tbuckley/cabot-search huggingface dataset:
Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer
Authors: T Hishida, J Yoshida, M Nishimura, Y Nishiwaki, K Nagai
Journal: Thorax (2007)

Background: Although clinical N1 (cN1) non-small cell lung cancer (NSCLC) is considered to be locoregional, the postoperative outcome is disappointing, with a 5 year survival of less than 50%. One possible reason may be that cN1disease diagnosed by current standard imaging modalities often contains unexpected N2 disease. This study was conducted to evaluate the surgical and pathological results of patients with cN1 NSCLC. Methods: Among 1782 patients with NSCLC who underwent intended curative resection from 1993 to 2003, 143 patients were identified as having cN1 disease and were enrolled in this study. The clinicopathological records and CT films of each patient were retrospectively reviewed to identify predictors for pN2–3 disease. Results: The pathological nodal status was pN0 in 23% (n = 33), pN1 in 47% (n = 67) and pN2–3 in 30% (n = 43) of patients. Patients with pN2–3 showed a significantly worse 5 year survival rate of 38% compared with patients with pN0 (68%) and pN1 (60%) (p = 0.017 and 0.007, respectively). Multivariate analysis showed that adenocarcinoma histology was a significant predictor for pN2–3 disease (OR 3.312, 95% CI 1.439 to 7.784; p = 0.005). The presence of N1 node separate from the main tumour on CT scans tended to predict pN2–3 disease although this did not reach statistical significance (OR 2.103, 95% CI 0.955 to 4.693; p = 0.066). Pathological N2–3 disease was found in 53% of patients with adenocarcinoma with a separate N1 pattern and in only 12% of patients with non-adenocarcinoma with a continuous N1 pattern. Conclusions: The diagnosis of N1 status by contrast enhanced CT scans is unsatisfactory with a high rate of unexpected pN2 disease. To avoid infertile lung resection, patients with CT diagnosed N1 adenocarcinoma, especially with a separate N1 pattern on CT, should be considered for additional invasive node biopsy modalities, including mediastinoscopy.
ARMY MEDICAL SCHOOL, NETLEY.
Authors: A.J.W. Wells, G.F. Sheehan, H.H. Scott, H.A.B. Bransbury, M.W. Falkner, R.N. Woodley, E. Ryan, E.E. Parkes, J.V. Roche, A.J. Hull, R.V. Cowey, J. Conway, J.H. Barbour, F.E. Robinson, S. Mason, J.S. Bostock
Journal: The Lancet (1901)
TRANSORBITAL LOBOTOMY IN CHRONICALLY DISTURBED PATIENTS
Authors: W. W. WILSON, A. R. PITTMAN, R. E. BENNETT, R. S. GARBER
Journal: American Journal of Psychiatry (1951)

Two hundred cases of transorbital lobotomy are reported with marked improvement in over one-half of cases of chronically disturbed patients. The results according to diagnosis are indicated. We urge that this type of operation be considered for all chronically disturbed patients in whom other less strenuous forms of therapy have failed after one year. The economic advantages in the improvement of such a group of patients are stressed.
Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells
Authors: Hewang Li, Ines Armando, Peiying Yu, Crisanto Escano, Susette C. Mueller, Laureano Asico, Annabelle Pascua, Quansheng Lu, Xiaoyan Wang, Van Anthony M. Villar, John E. Jones, Zheng Wang, Ammasi Periasamy, Yuen-Sum Lau, Patricio Soares-da-Silva, Karen Creswell, Gaétan Guillemette, David R. Sibley, Gilbert Eisner, Robin A. Felder, Pedro A. Jose
Journal: Journal of Clinical Investigation (2008)

