tbuckley/cabot-search huggingface dataset:
Effects of Alterations in Aortic Impedance on the Performance of the Ventricles
Authors: DAVID E. L. WILCKEN, ANDRÉ A. CHARLIER, JULIEN I. E. HOFFMAN, ABRAHAM GUZ
Journal: Circulation Research (1964)

We have investigated the effects of sudden changes in the load against which the left ventricle contracts in healthy conscious dogs. During a steady state, initial responses were assessed by comparing the beat before with the beat after such a change. Flow was measured by electromagnetic flowmeters and pressure usually by a catheter-tip transducer. Results show that under the conditions of these experiments the curves relating external work and power to load are consistent with the parabolic relationship shown for isolated hearts and muscle strips and that in each case the left ventricle normally functions near the peak of the curve. When an increased load was maintained until a new steady state was reached the left ventricle still functioned on the descending limbs of what presumably were different work-load and power-load curves. It was concluded from this that either the increase in load was too great or the time too short for reflex humoral and intrinsic mechanisms to readjust and permit the ventricle to function again at the peak of each curve, or that the circulatory system does not make relatively rapid adaptations in this way to an increase in systemic load. The immediate effects of changes in load on left ventricular stroke volume were similar to those seen in isolated preparations. Stroke volume varied inversely with the load. Stroke volume changes were accompanied by changes in the duration, rate, and velocity of ejection. The duration of the isovolumetric phase was affected little but the period from valve closure to the end of ventricular relaxation varied with the load so that the total duration of contraction and relaxation of the ventricle was relatively unchanged, though an increase in load did tend to prolong it. Before the onset of the baroreceptor response the right ventricle was not affected, the two ventricles acting independently in relation to all these changes.
Evidence of non-deficient low-density lipoprotein receptor patients in a pool of subjects with clinical familial hypercholesterolemia profile
Authors: S. Lestavel-Delattre, S. Benhamamouch, G. Agnani, G. Luc, J.M. Bard, T. Brousseau, C. Billardon, J.P. Kusnierz, J.L. De Gennes, J.C. Fruchart, V. Clavey
Journal: Metabolism (1994)
Evaluation of the prevalence of skin prick test positivity to <i>Alternaria</i> and <i>Cladosporium</i> in patients with suspected respiratory allergy
Authors: G. D'Amato, G. Chatzigeorgiou, R. Corsico, D. Gioulekas, L. Jäger, S. Jäger, K. Kontou‐Fili, S. Kouridakis, G. Liccardi, A. Meriggi, A. Palma‐Carlos, M. L. Palma‐Carlos, A. Pagan Aleman, S. Parmiani, P. Puccinelli, M. Russo, F. Th. M. Spieksma, R. Torricelli, B. Wuthrich
Journal: Allergy (1997)

D'Amato G, Chatzigeorgiou G, Corsico R, Gioulekas D, Jäger L, Jäger S, Kontou‐Fili K, Kouridakis S, Liccardi G, Meriggi A, Palma‐Carlos A, Palma‐Carlos ML, Pagan Aleman A, Parmiani S, Puccinelli R Russo M, Spieksma FThM, Torricelli R, Wüthrich B. Evaluation of the prevalence of skin prick test positivity to Alternaria and Cladosporium in patients with suspected respiratory allergy. A European multicenter study promoted by the Subcommittee on Aerobiology and Environmental Aspects of Inhalant Allergens of the European Academy of Allergology and Clinical Immunology. This trial was undertaken to study, in several geographically spread European countries, the prevalence of skin prick test (SPT) positivity to Alternaria (A) and Cladosporium (C) in subjects with nasal and/or bronchial symptoms of suspected allergic cause. Each patient completed an anamnestic questionnaire and underwent SPT with a panel of common inhalant allergens and also A and C supplied by three different laboratories, to allow for manufacturer bias. Specific scrum IgE determination was carried out only in subjects with SPT positivity to A and/or C with an immunoassay system. In nine European allergology centers, a total of 877 subjects was enrolled in the trial; 83 of them showed SPT positivity to A and/or C; only nine patients showed monosensitization to A , and none to C The highest percentage of positive subjects was found in Spain (20%); the lowest in Portugal (3%). In the other seven centers, the variation was 7–10%. The age range of mold‐positive subjects was 5–60 years. Rhinitis was by far the most common symptom, whether associated or not with asthma and/or conjunctivitis.
Inhalation of steady-state sidestream smoke from one cigarette promotes arteriosclerotic plaque development.
Authors: A Penn, L C Chen, C A Snyder
Journal: Circulation (1994)

