tbuckley/cabot-search huggingface dataset:
Improved methodology for analyzing local and distant recurrence.
Authors: R Gelman, R Gelber, I C Henderson, C N Coleman, J R Harris
Journal: Journal of Clinical Oncology (1990)

Studies of radiation therapy and/or surgery in the treatment of cancer frequently use actuarial methods to estimate curves of time to local failure and compare two such curves with statistical methods originally developed for survival data. In such analyses, patients who fail first in distant sites or die before local failure are considered censored for time to local failure. While the arithmetic of these calculations is usually correct, the interpretation of the results is almost universally incorrect. For example, an actuarial Kaplan-Meier curve of time to breast recurrence after breast conserving treatment consistently overestimates the percentage of patients who would benefit from a subsequent mastectomy. Actuarial methods require the assumption that time to local failure and time to distant failure are statistically independent. For most human malignancies this is not a reasonable assumption, since there are always some patient subgroups at high risk of both local and distant failure and some patient subgroups at low risk for either type of failure. Without the assumption of independence, the time to local failure distribution is not well defined. The basic problem is that estimating time to local failure falls into the category of analyzing "competing risks," since the various causes of failure are competing for the same patient. For this reason, the effects of a particular treatment on local failure cannot be assessed separately from its effects on distant failure. This report explains the concepts of statistical independence, nonidentifiability, and competing risks and illustrates the pitfalls of using actuarial methods to assess local tumor control.(ABSTRACT TRUNCATED AT 250 WORDS)
Relative contribution of aortic and carotid baroreflexes to heart rate control in man during steady state and dynamic increases in arterial pressure.
Authors: D W Ferguson, F M Abboud, A L Mark
Journal: Journal of Clinical Investigation (1985)

We studied the contribution of carotid vs. extracarotid baroreceptors in control of heart rate in normal humans. We measured heart interval (HI) and arterial pressure during steady-state infusion of phenylephrine (PE). PE increased mean arterial pressure (MAP) by 13 +/- 2 mmHg (mean +/- SEM; n = 10) and thus stimulated both carotid and aortic baroreceptors. Neck pressure (NP) was applied during PE infusion to counter the increase in transmural carotid sinus pressure, thus leaving only aortic baroreceptors stimulated by the increase in arterial pressure. PE infusion alone prolonged HI by 230 +/- 24 ms (P less than 0.05). Application of NP attenuated the HI response to 65 +/- 22 ms above control (P less than 0.05 vs. PE alone). During these steady-state increases in arterial pressure, elimination of the carotid baroreflex contribution reduced the HI prolongation by 41-70% in five subjects and by greater than 93% in five subjects. We also measured the HI response to dynamic ramp elevation of systolic arterial pressure (SAP) using bolus administrations of PE. Baroreflex control was calculated from the slope of the regression correlating SAP to succeeding HI for PE alone (carotid and aortic baroreceptor activation) and for PE plus superimposed dynamic NP at levels equal to the increases in SAP (aortic baroreceptor activation). During PE alone, the baroreflex slope was 20.2 +/- 2.9 ms/mmHg (n = 10). During PE plus NP, the baroreflex slope was reduced by 30% to 14.1 +/- 2.8 ms/mmHg (P less than 0.02 vs. during PE alone). Thus, during dynamic increases in arterial pressure, eliminating the carotid baroreflex contribution reduced the HI response by 30%. These studies indicate that extracarotid (presumably aortic) and carotid baroreflexes both participate in control of heart rate in humans. Extracarotid (aortic) baroreflexes appear to have the greater role in control of heart rate during dynamic increases in arterial pressure.
Comparison of vascular growth factors in the murine brain reveals placenta growth factor as prime candidate for CNS revascularization
Authors: Emília Ilona Gaál, Tuomas Tammela, Andrey Anisimov, Serge Marbacher, Petri Honkanen, Georgia Zarkada, Veli-Matti Leppänen, Turgut Tatlisumak, Juha Hernesniemi, Mika Niemelä, Kari Alitalo
Journal: Blood (2013)
Subclassification and Individual Survival Time Prediction from Gene Expression Data of Neuroblastoma Patients by Using CASPAR
Authors: André Oberthuer, Lars Kaderali, Yvonne Kahlert, Barbara Hero, Frank Westermann, Frank Berthold, Benedikt Brors, Roland Eils, Matthias Fischer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To predict individual survival times for neuroblastoma patients from gene expression data using the cancer survival prediction using automatic relevance determination (CASPAR) algorithm. Experimental Design: A first set of oligonucleotide microarray gene expression profiles comprising 256 neuroblastoma patients was generated. Then, CASPAR was combined with a leave-one-out cross-validation to predict individual times for both the whole cohort and subgroups of patients with unfavorable markers, including stage 4 disease (n = 67), unfavorable genetic alterations, intermediate-risk or high-risk stratification by the German neuroblastoma trial, and patients predicted as unfavorable by a recently described gene expression classifier (n = 83). Prediction accuracy of individual survival times was assessed by Kaplan-Meier analyses and time-dependent receiver operator characteristics curve analyses. Subsequently, classification results were validated in an independent cohort (n = 120). Results: CASPAR separated patients with divergent outcome in both the initial and the validation cohort [initial set, 5y-OS 0.94 ± 0.04 (predicted long survival) versus 0.38 ± 0.17 (predicted short survival), P &amp;lt; 0.0001; validation cohort, 5y-OS 0.94 ± 0.07 (long) versus 0.40 ± 0.13 (short), P &amp;lt; 0.0001]. Time-dependent receiver operator characteristics analyses showed that CASPAR-predicted individual survival times were highly accurate (initial set, mean area under the curve for first 10 years of overall survival prediction 0.92 ± 0.04; validation set, 0.81 ± 0.05). Furthermore, CASPAR significantly discriminated short (&amp;lt;5 years) from long survivors (&amp;gt;5 years) in subgroups of patients with unfavorable markers with the exception of MYCN-amplified patients (initial set). Confirmatory results with high significance were observed in the validation cohort [stage 4 disease (P = 0.0049), NB2004 intermediate-risk or high-risk stratification (P = 0.0017), and unfavorable gene expression prediction (P = 0.0017)]. Conclusions: CASPAR accurately forecasts individual survival times for neuroblastoma patients from gene expression data.
The burden of carotid artery plaques is higher in patients with psoriatic arthritis compared with those with psoriasis alone
Authors: Lihi Eder, Jai Jayakar, Sutha Shanmugarajah, Arane Thavaneswaran, Daniel Pereira, Vinod Chandran, Cheryl F Rosen, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2012)