Hypertension is a multigenic disorder in which abnormal counterregulation between dopamine and Ang II plays a role. Recent studies suggest that this counterregulation results, at least in part, from regulation of the expression of both the antihypertensive dopamine 5 receptor (D5R) and the prohypertensive Ang II type 1 receptor (AT1R). In this report, we investigated the in vivo and in vitro interaction between these GPCRs. Disruption of the gene encoding D5R in mice increased both blood pressure and AT1R protein expression, and the increase in blood pressure was reversed by AT1R blockade. Activation of D5R increased the degradation of glycosylated AT1R in proteasomes in HEK cells and human renal proximal tubule cells heterologously and endogenously expressing human AT1R and D5R. Confocal microscopy, Förster/fluorescence resonance energy transfer microscopy, and fluorescence lifetime imaging microscopy revealed that activation of D5R initiated ubiquitination of the glycosylated AT1R at the plasma membrane. The regulated degradation of AT1R via a ubiquitin/proteasome pathway by activation of D5R provides what we believe to be a novel mechanism whereby blood pressure can be regulated by the interaction of 2 counterregulatory GPCRs. Our results therefore suggest that treatments for hypertension might be optimized by designing compounds that can target the AT1R and the D5R.
Regulatory Role of G Protein–Coupled Estrogen Receptor for Vascular Function and Obesity
Authors: Elvira Haas, Indranil Bhattacharya, Eugen Brailoiu, Marlen Damjanović, G. Cristina Brailoiu, Xin Gao, Laurence Mueller-Guerre, Nicole A. Marjon, André Gut, Roberta Minotti, Matthias R. Meyer, Kerstin Amann, Emerita Ammann, Ana Perez-Dominguez, Michele Genoni, Deborah J. Clegg, Nae J. Dun, Thomas C. Resta, Eric R. Prossnitz, Matthias Barton
Journal: Circulation Research (2009)

We found that the selective stimulation of the intracellular, transmembrane G protein–coupled estrogen receptor (GPER), also known as GPR30, acutely lowers blood pressure after infusion in normotensive rats and dilates both rodent and human arterial blood vessels. Stimulation of GPER blocks vasoconstrictor-induced changes in intracellular calcium concentrations and vascular tone, as well as serum-stimulated cell proliferation of human vascular smooth muscle cells. Deletion of the GPER gene in mice abrogates vascular effects of GPER activation and is associated with visceral obesity. These findings suggest novel roles for GPER in protecting from cardiovascular disease and obesity.
Therapeutic angiogenesis in cardiology using protein formulations
Authors: M Post
Journal: Cardiovascular Research (2001)

Therapeutic angiogenesis in cardiovascular disease aims at improving myocardial function by increasing blood flow to ischemic myocardium that is not amenable to traditional forms of revascularization. Preclinical data have provided proof of the concept that angiogenic growth factors such as fibroblast growth factor 2 (FGF-2) and vascular endothelium growth factor (VEGF) may indeed improve myocardial flow and function when administered in ways that ensure prolonged tissue exposure to these short-lived molecules. Although other cytokines have been shown to enhance angiogenesis in vivo, FGF-2 and VEGF have been most widely studied and may serve as prototype proangiogenic drugs. Currently, several delivery techniques that are clinically applicable are being studied with respect to tissue distribution and retention as well as angiogenic efficacy of FGF-2 and VEGF. Although tissue distribution and retention of FGF-2 after intramyocardial injection compares favorably with other routes of administration, efficacy studies are not yet conclusive. At the same time, different protein- and gene-based formulations are being investigated. Arguments for and against protein and gene therapy are presented, showing that protein-based therapy seems to have advantages over gene therapy at the present time, although continuous efforts should be made to increase the tissue exposure time after a single administration of protein. While delivery systems and growth factor formulations are being improved, double-blind, placebo-controlled trials designed with existing animal data in mind, are needed to firmly establish the utility of therapeutic angiogenesis in cardiovascular disease.
Does occupational success influence longevity among England test cricketers?
Authors: P J Boyle
Journal: British Journal of Sports Medicine (2008)

To determine whether the longevity of England test cricketers is influenced by occupational success, controlling for the influence of social background.Archival survey.England.Those 418 cricketers who played for England in a test match from the first test in 1876 to 1963 when the distinction between amateur and professional status was removed.Length of life.Survival analysis of players born between 1827 and 1941 (349 dead, 69 alive) showed a significant relation between mortality and year of birth (p<0.001), amateur/professional status (p = 0.042) and the number of test matches played (p = 0.042). Captaining England was not related to survival.The link between longevity and both social background and occupational success is supported among test match cricketers. Amateur (or "gentlemen") cricketers from more privileged social backgrounds survived longer than professionals (or "players"). The most successful cricketers who played in a larger number of tests lived longer than those who played in a smaller number of tests. Captaining England, which could be regarded as a form of occupational "control", was not associated with longevity.
A Clinical Prediction Rule for Diagnosing Severe Acute Respiratory Syndrome in the Emergency Department
Authors: Gabriel M. Leung, Timothy H. Rainer, Fei-Lung Lau, Irene O.L. Wong, Anna Tong, Tai-Wai Wong, James H.B. Kong, Anthony J. Hedley, Tai-Hing Lam
Journal: Annals of Internal Medicine (2004)

