tbuckley/cabot-search huggingface dataset:
Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure.
Authors: J K Gwathmey, L Copelas, R MacKinnon, F J Schoen, M D Feldman, W Grossman, J P Morgan
Journal: Circulation Research (1987)

Intracellular Ca2+ release and reuptake are essential for contraction and relaxation of normal heart muscle. Intracellular Ca2+ transients were recorded with aequorin during isometric contraction of myocardium from patients with end-stage heart failure. In contrast to controls, contractions and Ca2+ transients of muscles from failing hearts were markedly prolonged, and the Ca2+ transients exhibited 2 distinct components. Muscles from failing hearts showed a diminished capacity to restore low resting Ca2+ levels during diastole. These experiments provide the first direct evidence from actively contracting human myocardium that intracellular Ca2+ handling is abnormal and may cause systolic and diastolic dysfunction in heart failure.
GMC should be relicensing doctors, not revalidating specialists
Authors: A. C. Skinner
Journal: BMJ (2015)

Early in the life of revalidation, medical royal colleges produced hugely prescriptive guidance about what constitutes proper appraisal,1 enough continuing professional development (CPD), and so on. Coincidentally, revalidation coincided with the genesis of the Postgraduate Medical Education and Training Board (PMETB), …
Respiratory impairment and airway closure in patients with untreated idiopathic scoliosis
Authors: J. Bjure, G. Grimby, J. Kasalicky, M. Lindh, A. Nachemson
Journal: Thorax (1970)

Fifty patients aged 11 to 78 years with untreated idiopathic scoliosis were studied. An increased frequency of respiratory impairment was found, especially in patients with a severe degree of scoliosis. Seven patients under 60 years were unable to work and all had thoracic curves exceeding 100°. None of the patients between 20 and 65 years of age was engaged in hard work and 22% had a disability pension, all because of respiratory impairment. A tendency to increased shortness of breath was noted with increasing curves as well as age. Dynamic and static spirometry was performed and airway closure was studied with the xenon-133 bolus technique. With increasing degrees of scoliosis there was a reduction in all lung volumes. Seventeen of 40 patients showed evidence of airway closure at lung volumes greater than functional residual capacity; 6 of these patients were under 40 years of age, and all had thoracic scoliosis exceeding 90°.
Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals
Authors: SP Aries, B Schaaf, F Hansen, K Weyrich, V Kurowski, R Dennin, K Dalhoff
Journal: European Respiratory Journal (1997)

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.
AT-37PHASE I STUDY OF PLERIXAFOR AND BEVACIZUMAB IN RECURRENT HIGH-GRADE GLIOMA
Authors: Eudocia Lee, Katrina Smith, Alona Muzikansky, Elizabeth Gerstner, John Kuhn, David Reardon, Lakshmi Nayak, Andrew Norden, Jennifer Rifenburg, Julee Pulverenti, Deirdre Stokes, Priscilla Lam, Tiago Martins, Kelly Hempfling, Christine McCluskey, Sarah Gaffey, Tracy Batchelor, Dan Duda, Rakesh Jain, Patrick Wen
Journal: Neuro-Oncology (2014)

