tbuckley/cabot-search huggingface dataset:
S113 Long Term Exercise (LTE) For COPD Patients Post-Pulmonary Rehabilitation (PR) Prolongs the Duration of Benefits Derived from PR: Abstract S113 Table 1
Authors: SE Roberts, S Rogers, A Segal, S Purcell, H Broomfield, G Fabris, M Calonge-Contreras, J Billet, L Restrick, M Stern
Journal: Thorax (2012)

<h3>Introduction</h3> PR is associated with functional, emotional and resource benefits for breathless COPD patients which decline over 12–18 months. Patients who complete PR express the desire to continue exercising regularly with other breathless patients but there is currently no evidence for efficacy. This study evaluated regular community-based LTEfor these patients. <h3>Methods</h3> Patients completing PR were recruited to once weekly LTE held in accessible venues by 2 exercise instructors (Loughborough trained for exercising patients with chronic respiratory disease). Baseline demographics and disease severity were collected and outcomes: 6 minute walk test (6MWT), Hospital Anxiety &amp; Depression (HAD) score, COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ) and patient satisfaction measured at baseline, 6 and 12 months. Patients who accepted referral for LTE but never attended or dropped-out were recalled for outcomes at 12 months. Hospital admissions were audited for 12 months after PR-completion. <h3>Results</h3> Between June-2010 and January-2012 75 patients mean(SD) age 69.3(9.7)yrs, FEV1 1.26(0.54)L, MRC 3.16(0.81) 63% female, 19.2% current smokers and 3 on LTOT accepted referral to LTE. 35% (26/75) never attended and 27%(20/75) dropped out after starting; 39% (29/75) continued to exercise for at least 6 months and 25% (19/75) exercised to 1 yr. For patients who exercised for 12 months there was no significant decline in exercise capacity (6MWT), a significant improvement in CAT over 6/12 (p=0.002) maintained to 12/12 (p=0.02) and no increase in anxiety levels, which remained below clinical relevance for the 12 months post PR. In comparison, patients who did not continue LTE had a significant (p=0.001) decline in 6MWT, no change in CAT score and a significant(p=0.04) increase in anxiety to a clinically important range (table 1). Self reported hospital admissions in the year following PR were higher for patients who did not exercise (mean 0.61 (SD 1.47)) compared to those who did, 0.16 (0.50). <h3>Conclusions</h3> This pilot demonstrates that community-based LTE with trained instructors is safe and realistic for breathless patients after completing PR and, for the first time, demonstrates significant prolongation of functional and emotional benefits. This offers acheaper, more durable alternative to repeating PR.
Phase I Trial of Interleukin-12 Plasmid Electroporation in Patients With Metastatic Melanoma
Authors: Adil I. Daud, Ronald C. DeConti, Stephanie Andrews, Patricia Urbas, Adam I. Riker, Vernon K. Sondak, Pamela N. Munster, Daniel M. Sullivan, Kenneth E. Ugen, Jane L. Messina, Richard Heller
Journal: Journal of Clinical Oncology (2008)

Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection of DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA.A phase I dose escalation trial of plasmid interleukin (IL)-12 electroporation was carried out in patients with metastatic melanoma. Patients received electroporation on days 1, 5, and 8 during a single 39-day cycle, into metastatic melanoma lesions with six 100-mus pulses at a 1,300-V/cm electric field through a penetrating six-electrode array immediately after DNA injection. Pre- and post-treatment biopsies were obtained at defined time points for detailed histologic evaluation and determination of IL-12 protein levels.Twenty-four patients were treated at seven dose levels, with minimal systemic toxicity. Transient pain after electroporation was the major adverse effect. Post-treatment biopsies showed plasmid dose proportional increases in IL-12 protein levels as well as marked tumor necrosis and lymphocytic infiltrate. Two (10%) of 19 patients with nonelectroporated distant lesions and no other systemic therapy showed complete regression of all metastases, whereas eight additional patients (42%) showed disease stabilization or partial response.This report describes the first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation. The results indicated this modality to be safe, effective, reproducible, and titratable.
Brothers and Sisters
Authors: Julius Aitsebaomo, Andrea L. Portbury, Jonathan C. Schisler, Cam Patterson
Journal: Circulation Research (2008)