BACKGROUND A number of epidemiologic studies have suggested that every year environmental tobacco smoke (second-hand smoke) is responsible for tens of thousands of deaths, mostly from heart disease, in the United States. Environmental tobacco smoke is composed mainly (80% to 85%) of aged and diluted sidestream smoke. The remainder is exhaled mainstream smoke. Among the thousands of compounds that have been identified in environmental tobacco smoke are a number of carcinogens, including polynuclear aromatic hydrocarbon carcinogens, such as benzo(a)pyrene. We have demonstrated previously that a number of carcinogens, including benzo(a)pyrene, promote plaque development after injection into cockerels. There have been almost no studies showing a direct stimulatory effect of environmental tobacco smoke on plaque development. Recently we demonstrated that cockerels exposed to sidestream smoke for approximately 0.4% of their projected lifespan exhibited accelerated development of arteriosclerotic plaques. In that study, cockerels in specially designed inhalation chambers were exposed to the steady-state sidestream smoke from 5 cigarettes for 6 h/d for 16 weeks. This level of exposure is high but environmentally plausible. Statistically significant increases in plaque size were demonstrated in the smoke-exposed cockerels. METHODS AND RESULTS In the present study, exposure levels were decreased by a factor of 5. Thirty cockerels were exposed to the steady-state sidestream smoke from 1 cigarette for 6 hours per day for 16 weeks. The smoke was mixed with filtered air. Ten control cockerels were exposed to filtered air only. Levels of smoke surrogates, including carbon monoxide and total suspended particulates, were measured three times a day. Again, there was a statistically significant increase in plaque size in the smoke-exposed cockerels. To place these studies within a context of environmental relevance, levels of carbon monoxide were measured independently over 1 to 3 hours in four bars where there was heavy smoking. Measured carbon monoxide levels were as high or higher in the bars than they were in the exposure chambers during the 1-cigarette sidestream-smoke study. CONCLUSIONS Experimental exposure to secondhand smoke at levels equal to or even below those routinely encountered by people in smoke-filled environments is sufficient to promote arteriosclerotic plaque development.
Purine enzyme activities in recent onset rheumatoid arthritis: are there differences between patients and healthy controls?
Authors: J N Stolk, A M Boerbooms, R A De Abreu, P J Kerstens, D G de Koning, R de Graaf, J Mulder, L B van de Putte
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: Purine enzyme activities may predict the effectiveness of azathioprine treatment and be associated with increased deaths from infectious diseases. In rheumatoid arthritis, patients show variable responses to azathioprine and a higher percentage of death is caused by infections. The aim of the study was to investigate possible rheumatoid arthritis associated abnormalities of purine enzyme activities by measuring several of these enzymes in patients with recent onset rheumatoid arthritis before treatment with disease modifying antirheumatic drugs or prednisone. METHODS: 23 patients with recent onset rheumatoid arthritis and 28 healthy controls were studied. Activities of the enzymes 59-nucleotidase, purine nucleoside phosphorylase (PNP), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were measured. Assessment of disease activity and blood sampling for routine measurements and HLA typing were done simultaneously. RESULTS: Purine enzyme activities did not differ between patients and healthy controls. Enzyme activities had no significant relations with indices of disease activity or rheumatoid factor titre or with the rheumatoid arthritis associated HLA types. Activity of 59nucleotidase decreased with age (P &lt; or = 0.05) and was lower by about 27% (P = 0.007) in males than in females. CONCLUSIONS: In rheumatoid arthritis patients, neither the variability in azathioprine effectiveness nor the increased death rate from infections can be explained by pre-existing abnormalities in the activities of the purine enzymes 59-nucleotidase, PNP, HGPRT, or TPMT at an early stage of the disease, before disease modifying antirheumatic drugs or prednisone treatment. Besides adjustment for age, results of studies involving purine 59 nucleotidase activity should also be adjusted for sex.