Although anti-angiogenic therapy for high-grade glioma is promising, responses are not durable. The SDF-1/CXCR4 axis may help mediate resistance to VEGFR inhibition. Plerixafor is a reversible CXCR4 inhibitor that has demonstrated growth inhibition in glioblastoma xenografts. We conducted a Phase I study to determine the safety and tolerability of plerixafor in combination with bevacizumab in patients with recurrent HGG. A 3 x 3 dose escalation design to a maximum planned dose level of plerixafor 320 µg/kg on Days 1-21 and bevacizumab 10 mg/kg on Days 1 and 15 of each 28 day cycle was used. DLTs were determined during the initial 4 weeks of therapy and included drug-related Grade ≥ 3 non-hematologic toxicities and Grade ≥ 4 hematologic toxicities. Part 1 of the study has been completed with a total of 23 patients enrolled with the following characteristics: median age 58 (23-72), median KPS 90 (70-100), 11 women (47.8%). One DLT (grade 3 rectal fistula) was seen at a dose level of plerixafor 240 µg/kg + bevacizumab and the cohort was expanded. Because no further DLTs were seen at the 240 µg/kg dose level, the maximum planned dose level of plerixafor 320 µg/kg + bevacizumb opened and a total of 12 patients were treated with no DLTs. Treatment was well tolerated with one grade 3 hypophosphatemia and one grade 3 rectal fistula. Preliminary pharmacokinetic data on plerixafor from the first two cohorts compares well with historical PK data. Combination treatment with bevacizumab and plerixafor was well tolerated in the studied HGG patients. No DLTs were encountered at the maximum planned dose level. The study will now expand to a surgical cohort to examine tumor tissue penetration as well as a separate non-surgical cohort with patients treated with continuous daily dosing of plerixafor 320 µg/kg and bevacizumab. Updated results will be presented.
Retroviral infection of neonatal Peyer's patch lymphocytes: the mouse mammary tumor virus model.
Authors: O Karapetian, A N Shakhov, J P Kraehenbuhl, H Acha-Orbea
Journal: The Journal of Experimental Medicine (1994)

Mouse mammary tumor virus is known to infect newborn mice via mother's milk. A proposed key step for viral spread to the mammary gland is by the infection of lymphocytes. We show here that although in suckling mice retroviral proteins are found in all epithelial cells of the gut, viral DNA is exclusively detectable in the Peyer's patches. As early as 5 d after birth the infection leads to a superantigen response in the Peyer's patches but not in other lymphoid organs draining the intestine. Viral DNA can be detected before the superantigen response and becomes first evident in the Peyer's patches followed by mesenteric lymph nodes and finally all lymphoid organs.
Tumor-Infiltrating CD8<sup>+</sup> Lymphocytes Predict Clinical Outcome in Breast Cancer
Authors: Sahar M.A. Mahmoud, Emma Claire Paish, Desmond G. Powe, R. Douglas Macmillan, Matthew J. Grainge, Andrew H.S. Lee, Ian O. Ellis, Andrew R. Green
Journal: Journal of Clinical Oncology (2011)

Breast carcinomas are often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma. CD8(+) lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+) cytotoxic lymphocytes in breast cancer. Tumor-infiltrating CD8(+) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up. The number of CD8(+) T cells was counted in tumor nests (intratumoral), in stroma adjacent to tumor cells, and in stroma distant to tumor cells, and their relationship with clinical outcome was determined. The total number of CD8(+) cells was positively correlated with tumor grade (r(s) = 0.20; P < .001) and inversely correlated with patient's age at diagnosis, estrogen receptor-alpha (ER-α), and progesterone receptor (PgR) expression (Mann-Whitney U test, P < .001). The total patient cohort was randomly divided into two separate training and validation sets before performing univariate survival analysis. Total number and distant stromal CD8(+) lymphocytes were associated with better patient survival (P = .041 and P < .001, respectively) in the training set. In multivariate analysis, total CD8(+) T-cell count was an independent prognostic factor in both training and validation sets. These results suggest that tumor-infiltrating CD8(+) T lymphocytes have antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of breast cancer.
STAT3, a key regulator of cell-to-cell communication in the heart
Authors: Arash Haghikia, Melanie Ricke-Hoch, Britta Stapel, Irina Gorst, Denise Hilfiker-Kleiner
Journal: Cardiovascular Research (2014)