The molecular differences between arteries and veins are genetically predetermined and are evident even before the first embryonic heart beat. Although ephrinB2 and EphB4 are expressed in cells that will ultimately differentiate into arteries and veins, respectively, many other genes have been shown to play a significant role in cell fate determination. The expression patterns of ephrinB2 and EphB4 are restricted to arterial–venous boundaries, and Eph/ephrin signaling provides repulsive cues at arterial–venous boundaries that are thought to prevent intermixing of arterial- and venous-fated cells. However, the maintenance of arterial–venous fate is susceptible to some degree of plasticity. Thus, in response to signals from the ambient microenvironment and shear stress, there is flow-mediated intercalation of the arteries and veins that ultimately leads to the formation of a functional, closed-loop circulation. In addition, cells in the blood vessels of each organ undergo epigenetic, morphological, and functional adaptive changes that are specific to the proximate function of their cognate organ(s). These adaptive changes result in an interorgan and intraorgan vessel heterogeneity that manifest clinically in a disparate response of different organs to identical risk factors and injury in the same animal. In this review, we focus on the molecular and physiological factors influencing arterial–venous heterogeneity between and within different organ(s). We explore arterial–venous differences in selected organs, as well as their respective endothelial cell architectural organization that results in their inter- and intraorgan heterogeneity.
Medical Futility in End-of-Life Care: Report of the Council on Ethical and Judicial Affairs
Authors: None Council on Ethical and Judician Affairs, American Medical Association
Journal: JAMA (1999)

Use of life-sustaining or invasive interventions in patients in a persistent vegetative state or who are terminally ill may only prolong the dying process. What constitutes futile intervention remains a point of controversy in the medical literature and in clinical practice. In clinical practice, controversy arises when the patient or proxy and the physician have discrepant values or goals of care. Since definitions of futile care are value laden, universal consensus on futile care is unlikely to be achieved. Rather, the American Medical Association Council on Ethical and Judicial Affairs recommends a process-based approach to futility determinations. The process includes at least 4 steps aimed at deliberation and resolution including all involved parties, 2 steps aimed at securing alternatives in the case of irreconcilable differences, and a final step aimed at closure when all alternatives have been exhausted. The approach is placed in the context of the circumstances in which futility claims are made, the difficulties of defining medical futility, and a discussion of how best to implement a policy on futility.
The Threat of an Avian Influenza Pandemic
Authors: Arnold S. Monto
Journal: New England Journal of Medicine (2005)

There have been three influenza pandemics during the past century — in 1918, 1957, and 1968. Although the severity of the epidemics and the primary age groups affected varied, each was caused by a novel type A virus of avian origin. In 1957 and 1968, the new viruses had components of previous human viruses as well as avian viruses. The genome of the influenzavirus is made up of eight segments of RNA, and it was determined retrospectively that in both cases, there had been a reassortment of avian and human genes — most likely the result of the coinfection of . . .
NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis
Authors: Ramón Bataller, Robert F. Schwabe, Youkyung H. Choi, Liu Yang, Yong Han Paik, Jeffrey Lindquist, Ting Qian, Robert Schoonhoven, Curt H. Hagedorn, John J. Lemasters, David A. Brenner
Journal: Journal of Clinical Investigation (2003)

Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II–induced effects in hepatic stellate cells (HSCs), a fibrogenic cell type. Human HSCs express mRNAs of key components of nonphagocytic NADPH oxidase. Ang II phosphorylated p47phox, a regulatory subunit of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase activity. Ang II phosphorylated AKT and MAPKs and increased AP-1 DNA binding in a redox-sensitive manner. Ang II stimulated DNA synthesis, cell migration, procollagen α1(I) mRNA expression, and secretion of TGF-β1 and inflammatory cytokines. These effects were attenuated by N-acetylcysteine and diphenylene iodonium, an NADPH oxidase inhibitor. Moreover, Ang II induced upregulation of genes potentially involved in hepatic wound-healing response in a redox-sensitive manner, as assessed by microarray analysis. HSCs isolated from p47phox–/– mice displayed a blunted response to Ang II compared with WT cells. We also assessed the role of NADPH oxidase in experimental liver fibrosis. After bile duct ligation, p47phox–/– mice showed attenuated liver injury and fibrosis compared with WT counterparts. Moreover, expression of smooth muscle α-actin and expression of TGF-β1 were reduced in p47phox–/– mice. Thus, NADPH oxidase mediates the actions of Ang II on HSCs and plays a critical role in liver fibrogenesis.
The Diverse Roles of Mast Cells
Authors: Michael F. Gurish, K. Frank Austen
Journal: The Journal of Experimental Medicine (2001)

In this issue, Matsumoto et al. ([1][1]) report that histamine exocytosed from brain mast cells (MCs) after activation by antigenic cross-linking of the high affinity IgE receptor (FceRI) acts via Hl receptors at the hypothalamus to elicit corticotropin-releasing factor (CRF). These findings reveal
Changes in Atrial Fibrillation Cycle Length and Inducibility During Catheter Ablation and Their Relation to Outcome
Authors: Michel Haïssaguerre, Prashanthan Sanders, Mélèze Hocini, Li-Fern Hsu, Dipen C. Shah, Christophe Scavée, Yoshihide Takahashi, Martin Rotter, Jean-Luc Pasquié, Stéphane Garrigue, Jacques Clémenty, Pierre Jaïs
Journal: Circulation (2004)

