Thorax (2011)

<h3>Background</h3> Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β<sub>2</sub> agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease. <h3>Objectives</h3> To determine the optimal dose(s) of FF for treating patients with asthma. <h3>Methods</h3> An 8-week multicentre, randomised, double-blind study. 627 patients with persistent moderate-to-severe asthma, symptomatic on medium-dose inhaled corticosteroid therapy, were randomised to placebo, FF 200, 400, 600 or 800 μg (once daily in the evening using a novel dry powder inhaler), or fluticasone propionate 500 μg twice daily (via Diskus™/Accuhaler™). The primary efficacy measure was mean change from baseline in pre-dose evening forced expiratory volume in one second (FEV<sub>1</sub>). Other endpoints included morning and evening peak expiratory flow, and rescue/symptom-free 24 h periods. <h3>Results</h3> Each dose was significantly superior to placebo for the primary endpoint (p&lt;0.001) with efficacy at least similar to that reported with fluticasone propionate. There was no dose–response relationship across the FF doses studied. Peak expiratory flow improved in all groups (p&lt;0.001 vs placebo), and there were significant treatment effects on rescue/symptom-free 24 h periods with all active treatments. FF was generally well tolerated. The incidence of oral candidiasis was higher with FF 800 μg than placebo; pharmacokinetic and 24 h urinary cortisol analyses confirmed a higher systemic exposure of FF at this highest dose level. <h3>Conclusions</h3> FF doses &lt;800 μg have a favourable therapeutic index. The absence of an efficacy dose response suggests that 200 μg is an appropriate dose in patients with moderate persistent asthma. <h3>ClinicalTrials.gov identifier</h3> NCT00603746.
Physical therapist's clinical companion.
Authors: Roisin Fearon
Journal: British Journal of Sports Medicine (2001)

The football club doctor system EDITOR,-I read with interest the paper by Waddington et al 1 highlighting the inadequacies of the football club doctor system in Britain.This paper confirms the situation that many people already knew to exist.Advertisements for club doctors are rarely published in medical journals, doctors normally being appointed on a "who you know" basis.It is also particularly disappointing that, at a time when the specialty of sports and exercise medicine is being established in this country, the majority of doctors working with professional footballers have no qualifications or little experience in the specialty.However, this is not confined to football clubs and probably also applies to rugby clubs and many other sporting associations.One aspect not mentioned in the paper is medical litigation.It is to be hoped that doctors involved with football clubs have arranged medical defence cover, because, if a situation arises in which a player's sporting career is threatened by medical mismanagement and the doctor involved has no professionally recognised sports medicine qualification, he or she could be found guilty of medical negligence.With the amount of money involved in professional football, this could lead to dire consequences for the medical career of the practitioner involved.From a report commissioned by the Football League on the Hillsborough tragedy, the concept of the "crowd doctor" was introduced, meaning that any doctor involved in the medical care of the crowd at a football stadium would be required to possess at least the Diploma in Immediate Medical Care. 2 Before that, the situation was similar to that of the present club doctor system, and few doctors held any recognisable qualifications or training in medical emergencies and resuscitation.A similar recommendation by sports medicine authorities is required to enhance the quality of service provided to football clubs and increase the stature of the specialty.However, it is not a one sided situation.Football clubs must realise the importance of a medical team in looking after their prime assets, the players.Advertising of jobs in medical journals, insisting on experience and qualifications, adequate remuneration, and the provision of job descriptions and contracts should all be implemented.By working together to improve the current situation, a service can be provided in which both professional football players and the medical profession can have confidence.
Melanin content and distribution in the surface corneocyte with skin phototypes
Authors: H. LU, C. EDWARDS, S. GASKELL, A. PEARSE, R. MARKS
Journal: British Journal of Dermatology (1996)

An individual's sensitivity to sunlight is traditionally assessed by the Boston or Fitzpatrick classification of skin type. The ability to tan depends, to some degree, on the melanin content of the epidermis. In the study reported here, surface corneocytes in exposed skin and unexposed skin have been assessed using a surface stripping slide mounting technique and an Optomax V image analyser, with which the percentage of corneocyte area occupied by melanin granules has been taken as the melanin content index (MCI). There was a significantly different MCI between different skin types for both exposed (P < 0.0001) and unexposed (P < 0.0001) areas using the Kruskal-Wallis one-way ANOVA test. There was also a positive significant correlation between MCI and skin types II-VI in both exposed (r = 0.95, P < 0.001) and unexposed areas (r = 0.89, P < 0.005). Image analysis also demonstrated that the number of melanin granules in surface corneocytes was significantly higher in the exposed area compared with the unexposed area, for skin types II, III, IV, V and VI. Melanin cap-like structures were also observed in exposed corneocytes and heavily pigmented skin contained larger melanin particles than fairer skin. The results indicate that an individual's skin phototype and melanin content, assessed by image analysis, have a significant correlation.
Minding the Aging Brain: Are We Ready for Personalized Medicine?
Authors: Jason Karlawish, Robert C. Green
Journal: American Journal of Psychiatry (2014)

