tbuckley/cabot-search huggingface dataset:
Synchronization of the Cardiac Pacemaker with Repetitive Stimulation of the Carotid Sinus Nerve in the Dog
Authors: MATTHEW N. LEVY, HARRISON ZIESKE
Journal: Circulation Research (1972)

In anesthetized open-chest dogs, the right carotid sinus nerve was stimulated with brief bursts of electrical impulses. When a single burst was given with each heart beat, the reflexly induced change in heart rate depended on the time within the cardiac cycle that the stimulus was applied. The maximum response was obtained when the P-St interval (i.e., the time from the beginning of the P wave to the beginning of the stimulus burst) was approximately zero. At this P-St interval the cardiac cycle (P-P interval) was prolonged to a mean value of 583 ± 145 (SD) msec from a prestimulation control value of 408 ± 80 msec. The minimum response, a mean P-P interval 45 ± 20 msec less than the maximum, was obtained at a mean P-St interval of 322 ± 48 msec. As a consequence of this phase dependency, over a definite but small range of stimulation frequencies, the discharge of the cardiac pacemaker became synchronized with the neural activity in the baroreceptor reflex arc. Within this critical range of stimulation frequencies, the cardiac pacemaker responded paradoxically to carotid sinus nerve stimulation: a change in the frequency of stimulation evoked a parallel, rather than the well-known inverse, change in heart rate.
Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study
Authors: G.P. Stathopoulos, K. Syrigos, A. Polyzos, G. Fountzilas, S.K. Rigatos, N. Ziras, A. Potamiannou, I. Tsiakopoulos, N. Androulakis, G. Aravantinos, A. Athanasiadis, P. Papakotoulas, V. Georgoulias
Journal: Annals of Oncology (2004)
L'Actualite rhumatologique 1972. Presentee au praticien
Authors: C. G. Barnes
Journal: Annals of the Rheumatic Diseases (1973)

In the words of the authors, this is a reference book which is not intended for reading, but for consultation when information is required.It is written in note form and covers the arthropathies under about 150 titles.Each is then subdivided under definition, incidence, joints affected, symptoms, signs, course, associations, radiological and laboratory tests, treatment, and variants; a few phrases being written on each.The term arthropathy is not defined, but seems to include the majority ofconditions which are associated with deformity or pain in or near a joint.It is, therefore, surprising that tennis elbow, the carpal tunnel syndrome, and neuralgic amyotrophy are all classified as arthropathies, whereas cervical and lumbar spondylosis are only briefly mentioned under osteoarthrosis, although hypophosphataemic spondy- lopathy and ankylosing vertebral hyperostosis are given separate sections.The space allotted to each disease varies from a few lines for uncommon conditions to three pages for rheumatoid arthritis.At least one reference is given to each condition, but it is a pity that titles of articles are not given.This is a surprising omission, because each condition is described on a separate page and there are many blank half pages which could have have been used not only for the titles but for further references, which would have greatly increased the value of this book.The authors have compiled useful information about arthropathies occurring in association with a wide range of conditions, including virus and tropical diseases, and the sections on incidence, complications, and associations are particularly helpful.The brevity of the style becomes misleading, however, in some of the sections on treatment.It is doubtful whether a rheumatologist would refer to this book for guidance on treatment, and other clinicians with little knowledge of the subject would have difficulty in managing an individual case from the available informa- tion, particularly where treatment is complicated, as in rheumatoid arthritis.For instance, no mention is made of systemic steroid treatment, unless it is concealed in the cryptic term 'immuno-suppressive' drugs, sandwiched in between penicillamine and chloroquine, and the phrase 'synovectomy, if all else fails' is capable of misinterpretation.The authors may have strong views about the use of steroids in rheumatoid arthritis, but since these substances are so widely used, they should not be ignored.It is stated that temporal arteritis and polymyalgia rheumatica are probably different manifestations of the same pathological process, and that 50 per cent of patients with polymyalgia rheumatica have giant cell arteritis.For the treatment of polymyalgia rheumatica 7-5 to 15 mg.prednisolone daily is recommended, but 40 mg.daily is suggested for temporal arteritis.This appears to be illogical and the authors are doubtless aware of this inconsistency.The statement that 'steroids have no effect on the arterial
Phylogenetic relationship of muscle tissues deduced from superimposition of gene trees
Authors: S. OOta, N. Saitou
Journal: Molecular Biology and Evolution (1999)

