tbuckley/cabot-search huggingface dataset:
Long-term Leisure-time Physical Activity and Serum Metabolome
Authors: Urho M. Kujala, Ville-Petteri Mäkinen, Ilkka Heinonen, Pasi Soininen, Antti J. Kangas, Tuija H. Leskinen, Paavo Rahkila, Peter Würtz, Vuokko Kovanen, Sulin Cheng, Sarianna Sipilä, Mirja Hirvensalo, Risto Telama, Tuija Tammelin, Markku J. Savolainen, Anneli Pouta, Paul F. O’Reilly, Pekka Mäntyselkä, Jorma Viikari, Mika Kähönen, Terho Lehtimäki, Paul Elliott, Mauno J. Vanhala, Olli T. Raitakari, Marjo-Riitta Järvelin, Jaakko Kaprio, Heikki Kainulainen, Mika Ala-Korpela
Journal: Circulation (2012)

Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk.Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their >30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31-52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the significance of the multivariate effect combined across all metabolic measures; univariate effects were estimated by paired testing in twins and in matched pairs in the cohorts, and by meta-analysis over all substudies. Persistent physical activity was associated with the multivariate metabolic profile in the twins (P=0.003), and a similar pattern was observed in all 3 population cohorts with differing mean ages. Isoleucine, α1-acid glycoprotein, and glucose were lower in the physically active than in the inactive individuals (P<0.001 in meta-analysis); serum fatty acid composition was shifted toward a less saturated profile; and lipoprotein subclasses were shifted toward lower very-low-density lipoprotein (P<0.001) and higher large and very large high-density lipoprotein (P<0.001) particle concentrations. The findings persisted after adjustment for body mass index.The numerous differences found between persistently physically active and inactive individuals in the circulating metabolome together indicate better metabolic health in the physically active than in inactive individuals.
Medicaid Coverage for Young Women and Children: Whose Welfare Is at Stake?-Reply
Authors: Katherine Swartz
Journal: JAMA (1997)

<h3>In Reply.</h3> —The fact that 39% of all births in 1994 were paid for with Medicaid funds is shocking. However, as I pointed out in the Editorial, the 1991 through 1994 increase to 39% is not due to an increase in the number of babies whose births are paid for by Medicaid but by a decline in the number of babies born to women with private health insurance. Part of this decline has occurred because women with higher incomes are not having as many babies as in previous years. But an increasingly important part of the decline in private health insurance coverage of births is due to employers' either not offering health insurance to their employees or increasing the premium share paid by employees for dependent coverage. A large majority of the women affected by the expanded eligibility for Medicaid are working or are dependents of workers—they simply cannot afford or do
Hand Pain and Impairment
Authors: Reginald R. Cooper
Journal: JAMA (1971)

The title, evidently chosen to conform to titles in a series, is somewhat misleading, for only those portions devoted to nerve lesions and related syndromes revolve primarily around pain as a central theme. A review of functional anatomy comprises about one third of the monograph. Chapters on nerve, tendon, bone, and joint injuries, infection, arthritis, and vascular disease complete the treatise.  In many instances, the author fails to fulfill his avowed goal—to provide the nonspecialist physician, who first sees the patient, with sufficient knowledge to properly evaluate the hand and initiate proper treatment. The section on tendon injuries lacks a discussion on diagnosis. The author does not emphasize maintenance of passive joint mobility, the prime requisite in instances where immediate tendon suture is not indicated. Discussions of mallet finger, extensor tendon central slip rupture, and carpal dislocation oversimplify treatment. The discourse on functional anatomy provides a cursory examination of a
Phenotypic Expression of Diabetes Secondary to a T14709C Mutation of Mitochondrial DNA: Comparison with MIDD syndrome (A3243G mutation): a case report
Authors: B H Vialettes, V Paquis-Flucklinger, J F Pelissier, D Bendahan, H Narbonne, P Silvestre-Aillaud, M F Montfort, M Righini-Chossegros, J Pouget, P J Cozzone, C Desnuelle
Journal: Diabetes Care (1997)

