tbuckley/cabot-search huggingface dataset:
Angiographic validation of eigenvolume to measure left ventricular size.
Authors: A C Chagas, S A Glantz
Journal: Circulation Research (1988)

Radiopaque markers implanted in the left ventricle allow one to follow the motion of specific elements of myocardium and compute a measure of relative left ventricular volume, called "eigenvolume." Workers in our laboratory partially validated this measure in excised dog hearts by comparing eigenvolumes with volumes of balloons in the left ventricle. Perhaps because the balloon did not fully fill the left ventricle, there was a significant nonzero intercept in the relation between eigenvolume and balloon volume. Therefore, the results only partially confirmed the eigenvolume theory because eigenvolume should be proportional to cavity volume. This study compares eigenvolume with left ventricular volume measured by biplane angiography in intact beating hearts following hemodynamic interventions (atropine, phenylephrine, nitroprusside, volume loading, and propranolol). We performed 32 angiograms in five dogs. A high correlation (r = 0.958 +/- 0.029 [SD]) was found between eigenvolumes and left ventricular volumes. In contrast to earlier in vitro validations and consistent with theory, the intercept of the relation between eigenvolume and left ventricular cavity volume (angiovolume) was not significantly different from zero. These data strengthen the hypothesis that eigenvolume accurately reflects true left ventricular volume in vivo. These same data were used to assess the immediate (i.e., within a few beats) effect of angiography. Left ventricular volume loading associated with the angiogram modestly (6%) increases left ventricular end-diastolic and end-systolic eigenvolumes without changing stroke volume or pressures, consistent with a mild negative inotropic effect.
Expression profiling: a cost-effective biomarker discovery tool for the personal genome era
Authors: David Gurwitz
Journal: Genome Medicine (2013)

Despite the declining cost of 'personal genomes' and the acknowledged usefulness of individual genome sequences to understand human health, for the near future, personal genomes alone are unlikely to become the leading research tool in genomic medicine.I argue that, at present, expression profi ling studies are the most promising and costeff ective tool for discovering new disease and drugresponse biomarkers.$1,000 personal genomes?Not around the corner Th e proliferation of studies on personal genomes is fueled by reduced sequencing costs and improved bio informatics software tools.Substantial advances in understanding human biology in health and disease and improved diagnostic capacities are foreseen with the availability of personal genome sequences [1,2].Yet, ex pec tations from personal genomes should not be over stated: individual genome sequencing per se even when combined with comprehensive individual medical records will not suffi ce to decipher the overwhelming complexity of human biology and disease pathology.Our current level of understanding of biology in general, and human biology in particular, is simply too low to interpret the information encoded in individual DNA sequences [3].Moreover, even with dramatically reduced DNA se quen cing costs, the high costs of data interpretation subsequent to the tremendous bioinformatics eff ort of analyzing 6.2 Gb nucleotides of two copies of one individual genome means that personal genome sequen cing will not become clinically routine in the near future.Currently, at the 10th anniversary of the Human Genome Project's conclusion, whole genome sequencing is being put into practice in leading medical academic centers, predominantly for cancer diagnosis and treatment.But it will be many years before it becomes a widespread, routine clinical tool.
The effect of the vehicle formulation on the stratum corneum penetration characteristics of clobetasol 17-propionate in vivo
Authors: W.S. WATSON, A.Y. FINLAY
Journal: British Journal of Dermatology (1988)

The multiple skin surface biopsy technique to measure stratum corneum (SC) penetration characteristics in vivo has been more accurately quantified and used to provide information on the kinetics of transfer of a topical steroid through the SC. Radiolabelled clobetasol 17-propionate formulated in two different vehicles, consisting primarily of dibutyl adipate or of propylene glycol, was applied and the penetration characteristics compared. Using exponential expressions for radioactivity in skin surface biopsies as a function of SC depth, and total SC radioactivity as a function of time, a mathematical model was developed to calculate the rate of loss of steroid through superficial shedding and the rate of transfer of steroid from the SC into the epidermis. When a topical steroid was applied for 8 h under gauze occlusion, over 80% was recovered from the gauze.
'Low sodium' diuresis and ileal loss in patients with ileostomies: effect of desmopressin.
Authors: M Sutters, D J Carmichael, R J Unwin, C Sozi, M Hunter, J Calam, S L Lightman, W S Peart
Journal: Gut (1991)