Muscle tissues can be divided into six classes; smooth, fast skeletal, slow skeletal and cardiac muscle tissues for vertebrates, and striated and smooth muscle tissues for invertebrates. We reconstructed phylogenetic trees of six protein genes that are expressed in muscle tissues and, using a newly developed program, inferred the phylogeny of muscle tissues by superimposition of five of those gene trees. The proteins used are troponin C, myosin essential light chain, myosin regulatory light chain, myosin heavy chain, actin, and muscle regulatory factor (MRF) families. Our results suggest that the emergence of skeletal-cardiac muscle type tissues preceded the vertebrate/arthropod divergence (ca. 700 MYA), while vertebrate smooth muscle seemed to evolve independent of other muscles. In addition, skeletal muscle is not monophyletic, but cardiac and slow skeletal muscles make a cluster. Furthermore, arthropod striated muscle, urochordate smooth muscle, and vertebrate muscles except for smooth muscle share a common ancestor. On the other hand, arthropod nonmuscle and vertebrate smooth muscle and nonmuscle share a common ancestor.
Modulating progenitor accumulation attenuates lung angiogenesis in a mouse model of asthma
Authors: T. M. Doyle, R. Ellis, H. J. Park, M. D. Inman, R. Sehmi
Journal: European Respiratory Journal (2010)

Asthmatic responses are associated with the lung homing of bone marrow (BM)-derived progenitors implicated as effectors of disease pathology. Studies have shown that increases in lung extracted vascular endothelial progenitor cells (VEPCs) correlate with airway angiogenesis and declining lung function. We investigated the effect of modulating lung homing of VEPCs on tissue remodelling and airway hyperresponsiveness (AHR). BALB/c mice were sensitised to ovalbumin, subjected to a chronic exposure protocol and given early concurrent or delayed treatment with a modulator of progenitor traffic, AMD3100 (CXC chemokine receptor 4 antagonist; inhibits chemotactic activity of stromal-derived factor-1α on VEPCs). After ovalbumin challenge, early haemopoietic stem cells (HSCs) and VEPCs were enumerated along with indices of airway inflammation, lung morphometry and AHR. Following ovalbumin challenge, there was a decrease in BM and an associated increase in the lung tissue-extracted HSCs and VEPCs, together with increases in airway eosinophilia, microvessel density and AHR. These outcomes were significantly inhibited by early concurrent treatment with AMD3100. Where lung disease was established, delayed treatment with AMD3100 significantly attenuated HSC numbers and lung angiogenesis but only partially reversed sustained AHR compared with untreated ovalbumin-exposed mice. Progenitor lung homing is associated with the development of asthma pathology, and early modulation of this accumulation can prevent airway remodelling and lung dysfunction.
Disease management in the American market
Authors: T. Bodenheimer
Journal: BMJ (2000)

In developed nations, the care of people with chronic disease consumes a large portion of the total expenditure on health. Yet chronic disease is often poorly treated and inadequately prevented. Disease management was introduced in the 1990s as an attempt to improve the quality and reduce the cost of caring for people with chronic disease. The peculiar configuration of disease management programmes in the United States may provide lessons for countries seeking solutions to the problem of caring for patients with chronic disease.

#### Summary points

The goal of disease management programmes is to improve the quality and reduce the cost of caring for patients with chronic disease

Many disease management programmes in the United States are run by commercial firms that sell their programmes to employers, health maintenance organisations, and hospitals

Some disease management programmes cut costs and improve outcomes, however the data are not conclusive for the disease management movement in general

Commercial disease management programmes may take needed money away from actual caregiving in order to enhance companies' profits

Disease management should be performed within healthcare institutions and be integrated with primary care rather than being outsourced to specialised commercial entities

This article is based on a Medline search using the term “disease management,” review of websites run by companies engaged in running disease management programmes, and 20 interviews with experts and company executives who work in disease management.

Over the past quarter century, the United States has searched for ways to control the growth of healthcare costs. Rather than rely on governmental regulation, the United States has chosen to use the private marketplace as an instrument of cost cutting.