The signal transducer and activator of transcription 3 (STAT3) is fundamental for physiological homeostasis and stress-induced remodelling of the heart as deregulated STAT3 circuits are sufficient to induce dilated and peripartum cardiomyopathy and adverse remodelling after myocardial infarction. STAT3 activity depends on multiple post-translational modifications (phosphorylation, acetylation, and dimerization). It is regulated by multiple receptor systems, which are coupled to positive and negative feedback loops to ensure physiological and beneficial action. Its intracellular functions are diverse as it acts as a signalling protein, a transcription factor but also participates in mitochondria energy production and protection. STAT3 modulates proliferation, differentiation, survival, oxidative stress, and/or metabolism in cardiomyocytes, fibroblasts, endothelial cells, progenitor cells, and various inflammatory cells. By regulating the secretome of these cardiac cells, STAT3 influences a broad range of intercellular communication systems. It thereby impacts on the communication between cardiomyocytes, the plasticity of the cardiac microenvironment, the vasculature, the extracellular matrix, and the inflammation in response to physiological and pathophysiological stress. Here, we sum up current knowledge on STAT3-mediated intra- and intercellular communication within the heterogeneous cellular network of the myocardium to co-ordinate complex biological processes and discuss STAT3-dependent targets as novel therapeutic concepts to treat various forms of heart disease.
OC-039 Oral nutritional supplements are cost effective in improving quality adjusted life years in malnourished care home residents
Authors: E L Parsons, R J Stratton, J M Jackson, M Elia
Journal: Gut (2012)

<h3>Introduction</h3> Malnutrition has a detrimental effect on quality of life (QOL) but the extent to which nutrition support can improve QOL in a cost effective manner is unclear. This study aimed to examine whether oral nutritional supplements are cost effective in improving quality adjusted life years (QALY9s) (an index of quality and quantity of life) in malnourished care home residents. <h3>Methods</h3> A randomised controlled trial (RCT) of 104 malnourished residents (medium + high risk according to Malnutrition Universal Screening Tool (“MUST”)) (mean age 88.3±7.7 y, 86% female) in residential and nursing homes in Hampshire received either oral nutritional supplements (ONS) with guidance on how to use them (Nutricia range; mean intake 333±237 kcal/d; n=53) or written and verbal dietary advice (DA) for 12 weeks. QALY9s were calculated using quality of life, measured with EuroQol Time Trade Off (EQ-5D TTO) and information on mortality. Expenditure on healthcare use (healthcare professional visits and hospital admissions (for the 3 months prior to and during the RCT)) and the interventions were calculated using unit costs.<sup>1 2</sup> The expenditure and QALY9s were used to establish the Incremental Cost Effectiveness Ratio (ICER). <h3>Results</h3> QALY TTO was significantly higher in the ONS group than the DA group (0.14±0.04 vs 0.12±0.03, p=0.023, total n=70). Total expenditure was greater in the ONS group than the DA group (ONS: £375.70±213.78, DA: £173.85±240.15, p&lt;0.0001) due to the cost of the intervention (ONS: £173.71±126.06, DA: £39.75±32.25, p&lt;0.0001). Healthcare use costs were not significantly different between groups (ONS: £153.62±208.44, DA: £127.27±250.03, p=0.639). The mean ICER (cost/QALY TTO) was £10 698 (95% CI £3793 to £76 932), which is well below the typically considered threshold of £25 000/QALY indicative of cost effectiveness. <h3>Conclusion</h3> This RCT indicates that compared to simple dietary advice, oral nutritional supplements are cost effective in improving the quality adjusted life years of malnourished care home residents. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Curtis L</b>. <i>Unit Costs of Health and Social Care</i>. University of Kent, 2009. 2. <b>British National Formulary</b>. 42 edn. 2006.
Knowledge is only rumour, until it is in the muscle
Authors: Robert-Jan de Vos
Journal: British Journal of Sports Medicine (2014)

Knowledge is only rumour, until it is in the muscle Robert-Jan de VosLearning is not only knowledge acquirement; it is about taking action, generating results and mobilising others.An essential component of acquiring knowledge is the willingness to change, reflected in an old New Guinean proverb "Knowledge is only rumour, until it is in the muscle."With this fundamental idea, the Dutch Association of Sports Medicine (Vereniging voor Sportgeneeskunde)-founded in the Netherlands nearly 50 years ago-started a mission to make Sports Medicine an independent specialty.A task force, established in 2009, was able to gain from their previous experience in 2002, when the specialist application from the VSG was first rejected.Since then, Dutch Sports Medicine has made significant efforts to improve the quality, training, scientific research and reputation of the specialty.Thanks to the concerted efforts of the task force, Sports Medicine is now a recognised specialty in the Netherlands.The Minister of Health, Welfare and Sport confirmed this decision on 8 April 2014, on the recommendation of the College of Medical Specialties of the doctors' federation. 1 This is a major milestone in the history of the VSG and it is also the start of a new era for Sports Medicine in the Netherlands.The Dutch sports physicians have to keep their eye on the ball now, as we learned from football that cheering too excessively can cause serious problems. 2We have to overcome many challenges in providing healthcare for athletes, but I am sure that the board of the Dutch Association of Sports Medicine will flex their muscles to achieve this.
Towards a dynamic connectionist model of memory
Authors: Douglas Vickers, Michael D. Lee
Journal: Behavioral and Brain Sciences (1997)