Patients with ileostomies show an early diuresis when sodium restricted; this, together with an obligatory ileal sodium loss, predisposes them to severe salt and water depletion. The role of arginine vasopressin in this circumstance and whether it is natriuretic, or antinatriuretic, is unclear. There is also controversy over its likely effect on small bowel fluid reabsorption. We have examined the effect of the non-pressor (V2) synthetic vasopressin analogue 1-deamino-8-D-arginine (desmopressin) on renal and ileal sodium and water excretion in ileostomy patients during acute adaptation to a low sodium diet. Patients were studied on two separate occasions (nonrandomised) with and without the administration of desmopressin (0.75 micrograms intramuscular, three times a day). In eight subjects without desmopressin there was pronounced diuresis on the first low sodium day, associated with a fall in renal sodium excretion and no change in ileal output or composition. In five (of the original) subjects with desmopressin there was pronounced antidiuresis, no change in renal sodium excretion, and no change in ileal output or composition. In both studies rises in plasma renin activity and salivary aldosterone concentration lagged behind the early decline in renal sodium excretion. We have confirmed the phenomenon of 9low sodium9 diuresis after sodium restriction in ileostomy patients and shown that it can be prevented by desmopressin. Desmopressin has no direct or indirect effect on renal sodium excretion or ileal fluid and electrolyte loss in humans.
Oxidant stress from nitric oxide synthase–3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load
Authors: Eiki Takimoto, Hunter C. Champion, Manxiang Li, Shuxun Ren, E. Rene Rodriguez, Barbara Tavazzi, Giuseppe Lazzarino, Nazareno Paolocci, Kathleen L. Gabrielson, Yibin Wang, David A. Kass
Journal: Journal of Clinical Investigation (2005)

Cardiac pressure load stimulates hypertrophy, often leading to chamber dilation and dysfunction. ROS contribute to this process. Here we show that uncoupling of nitric oxide synthase–3 (NOS3) plays a major role in pressure load–induced myocardial ROS and consequent chamber remodeling/hypertrophy. Chronic transverse aortic constriction (TAC; for 3 and 9 weeks) in control mice induced marked cardiac hypertrophy, dilation, and dysfunction. Mice lacking NOS3 displayed modest and concentric hypertrophy to TAC with preserved function. NOS3–/– TAC hearts developed less fibrosis, myocyte hypertrophy, and fetal gene re-expression (B-natriuretic peptide and α–skeletal actin). ROS, nitrotyrosine, and gelatinase (MMP-2 and MMP-9) zymogen activity markedly increased in control TAC, but not in NOS3–/– TAC, hearts. TAC induced NOS3 uncoupling in the heart, reflected by reduced NOS3 dimer and tetrahydrobiopterin (BH4), increased NOS3-dependent generation of ROS, and lowered Ca2+-dependent NOS activity. Cotreatment with BH4 prevented NOS3 uncoupling and inhibited ROS, resulting in concentric nondilated hypertrophy. Mice given the antioxidant tetrahydroneopterin as a control did not display changes in TAC response. Thus, pressure overload triggers NOS3 uncoupling as a prominent source of myocardial ROS that contribute to dilatory remodeling and cardiac dysfunction. Reversal of this process by BH4 suggests a potential treatment to ameliorate the pathophysiology of chronic pressure-induced hypertrophy.
The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis
Authors: A P Anandarajah, E M Schwarz, S Totterman, J Monu, C Y Feng, T Shao, S A Haas-Smith, C T Ritchlin
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> The frequency of osteoclast precursors (OCPF) and the presence of bone marrow oedema (BMO) are potential response biomarkers in psoriatic arthritis (PsA). Previous studies suggest a central role for tumour necrosis factor (TNF) in the formation of osteoclast precursors. To better understand this association, the effect of etanercept on OCPF and BMO was analysed in PsA patients with erosive arthritis. <h3>Methods:</h3> A total of 20 PsA patients with active erosive PsA were enrolled. Etanercept was administered twice weekly for 24 weeks. OCPF was measured and clinical assessments were performed at baseline, 2, 12 and 24 weeks. Gadolinium enhanced MR images were obtained at baseline and 24 weeks. <h3>Results:</h3> Significant improvements in joint score (p&lt;0.001), HAQ scores (p&lt;0.001) and SF-36 parameters were observed after 6 months of therapy with etanercept compared to baseline. The median OCPF decreased from 24.5 to 9 (p = 0.04) and to 7 (p = 0.006) after 3 months and 6 months of treatment, respectively. MR images were available for 13 patients. The BMO volume decreased in 47 and increased in 31 sites at 6 months. No correlation was noted between OCPF, BMO and clinical parameters. <h3>Conclusion:</h3> The rapid decline in OCPF and overall improvement in BMO after anti-TNFα therapy provides one mechanism to explain the anti-erosive effects of TNF blockade in PsA. Persistence of BMO after etanercept treatment, despite a marked clinical response, was unexpected, and suggests ongoing subchondral inflammation or altered remodelling in PsA bone.
Drug-disease and drug-drug interactions: systematic examination of recommendations in 12 UK national clinical guidelines
Authors: S. Dumbreck, A. Flynn, M. Nairn, M. Wilson, S. Treweek, S. W. Mercer, P. Alderson, A. Thompson, K. Payne, B. Guthrie
Journal: BMJ (2015)

