tbuckley/cabot-search huggingface dataset:
Intramitochondrial free calcium in cardiac myocytes in relation to dehydrogenase activation
Authors: F. D. Lisa, G. Gambassi, H. Spurgeon, R. G Hansford
Journal: Cardiovascular Research (1993)

The aim was to quantitate intramitochondrial free Ca2+ ([Ca2+]m) in cardiac myocytes under conditions of stimulation previously shown to cause activation of pyruvate dehydrogenase.[Ca2+]m was monitored in single, isolated rat cardiac myocytes using fluorescence microscopy following the loading of the cells with the fluorescent chelating agent indo-1, in its permeant acetoxymethylester form, and the selective quenching of cytosolic fluorescence with MnCl2. The extent of contraction upon electrical stimulation was also measured.Electrical stimulation at 2 Hz and higher frequency raised [Ca2+]m significantly, and this was potentiated by exposure to isoprenaline. However, isoprenaline had no effect in quiescent cells, in which [Ca2+]m was raised above resting values by partial replacement of Na+ in the medium. The mitochondrial uncoupling agent carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) raised [Ca2+]m in unstimulated cells, but lowered it in cells subjected to electrical stimulation at 2 Hz or more, to partial Na+ replacement, or to the alkaloid veratridine.The values of [Ca2+]m in quiescent myocytes (approximately 100 nmol.litre-1) would be associated with very little activation by Ca2+ of pyruvate dehydrogenase phosphatase, based on determination of K0.5 value of 650 nmol.litre-1 in work with mitochondrial suspensions. By contrast, the values of [Ca2+]m associated with electrical stimulation at 2 Hz or greater in the presence of beta adrenergic activation (> 500 nmol.litre-1) would be associated with significant dehydrogenase activation. The effect of beta adrenergic activation is only seen in the presence of electrical stimulation and probably involves enhancement of systolic transients in cytosol [Ca2+]. Effects of uncoupling agents validate the conclusions on the direction and magnitude of the mitochondrial Ca2+ gradient in situ in living myocytes.
Managers accuse ministers of spin over money for NHS
Authors: L. Beecham
Journal: BMJ (2000)

The health secretary's announcement last week that he was going to use his powers of direction to ensure that £600m ($960m) of new NHS money went to front line services has angered representatives of health authorities.

Alan Milburn told the House of Commons last week that £600m of the extra £2bn which the chancellor of the exchequer announced in the budget for the next financial year (1 April, p 889) would “put local hospital and GP services on to a sound financial footing.” The health secretary said that the money had to be spent on real services: “That …
Vandetanib Plus Chemotherapy for Induction Followed by Vandetanib or Placebo As Maintenance for Patients with Advanced Non–Small-Cell Lung Cancer: A Randomized Phase 2 PrECOG Study (PrE0501)
Authors: Joseph Aisner, Judith B. Manola, Shaker R. Dakhil, Philip J. Stella, Mika A. Sovak, Joan H. Schiller
Journal: Journal of Thoracic Oncology (2013)
Group Psychotherapy of Dysfunctional Fear of Progression in Patients with Chronic Arthritis or Cancer
Authors: Peter Herschbach, Petra Berg, Sabine Waadt, Gabriele Duran, Ursula Engst-Hastreiter, Gerhard Henrich, Katrin Book, Andreas Dinkel
Journal: Psychotherapy and Psychosomatics (2009)

&lt;i&gt;Background:&lt;/i&gt; This study investigated the effectiveness of brief psychotherapeutic group interventions in reducing dysfunctional fear of disease progression (FoP). The interventions comprised either cognitive-behavioral group therapy or supportive-experiential group therapy. We tested whether these generic interventions would prove effective in different illness types. &lt;i&gt;Methods:&lt;/i&gt; Chronic arthritis in- patients (n = 174) and cancer in-patients (n = 174), respectively, were randomized to receive one of the two interventions. The patients provided data before intervention, at discharge, and at 3 and 12 months of follow-up. FoP was the primary outcome, secondary outcomes were anxiety, depression and quality of life. A treatment-as-usual control group provided data on the primary outcome. &lt;i&gt;Results:&lt;/i&gt; Patients with chronic arthritis indicated higher levels of FoP than cancer patients. The results revealed that, compared with no specialized intervention, both group therapies were effective in reducing dysfunctional FoP, but only among cancer patients. The effect sizes were 0.54 (cognitive-behavioral therapy) and 0.50 (supportive experiential therapy). The interventions were not differently effective in reducing the secondary outcomes. &lt;i&gt;Conclusions:&lt;/i&gt; Dysfunctional FoP can be effectively targeted with brief group interventions. Psychotherapeutic interventions for reducing FoP should focus on specific illness characteristics.
Abstract 3158: MicroRNA signatures associate with pathogenesis and progression of osteosarcoma
Authors: Zaidoun Salah, Kevin B. Jones, Sara Del Mare, Rami Aqeilan
Journal: Cancer Research (2012)