In this issue, Lineweaver and colleagues (1) report two remarkable findings: After cognitively normal older adults learn they have the ε4 allele of the APOE gene that increases the risk of developing Alzheimer's disease, they perform worse on measures of subjective and objective cognition compared with older adults who have this genotype but do not know their genotype.Conversely, those who learn that they do not carry an ε4 allele perform better on measures of subjective cognition compared with ε4-negative individuals who do not know they are ε4 negative.
Long-Term Clinical Outcomes With Sirolimus-Eluting Coronary Stents
Authors: Marie-Claude Morice, Patrick W. Serruys, Paul Barragan, Christoph Bode, Gerrit-Anne Van Es, Hans-Peter Stoll, David Snead, Laura Mauri, Donald E. Cutlip, Eduardo Sousa
Journal: Journal of the American College of Cardiology (2007)
Reliability of international normalised ratios from two point of care test systems: comparison with conventional methods
Authors: L. Poller
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Design</b> Comparison of the INRs from the two systems with a “true” INR on a conventional manual test from the same sample of blood. <b>Setting</b> 10 European Concerted Action on Anticoagulation centres. <b>Participants</b> 600 patients on long term dosage of warfarin. <b>Main outcome measures</b> Comparable results between the different methods. <b>Results</b> The mean displayed INR differed by 21.3% between the two point of care test monitoring systems. The INR on one system was 15.2% higher, on average, than the true INR, but on the other system the INR was 7.1% lower. The percentage difference between the mean displayed INR and the true INR at individual centres varied considerably with both systems. <b>Conclusions</b> Improved international sensitivity index calibration of point of care test monitors by their manufacturers is needed, and better methods of quality control of individual instruments by their users are also needed.
Transplacental Effects of 3'-Azido-2',3'-Dideoxythymidine (AZT): Tumorigenicity in Mice and Genotoxicity in Mice and Monkeys
Authors: O. A. Olivero, S. H. Yuspa, M. C. Poirier, L. M. Anderson, A. B. Jones, C. Wang, B. A. Diwan, D. C. Haines, D. Logsdon, S. W. Harbaugh, T. J. Moskal, J. M. Rice, C. W. Riggs
Journal: JNCI Journal of the National Cancer Institute (1997)

When given during pregnancy, the drug 3'-azido-2',3'-dideoxythymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed the transplacental tumorigenic and genotoxic effects of AZT in the offspring of CD-1 mice and Erythrocebus patas monkeys given AZT orally during pregnancy.Pregnant mice were given daily doses of either 12.5 or 25.0 mg AZT on days 12 through 18 of gestation (last 37% of gestation period). Pregnant monkeys were given a daily dose of 10.0 mg AZT 5 days a week for the last 9.5-10 weeks of gestation (final 41%-43% of gestation period). AZT incorporation into nuclear and mitochondrial DNA and the length of chromosomal end (telomere) DNA were examined in multiple tissues of newborn mice and fetal monkeys. Additional mice were followed from birth and received no further treatment until subjected to necropsy and complete pathologic examination at 1 year of age. An anti-AZT radioimmunoassay was used to monitor AZT incorporation into DNA.At 1 year of age, the offspring of AZT-treated mice exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys.AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate.
Hepatitis virus hijacks shuttle: Exosome-like vesicles provide protection against neutralizing antibodies
Authors: Vedashree Ramakrishnaiah, Luc J.W. van der Laan
Journal: Hepatology (2013)

Abstract Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane, attributes that profoundly affect stability, transmission and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically transmitted hepatitis. HAV infects in a stealth-like manner and replicates efficiently in the liver. Virus-specific antibodies appear only after 3-4 weeks of infection, and typically herald its resolution. Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure, when virus replication is well established in the liver. Here we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (‘eHAV’) resemble exosomes, small vesicles that are increasingly recognized to be important in intercellular communications. They are fully infectious, sensitive to extraction with chloroform, and circulate in the blood of infected humans. Their biogenesis is dependent on host proteins associated with endosomal-sorting complexes required for transport (ESCRT), namely VPS4B and ALIX. Whereas the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and probably promotes virus spread within the liver, anti-capsid antibodies restrict replication after infection with eHAV, suggesting a possible explanation for prophylaxis after exposure. Membrane hijacking by HAV blurs the classic distinction between ‘enveloped’ and ‘non-enveloped’ viruses and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses.
Cannibalism of Live Lymphocytes by Human Metastatic but Not Primary Melanoma Cells
Authors: Luana Lugini, Paola Matarrese, Antonella Tinari, Francesco Lozupone, Cristina Federici, Elisabetta Iessi, Massimo Gentile, Francesca Luciani, Giorgio Parmiani, Licia Rivoltini, Walter Malorni, Stefano Fais
Journal: Cancer Research (2006)