Magnetic fields of high voltage power lines and risk of cancer in Finnish adults: nationwide cohort study
Authors: P. K Verkasalo, E. Pukkala, J. Kaprio, K. V Heikkila, M. Koskenvuo
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To investigate the risk of cancer in association with magnetic fields in Finnish adults living close to high voltage power lines. <b>Design</b>: Nationwide cohort study. <b>Subjects</b>: 383 700 people who lived during 1970–89 within 500 metres of overhead power lines of 110–400 kV in a magnetic field calculated to be &gt;/=0.01 μT. Study subjects were identified by record linkages of nationwide registers. <b>Main outcome measures</b>: Numbers of observed and expected cases of cancer, standardised incidence ratios, and incidence rate ratios adjusted for sex, age, calendar year, and social class—for example, by continuous cumulative exposure per 1 μT year—with 95% confidence intervals from multiplicative models for all cancers combined and 21 selected types. <b>Results</b>: Altogether 8415 cases of cancer were observed (standardised incidence ratio 0.98; 95% confidence interval 0.96 to 1.00) in adults. All incidence rate ratios for both sexes combined were non-significant and between 0.91 and 1.11. Significant excesses were observed in multiple myeloma in men (incidence rate ratio 1.22) and in colon cancer in women (1.16). <b>Conclusions</b>: Typical residential magnetic fields generated by high voltage power lines do not seem to be related to the risk of overall cancer in adults. The previously suggested associations between extremely low frequency magnetic fields and tumours of the nervous system, lymphoma, and leukaemia in adults and breast cancer in women were not confirmed. <h3>Key messages</h3> The present population based cohort study among Finnish adults with 8500 observed cancer cases found no increase in the risk of overall cancer in adults exposed to magnetic fields of high voltage power lines The previously suggested associations between magnetic fields and tumours of the nervous system, lymphoma, leukaemia, and breast cancer in women were not confirmed The results of the present study suggest strongly that typical residential magnetic fields generated by high voltage power lines are not related to cancer in adults The possibility of an increase in risk at higher magnetic field levels, or in more specific cancer subtypes, cannot be excluded on the basis of this study
Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study
Authors: N. Schlesinger, E. Mysler, H.-Y. Lin, M. De Meulemeester, J. Rovensky, U. Arulmani, A. Balfour, G. Krammer, P. Sallstig, A. So
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. <h3>Methods</h3> In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. <h3>Results</h3> A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p&lt;0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. <h3>Conclusions</h3> Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.
Estrogen receptor–α in medial amygdala neurons regulates body weight
Authors: Pingwen Xu, Xuehong Cao, Yanlin He, Liangru Zhu, Yongjie Yang, Kenji Saito, Chunmei Wang, Xiaofeng Yan, Antentor Othrell Hinton, Fang Zou, Hongfang Ding, Yan Xia, Chunling Yan, Gang Shu, San-Pin Wu, Bin Yang, Yuxin Feng, Deborah J. Clegg, Richard DeMarchi, Sohaib A. Khan, Sophia Y. Tsai, Francesco J. DeMayo, Qi Wu, Qingchun Tong, Yong Xu
Journal: Journal of Clinical Investigation (2015)