OBJECTIVE To analyze the clinical and biochemical features of a recently described point mutation of mitochondrial DNA associated with diabetes. This mutation, characterized by a T14709C transition of a highly conserved nucleotide in the region coding for the glutamic acid tRNA, is heteroplasmic. RESEARCH DESIGN AND METHODS The phenotypic expression in the insulin-requiring diabetic proband from the pedigree was compared to that of diabetic probands from three families with the classic A3243G mtDNA mutation (maternally inherited diabetes and deafness [MIDD] syndrome). The same investigations to evaluate pancreatic neurosensorial and muscle involvement were performed in all four patients. RESULTS The natural courses of the diabetes and the hearing defects were not different between the two mutations. The patient with the 14,709 mutation, however, exhibited a milder alteration of pigmentary epithelium of retina and a much more severe muscle involvement, as attested by the clinical expression and the concurrent anomalies of muscle energy production evidenced by 31P magnetic resonance spectroscopy, confirming the profound impairment of oxidative processes. CONCLUSIONS This novel mutation has to be added to the other known mtDNA anomalies in order to ascribe some diabetes suspected to arise from mitochondrial defects to this nosological framework.
Terbutaline-induced desensitization of human cardiac β2-adrenoceptor-mediated positive inotropic effects: attenuation by ketotifen
Authors: Ulrike Poller, Birgit Fuchs, Antje Gorf, Jens Jakubetz, Joachim Radke, Klaus Pönicke, Otto-Erich Brodde
Journal: Cardiovascular Research (1998)

Background: In patients with chronic heart failure cardiac β1-adrenoceptors are desensitized whereas β2-adrenoceptors are only marginally affected. The mechanism underlying this differential regulation is not known. Objectives: To find out whether or not human cardiac β2-adrenoceptors might be 'resistant' to agonist-induced desensitization and whether or not the antiallergic drug ketotifen might attenuate possible desensitization. Methods: We investigated, in a single blinded, randomised, placebo-controlled, cross-over study of ten healthy male volunteers (mean age, 25.3±0.7 years), the effects of two weeks treatment with the β2-adrenoceptor agonist terbutaline (3×5 mg/day p.o.) with and without simultaneous treatment with ketotifen (2×1 mg/day p.o. for three weeks) or placebo on β-adrenoceptor-mediated cardiovascular effects. Cardiovascular effects were assessed as isoprenaline (3.5–35 ng/kg/min)- and terbutaline (25–150 ng/kg/min)-infusion-induced increases in heart rate and systolic blood pressure, decreases in diastolic blood pressure and shortening of the systolic time intervals (STIs), heart rate corrected duration of electromechanical systole (QS2c) and pre-ejection period (PEP; as a measure of inotropism). Results: Ketotifen did not significantly affect basal haemodynamics in the volunteers. Isoprenaline- and terbutaline-infusion caused dose-dependent increases in systolic blood pressure and heart rate, decreases in diastolic blood pressure and shortening of QS2c and PEP, whereby isoprenaline effects were more pronounced. After two weeks of treatment with terbutaline p.o., isoprenaline- and terbutaline-infusion-induced increases in heart rate, shortening of QS2c and PEP were significantly reduced whereby terbutaline-infusion effects were markedly more attenuated than isoprenaline-infusion effects. Ketotifen significantly reduced terbutaline p.o. treatment-induced attenuation of all terbutaline-infusion effects (largely β2-adrenoceptor-mediated) and the isoprenaline-infusion-induced increase in heart rate (β1- and β2-adrenoceptor-mediated), but did not (or only marginally) affect reduction in isoprenaline-induced shortening of QS2c and PEP (largely β1-adrenoceptor-mediated). Conclusion: Human cardiac β2-adrenoceptors are not 'resistant' to agonist-induced desensitization: Ketotifen might prevent such β2-adrenoceptor-agonist-evoked desensitization.
Arthritis, Medicine and the Spiritual Laws; the Power Beyond Science
Authors: R. W. Lamont-Havers
Journal: JAMA (1962)