Background: Accurate, objective models of triage for patients with suspected severe acute respiratory syndrome (SARS) could assess risks and improve decisions about isolation and inpatient treatment. Objective: To develop and validate a clinical prediction rule for identifying patients with SARS in an emergency department setting. Design: Retrospective analysis using a 2-step coefficient-based multivariable logistic regression scoring method with internal validation by bootstrapping. Setting: 2 hospitals in Hong Kong. Participants: 1274 consecutive patients from 1 hospital and 1375 consecutive patients from another hospital. Measurements: Points were assigned on the basis of history, physical examination, and simple investigations obtained at presentation. The outcome measure was a final diagnosis of SARS, as confirmed by World Health Organization laboratory criteria. Results: Predictors for SARS on the basis of history (step 1) included previous contact with a patient with SARS and the presence of fever, myalgia, and malaise. Age 65 years and older and younger than 18 years and the presence of sputum, abdominal pain, sore throat, and rhinorrhea were inversely related to having SARS. In step 2, haziness or pneumonic consolidation on chest radiographs and low lymphocyte and platelet counts, in addition to a positive contact history and fever were associated with a higher probability of SARS. A high neutrophil count, the extremes of age, and sputum production were associated with a lower probability of SARS. In the derivation sample, the observed incidence of SARS was 4.4% for those assigned to the low-risk group (in steps 1 or 2); in the high-risk group, incidence of SARS was 21.0% for quartile 1, 39.5% for quartile 2, 61.2% for quartile 3, and 79.7% for quartile 4. This prediction rule achieved an optimism-corrected sensitivity of 0.90, a specificity of 0.62, and an area under the receiver-operating characteristic curve of 0.85. Limitations: The prediction rule may not apply to isolated cases occurring during an interepidemic period. Generalizability of the findings should be confirmed in other SARS-affected countries and should be prospectively validated if SARS returns. Conclusions: Our findings suggest that a simple model that uses clinical data at the time of presentation to an emergency department during an acute outbreak predicted the incidence of SARS and provided good diagnostic utility. For the free electronic version of the decision aid for this article, go to www.annals.org/pda.
Psychological Aspects of Hypertension: II. The Differential Influence of Interview Variables on Blood Pressure
Authors: F. PATRICK MCKEGNEY, REDFORD B. WILLIAMS
Journal: American Journal of Psychiatry (1967)

The blood pressure responses of normotensive and hypertensive subjects to a three-phase experimental interview situation were recorded. The greatest elevations occurred in both groups during a personal discussion phase, and the elevation was more pronounced among the hypertensive subjects. These results, although based upon a small sample, raise questions about the reliability of clinical blood pressure determinations conducted during or following a medical interview.
Dose–response association of screen time-based sedentary behaviour in children and adolescents and depression: a meta-analysis of observational studies
Authors: Mingli Liu, Lang Wu, Shuqiao Yao
Journal: British Journal of Sports Medicine (2015)

Background Depression represents a growing public health burden. Understanding how screen time (ST) in juveniles may be associated with risk of depression is critical for the development of prevention and intervention strategies. Findings from studies addressing this question thus far have been inconsistent. Therefore, we conducted a comprehensive systematic review and meta-analysis of data related to this question. Methods The meta-analysis was conducted in accordance with the PRISMA guideline. We searched the electronic databases of PubMed, Web of Science and EBSCO systematically (up to 6 May 2015). OR was adopted as the pooled measurement of association between ST and depression risk. Dose–response was estimated by a generalised least squares trend estimation. Results Twelve cross-sectional studies and four longitudinal studies (including 1 cohort study) involving a total of 127 714 participants were included. Overall, higher ST in preadolescent children and adolescents was significantly associated with a higher risk of depression (OR=1.12; 95% CI 1.03 to 1.22). Screen type, age, population and reference category acted as significant moderators. Compared with the reference group who had no ST, there was a non-linear dose–response association of ST with a decreasing risk of depression at ST&lt;2 h/day, with the lowest risk being observed for 1 h/day (OR=0.88; 95% CI 0.84 to 0.93). Conclusions Our meta-analysis suggests that ST in children and adolescents is associated with depression risk in a non-linear dose–response manner.
Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series
Authors: I Nyoman Kandun, Erna Tresnaningsih, Wilfried H Purba, Vernon Lee, Gina Samaan, Syahrial Harun, Eka Soni, Chita Septiawati, Tetty Setiawati, Elvieda Sariwati, Toni Wandra
Journal: The Lancet (2008)
Effects of Norethandrolone on the Transport and Peripheral Metabolism of Thyroxine in Patients Lacking Thyroxine-Binding Globulin
Authors: Lewis E. Braverman, Theodore AvRuskin, Michael J. Cullen, Apostolos G. Vagenakis, Sidney H. Ingbar
Journal: Journal of Clinical Investigation (1971)