Glenberg's account falls short in several respects. Besides requiring clearer explication of basic concepts, his account fails to recognize the autonomous nature of perception. His account of what is remembered, and its description, is too static. His strictures against connectionist modeling might be overcome by combining the notions of psychological space and principled learning in an embodied and situated network.
Diagnosis of natural rubber latex allergy: Multicenter latex skin testing efficacy study
Authors: Robert G. Hamilton, N.Franklin Adkinson
Journal: Journal of Allergy and Clinical Immunology (1998)

No characterized diagnostic natural rubber latex skin testing material is licensed for use in the United States.We have conducted a multicenter clinical skin testing study to document the safety and diagnostic sensitivity and specificity of a candidate Hevea brasiliensis nonammoniated latex (NAL) extract. These data are intended to support the licensing of this reagent for the diagnosis of latex allergy in high-risk populations.Three hundred twenty-four subjects (304 adults and 20 children) were classified by their clinical history as having latex allergy (LA group, 124 adults and 10 children) or having no latex allergy (NLA group, 180 adults and 10 children). All subjects provided blood samples and then received sequential puncture skin tests (PSTs) at 1, 100, or 1000 microg/mL protein with a bifurcated needle and NAL (Greer Laboratories) from Malaysian Hevea brasiliensis (clone 600) sap. A 2-stage glove provocation test was used to clarify latex allergy status of individuals with positive history/negative PST result and negative history/positive PST result mismatches.Twenty-four subjects (15%) originally designated as having LA on the basis of their initial clinical history were reclassified to the NLA group on the basis of a negative glove provocation test result. Of the 134 subjects with LA, 54 (40%) were highly sensitive to latex, with a positive PST result at 1 microg/mL NAL. The Greer NAL reagent produced a positive PST rate (sensitivity) of 95% and 99% in subjects with LA at 100 microg/mL and 1 mg/mL, respectively. The negative PST rate (specificity) in 190 subjects with a negative history with the NAL extract at 100 microg/mL and 1 mg/mL, was 100% and 96%, respectively. Immediately after the PST, mild systemic reactions (mainly pruritus) were recorded in 16.1 % of the adults in the LA group and 4.4% of the adults in the NLA group. No reactions required treatment with epinephrine. Only mild delayed reactions were observed in 9.6% (LA group) and 2.8% (NLA group) of subjects 24 to 48 hours after PST. Mean wheal and erythema diameters measured in the 10 children in the LA group with spina bifida at 100 microg/mL and 1 mg/mL were similar to those observed in the adults in the LA group, suggesting that children are not at increased risk for systemic reactions compared with adults.A suggestive clinical history is necessary but not sufficient for a definitive diagnosis of IgE-dependent latex allergy. These data support the safety and diagnostic efficacy of the Greer NAL, skin test reagent at 100 micro/mL and 1 mg/mL for confirmatory PSTs.
Replication error phenotype, clinicopathological variables, and patient outcome in Dukes' B stage II (T3,N0,M0) colorectal cancer
Authors: B Curran
Journal: Gut (2000)