The importance of environmental and emotional factors in modifying the patient's reactions to rheumatic diseases and many other disease processes is well recognized. The wise physician will attempt to assist the patient in recognizing and overcoming these factors as part of the over-all program of disease control. The manner in which this is accomplished will depend in large measure upon the social background, mores, beliefs, training, and convictions of the physician. Dr. Swaim, in this very personal book written primarily for the patient, outlines his practices based upon his own deep convictions in Christian philosophy. The author is revealed as a very kind, humble, and humane physician deeply interested in his patients as human beings. There is no doubt that many patients in a predominantly Judeo-Christian society would benefit by reading of how others have been helped to control their diseases by realizing and overcoming their underlying emotional conflicts through
Physiologic Assessment of Coronary Artery Fistula
Authors: NARESH C. GUPTA, JOHN BEAUVAIS
Journal: Clinical Nuclear Medicine (1991)

Coronary artery fistula is an uncommon clinical entity. The most common coronary artery fistula is from the right coronary artery to the right side of the heart, and it is less frequent to the pulmonary artery. The effect of a coronary artery fistula may be physiologically significant because of the steal phenomenon resulting in coronary ischemia. Based on published reports, it is recommended that patients with congenital coronary artery fistulas be considered candidates for elective surgical correction to prevent complications including development of congestive heart failure, angina, subacute bacterial endocarditis, myocardial infarction, and coronary aneurysm formation with rupture or embolization. A patient is presented in whom treadmill-exercise thallium imaging was effective in determining the degree of coronary steal from a coronary artery fistula, leading to successful corrective surgery.
Monoclonal origin of B lymphocyte colony-forming cells in spleen colonies formed by multipotential hemopoietic stem cells
Authors: PK Lala, GR Johnson
Journal: The Journal of Experimental Medicine (1978)

Spleen colonies produced by transplanting lethally irradiated mice with either 12 day fetal liver or adult bone marrow cells were found to contain B- lymphocyte colony-forming cells (BL-CFC) . The proportion of BL-CFC positive spleen colonies did not increase substantially between 8 and 14 days after transplantation, the range being 18-45 percent. However, the absolute number of BL-CFC per spleen colony varied considerably (between 1 and 10,318), although the majority of colonies contained less than 200 BL-CFC. Irrespective of the time after transplantation, smaller spleen colonies were found to have a higher frequency of BL-CFC than larger spleen colonies. To determine the possible clonal origin of BL-CFC from spleen colony- forming unit (CFU-S), CBA mice were injected with equal numbers of CBA and CBA T(6)/T(6) fetal liver or adult bone marrow cells. Analysis of 7-15-day spleen colonies demonstrated that 90 percent were either exclusively T(6) positive or T(6) negative and approximately equal numbers ofboth colony types were observed. B-lymphocyte colonies were grown and successfully karyotyped from 19 spleen colonies. When compared with the original spleen colony karyotype the B-lymphocyte colony cells karyotype was identical in all 19 cases. In 3 of the 19 colonies analyzed a mixture of T(6) positive and T(6) negative karyotypes was present and identical proportions of the karyotypes were present in the pooled B-lymphocyte colony cells and spleen colony cells. The data indicate that the B-lymphocyte colony-forming cells detected in spleen colonies are genuine members of the hemopoietic clone derived from the initiating hemopoietic stem cell (CFU-S).
HLA-E–dependent Presentation of Mtb-derived Antigen to Human CD8+ T Cells
Authors: Amy S. Heinzel, Jeff E. Grotzke, Rebecca A. Lines, Deborah A. Lewinsohn, Andria L. McNabb, Daniel N. Streblow, Veronique M. Braud, Heather J. Grieser, John T. Belisle, David M. Lewinsohn
Journal: The Journal of Experimental Medicine (2002)

Previous studies in mice and humans have suggested an important role for CD8+ T cells in host defense to Mtb. Recently, we have described human, Mtb-specific CD8+ cells that are neither HLA-A, B, or C nor group 1 CD1 restricted, and have found that these cells comprise the dominant CD8+ T cell response in latently infected individuals. In this report, three independent methods are used to demonstrate the ability of these cells to recognize Mtb-derived antigen in the context of the monomorphic HLA-E molecule. This is the first demonstration of the ability of HLA-E to present pathogen-derived antigen. Further definition of the HLA-E specific response may aid development of an effective vaccine against tuberculosis.
Behavioral and Pharmacological Therapies for Late-Life Insomnia
Authors: Charles M. Morin, Cheryl Colecchi, Jackie Stone, Rakesh Sood, Douglas Brink
Journal: JAMA (1999)

