tbuckley/cabot-search huggingface dataset:
Assessment of left ventricular mechanics in patients with asymptomatic aortic regurgitation: a two-dimensional echocardiographic study.
Authors: M G St John Sutton, T A Plappert, J W Hirshfeld, N Reichek
Journal: Circulation (1984)

We describe a noninvasive method for determining end-systolic meridional and circumferential wall stress and left ventricular architecture as the ratio of muscle to cavity area. With this technique, which uses two-dimensional echocardiography and cuff-determined values for systolic blood pressure, we assessed wall stress and left ventricular architecture in 15 normal subjects and 15 asymptomatic patients with severe chronic aortic regurgitation at rest and after load manipulations with sublingual nitroglycerin. Resting end-systolic meridional and circumferential stress were increased in patients with aortic regurgitation (113.9 +/- 29 and 260 +/- 50.7 X 10(3) dynes/cm2) compared with those in normal subjects (85.6 +/- 15.4 and 214.1 +/- 28.4 X 10(3) dynes/cm2) (both p less than .01) and remained significantly greater after nitroglycerin. Meridional stress values obtained from two-dimensional echocardiographic studies correlated closely (r = .89) with values calculated from simultaneously recorded M mode echocardiograms. Ejection fraction in patients with aortic regurgitation and normal subjects were similar at rest (55 +/- 10% vs 59 +/- 6%) and were unchanged by nitroglycerin. In spite of the increased left ventricular mass in patients with aortic regurgitation (227 +/- 60 g vs 130 +/- 22 g in normal subjects), the mass-to-volume ratio and the ratio of muscle to cavity area in diastole in patients with aortic regurgitation were significantly lower than normal (0.90 +/- 0.23 vs 1.30 +/- 0.21 and 0.91 +/- 0.23 vs 1.11 +/- 0.18 [p less than .005 and p less than .02]). These differences were exaggerated after nitroglycerin, while concomitant changes in relative wall thickness were virtually undetected by M mode echocardiography. Thus this technique can be used for early recognition of afterload excess and changes in left ventricular architecture in patients with aortic regurgitation. Furthermore, the mean slopes of the circumferential stress-diameter and meridional stress-length lines, which represent load-independent indexes of myocardial contractile state, could be assessed and were similar in the group of patients with asymptomatic aortic regurgitation and normal subjects, indicating that overall myocardial contractility was still normal. We conclude that circumferential and meridional wall stress, myocardial contractility, and left ventricular architecture can be determined noninvasively. These measurements may prove to be useful in assessing patients with primary myocardial or valvular heart disease and determining their long-term management.
Endocrine and lung function in asthmatic children on inhaled corticosteroids.
Authors: W H Nicolaizik, J L Marchant, M A Preece, J O Warner
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The safety of inhaled corticosteroids in the treatment of chronic asthma has been questioned. In a prospective crossover study asthmatic children not controlled on other medications were commenced on beclomethasone dipropionate (BDP) or budesonide (BUD), both administered at the dose of 200 micrograms twice per day for 2 wk each in randomized order. Recordings at home included twice daily symptom scores, peak expiratory flow readings, and the use of additional antiasthma medications. Before and after each treatment period the patients were admitted for overnight blood sampling for cortisol, ACTH, and growth hormone, 24-h urine collections for cortisol, and detailed lung function tests. A total of 12 children completed the study. The nocturnal serum cortisol production was significantly reduced by 27 and 35% after 2 and 4 wk of treatment (p = 0.005, p = 0.004; Wilcoxon test), and the urinary free cortisol showed a similar reduction of 33 and 48% (p = 0.023, p = 0.005). Such suppression could be shown on both drugs, BDP and BUD, and there was no significant difference between them. The ACTH and growth hormone values were not significantly changed on any treatment. Lung function tests showed an impressive improvement in FVC, FEV1, FEF50, and FEF25 after 2 wk of treatment regardless of the medication. Differences in lung function improvements between the two drugs were very small and not of clinical relevance. The observations indicate that even low-dose inhaled corticosteroids in the form of BDP or BUD have a systemic effect, which emphasizes the importance of using the minimum dose compatible with good control of asthma.
Endocannabinoids limit excessive mast cell maturation and activation in human skin
Authors: Koji Sugawara, Tamás Bíró, Daisuke Tsuruta, Balázs I. Tóth, Arno Kromminga, Nóra Zákány, Anne Zimmer, Wolfgang Funk, Bernhard F. Gibbs, Andreas Zimmer, Ralf Paus
Journal: Journal of Allergy and Clinical Immunology (2012)
Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E.
Authors: L M Pelus
Journal: Journal of Clinical Investigation (1982)