Abstract Osteosarcoma is the most common sarcoma in the skeleton, but remains elusive with regard to molecular etiology. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development as well as oncogenesis. Here we identify an miRNA signature reflecting the pathogenesis of conventional (osteoblastic/fibroblastic) osteosarcoma from surgically procured samples from human patients. The signature includes high expression of miR-181a, miR-181b, and miR-181c as well as reduced expression of miR-29b, miR-16, and miR-142-5p. Osteosarcomas of varied histology subtype co-localized on unsupervised hierarchical clustering, suggesting that the signature profile relates to oncogenesis itself, rather than simply a differentiation phenotype. We also demonstrated that miR-181b and miR-29b exhibit restricted expression to distinct cell populations in the tumor tissue. Further, higher expression of miR-27a and miR-181c* in pre-treatment biopsy samples characterized patients who developed clinical metastatic disease. In addition, higher expression of miR-451 and miR-15b in pre-treatment samples correlated with subsequent positive response to chemotherapy. In vitro functional validation of miR-16 and miR-27a confirmed opposing roles in human osteoblast and osteosarcoma cell lines. Furthermore, predicted target genes for miR-16 and miR-27a were confirmed as down-regulated by real-time PCR. Affymetrix array profiling of cDNAs from osteosarcoma specimens and controls were interrogated according to predicted targets of miR-16, miR142-5p, miR-29b, miR-181a/b, and miR-27a. This analysis revealed positive and negative correlations highlighting pathways of known importance to osteosarcoma, as well as novel genes. Thus, our findings establish miRNA signatures associated with pathogenesis, metastasis, and responsiveness to treatment in osteosarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3158. doi:1538-7445.AM2012-3158
Abstract 1349: Ablation of <i>E2f3</i> in macrophages reduces the incidence of lung metastasis
Authors: Prashant Trikha, Clarissa Pena, Nidhi Sharma, Andreas Reyes, Gustavo Leone
Journal: Cancer Research (2010)

Abstract The tumor stroma is predominantly composed of cells of the immune system, one of them are the tumor-associated macrophages (TAMs). Tumor macrophages are recruited to the tumor in response to cytokines secreted by the tumor epithelial cells. TAMs secrete proteases into the extracellular matrix (ECM) that contributes to tumor cell intravasation. Rb-E2F axis represents one of the important pathways involved during cell cycle and is deregulated in number of cancers. E2Fs have distinct roles in the control of cell proliferation, apoptosis and differentiation pathways. We have previously shown that E2F are important downstream targets in CSF-1 signaling cascade that are involved in macrophage survival and proliferation. Present study is aimed at exploring the link between conditional ablation of E2f3 in TAM and its effect on lung metastasis using MMTV-PyMT mouse model of breast cancer. Ablation of E2f3 in the tumor macrophages resulted in a reduction of lung metastasis without affecting tumor onset or macrophage numbers. Microarray analysis of E2f3 deleted TAMs showed an up-regulation in expression of genes involved during metastasis. Our results show that E2f3 regulates the physiological processes in TAMs that inhibit lung metastasis. 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 1349.
Clinical significance of intrahepatic hepatitis B virus covalently closed circular DNA in chronic hepatitis B patients who received cytotoxic chemotherapy
Authors: Chee-kin Hui, Scott Bowden, Kathy Jackson, Wing-yan Au, Daniel Y. T. Fong, Albert K. W. Lie, Chor-sang Chim, Raymond Liang, George K. K. Lau
Journal: Blood (2005)
A mystery shopper reports
Authors: Rob Hull
Journal: BMJ (2008)

As the spouse of a practising GP I did not make much call on the resources of the NHS during my working life. Domestic treatment and occasional short cuts to the right expert usually solved the problem. But now that I am retired I have the leisure to try out the NHS as a consumer—and to report back. In other retail spheres, anecdotal evidence from “mystery shoppers” gives valuable insight into the weaknesses of management systems. I am able to offer the same service to the medical profession—on an occasional basis, I hope.