ContextInsomnia is a prevalent health complaint in older adults. Behavioral and pharmacological treatments have their benefits and limitations, but no placebo-controlled study has compared their separate and combined effects for late-life insomnia.ObjectiveTo evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for late-life insomnia.Design and SettingRandomized, placebo-controlled clinical trial, at a single academic medical center. Outpatient treatment lasted 8 weeks with follow-ups conducted at 3, 12, and 24 months.SubjectsSeventy-eight adults (50 women, 28 men; mean age, 65 years) with chronic and primary insomnia.InterventionsCognitive-behavior therapy (stimulus control, sleep restriction, sleep hygiene, and cognitive therapy) (n=18), pharmacotherapy (temazepam) (n=20), or both (n=20) compared with placebo (n=20).Main Outcome MeasuresTime awake after sleep onset and sleep efficiency as measured by sleep diaries and polysomnography; clinical ratings from subjects, significant others, and clinicians.ResultsThe 3 active treatments were more effective than placebo at posttreatment assessment; there was a trend for the combined approach to improve sleep more than either of its 2 single components (shorter time awake after sleep onset by sleep diary and polysomnography). For example, the percentage reductions of time awake after sleep onset was highest for the combined condition (63.5%), followed by cognitive-behavior therapy (55%), pharmacotherapy (46.5%), and placebo (16.9%). Subjects treated with behavior therapy sustained their clinical gains at follow-up, whereas those treated with drug therapy alone did not. Long-term outcome of the combined intervention was more variable. Behavioral treatment, singly or combined, was rated by subjects, significant others, and clinicians as more effective than drug therapy alone. Subjects were also more satisfied with the behavioral approach.ConclusionsBehavioral and pharmacological approaches are effective for the short-term management of insomnia in late life; sleep improvements are better sustained over time with behavioral treatment.
IS SIZE A GOOD PREDICTOR OF DISSECTION RISK IN PATIENTS WITH MARFAN SYNDROME OR BICUSPID AORTIC VALVES? INSIGHTS FROM THE INTERNATIONAL REGISTRY OF ACUTE AORTIC DISSECTION (IRAD)
Authors: Hasan Siddiqi, Eric Isselbacher, Toru Suzuki, Daniel Montgomery, Linda Pape, Rossella Fattori, Patrick O&apos;Gara, Guillaume Jondeau, Emil Missov, Alberto Forteza, Eduardo Bossone, Alan Hirsch, Adam Rogers, Christoph Nienaber, Kim Eagle
Journal: Journal of the American College of Cardiology (2012)
Is the diarrhoea in ulcerative colitis related to impaired colonic salvage of carbohydrate?
Authors: S S Rao, N W Read, C D Holdsworth
Journal: Gut (1987)

In order to determine whether failure of the colon to salvage carbohydrate could contribute to the diarrhoea of ulcerative colitis we investigated the effect of ingesting a drink containing 20 g lactulose on stool output and breath hydrogen production in 39 colitic patients subdivided according to their disease extent and activity and in 14 normal volunteers. Each subject took a standard diet for four days and stool output was monitored throughout this period. Administration of lactulose on day three significantly increased stool weight and frequency in patients with both active and quiescent total colitis (p less than 0.01), but not in patients with distal colitis or in the volunteers. The basal and peak breath hydrogen responses to ingested lactulose were similar to normal controls in all patient groups but the hydrogen concentration tended to be higher in colitics. The mouth to caecum transit of the lactulose meal was slower in all groups of colitics (p less than 0.02) when compared with controls. These results suggest that impaired colonic salvage of carbohydrate could contribute to the diarrhoea in patients with total colitis who are ingesting a diet rich in unabsorbed carbohydrate, or who are hypolactasic.
Doctors can do something about poverty
Authors: I. Heath
Journal: BMJ (1998)

EDITOR—The attitudes of doctors to poverty matter. In their individual behaviour and in the work of their medical associations, doctors can either contribute to the health of the poor or help to undermine it. This was the message of an international meeting in December in London on poverty and health, the fourth in a series that has already produced the London declaration on poverty and health and the Baltimore charter on partnership for a healthy urban future.1 The latest meeting was about how to turn the rhetoric of these statements into action.