Studies of the effect of norethandrolone on the transport and peripheral metabolism of thyroxine were carried out in four patients lacking thyroxine-binding globulin. Before norethandrolone administration, values for serum protein-bound iodine (PBI) were decreased (1.8 ±0.5 μg/100 ml) and the proportion of free thyroxine increased (0.036 ±0.008%). As a result, values for the absolute concentration of free thyroxine iodine were at the lower end of the normal range (0.63 ±0.12 mμg/100 ml). During the control thyroxine-turnover study, the thyroxine distribution space was strikingly increased (18.2 ±7.9 liters) and the fractional rate of thyroxine turnover moderately increased (17.1 ±11.3%/day), as compared to the expected mean values for normal subjects. Therefore, calculated values for the daily rate of thyroxine clearance were increased even more, ranging between 255 and 500% of normal values. However, owing to the low PBI in these patients, the daily disposal of thyroxine iodine was similar to that expected in normals on the basis of age and weight. During the administration of norethandrolone, the thyroxine-binding capacity of the thyroxine-binding prealbumin increased strikingly in all patients, values averaging 162% of those found during the control period. This increase was associated with a highly significant increase in PBI (133% of control values) and a small but significant decrease in the proportion of free thyroxine, resulting in no significant change in the absolute concentration of free thyroxine iodine. In all four patients, administration of norethandrolone was associated with a pronounced decrease in the thyroxine distribution space to values which averaged 69% of those found during the control period. Values for the fractional rate of thyroxine turnover increased slightly. As a result, thyroxine-clearance rate decreased in all patients. Owing to the reciprocal changes in clearance rate and PBI, no significant change in total daily thyroxine disposal was observed. The present studies reveal that when the thyroxine-binding prealbumin is increased in patients lacking thyroxine-binding globulin, several indices of peripheral thyroxine transport and metabolism are altered. However, these changes were small, even in the absence of thyroxine-binding globulin. It is suggested, therefore, that the effect of changes in thyroxine-binding prealbumin would be even smaller in individuals in whom thyroxine-binding globulin is present.
Novel insights into human endometrial paracrinology and embryo-maternal communication by intrauterine microdialysis
Authors: P Licht
Journal: Human Reproduction Update (1998)

The regulation of human implantation is still unknown. Evidence from mice suggests an essential role for several paracrine mediators but species differences with implantation in the human preclude the extrapolation of these concepts to humans. An intrauterine microdialysis device (IUMD), consisting of microdialysis tubing glued into a balloon catheter on one side and into a polypropylene tube on the other, allows a dynamic and accurate in-vivo measurement of uterine paracrine interactions in humans. Inserted into the uterine cavity in the form of a loop, it can be continuously perfused with saline to reveal a number of relevant cytokines and growth factors in uterine effluents of non-pregnant women in both follicular and luteal phases. These included interleukin (IL)-1α, IL-1β, IL-6, leukaemia inhibitory factor (LIF), macrophage colony-stimulating factor (M-CSF), epidermal growth factor, vascular endothelial growth factor (VEGF), insulin-like growth factor binding protein-1 (IGFBP-1), prolactin, and human chorionic gonadotrophin (HCG). The source of intrauterine HCG is unclear since endometrial mRNA for the HCG β-subunit is not revealed using reverse transcriptase polymerase chain reaction analysis. Applying urinary HCG locally via the IUMD profoundly alters endometrial secretory parameters. Prolactin, IGFBP-1, and M-CSF are significantly inhibited and VEGF is regulated in a biphasic manner involving early stimulation followed by inhibition of intrauterine levels. Use of the IUMD has thus shown that the urinary HCG preparations routinely used for ovulation induction and luteal support may directly alter endometrial function.
Brain Uptake of lodine-131 Metaiodobenzylguanidine Following Therapy of Malignant Pheochromocytoma
Authors: BEN A. DWAMENA, SHIRLEY ZEMPEL, JOHANNES F. KLOPPER, BAREND VAN HEERDEN, DON WIELAND, BRAHM SHAPIRO
Journal: Clinical Nuclear Medicine (1998)