The expression of Ia-like antigens on human colony forming units-granulocyte macrophage (CFU-GM) is related to S-phase of the cell cycle, and associated with the control of normal granulocyte and macrophage production by prostaglandin E and acidic isoferritins in vitro. Ia-antigen expression by CFU-GM is lost within 3-6 h of culture at 37 degrees C and occurs simultaneously with loss of responsiveness to inhibition by these factors. Culture of bone marrow CFU-GM in a limited exposure suspension culture with 1 microM-1pM prostaglandin E (PGE1 or PGE2), but not prostaglandin F2 alpha or dibutyryl-cyclic-3'-5'-AMP results in the detection of CFU-GM Ia-antigen after 24 h. Antigen expression is associated with an absolute increase in total and S-phase CFU-GM, and restoration of responsiveness to inhibition by prostaglandin E and acidic isoferritins. The detection of Ia-antigen on CFU-GM after suspension culture with prostaglandin E results both from Ia-antigen reexpression as well as stimulation of noncycling cells to enter S-phase, express Ia-antigen and give rise to CFU-GM sensitive to inhibition by prostaglandin E and acidic isoferritins. The sensitivity of CFU-GM to inhibition by these factors after suspension culture with prostaglandin E is identical to that of the same cells tested prior to the suspension culture. These studies provide evidence for a direct regulatory association between Ia-antigen expression and control of myeloid progenitor cell differentiation, and suggest a role for prostaglandin E in the control of CFU-GM cell cycle, Ia-antigen expression, and growth regulation.
Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI
Authors: L Thorsson, S Edsbacker, TB Conradson
Journal: European Respiratory Journal (1994)

The pulmonary and systemic availability of budesonide after inhalation from a dry powder inhaler, Turbuhaler, and from a pressurized metered-dose inhaler (P-MDI) were compared in healthy volunteers. Two different methods were used to assess pulmonary availability: 1) calculated from the systemic availability corrected for an oral availability of 13% (n = 24); and 2) after blocking of gastrointestinal absorption by administration of a charcoal suspension (n = 13). An intravenous infusion of budesonide was used as a reference. The systemic availability of budesonide, calculated as a geometric mean and expressed as percentage of the metered dose, was 38% for Turbuhaler and 26% for P-MDI. The pulmonary availability, calculated using the first method, was 32% and 15% for Turbuhaler and P-MDI, respectively; and, using the second method, 32% and 18%, respectively. The results of the present study indicate that administration of budesonide via Turbuhaler gives rise to a lung deposition which is approximately twice that of a P-MDI, with less variability, but that systemic availability is only increased by approximately 50%. Thus, the present data suggest that by administrating budesonide via Turbuhaler, instead of a P-MDI, the same degree of asthma control can be achieved with a lower dose, which, in turn, reduces the risk of undesired systemic effects.
Age as a Risk Factor for Inadequate Treatment
Authors: Edward R. Sodaro
Journal: JAMA (1988)