As the World Bank has coerced governments to reduce investment in state health sectors in the name of structural readjustment, so inadequately paid doctors and frightened, dissatisfied patients have been driven into the …
Cell Fate Control Gene Therapy Based on Engineered Variants of Human Deoxycytidine Kinase
Authors: Anton Neschadim, James Cm M. Wang, Takeya Sato, Daniel H. Fowler, Arnon Lavie, Jeffrey A. Medin
Journal: Molecular Therapy (2012)

The safety of cell therapy applications can be enhanced by the introduction of Cell Fate Control (CFC) elements, which encode pharmacologically controlled cellular suicide switches. CFC Gene Therapy (CFCGT) offers the possibility of establishing control over gene-modified cells (GMCs) with regards to their proliferation, differentiation, or function. However, enzymes commonly employed in these approaches often possess poor kinetics and high immunogenicity. We describe a novel CFCGT system based on engineered variants of human deoxyCytidine Kinase (dCK) that overcomes limitations of current modalities. Mutants of dCK with rationally designed active sites that make them thymidine-activating were stably introduced into cells by recombinant lentiviral vectors (LVs). Transduced cells maintained growth kinetics and function. These dCK mutants efficiently activate bromovinyl-deoxyuridine (BVdU), L-deoxythymidine (LdT), and L-deoxyuridine (LdU), which are otherwise not toxic to wild-type cells. We show that mutant dCK-expressing Jurkat, Molt-4, and U87mg cells could be efficiently eliminated in vitro and in xenogeneic leukemia and tumor models in vivo. We also describe a fusion construct of the thymidine-activating dCK to the cytoplasmic tail-truncated LNGFR molecule and applications to in vivo eradication of primary human T cells. This novel CFCGT system offers unique plasticity with respect to the wide range of prodrugs it can potentiate, and can be used as a reliable safety switch in cell and gene therapy.
GP suspended for enrolling patients in drug trials without consent
Authors: O. Dyer
Journal: BMJ (2003)

A Hertfordshire GP who included his patients in drug trials without their knowledge was last week suspended by the General Medical Council.

Dr Robert Macindoe Adams, 58, admitted enrolling 12 patients in seven drug trials for pharmaceutical companies including AstraZeneca and SmithKline Beecham without providing an opportunity for informed consent.

The trials involved drugs for depression and hypertension. In two cases Dr Adams was found to have overstated the patients' symptoms to meet the strict criteria for antidepressant trials. He was also found to have changed patients' treatment and prescribed …
Regional Deposition of Aerosolized Pentamidine
Authors: Martin I. Baskin
Journal: Annals of Internal Medicine (1990)

Objective: To evaluate the effects of varying body position and breathing pattern on overall lung distribution of aerosolized pentamidine. Design: Nonrandomized control trial with four weekly inhalational treatments. Setting: The nuclear medicine department of a voluntary hospital. Patients: Sixteen men with the acquired immunodeficiency syndrome (AIDS) or positive serology for the human immunodeficiency virus (HIV). Thirteen patients (81%) completed the study. Interventions: Patients inhaled a solution of either saline and technetium-99m bound to diethylenetriamine penta-acetic acid or sterile water, pentamidine (60 mg), and technetium-99m bound to human serum albumin. On weekly visits, the patients inhaled the aerosol solution using four methods: sitting, supine, sitting with an abdominal binder, and sitting and breathing from residual volume with a shallow inspiration. Measurements and Main Results: Deposition scans, obtained after each aerosol inhalation, were superimposed on each patient's equilibrium xenon scan, and a frequency distribution histogram was constructed. An asymmetry index was determined from this histogram. The lower the asymmetry index, the more homogeneous the aerosol distribution. Only use of the supine position showed a significant decrease in the asymmetry index (mean, 0.34 ± 0.02 in the supine position, 0.48 ± 0.03 in the sitting position; P < 0.001). Conclusions: Aerosol distribution in the lungs was more uniform when administered to patients in the supine position. Patients receiving aerosolized pentamidine may benefit from inhalation in the supine position; these results should be verified by clinical study.