In the 1980s, the vehicle chosen by large employers and the federal and state governments to control costs was the health maintenance organisation.1 Many entrepreneurs interested in making profits …
Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT
Authors: Charles Crawley, Richard Szydlo, Marc Lalancette, Andrea Bacigalupo, Andrzej Lange, Mats Brune, Gunnar Juliusson, Arnon Nagler, Alois Gratwohl, Jacob Passweg, Mieczyslaw Komarnicki, Antonin Vitek, Jiri Mayer, Axel Zander, Jorge Sierra, Alesssandro Rambaldi, Olle Ringden, Dietger Niederwieser, Jane F Apperley
Journal: Blood (2005)
STUDIES ON PNEUMOCOCCUS IMMUNITY
Authors: William A. Perlzweig, Gustav I. Steffen
Journal: The Journal of Experimental Medicine (1923)

1. Active immunity against many lethal doses of Pneumococcus Types I, II, and III may be produced in mice by two or three subcutaneous injections of the homologous type of pneumococcus saline vaccine. 2. Mice may be actively immunized with the protein fraction obtained by treating pneumococci with anhydrous sodium sulfate or by solution of pneumococci in bile salts and precipitation with alcohol. Pneumococcus antigen is therefore carried within or adheres to the protein fraction of the organism. 3. Pneumococcus antigen is resistant to prolonged autolysis and to tryptic digestion, and can be recovered from the soluble portions of digests of either the intact bacteria or the bacterial protein. 4. The antigen may be isolated from each of the three fixed types of pneumococcus by tryptic digestion of the pneumococci and extraction of the digest with 70 to 90 per cent alcohol. The antigen is not soluble in absolute alcohol, nor is it soluble in ether or in the other lipoidal solvents. 5. The immunizing property of slightly acid solutions of the antigen is not impaired by boiling for 5 minutes, nor by heating at 56 degrees C. for 1 hour. Sterile unpreserved solutions of the antigen did not deteriorate by standing in the refrigerator for 3(1/2) months. 6. The exact chemical nature of pneumococcus antigen still remains to be determined. From the experiments reported it appears that the antigen is non-lipoidal, that it probably adheres to the protein fraction in a loose chemical or physical union rather than representing a protein complex of a large molecular size, as shown by its solubility in alcohol, its thermostability, and its resistance to proteolytic digestion. 7. Some of the antigens studied have been shown to contain a non-specific factor promoting the growth of bacteria. 8. The purified pneumococcus antigen solutions are non-toxic for mice.
Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection
Authors: K. Fitzmaurice, D. Petrovic, N. Ramamurthy, R. Simmons, S. Merani, S. Gaudieri, S. Sims, E. Dempsey, E. Freitas, S. Lea, S. McKiernan, S. Norris, A. Long, D. Kelleher, P. Klenerman
Journal: Gut (2011)

<h3>Background and aims</h3> CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. <h3>Methods</h3> A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. <h3>Results</h3> A strong 'HLA footprint' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03-positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. <h3>Conclusions</h3> It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies.
Revisiting comorbidities in gout: a cluster analysis
Authors: Pascal Richette, Pierre Clerson, Laure Périssin, René-Marc Flipo, Thomas Bardin
Journal: Annals of the Rheumatic Diseases (2013)

Objectives The reciprocal links between comorbidities and gout are complex. We used cluster analysis to attempt to identify different phenotypes on the basis of comorbidities in a large cohort of patients with gout. Methods This was a cross-sectional multicentre study of 2763 gout patients conducted from November 2010 to May 2011. Cluster analysis was conducted separately for variables and for observations in patients, measuring proximity between variables and identifying homogeneous subgroups of patients. Variables used in both analyses were hypertension, obesity, diabetes, dyslipidaemia, heart failure, coronary heart disease, renal failure, liver disorders and cancer. Results Comorbidities were common in this large cohort of patients with gout. Abdominal obesity, hypertension, metabolic syndrome and dyslipidaemia increased with gout duration, even after adjustment for age and sex. Five clusters (C1–C5) were found. Cluster C1 (n=332, 12%) consisted of patients with isolated gout and few comorbidities. In C2 (n=483, 17%), all patients were obese, with a high prevalence of hypertension. C3 (n=664, 24%) had the greatest proportion of patients with type 2 diabetes (75%). In C4 (n=782, 28%), almost all patients presented with dyslipidaemia (98%). Finally, C5 (n=502, 18%) consisted of almost all patients with a history of cardiovascular disease and renal failure, with a high rate of patients receiving diuretics. Conclusions Cluster analysis of comorbidities in gout allowed us to identify five different clinical phenotypes, which may reflect different pathophysiological processes in gout.
Host- rather than virus-related factors reduce health-related quality of life in hepatitis C virus infection
Authors: B Helbling, K Overbeck, J-J Gonvers, R Malinverni, J-F Dufour, J Borovicka, M Heim, A Cerny, F Negro, S Bucher, M Rickenbach, E L Renner, B Mullhaupt
Journal: Gut (2008)