<h3>To the Editor.</h3> —In his editorial entitled "Age as a Risk Factor for Inadequate Treatment," Dr Wetle<sup>1</sup>proposed that misguided physician prejudice against elderly patients was the explanation for the possibly less-aggressive level of medical care that this population is being offered when compared with the care provided younger age groups. While this analysis merits our attention and concern, there is unfortunately a simpler and far more likely explanation for the increasingly inadequate treatment our elderly may be receiving. Substantial declines in the amount and quality of geriatric health insurance have occurred in recent years through federally legislated coverage reductions such as the diagnosis related group and maximum allowable actual charge schemes. Dr Wetle's home state of Massachusetts is the site of even more draconian cutbacks in financial coverage for medical care to older citizens. The Massachusetts legislature and the governor have eliminated the right of physicians to receive
Effect of glycerol-l-lactide coating polymer on bone ingrowth of bFGF-coated hydroxyapatite implants
Authors: Volker Alt, Hans-Joachim Pfefferle, Jörg Kreuter, Jens-Peter Stahl, Theodoros Pavlidis, Christof Meyer, Jürgen Mockwitz, Sabine Wenisch, Reinhard Schnettler
Journal: Journal of Controlled Release (2004)
Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results
Authors: Nicole Dastugue, Stefan Suciu, Geneviève Plat, Frank Speleman, Hélène Cavé, Sandrine Girard, Marleen Bakkus, Marie Pierre Pagès, Karima Yakouben, Brigitte Nelken, Anne Uyttebroeck, Carine Gervais, Patrick Lutz, Manuel R. Teixeira, Pierre Heimann, Alice Ferster, Pierre Rohrlich, Marie Agnès Collonge, Martine Munzer, Isabelle Luquet, Patrick Boutard, Nicolas Sirvent, Matthias Karrasch, Yves Bertrand, Yves Benoit
Journal: Blood (2013)
B-Type Natriuretic Peptide in Organic Mitral Regurgitation
Authors: Delphine Detaint, David Messika-Zeitoun, Jean-François Avierinos, Christopher Scott, Horng Chen, John C. Burnett, Maurice Enriquez-Sarano
Journal: Circulation (2005)

B-type natriuretic peptide (BNP) activation observed in cardiac diseases is a predictor of poor outcome; however, in organic mitral regurgitation (MR), BNP determinants and prognostic value are unknown.We prospectively enrolled 124 patients with chronic organic MR (aged 63+/-15 years, 60% males) in whom we measured BNP level and simultaneously quantified MR degree, left ventricular (LV) remodeling, and left atrial (LA) volumes and analyzed long-term outcome. Baseline BNP level (54+/-67 pg/mL, median 31 pg/mL) was associated univariately with multiple clinical and echocardiographic characteristics, but in multivariate analysis, independent determinants of BNP, beyond age and sex (both P< or =0.01), were LV end-systolic volume index, LA volume, atrial fibrillation, and symptoms (all P<0.02). Conversely, MR degree was not independently associated with BNP. During follow-up, patients with high versus low BNP (> or =31 versus <31 pg/mL) displayed lower survival rates (at 5 years, 72+/-10% versus 95+/-5%, P=0.03) and higher rates of the combined end point of death and heart failure (at 5 years, 42+/-10% versus 16+/-7%, P=0.03). In multivariate analysis, with adjustment for age, sex, functional class, MR severity, and ejection fraction, BNP was independently predictive of mortality (hazard ratio per 10 pg/mL, 1.23 [95% CI 1.07 to 1.48], P=0.004) and of death or heart failure (hazard ratio per 10 pg/mL, 1.09 [95% CI 1.001 to 1.19], P=0.04).BNP activation in organic MR reflects primarily ventricular and atrial consequences rather than degree of MR. Higher BNP level in patients with organic MR independently predicts adverse events under conservative management. Therefore, BNP activation in organic MR is an emerging biomarker of severity of MR consequences and of poor clinical outcome, and its assessment should be considered in the clinical evaluation and risk stratification of patients with MR.
To opt in or opt out of electronic patient records?: Electronic patient record is incompatible with confidentiality
Authors: Michael Foley
Journal: BMJ (2006)

EDITOR—From the website of the General Medical Council on the duties of registered doctors:

> Doctors hold information about patients which is private and sensitive. This information must not be given to others unless the patient consents or you can justify the disclosure. 
> 
> Patients have a right to expect that information about them will be held in confidence by their doctors. Confidentiality is central to trust between doctors and patients. Without assurances about confidentiality, patients may be reluctant to give doctors the information they need in order to provide good care. …
Iron Enrichment of Food
Authors: Robert C. Wetherell
Journal: JAMA (1974)