<b>Objective</b> To identify the number of drug-disease and drug-drug interactions for exemplar index conditions within National Institute of Health and Care Excellence (NICE) clinical guidelines. <b>Design</b> Systematic identification, quantification, and classification of potentially serious drug-disease and drug-drug interactions for drugs recommended by NICE clinical guidelines for type 2 diabetes, heart failure, and depression in relation to 11 other common conditions and drugs recommended by NICE guidelines for those conditions. <b>Setting</b> NICE clinical guidelines for type 2 diabetes, heart failure, and depression <b>Main outcome measures</b> Potentially serious drug-disease and drug-drug interactions. <b>Results</b> Following recommendations for prescription in 12 national clinical guidelines would result in several potentially serious drug interactions. There were 32 potentially serious drug-disease interactions between drugs recommended in the guideline for type 2 diabetes and the 11 other conditions compared with six for drugs recommended in the guideline for depression and 10 for drugs recommended in the guideline for heart failure. Of these drug-disease interactions, 27 (84%) in the type 2 diabetes guideline and all of those in the two other guidelines were between the recommended drug and chronic kidney disease. More potentially serious drug-drug interactions were identified between drugs recommended by guidelines for each of the three index conditions and drugs recommended by the guidelines for the 11 other conditions: 133 drug-drug interactions for drugs recommended in the type 2 diabetes guideline, 89 for depression, and 111 for heart failure. Few of these drug-disease or drug-drug interactions were highlighted in the guidelines for the three index conditions. <b>Conclusions</b> Drug-disease interactions were relatively uncommon with the exception of interactions when a patient also has chronic kidney disease. Guideline developers could consider a more systematic approach regarding the potential for drug-disease interactions, based on epidemiological knowledge of the comorbidities of people with the disease the guideline is focused on, and should particularly consider whether chronic kidney disease is common in the target population. In contrast, potentially serious drug-drug interactions between recommended drugs for different conditions were common. The extensive number of potentially serious interactions requires innovative interactive approaches to the production and dissemination of guidelines to allow clinicians and patients with multimorbidity to make informed decisions about drug selection.
Puberty timing has profound effect on later health, study finds
Authors: J. Wise
Journal: BMJ (2015)

Early puberty in men and women is linked with higher risks for type 2 diabetes, cardiovascular disease, and a range of other adverse health outcomes, a large study published in Scientific Reports has found.1

Research carried out by the Medical Research Council Epidemiology Unit at the University of Cambridge found that earlier and later puberty timing in men and women were both associated with 48 adverse outcomes across a range of cancers, as well as cardiometabolic, gynaecological/obstetric, gastrointestinal, musculoskeletal, and neurocognitive categories. Early and late menarche were both associated with a higher risk of early natural menopause in women.