The modification of atrial fibrillation cycle length (AFCL) during catheter ablation in humans has not been evaluated.Seventy patients undergoing ablation of prolonged episodes of AF were randomized to pulmonary vein (PV) isolation or additional ablation of the mitral isthmus. Mean AFCL was determined at a distance from the ablated area (coronary sinus) at the following intervals: before ablation, after 2- and 4-PV isolations, and after linear ablation. Inducibility of sustained AF (> or =10 minutes) was determined before and after ablation. Spontaneous sustained AF (715+/-845 minutes) was present in 30 patients and induced in 26 (AFCL, 186+/-19 ms). PV isolation terminated AF in 75%, with the number of PVs requiring isolation before termination increasing with AF duration (P=0.018). PV isolation resulted in progressive or abrupt AFCL prolongation to various extents, depending on the PV: to 214+/-24 ms (P<0.0001) when AF terminated and to 194+/-19 ms (P=0.002) when AF persisted. The increase in AFCL (30+/-17 versus 14+/-11 ms; P=0.005) and the decrease in fragmentation (30.0+/-26.8% to 10.3+/-14.5%; P<0.0001) were significantly greater in patients with AF termination. Linear ablation prolonged AFCL, with a greater prolongation in patients with AF termination (44+/-13 versus 22+/-23 ms; P=0.08). Sustained AF was noninducible in 57% after PV isolation and in 77% after linear ablation. At 7+/-3 months, 74% with PV isolation and 83% with linear ablation were arrhythmia free without antiarrhythmics, which was significantly associated with noninducibility (P=0.03) with a recurrence rate of 38% and 13% in patients with and without inducibility, respectively.AF ablation results in a decline in AF frequency, with a magnitude correlating with termination of AF and prevention of inducibility that is predictive of subsequent clinical outcome.
Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls.
Authors: O Björkman, R Gunnarsson, E Hagström, P Felig, J Wahren
Journal: Journal of Clinical Investigation (1989)

Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.
Proactive integrated care improves quality of life in patients with COPD
Authors: P. B. Koff, R. H. Jones, J. M. Cashman, N. F. Voelkel, R. W. Vandivier
Journal: European Respiratory Journal (2009)

Self-management strategies improve a variety of health-related outcomes for patients with chronic obstructive pulmonary disease (COPD). These strategies, however, are primarily designed to improve chronic disease management and have not focused on early detection and early treatment of exacerbations. In COPD, the majority of exacerbations go unreported and treatment is frequently delayed, resulting in worsened outcomes. Therefore, a randomised clinical trial was designed to determine whether integration of self-management education with proactive remote disease monitoring would improve health-related outcomes. A total of 40 Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 COPD patients were randomised to receive proactive integrated care (PIC) or usual care (UC) over a 3-month period. The primary and secondary outcomes were change in quality of life, measured by the St George’s Respiratory Questionnaire (SGRQ), and change in healthcare costs. PIC dramatically improved SGRQ by 10.3 units, compared to 0.6 units in the UC group. Healthcare costs declined in the PIC group by US$1,401, compared with an increase of US$1,709 in the UC group, but this was not statistically significant. PIC uncovered nine exacerbations, seven of which were unreported. Therefore, proactive integrated care has the potential to improve outcomes in chronic obstructive pulmonary disease patients through effects of self-management, as well as early detection and treatment of exacerbations.
Incidence of RA in people with persistently raised RF
Authors: O M P JOLOBE;
Journal: Annals of the Rheumatic Diseases (2000)