ABSTRACT To the Editor.— For the past several years, the Food and Drug Administration (FDA) and other nongovernmental scientific groups have been reviewing the issues relating to increasing the amounts of iron and other nutrients permitted by the standards for certain flours, farina, and bakery products. Proposals concerning this were first published in the Federal Register of April 1, 1970, and revisions in the Federal Register of Dec 3, 1971. Comments were invited on the proposals.A final order establishing new enrichment levels for certain flours and bakery products was published in the Federal Register of Oct 15, 1973. As provided in the Federal Food, Drug, and Cosmetic Act, time was allowed for the filing of objections and the requesting of a public hearing on the order. Because of the objections and the requests received, on Feb 11, 1974, we published certain revisions to the order (including a stay of that section
The Dysregulation of Human Subjects Research
Authors: Norman Fost, Robert J. Levine
Journal: JAMA (2007)

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Abstract LB-302: Activity of PF-04691502, A dual PI3K/mTOR inhibitor in breast cancer cell lines and models discriminates between ER, PR and HER2 positive and negative segments
Authors: Jing Yuan, Nathan Van Lee, Adam Pavlicek, Keith Ching, Joan Cao, Scott Garza, Kenneth E. Hook, Mark Ozeck, Matthew A. Marx, James G. Christensen, Julie L.C. Kan
Journal: Cancer Research (2010)

Abstract The PI3K pathway plays a role in key cellular functions that include regulation of cell growth, proliferation, survival, angiogenesis, and motility. PI3K/AKT pathway aberrations are common in cancer comprising PTEN loss of function through mutations, deletion, and methylation events and gain of function at the PIK3CA locus including mutations and amplification events resulting in deregulation of this pathway. Thus, pharmacological intervention of this pathway should impact cellular functions central to survival of cancer cells. PIK3CA mutations/amplification and PTEN loss of heterozygosity have been reported to occur in approximately 35-40% and 20% of breast cancer, respectively and suggest this patient population could benefit from treatment using a small molecule inhibitor that targets the PI3K pathway. PF-04691502 which is a potent inhibitor of all PI3K isoforms and mTOR (TORC1 and TORC2) presently in Phase 1 trials was evaluated for its growth inhibitory or cytoreductive activity over a panel of 30 breast cancer cell lines. PF-04691502 had robust &amp;lt;300nM (IC50%) antiproliferative activity across the panel of breast cell lines. We observed a trend whereby cell lines that were hormone receptor (ER and/or PR) and HER2 negative (triple negative) were least sensitive and cell lines that were HER2(+) and/or hormone receptor positive (ER and/or PR) were more sensitive to PF-04691502. These studies were extended in vivo with PF-04691502 as a single agent and in combination in a HER2, ER and PR positive xenograft model with robust tumor growth inhibition in combination with docetaxel or with the pan-HER inhibitor, PF-00299804. In a xenograft that was triple negative, administration of single agent PF-4691502 at the MTD resulted in 60% tumor growth inhibition. In conclusion, our findings suggest that the ER/PR and/or HER2 positive breast cancer segment may particularly benefit from PI3K/mTOR inhibitor based treatment regimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-302.
THE PARTICIPATION OF BONE IN TOTAL BODY SODIUM METABOLISM IN THE RAT 1
Authors: William H. Bergstrom
Journal: Journal of Clinical Investigation (1955)