My opportunity to do so arose last year when I developed painful capsulitis in my shoulder. Luckily, I was able to make a direct comparison with the treatment of the other shoulder five years earlier. On that occasion I gained immediate relief through a steroid injection. I looked forward to the same treatment and was encouraged to learn that it is on offer at many GPs’ surgeries. I duly booked an appointment at the practice where I am registered. Despite my saying there was no hurry, they insisted on an appointment at a busy Monday morning surgery, two working days later. So far, so good.

Like policemen, the GP I met was plainly younger than me, but as a layman I had no reason to doubt his judgment. …
Dystocia after Amputation of Cervix
Authors: W. Calvert
Journal: BMJ (1949)

Until this is appreciated, non-existent disease of the central nervous system will frequently be suspected or even diag- nosed.I have often seen clinical combinations suggesting tabes dorsalis or progressive muscular atrophy in pensioners who were really healthy.Doubtless others have had a similar experience.Summary The results of neurological examination in 200 healthy Chelsea pensioners are given.Absent pupillary reactions, missing tendon-jerks, and super- ficial reflexes were common motor findings.Absent vibration sense in sacrum and lower limbs, dysmetria, and patchy analgesia in the forearms and shins were not unusual.Anatomical location of lesions accounting for such findings was difficult or impossible.The possibility of misdiagnosis owing to such results of senile deterioration is stressed.
Evaluating Hypotheses of Deuterostome Phylogeny and Chordate Evolution with New LSU and SSU Ribosomal DNA Data
Authors: Christopher J. Winchell, Jack Sullivan, Christopher B. Cameron, Billie J. Swalla, Jon Mallatt
Journal: Molecular Biology and Evolution (2002)

We investigated evolutionary relationships among deuterostome subgroups by obtaining nearly complete large-subunit ribosomal RNA (LSU rRNA)-gene sequences for 14 deuterostomes and 3 protostomes and complete small-subunit (SSU) rRNA-gene sequences for five of these animals. With the addition of previously published sequences, we compared 28 taxa using three different data sets (LSU only, SSU only, and combined LSU + SSU) under minimum evolution (with LogDet distances), maximum likelihood, and maximum parsimony optimality criteria. Additionally, we analyzed the combined LSU + SSU sequences with spectral analysis of LogDet distances, a technique that measures the amount of support and conflict within the data for every possible grouping of taxa. Overall, we found that (1) the LSU genes produced a tree very similar to the SSU gene tree, (2) adding LSU to SSU sequences strengthened the bootstrap support for many groups above the SSU-only values (e.g., hemichordates plus echinoderms as Ambulacraria; lancelets as the sister group to vertebrates), (3) LSU sequences did not support SSU-based hypotheses of pterobranchs evolving from enteropneusts and thaliaceans evolving from ascidians, and (4) the combined LSU + SSU data are ambiguous about the monophyly of chordates. No tree-building algorithm united urochordates conclusively with other chordates, although spectral analysis did so, providing our only evidence for chordate monophyly. With spectral analysis, we also evaluated several major hypotheses of deuterostome phylogeny that were constructed from morphological, embryological, and paleontological evidence. Our rRNA-gene analysis refutes most of these hypotheses and thus advocates a rethinking of chordate and vertebrate origins.
Relationship between echocardiography, cardiac output, and abnormally contracting segments in patients with ischemic heart disease.
Authors: R L Sweet, R E Moraski, R O Russell, C E Rackley
Journal: Circulation (1975)