Estrogen receptor–α (ERα) activity in the brain prevents obesity in both males and females. However, the ERα-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded–1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERα. Specific deletion of the gene encoding ERα (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight–lowering effects of a glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate. Furthermore, selective adeno-associated virus-mediated deletion of Esr1 in the MeA of adult male mice produced a rapid body weight gain that was associated with remarkable reductions in physical activity but did not alter food intake. Conversely, overexpression of ERα in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERα agonist depolarized MeA SIM1 neurons and increased their firing rate, and designer receptors exclusively activated by designer drug–mediated (DREADD-mediated) activation of these neurons increased physical activity in mice. Collectively, our results support a model where ERα signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain.
Vascular Effects of Synthetic or Natural Progestagen Combined With Conjugated Equine Estrogen in Healthy Postmenopausal Women
Authors: Kwang Kon Koh, Dong Kyu Jin, Seong Hee Yang, Seon-Kyu Lee, Hee Young Hwang, Moon Ho Kang, Wan Kim, Dae Sung Kim, In Suck Choi, Eak Kyun Shin
Journal: Circulation (2001)

Background —Synthetic, not natural, progestagen may negate the favorable effects of estrogen. Nonetheless, observational studies report no differences in risk for clinical cardiovascular events between users of unopposed estrogen and users of estrogen combined with synthetic progestin. Methods and Results —In a double-blind study, we randomly assigned 20 healthy postmenopausal women to micronized progesterone (MP) 200 mg or medroxyprogesterone acetate (MPA) 10 mg for 10 days with conjugated equine estrogen (CEE) 0.625 mg for 25 days and the remaining 5 days off cyclically during 2 months, followed by crossover to the alternate therapy. CEE+MP and CEE+MPA significantly improved the percent flow-mediated dilator response to hyperemia relative to baseline measurements ( P =0.004 by ANOVA) by a similar degree ( P =0.863). Both therapies significantly decreased E-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 levels from baseline values ( P &lt;0.001, P =0.048, and P =0.016 by ANOVA, respectively) by a similar degree ( P =0.977 for ICAM-1 and P =0.541 for VCAM-1, respectively). CEE+MPA decreased E-selectin levels more than CEE+MP did ( P =0.040). Both therapies significantly decreased monocyte chemoattractant protein-1 levels from baseline values ( P &lt;0.005 by ANOVA) by a similar degree ( P =0.194). Both therapies significantly decreased tissue factor antigen and increased tissue factor activity levels from baseline values ( P =0.003 and P &lt;0.001 by ANOVA, respectively) by a similar degree ( P =0.652 for antigen and P =0.173 for activity). Both therapies significantly lowered plasma plasminogen activator inhibitor-1 levels from baseline values ( P &lt;0.001 by ANOVA) by a similar degree ( P =0.533). Conclusions —CEE+MP and CEE+MPA provide similar improvement in endothelium-dependent vasodilator responsiveness and effects on markers of inflammation, hemostasis, and fibrinolysis inhibition in healthy postmenopausal women.
Changing Public Health Training Needs: Professional Education and the Paradigm of Public Health
Authors: Harvey V. Fineberg, Gareth M. Green, James H. Ware, Bernita L. Anderson
Journal: Annual Review of Public Health (1994)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris
Authors: Judith R. Abrams, Mark G. Lebwohl, Cynthia A. Guzzo, Brian V. Jegasothy, Michael T. Goldfarb, Bernard S. Goffe, Alan Menter, Nicholas J. Lowe, Gerald Krueger, Michael J. Brown, Russell S. Weiner, Martin J. Birkhofer, Garvin L. Warner, Karen K. Berry, Peter S. Linsley, James G. Krueger, Hans D. Ochs, Susan L. Kelley, Sewon Kang
Journal: Journal of Clinical Investigation (1999)

Engagement of the B7 family of molecules on antigen-presenting cells with their T cell–associated ligands, CD28 and CD152 (cytotoxic T lymphocyte–associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell–dependent neoantigens, bacteriophage φX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell–dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell–mediated diseases.
APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy
Authors: Jeffrey B. Kopp, George W. Nelson, Karmini Sampath, Randall C. Johnson, Giulio Genovese, Ping An, David Friedman, William Briggs, Richard Dart, Stephen Korbet, Michele H. Mokrzycki, Paul L. Kimmel, Sophie Limou, Tejinder S. Ahuja, Jeffrey S. Berns, Justyna Fryc, Eric E. Simon, Michael C. Smith, Howard Trachtman, Donna M. Michel, Jeffrey R. Schelling, David Vlahov, Martin Pollak, Cheryl A. Winkler
Journal: Journal of the American Society of Nephrology (2011)

Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.
Neurological complications of cervical spine manipulation
Authors: Clare Stevinson, Will Honan, Brian Cooke, Edzard Ernst
Journal: Journal of the Royal Society of Medicine (2001)

To obtain preliminary data on neurological complications of spinal manipulation in the UK all members of the Association of British Neurologists were asked to report cases referred to them of neurological complications occurring within 24 hours of cervical spine manipulation over a 12-month period. The response rate was 74%. 24 respondents reported at least one case each, contributing to a total of about 35 cases. These included 7 cases of stroke in brainstem territory (4 with confirmation of vertebral artery dissection), 2 cases of stroke in carotid territory and 1 case of acute subdural haematoma. There were 3 cases of myelopathy and 3 of cervical radiculopathy. Concern about neurological complications following cervical spine manipulation appears to be justified. A large long-term prospective study is required to determine the scale of the hazard.
Epigenetic Biomarkers and Breast Cancer: Cause for Optimism
Authors: Kala Visvanathan, Saraswati Sukumar, Nancy E. Davidson
Journal: Clinical Cancer Research (2006)

The term “epigenetics” was first coined in the 1940s to describe the interaction between genes and environment in the development of specific phenotypical traits ([1][1]). Within a decade, DNA methylation was identified as the first epigenetic marker ([2][2]). Sixty years later, there is