The UK …
Genetic Variation at the <i>CYP19A1</i> Locus Predicts Circulating Estrogen Levels but not Breast Cancer Risk in Postmenopausal Women
Authors: Christopher A. Haiman, Laure Dossus, V. Wendy Setiawan, Daniel O. Stram, Alison M. Dunning, Gilles Thomas, Michael J. Thun, Demetrius Albanes, David Altshuler, Eva Ardanaz, Heiner Boeing, Julie Buring, Noël Burtt, Eugenia E. Calle, Stephen Chanock, Françoise Clavel-Chapelon, Graham A. Colditz, David G. Cox, Heather Spencer Feigelson, Susan E. Hankinson, Richard B. Hayes, Brian E. Henderson, Joel N. Hirschhorn, Robert Hoover, David J. Hunter, Rudolf Kaaks, Laurence N. Kolonel, Loïc Le Marchand, Per Lenner, Eiliv Lund, Salvatore Panico, Petra H. Peeters, Malcolm C. Pike, Elio Riboli, Anne Tjonneland, Ruth Travis, Dimitrios Trichopoulos, Sholom Wacholder, Regina G. Ziegler
Journal: Cancer Research (2007)

The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (> or =5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5' region of CYP19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 x 10(-15)]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer.
Improving draft assemblies by iterative mapping and assembly of short reads to eliminate gaps
Authors: Isheng J Tsai, Thomas D Otto, Matthew Berriman
Journal: Genome biology (2010)

Advances in sequencing technology allow genomes to be sequenced at vastly decreased costs. However, the assembled data frequently are highly fragmented with many gaps. We present a practical approach that uses Illumina sequences to improve draft genome assemblies by aligning sequences against contig ends and performing local assemblies to produce gap-spanning contigs. The continuity of a draft genome can thus be substantially improved, often without the need to generate new data.
A Randomized, Controlled Trial of the Use of Pulmonary-Artery Catheters in High-Risk Surgical Patients
Authors: James Dean Sandham, Russell Douglas Hull, Rollin Frederick Brant, Linda Knox, Graham Frederick Pineo, Christopher J. Doig, Denny P. Laporta, Sidney Viner, Louise Passerini, Hugh Devitt, Ann Kirby, Michael Jacka
Journal: New England Journal of Medicine (2003)

Some observational studies suggest that the use of pulmonary-artery catheters to guide therapy is associated with increased mortality.
Experimental autoimmune encephalomyelitis repressed by microglial paralysis
Authors: Frank L Heppner, Melanie Greter, Denis Marino, Jeppe Falsig, Gennadij Raivich, Nadine Hövelmeyer, Ari Waisman, Thomas Rülicke, Marco Prinz, Josef Priller, Burkhard Becher, Adriano Aguzzi
Journal: Nature Medicine (2005)
Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection
Authors: Atsushi Ozasa, Yasuhito Tanaka, Etsuro Orito, Masaya Sugiyama, Jong-Hon Kang, Shuhei Hige, Tomoyuki Kuramitsu, Kazuyuki Suzuki, Eiji Tanaka, Shunichi Okada, Hajime Tokita, Yasuhiro Asahina, Kazuaki Inoue, Shinichi Kakumu, Takeshi Okanoue, Yoshikazu Murawaki, Keisuke Hino, Morikazu Onji, Hiroshi Yatsuhashi, Hiroshi Sakugawa, Yuzo Miyakawa, Ryuzo Ueda, Masashi Mizokami
Journal: Hepatology (2006)