Twenty-four patients with proven coronary artery disease and abnormally-contracting segments were studied by both echocardiography and biplane angiographic techniques. Comparison was made between the left ventricular biplane angiographic volumes and those obtained from echocardiographic measurements which were calculated from cubed function and regression equaltion methods. The percent abnormally contracting segment (ACS) was obtained from biplane left ventricular angiography and was calculated from the diastolic and systolic anteroposterior and lateral angiocardiograms. The angiographic end-diastolic volume correlated with that calculated from the echocardiographic dimensions with an r value of 0.865 and SEE of +/- 22.64 ml. The angiographic end-systolic volume and echo end-systolic volume did not correlate as well, with an r = 0.7063. The difference in stroke volume predicted by the diastolic and systolic echocardiographic dimensions and the actual stroke volume determined by Fick technique was related to the percent abnormally contracting segment of the left ventricle (r = 0.8967). The percent ACS could be estimated from echo and Fick stroke volume measurements by the cube function and regression equations. Echo ventricular volume determinations were analyzed for the cube function method and the regression equations of Fortuin et al. and Teichholz and coworkers, with the method of Fortuin et al. producing the most sensitive relationship: % ACS = 0.32 (SVecho - SVFick) % + 8.9%. The correlation coefficient for the estimate was 0.8967 with a SEE of +/- 4.78%. In patients with coronary artery disease and abnormally contracting segments, echocardiography can provide reliable measurements of left ventricular end-diastolic volume but estimates of end-systolic volume are less accurate. If mitral regurgitation or a ventricular aneurysm can be excluded, the difference in echocardiographic and forward stroke volume by an independent method is related to the angiographic and forward stroke volume by an independent method is related to the angiographic abnormally contracting segment, and this relationship permits estimation of the size of the abnormally, contracting segment.
DIAGNOSIS OF CHOLECYSTITIS AND CHOLELITHIASIS.
Authors: PARKER SYMS
Journal: JAMA (1904)

According to generally accepted statistics, one adult in every ten is the subject of gallstone. Of these about 5 per cent. suffer from symptoms of the disease. A proportion of these cases show such marked symptoms that the diagnosis is easily made, and the condition is readily recognized. A larger proportion of cases, however, present such vague symptoms, or symptoms so little understood by the general practitioner, that diagnosis is not made, and many patients who are much in need of relief which surgery might give, continue as chronic invalids for years until some severe crisis brings them to an untimely end. Owing to the efforts of many able scientists, prominent among whom are Mayo Robson, Kehr, Brewer, the Mayos, Murphy and Richardson, much has been done toward throwing the searchlight of knowledge into that region which has been called the mysterious realm of surgical romance, namely, the right
TCT-306 Intravascular Ultrasound Findings In Complex Coronary Bifurcation Lesions Treated with Single Stenting Versus Double Stenting Strategies
Authors: RICARDO COSTA, Fausto Feres, Rodolfo Staico, Jose Costa, Dimytri Siqueira, Alexandre Abizaid, Luiz Fernando Tanajura, Amanda Sousa, J. Eduardo Sousa, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
Changes Over Time in Risk Profiles of Patients Who Undergo Coronary Artery Bypass Graft Surgery
Authors: Lorraine D. Cornwell, Shuab Omer, Todd Rosengart, William L. Holman, Faisal G. Bakaeen
Journal: JAMA Surgery (2015)

Today's coronary artery bypass grafting (CABG) population appears to comprise sicker patients than in the past; however, little is known about the change in the risk profile.To evaluate the change with time in the risk profile of patients who undergo CABG.Retrospective review of records from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP); 65,097 patients who underwent isolated primary CABG from October 1, 1997, to April 30, 2011, were evaluated.Trends in risk profiles, surgical volume, and modern outcomes in the VA system. We determined the significance of changes in age and major comorbidities across time with simple linear regression analysis and evaluated the rates of perioperative mortality (30-day or in-hospital) and VASQIP predicted risk of mortality trends over time.From 1997 to 2011, there were increases in mean (SD) patient age (63.1 [9.4] vs 64.3 [7. 8] years; R² = 0.34; P = .02) and body mass index (28.3 [5.1] vs 30.1 [5.8]; R² = 0.95). There were also increases in the prevalence of diabetes mellitus (32.8% vs 41.3%; R² = 0.82), preoperative New York Heart Association (NYHA) class III or IV heart failure status (14.3% vs 34.2%; R² = 0.74), and left main coronary artery disease (26.0% vs 32.8%; R² = 0.82) (all P < .001). There was a decrease in the prevalence of advanced angina severity (Canadian Cardiovascular Society class III or IV) (R² = 0.95), previous myocardial infarction (R² = 0.82), and low ejection fraction (≤34%) (R² = 0.88) (all P < .05). There was no significant change in the prevalence of cerebrovascular and peripheral vascular disease, chronic obstructive pulmonary disease, or 3-vessel coronary artery disease. Perioperative mortality rates and the VASQIP predicted risk of mortality, respectively, decreased with time (3.2% and 3.1% vs 1.7% and 1.6%). From 2004 to 2011, there was a significant increase in the prevalence of previous percutaneous coronary intervention (18.6% to 29.2%; R² = 0.82; P = .002). Overall CABG volume decreased (5551 in 1998 vs 3857 in 2012; R² = 0.95; P < .001).From 1997 to 2011, there was a progressive increase in the prevalence of obesity, diabetes, left main coronary artery disease, and advanced NYHA heart failure class among VA patients undergoing CABG. The prevalence of previous myocardial infarction, low ejection fraction, and advanced angina decreased, perhaps because of earlier surgical referral, improvement in medical management, or a shift in patient selection for CABG. Operative mortality also decreased with time. These trends confirm the general perception of significant, ongoing improvement in the care of patients who undergo CABG in the VA, despite an older, sicker population.
Cutaneous Features of Crouzon Syndrome With Acanthosis Nigricans
Authors: Adnan Mir, Timothy Wu, Seth J. Orlow
Journal: JAMA Dermatology (2013)