Intracranial metaiodobenzylguanidine (MIBG) uptake is occasionally and only faintly visualized on diagnostic studies. Recently, intense normal cerebellar uptake was described on posttherapy MIBG images. Experience at the University of Michigan with posttherapy MIBG scintigraphy of pheochromocytoma was reviewed. The patterns and correlates of intracranial uptake after therapeutic I-131 MIBG in 25 patients (61 patient treatment encounters) were evaluated by review of records and blinded consensus interpretation of diagnostic and posttherapeutic MIBG scans. Thirty-nine (64%) patient treatment encounters demonstrated at least faint (grade 1) MIBG uptake in one or more brain sites; the most common site was the cerebellum. There was a statistically significant relation between intracranial uptake and 1) size of therapeutic dose and 2) patient age, but no relation between intracranial uptake and gender, body mass index, plasma epinephrine level, plasma norepinephrine level, urine metanephrine level, or the therapy-to-imaging interval. Although the influence of age on the pattern and intensity of intracranial uptake is unexplained, the relation to therapy dose may be explained by the possible generation of MIBG metabolites that can cross the blood-brain barrier (high activity administered and the delay until imaging). Further studies are needed to define mechanisms of intracranial uptake and relation to responses and toxicity after MIBG therapy of neuroendocrine tumors.
OC-086 Surgery alone vs chemoradiotherapy followed by surgery for stage I and II oesophageal cancer: final analysis of a randomised controlled phase III trial—FFCD 9901
Authors: W B Robb, C Mariette, L Dahan, E Maillard, F Mornex, B Meunier, V Boige, C Genet, D Pezet, P A Thomas, J P Triboulet
Journal: Gut (2012)

<h3>Introduction</h3> Resection remains the best treatment for local control of oesophageal carcinoma (OC), but local recurrence, distant metastasis and poor survival remain an issue after surgery. Often investigated in locally advanced OC, the impact of neoadjuvant chemoradiotherapy (NCRT) is unknown in patients with stage I or II OC. The aim of this multicentre randomised controlled phase III trial was to assess whether NCRT improves outcomes for patients with stage I or II OC. <h3>Methods</h3> 195 patients were randomly assigned to surgery alone (S group, n=98) or to NCRT group (NCRT group, n=97; 45Gy given in 25 fractions over 5 weeks with two courses of concomitant chemotherapy by 5-Fluorouracil 800 mg/m<sup>2</sup> on days 1–4 and cisplatin 75 mg/m<sup>2</sup> on day 1 or 2). The primary endpoint was overall survival. Secondary endpoints were progression free survival, postoperative morbidity and 30-day mortality, R0 resection rate and prognostic factor identification. Analysis was done by intention to treat. <h3>Results</h3> Patient and tumour characteristics were well-balanced between the two groups. Patients were preoperatively staged I in 18%, IIA in 49.7%, IIB in 31.8%, unknown in 0.5%. Postoperative morbidity and 30-day mortality rates were 49.5% vs 43.9% (p=0.17) and 1.1% vs 7.3% (p=0.054) in the S group and NCRT group, respectively. After a median follow-up of 5.7 years, 106 deaths were observed. Median survivals were 43.8 vs 31.8 months, respectively (HR 0.92, 95% CI 0.63 to 1.34, p=0.66). The trial was stopped due to futility. <h3>Conclusion</h3> Compared with surgery alone, NCRT with cisplatin and 5-Fluorouracil does not improve overall survival but enhances postoperative mortality for patients with stage I or II OC (Clinical Trial.gov identifier NCT 00047112). <h3>Funding</h3> Funded by the French ministry of Health—Programme Hospitalier de Recherche Clinique 1999. <h3>Competing interests</h3> None declared.
INFECTION OF CHIMPANZEES WITH LYMPHADENOPATHY-ASSOCIATED VIRUS
Authors: DonaldP. Francis, PaulM. Feorino, J.Roger Broderson, HaroldM. Mcclure, JaneP. Getchell, CorneliaR. Mcgrath, Brent Swenson, J.Steven Mcdougal, ErskineL. Palmer, AlyneK. Harrison, Francoise Barre-Sinoussi, Jean-Claude Chermann, Luc Montagnier, JamesW. Curran, CiriloD. Cabradilla, V.S. Kalyanaraman
Journal: The Lancet (1984)