The outcome of acute hepatitis B virus (HBV) infection is variable, influenced by host and viral factors. From 1982 through 2004, 301 patients with acute HBV infection entered a multi-center cross-sectional study in Japan. Patients with fulminant hepatitis (n = 40) were older (44.7 ± 16.3 vs. 36.0 ± 14.3 years, P &lt; .0017), less predominantly male (43% vs. 71%, P = .0005), less positive for hepatitis B e antigen (HBeAg) (23% vs. 60%, P &lt; .0001), less infected with subgenotype Ae (0% vs. 13%, P &lt; .05), and more frequently with Bj (30% vs. 4%, P &lt; .0001) than those with acute self-limited hepatitis (n = 261). Precore (G1896A) and core-promoter (A1762T/G1764A) mutations were more frequent in patients with fulminant than acute self-limited hepatitis (53% vs. 9% and 50% vs. 17%, P &lt; .0001 for both). HBV infection persisted in only three (1%) patients, and they represented 2 of the 23 infected with Ae and 1 of the 187 with the other subgenotypes (9% vs. 0.5%, P = .032); none of them received antiviral therapy. In multivariate analysis, age 34 years or older, Bj, HBeAg-negative, total bilirubin 10.0 mg/dL or greater, and G1896A mutation were independently associated with the fulminant outcome. In in vitro transfection experiments, the replication of Bj clone was markedly enhanced by introducing either G1896A or A1762T/G1764A mutation. In conclusion , persistence of HBV was rare (1%) and associated with Ae, whereas fulminant hepatitis was frequent (13%) and associated with Bj and lack of HBeAg as well as high replication due to precore mutation in patients with acute HBV infection. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Randomized Phase III Trial of High-Dose Interleukin-2 Versus Subcutaneous Interleukin-2 and Interferon in Patients With Metastatic Renal Cell Carcinoma
Authors: David F. McDermott, Meredith M. Regan, Joseph I. Clark, Lawrence E. Flaherty, Geoffery R. Weiss, Theodore F. Logan, John M. Kirkwood, Michael S. Gordon, Jeffrey A. Sosman, Marc S. Ernstoff, Christopher P.G. Tretter, Walter J. Urba, John W. Smith, Kim A. Margolin, James W. Mier, Jared A. Gollob, Janice P. Dutcher, Michael B. Atkins
Journal: Journal of Clinical Oncology (2004)

The Cytokine Working Group conducted a randomized phase III trial to determine the value of outpatient interleukin-2 (IL-2) and interferon alfa-2b (IFN) relative to high-dose (HD) IL-2 in patients with metastatic renal cell carcinoma.Patients were stratified for bone and liver metastases, primary tumor in place, and Eastern Cooperative Oncology Group performance status 0 or 1 and then randomly assigned to receive either IL-2 (5 MIU/m(2) subcutaneously every 8 hours for three doses on day 1, then daily 5 days/wk for 4 weeks) and IFN (5 MIU/m(2) subcutaneously three times per week for 4 weeks) every 6 weeks or HD IL-2 (600,000 U/kg/dose intravenously every 8 hours on days 1 through 5 and 15 to 19 [maximum 28 doses]) every 12 weeks.One hundred ninety-two patients were enrolled between April 1997 and July 2000. Toxicities were as anticipated for these regimens. The response rate was 23.2% (22 of 95 patients) for HD IL-2 versus 9.9% (nine of 91 patients) for IL-2/IFN (P = .018). Ten patients receiving HD IL-2 were progression-free at 3 years versus three patients receiving IL-2 and IFN (P = .082). The median response durations were 24 and 15 [corrected] months (P = .18) [corrected] and median survivals were 17.5 and 13 months (P = .24). For patients with bone or liver metastases (P = .001) or a primary tumor in place (P = .040), survival was superior with HD IL-2.This randomized phase III trial provides additional evidence that HD IL-2 should remain the preferred therapy for selected patients with metastatic renal cell carcinoma.
Vitamin D and autoimmunity: new aetiological and therapeutic considerations
Authors: Y. Arnson, H. Amital, Y. Shoenfeld
Journal: Annals of the Rheumatic Diseases (2007)

Vitamin D is frequently prescribed by rheumatologists to prevent and treat osteoporosis. Several observations have shown that vitamin D inhibits proinflammatory processes by suppressing the enhanced activity of immune cells that take part in the autoimmune reaction. Moreover, recent evidence strongly suggests that vitamin D supplementation may be therapeutically beneficial, particularly for Th1-mediated autoimmune disorders. Some reports imply that vitamin D may even be preventive in certain disorders such as multiple sclerosis and diabetes type 1. It seems that vitamin D has crossed the boundaries of calcium metabolism and has become a significant factor in a number of physiological functions, specifically as a biological inhibitor of inflammatory hyperactivity.