Crouzon syndrome with acanthosis nigricans is a distinct disorder caused by a mutation in the FGFR3 gene, featuring craniosynostosis, characteristic facial features, and atypical and extensive acanthosis nigricans. Other cutaneous findings have not been thoroughly described.We report 6 cases and summarize the existing literature with regard to the cutaneous manifestations of this disorder. All patients have widespread, early-onset acanthosis nigricans. Patients often have prominent hypopigmented scars at surgical sites and nevi arising early in childhood.In addition to craniofacial malformations, Crouzon syndrome with acanthosis nigricans results in characteristic cutaneous findings.
THE STUDY OF "ROCKY MOUNTAIN SPOTTED FEVER" (TICK FEVER?) BY MEANS OF ANIMAL INOCULATIONS.A PRELIMINARY COMMUNICATION.
Authors: H. T. RICKETTS
Journal: JAMA (1906)

I arrived in Missoula, Montana, April 21, 1906, equipped for the bacteriologic and hematologic study of the so-called Rocky Mountain spotted fever and for the study of the infectious agent by means of animal inoculations. Although the period during which the disease occurs is very limited and the cases very few, it was possible to carry the investigations to a point which affords encouragement for the ultimate solution of some of the problems involved. At this time I wish to give a brief and preliminary presentation of the most important results obtained this year, reserving for a future date a more detailed interpretation of the experiments, when the bacteriologic and histologic studies will have been completed. It will be remembered that the confidence which was at first manifested in the report of Wilson and Chowning concerning the presence of a piroplasma in the blood and erythrocytes of infected patients was
British Practitioners in France
Authors: E. Liveing
Journal: BMJ (1889)

<b>558</b> <h3><b>Objectives</b></h3> A preconditioned alternating projection algorithm (PAPA) using an isotropic total variation (iTV) penalty with higher order gradients is used to reconstruct simulated and physical PET brain data from GE D690 PET/CT. The comparative studies of image quality between PAPA and GE clinical reconstruction are performed. <h3><b>Methods</b></h3> Patients’ FDG brain scans were acquired on a D690 (370 MBq, 1-hour delay) in time-of-flight mode. Reconstructions were performed using a 256x256 matrix with a 300mm field-of-view using resolution recovery. Clinical reconstructions were based on OSEM (3 iterations, 32 subsets) with 2.6mm XY-Gaussian and 3-point [0.2, 0.6, 0.2] axial smoothing post-filtering. PAPA reconstructions were iterated to convergence (30 iterations, 16 subsets) using 1<sup>st</sup> &amp; 2<sup>nd</sup> order gradient penalties and no post filter. Prior to patients’ studies, simulated and physical ACR phantom data were evaluated with the penalty optimized in the root-mean-squared error (RMSE) sense. <h3><b>Results</b></h3> Reconstructions of simulated data shows that inclusion of the 2<sup>nd</sup> order gradient penalty reduces “staircase” artifacts, which are typical for iTV, and lowers the RMSE (up to 30%) compared to optimally filtered fully converged MLEM. Existence of a power-law relationship between the RMSE-optimal penalties and the noise equivalent counts per voxel is demonstrated. The patients’ images reconstructed with PAPA are sharper, have improved contrast, and less noise than the standard-of-care images with a similar convergence rate. <h3><b>Conclusions</b></h3> The use of a combined 1<sup>st</sup> and 2<sup>nd</sup> order gradient iTV penalty increases PET brain image quality by improving the resolution-noise tradeoff. Further, the PAPA algorithm’s fast convergence rate makes it competitive with existing optimization schemes.