The phenomenon of cell cannibalism, which generally refers to the engulfment of cells within other cells, was described in malignant tumors, but its biological significance is still largely unknown. In the present study, we investigated the occurrence, the in vivo relevance, and the underlying mechanisms of cannibalism in human melanoma. As first evidence, we observed that tumor cannibalism was clearly detectable in vivo in metastatic lesions of melanoma and often involved T cells, which could be found in a degraded state within tumor cells. Then, in vitro experiments confirmed that cannibalism of T cells was a property of metastatic melanoma cells but not of primary melanoma cells. In particular, morphologic analyses, including time-lapse cinematography and electron microscopy, revealed a sequence of events, in which metastatic melanoma cells were able to engulf and digest live autologous melanoma-specific CD8(+) T cells. Importantly, this cannibalistic activity significantly increased metastatic melanoma cell survival, particularly under starvation condition, supporting the evidence that tumor cells may use the eating of live lymphocytes as a way to "feed" in condition of low nutrient supply. The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function. In conclusion, our study shows that human metastatic melanoma cells may eat live T cells, which are instead programmed to kill them, suggesting a novel mechanism of tumor immune escape. Moreover, our data suggest that cannibalism may represent a sort of "feeding" activity aimed at sustaining survival and progression of malignant tumor cells in an unfavorable microenvironment.
The effects of vitamin D<sub>3</sub>supplementation on serum total 25[OH]D concentration and physical performance: a randomised dose–response study
Authors: Graeme L Close, Jill Leckey, Marcelle Patterson, Warren Bradley, Daniel J Owens, William D Fraser, James P Morton
Journal: British Journal of Sports Medicine (2013)

Vitamin D deficiency is common in the general public and athletic populations and may impair skeletal muscle function. We therefore assessed the effects of vitamin D3 supplementation on serum 25[OH]D concentrations and physical performance.30 club-level athletes were block randomised (using baseline 25[OH]D concentrations) into one of three groups receiving either a placebo (PLB), 20 000 or 40 000 IU/week oral vitamin D3 for 12 weeks. Serum 25[OH]D and muscle function (1-RM bench press and leg press and vertical jump height) were measured presupplementation, 6 and 12 weeks postsupplementation. Vitamin D deficiency was defined in accordance with the US Institute of Medicine guideline (<50 nmol/l).57% of the subject population were vitamin D deficient at baseline (mean±SD value 51±24 nmol/l). Following 6 and 12 weeks supplementation with 20 000 IU (79±14 and 85±10 nmol/l, respectively) or 40 000 IU vitamin D3 (98±14 and 91±24 nmol/l, respectively), serum vitamin D concentrations increased in all participants, with every individual achieving concentrations greater than 50 nmol/l. In contrast, vitamin D concentration in the PLB group decreased at 6 and 12 weeks (37±18 and 41±22 nmol/l, respectively). Increasing serum 25[OH]D had no significant effect on any physical performance parameter (p>0.05).Both 20 000 and 40 000 IU vitamin D3 supplementation over a 6-week period elevates serum 25[OH]D concentrations above 50 nmol/l, but neither dose given for 12 weeks improved our chosen measures of physical performance.
Subcutaneous seeding of hepatocellular carcinoma after percutaneous needle biopsy
Authors: S N SCHOTMAN, R A DE MAN, J STOKER, P E ZONDERVAN, J N M IJZERMANS
Journal: Gut (1999)

Background— In patients with a hepatic mass, malignancy can be diagnosed or excluded by a needle biopsy. However, this procedure can cause the formation of subcutaneous metastatic nodules in the needle tract. We present a case of recurrent subcutaneous seeding four years after a biopsy of a small hepatocellular carcinoma (HCC).

Case report— A 30 year old woman with hepatitis B liver cirrhosis presented with a raised serum α-fetoprotein (AFP) (271 μg/l; normal: <20 μg/l); ultrasound detected a liver mass. Additional spiral computed tomography showed a 2 cm diameter subcapsular mass in segment V. There were also two satellite lesions, measuring less than 1 cm in the same segment. To confirm the diagnosis of HCC, an ultrasound guided needle biopsy was performed using an 18 gauge Tru-cut needle and Biopty-gun. Two passes were needed to …