<h3>Background:</h3> Hepatitis C virus (HCV) infection is associated with decreased health-related quality of life (HRQOL). Although HCV has been suggested to directly impair neuropsychiatric functions, other factors may also play a role. <h3>Patients and methods:</h3> In this cross-sectional study, we assessed the impact of various host-, disease- and virus-related factors on HRQOL in a large, unselected population of anti-HCV-positive subjects. All individuals (n = 1736) enrolled in the Swiss Hepatitis C Cohort Study (SCCS) were asked to complete the Short Form 36 (SF-36) and the Hospital Anxiety Depression Scale (HADS). <h3>Results:</h3> 833 patients (48%) returned the questionnaires. Survey participants had significantly worse scores in both assessment instruments when compared to a general population. By multivariable analysis, reduced HRQOL (mental and physical summary scores of SF-36) was independently associated with income. In addition, a low physical summary score was associated with age and diabetes, whereas a low mental summary score was associated with intravenous drug use. HADS anxiety and depression scores were independently associated with income and intravenous drug use. In addition, HADS depression score was associated with diabetes. None of the SF-36 or HADS scores correlated with either the presence or the level of serum HCV RNA. In particular, SF-36 and HADS scores were comparable in 555 HCV RNA-positive and 262 HCV RNA-negative individuals. <h3>Conclusions:</h3> Anti-HCV-positive subjects have decreased HRQOL compared to controls. The magnitude of this decrease was clinically important for the SF-36 vitality score. Host and environmental, rather than viral factors, seem to impact on HRQOL level.
Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive pulmonary disease patients, stratified with the MRC dyspnoea scale
Authors: JA Wedzicha, JC Bestall, R Garrod, R Garnham, EA Paul, PW Jones
Journal: European Respiratory Journal (1998)

This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean+/-SEM) 191+/-22 m, post-rehabilitation 279+/-22 m (p&lt;0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 (p&lt;0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea.
Functional arm exercise capacity, activities of daily living and upper extremity muscle strength in patients with chronic obstructive pulmonary disease
Authors: Ebru Calik, Hulya Arikan, Melda Saglam, Naciye Vardar-Yagli, Cigdem Oksuz, Deniz Inal-Ince, Sema Savci, Tulin Duger, Lutfi Coplu
Journal: European Respiratory Journal (2013)

Introduction and background: Patients with chronic obstructive pulmonary disease (COPD) have reduced arm exercise capacity and frequently experience marked dyspnea and fatigue during the performance of arm tasks important for daily living.

Aims and objectives: The aim of this study was to investigate the relationship between functional arm exercise capacity, activities of daily living and upper extremity muscle strength in patients with COPD.

Methods: Fourteen patients with COPD were included in the study. Upper extremity muscle strength was measured with a hand-held dynamometer. Functional arm exercise capacity was evaluated with 6-minute pegboard and ring test (PBRT). Activities of daily living (ADL) was assessed using the ADL Field Test.

Results: The total number of rings moved during PBRT was correlated with shoulder abductors’ muscle strength (r=0.73, p=0.005), hand grip strength (r=0.66, p=0.019), the shuttles completed during the ADL Field Test (r=0.76, p=0.002) and change in general fatigue perception during the ADL test (r=0.70, p=0.005). Shoulder abductors’ muscle strength was also correlated with the shuttles completed (r=0.60, p=0.029) during the ADL Field Test.

Conclusions: Functional arm exercise capacity is related with upper extremity muscle strength and the ability to perform ADL and fatigue perception during ADL. Incorporation of arm strength training into a comprehensive pulmonary rehabilitation program, might be of considerable clinical significance and should result in an improvement in the ability of the patients to perform arm-involved daily activities and functional arm exercise capacity.