Incidence of RA in people with persistently raised RFA criticism of the study reported in the Annals 1 is that age was not taken into account in the evaluation of the probability of development of rheumatoid arthritis (RA) among symptom free subjects with persistently raised rheumatoid factor (RF).The prevalence of RF can be as high as 14.1% in apparently healthy people aged 67-95 (mean age 81). 2 RF is also 3.5 times more common in healthy elderly subjects (aged >65) than in their younger counterparts. 3All these factors may alter the natural history of arthritis in elderly patients who have RF either in good health or in a non-arthritic presentation of RA.The latter is exemplified by a patient admitted at the age of 76 with symptomatic, as well as echocardiographically validated rheumatoid pericarditis in the absence of arthritis.Rheumatoid arthritis latex fixation test (RA LFT) was positive with a titre of 1/160, antinuclear factor (ANF) titre was 1/250, and signs of active inflammatory disease included a platelet count of 750 × 10 9 /l, and an erythrocyte sedimentation rate (ESR) of 98 mm/1st h (Westergren).Arthralgia of the hands and wrists developed for the first time two years later (when she was no longer taking steroids), with a subsequent RA LFT titre of 1/80 and an ANF titre of 1/320 about four months after the onset of arthralgia.Radiography showed narrowing of the joint spaces of the hands 12 months later, but there were as yet no erosions at this stage.Erosions were seen in March 1992, approximately two and a half years after the onset of arthralgia, when the RA LFT titre was 1/160, ANF titre 1/160, platelet count 421 × 10 9 /l, ESR 18 mm/1st h.At her most recent attendance, on 2 February 2000, she was still very active, having continued to receive prednisolone (maximum dose 5 mg/d) continuously since 1989.Her only complaint was a little pain in the left thenar eminence and painful heels.RF was now 768 IU/ml, ANF titre 1/320, platelet count 340 × 10 9 /l, ESR 42 mm/1st h.Antibodies against double stranded DNA had not been reported at any stage. COMMENTThis case shows a remarkable dissociation between arthritic symptoms and levels of RF, perhaps signifying that when the immune status is altered in old age, 2 the relation between RF and the natural history of RA might be less clear than it is in younger people.
A population study on rheumatoid arthritis in Lesotho, southern Africa.
Authors: J D Moolenburgh, H A Valkenburg, P B Fourie
Journal: Annals of the Rheumatic Diseases (1986)

Motivated by the results of a hospital study on rheumatoid arthritis (RA) in Lesotho (southern Africa) a survey of inflammatory polyarthritis (IP) and RA was undertaken in a sample of the rural population of that country. Contrary to expectations the prevalence of IP grades 2-4 (definite disease) was low (0.4%) and equal in both sexes, while probable and definite RA combined (American Rheumatism Association (ARA) criteria) occurred in 1.8% of both males and females. RA was slightly more severe than in other rural African Negro studies but less so when compared with the disease condition of the patients observed in the hospital study. Rheumatoid factor and particularly that directed against heterologous antigen occurred in 41% of the RA patients and in 16% of the controls. Two thirds of the definite cases and 29% of the combined probable and definite group showed radiological abnormalities.
Association between rhinovirus C infection and respiratory symptom severity in an unselected pediatric population, the EUROPA-study
Authors: M.P. van der Schee, J.G. Wildenbeest, S. Hashimoto, K.S.M. Benschop, A.C. Schuurman, N. Adriaens, K.C. Wolthers, A.B. Sprikkelman, E.G. Haarman, W.M.C. van Aalderen, Peter J. Sterk
Journal: European Respiratory Journal (2012)

Rationale -In a paediatric population hospitalized for bronchiolitis rhinovirus (RV) type C is associated with more severe respiratory symptoms as compared to other RV genotypes (Bizzintino,ERJ,911). RV infections in infants are linked to the development of asthma but specific clinical features of RV-C infection in the general population are unknown. We therefore aim to study the occurrence and respiratory symptom severity associated with RV-C in an unselected paediatric population.   Methods -This is a cross-sectional study from the prospective EUROPA birth cohort, aimed at early prediction of asthma (N=1207;0-3 years). Nose and throat swabs were collected in both asymptomatic infants and infants whose parents consulted the GP for wheeze or dyspnea. RV presence was tested using a 59UTR rtPCR with genotyping based on the VP4/VP2 region. Symptom severity was assessed by parents scoring the presence and severity of 10 symptoms (range 0-50) and by clinicians using the validated PRAM-score (range 0-12).   Results -102 infants (13.3±5.5 months) presented with an infection of whom 53% had a positive RV PCR. RV-A, B & C were found in 35%, 4% and 24% of cases, respectively. 2/17 asymptomatic infants tested positive for RV-A. RV genotypes did not differ significantly regarding symptom severity as scored by parents (μ±SD=14±6.4; p=0.75) and clinicians (1.5±1.9; 0.33).   Conclusion -Rhinovirus-C infection occurred in 24% of the infants and is associated with similar symptom severity as other RV-genotypes. Since RV-C appears to be commonly involved in wheezy episodes not requiring hospitalization, it9s association with future development of asthma needs to be examined.
Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002
Authors: Andrew R Gennery, Khulood Khawaja, Paul Veys, Robbert G M Bredius, Luigi D Notarangelo, Evelina Mazzolari, Alain Fischer, Paul Landais, Marina Cavazzana-Calvo, Wilhelm Friedrich, Anders Fasth, Nico M Wulffraat, Susanne Matthes-Martin, D Bensoussan, P Bordigoni, Andrzej Lange, A Pagliuca, Marino Andolina, Andrew J Cant, E G Davies
Journal: Blood (2003)