<h3>AIMS</h3> To examine the relation between the replication error (RER) phenotype and other genetic events, clinical features, and long term survival in patients with Dukes9 B stage II (T3,N0,M0) colorectal cancer. <h3>METHODS</h3> RER phenotype was investigated in 159 patients by PCR amplification of microsatellite marker loci on chromosomes 5q, 17p, 17q, and 18q from tumour DNA extracted from archival tissue. Data on activating c-Ki-<i>ras</i> mutations were available from a previous study. Immunohistochemical detection of p53 and c-erbB-2 expression was performed on paraffin wax embedded tissue. <h3>RESULTS</h3> Of 159 colorectal cancers studied, 22 (14%) were RER+ while 137 (86%) were RER− for two or more loci. RER+ tumours were more commonly located in the right colon, tended to be larger than RER− tumours, and were more often poorly differentiated than RER− cancers. No significant associations were seen between RER status and the presence of a mutant c-Ki-<i>ras</i> gene, or between RER status and p53, c-erbB-2, or c-myc gene expression. Univariate survival analysis showed that outcome was similar in RER+ and RER− cases. Multivariate survival analysis showed that the relative risk of death for patients with RER+ cancers was 0.95 that of patients with RER− cancers. <h3>CONCLUSIONS</h3> The results suggest that, while the RER phenotype may be associated with some differences in tumour pathology (site, size, differentiation), it is not associated with the genetic alterations studied or with significant differences in long term survival.
Squamous cell carcinoma occurring in the wall of a chronic aspergilloma.
Authors: S M Andrew, M Bhattacharjee, D J Keenan, H Reid
Journal: Thorax (1991)

An aspergilloma that occurred within an area of bronchiectasis in a 52 year old man persisted for 12 years despite medical and surgical treatment. A squamous cell carcinoma developed in the wall of the cavity.
TCT-21 Use of IVUS Reduces Stent Thrombosis: Results from the Prospective, multicenter ADAPT-DES Study
Authors: Bernhard Witzenbichler, Akiko Maehara, Giora Weisz, Franz-Josef Neumann, Michael Rinaldi, D. Christopher Metzger, Timothy Henry, David Cox, Peter Duffy, Bruce Brodie, Thomas Stuckey, Ernest Mazzaferri, Ke Xu, Roxana Mehran, Helen Parise, Gary Mintz, Gregg Stone
Journal: Journal of the American College of Cardiology (2012)
Peter Stewart Macfarlane
Authors: W. L. S. P. Macfarlane
Journal: BMJ (2015)

Peter Stewart Macfarlane served with the Paratroop regiment in Palestine during his national service. He then worked in general practice in his home town of Greenock and trained as a general pathologist in Glasgow’s Western Infirmary before taking a consultant post in the Stirling and Falkirk royal infirmaries in 1959. In 1971 he supervised the organisation of the …
Lumbar Bone Mineral Density in Patients With Major Depression: Evidence of Increased Bone Loss at Follow-Up
Authors: Ulrich Schweiger, Bettina Weber, Michael Deuschle, Isabella Heuser
Journal: American Journal of Psychiatry (2000)

This study investigated whether an increase in the loss of bone mineral density occurs with major depression.The authors measured lumbar bone density with the use of quantitative computerized tomography in a longitudinal assessment of 18 depressed patients older than 40 years on hospital admission and 21 healthy women and men. The follow-up period lasted at least 24 months.A repeated measures analysis of variance model with depression and gender as factors showed that bone loss was greater for the depressed patients than for the comparison subjects and greater for men than for women.Major depression may be associated with increased bone loss, especially for men.
Abdominal Aspiration Biopsies
Authors: Juan Carlos Pelaez
Journal: JAMA (1983)

One hundred eighty-four diagnostic aspirations performed on 169 patients were reviewed (1) to define the decision process regarding which guidance method (sonography v computed tomography) should be used on any given patient, and (2) to determine, once a guidance method was chosen, its accuracy and complication rate. Sonographic guidance (84%) proved to be an effective method for obtaining a correct diagnosis in 98% (110/112) of cystic masses and 79% (34/43) of solid masses. Computed tomography (16%) was used when sonography could not identify the mass or when the mass was small, deeply located, and often solid. Computed tomographic guidance provided a correct diagnosis in 100% (13/13) of cystic masses and 81% (13/16) of solid masses.