Sixty years ago Gabriel demonstrated the pres- ence of substantial amounts of sodium in the chloride-free residue of bone which had been ex- tracted with alkaline glycol solutions (1).In 1936, Harrison, Darrow, and Yannet (2) defined "extra" bone sodium as that present in ex- cess of the amount predictable from chloride content and suggested that at least 25 per cent of the total body sodium content might be bound chemi- cally to bone salt.Subsequently, Kaltreider, Meneely, Allen, and Bale (3), Forbes and Perley (4), Stern, Cole, Bass, and Overman (5), and Edelman, James, Baden, and Moore (6) have shown that 30 to 40 per cent of bone sodium is ex- changeable with circulating radiosodium within 24 hours.These workers have confirmed the earlier impressions of Harrison, Darrow, and Yannet by finding approximately one-third of total body sodium to be in the skeleton.Reduction of bone sodium during acute acidosis has been demonstrated in dogs by Nichols and Nichols (7) and in rats by Bergstrom and Wallace (8).The former found an average decrease of 18.6 mEq. of sodium per kilogram of wet fat-free bone in dogs after four hours of sodium depletion by means of hemodialysis.Rats depleted of so- dium and made acidotic by intraperitoneal dialysis against ammonium chloride solutions lost 42 mEq. of sodium per kilogram of wet bone within 48 hours.This represents 28 per cent of the total extra bone sodium and corresponds closely in magnitude to the fraction shown previously to be exchangeable with circulating radioisotope.Darrow, Schwartz, lannucci, and Coville (9), Cotlove, Holliday, Schwartz, and Wallace (10), and others have indicated that intracellular sodium may undergo wide fluctuations around its normal
THE AUTOGENOUS PEG GRAFT IN CERTAIN FRACTURES OF THE FEMUR
Authors: W. Mercer
Journal: BMJ (1923)

AUTOGENOruS PEG GRAFT FOR FRACTURES OF FEMUR.[RITRN 5. Frequency of Dose.If 3 or 4 grains be adopted as a dose, and 16 grains as needful daily, it means that four or five doses a day must be given.For a full-sized adult this implies an amount just bordering on one sufficient to cause nervous symptoms, varying with the patient-symptoms which I always try to avoid.This will effect a fairly continuous, yet mild, quininization of the patient's system, with the idea of steadily lowering the vitality of the plasmodia till they become unable to reproduce their kind-just the opposite of the therapia sterilisans magna, or knock-out blow.It is this great evenness and persistence-of treatment that I venture to think affords this, and one which might be labelled " therapia sterilisans perstans."The doses should be given as far as possible at equal intervals, and therefore one should be given during the night, if possible, or at least the last thing at night, and another the first thing in the morning.
Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human
Authors: Yu-Hsun Lo, Yu-Wen Huang, Yung-Hsuan Wu, Chi-Shan Tsai, Yu-Chuan Lin, Shu-Ting Mo, Wen-Chih Kuo, Ya-Ting Chuang, Si-Tse Jiang, Hsiu-Ming Shih, Ming-Zong Lai
Journal: Blood (2013)
Impact of musculoskeletal disorders on quality of life: an inception cohort study
Authors: Clément Roux, Florence Guillemin, S. Boini, Fleur Longuetaud, Nathalie Arnault, Serge Hercberg, Serge Briançon
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To assess longitudinally the impact of new onset musculoskeletal (MSK) disorders on quality of life (QoL). <b>Methods:</b> An inception cohort of 1202 subjects in France aged 45–60 years was determined to be free of MSK problems at baseline. Over 28 months of follow up between 1996 and 1998, 310 were diagnosed with MSK disorders and matched for age and sex with 620 healthy controls. The impact of the MSK disorder onset on QoL was assessed by the change in SF-36 dimension scores over time, using a linear mixed ANOVA model to compare the groups. <b>Results:</b> The incidence of MSK disorder was 13.6% per person-year in the spine, 4.2% per person-year in a joint, and 4.6% per person-year at an extra-articular site. The greatest change in QoL was a 10 point drop in the 100 point SF-36 bodily pain dimension scale in the MSK group. Compared with controls, subjects with an MSK disorder had significantly greater reductions in the following dimensions: bodily pain (a −7.4 point difference in change), vitality (−2.7), general health (−1.8), and physical functioning (−1.3). Within the MSK group, chronic disorders had a greater impact than acute ones on the physical functioning (−2.1), role emotional (−8.4), and social functioning (−5.9) dimensions. <b>Conclusion:</b> New onset MSK disorders have a marked deleterious effect on QoL in the physical domain, with lesser effects on social and mental functioning. This evidence of an early significant impact on their QoL reinforces recent recommendations for early treatment and primary prevention.