To compare the extent of atherosclerosis in patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis without arthritis (PsC).In this cross-sectional study the authors compared patients with PsA with PsC patients. Psoriasis patients underwent a rheumatological assessment to exclude inflammatory arthritis. Ultrasonographic measurements of carotid total plaque area (TPA) and carotid intima-media thickness (cIMT) were performed. t Test was used to compare the imaging findings between the two groups. Multivariate linear regression analysis was used to assess the association between disease status and imaging findings after adjusting for potential confounders.Overall, 125 PsA and 114 PsC patients were compared. There were no significant differences in age, gender or cardiovascular risk factors between the two groups. Patients with PsA exhibited greater TPA than did PsC patients (TPA (square root of area in mm(2)) 3.33±3.34 vs 2.43±2.72, p=0.03). This difference remained statistically significant in the multivariate regression analysis after adjusting for potential confounders (p=0.03). The difference in cIMT between the groups did not achieve statistical significance (p=0.09). The following disease-related variables were associated with increase in TPA in multivariate regression analysis among PsA patients: duration of PsA (p=0.04), highest Psoriasis Area and Severity Index recorded in the first 3 years of follow-up (p=0.02) and erythrocyte sedimentation rate (p=0.005).PsA patients suffer from more severe subclinical atherosclerosis compared with patients with PsC. This difference is independent of traditional cardiovascular risk factors and correlates with PsA disease duration, more severe skin disease and increased inflammatory markers.
Immunology of Relapse and Remission in Multiple Sclerosis
Authors: Lawrence Steinman
Journal: Annual Review of Immunology (2014)

Eighty percent of individuals with multiple sclerosis (MS) initially develop a clinical pattern with periodic relapses followed by remissions, called relapsing-remitting MS (RRMS). This period of fluctuating disease may last for a decade or more. Clinical relapses reflect acute inflammation in the central nervous system (CNS), composed of the brain and spinal cord. Often, different anatomic areas in the CNS are involved each time a relapse occurs, resulting in varied clinical manifestations in each instance. Relapses are nearly always followed by some degree of remission, though recovery to baseline status before the flare is often incomplete. There are nine approved drugs for treatment of RRMS. The most potent drug for inhibiting relapses, the humanized anti-α4 integrin antibody known as Natalizumab, blocks homing of mononuclear cells to the CNS. The mechanisms of action of the approved drugs for RRMS provide a strong foundation for understanding the pathobiology of the relapse. Despite substantial progress in controlling relapses with the current armamentarium of medications, there is much to learn and ever more effective and safe therapies to develop.
Risk Factors for Methotrexate-Induced Lung Injury in Patients with Rheumatoid Arthritis: A Multicenter, Case-Control Study
Authors: Graciela S. Alarcon
Journal: Annals of Internal Medicine (1997)

Background: Toxicity limits the use of methotrexate. Objective: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. Design: Case-control study. Setting: One private and five academic rheumatology practices. Participants: Methotrexate recipients with rheumatoid arthritis with and without lung injury. Measurements: Potential risk factors examined were sociodemographic and lifestyle characteristics, medical history, clinical and ancillary features and treatment of rheumatoid arthritis before methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKendry. Results: Ninety-four percent of the study participants were white, and 67% were women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared with 54.5 years of age). The strongest predictors of lung injury, after adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to ∞]), rheumatoid pleuropulmonary involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5 [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and hypoalbuminemia had very large attributable risks. Conclusion: Knowledge of the risk factors that predispose patients with rheumatoid arthritis to the toxic effects of methotrexate on the lung may provide a rationale for monitoring high-risk patients and may facilitate their management.
Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors
Authors: Guosheng Xiang, Michael D. Schuster, Tetsunori Seki, Alfred A. Kocher, Shawdee Eshghi, Andrew Boyle, Silviu Itescu
Journal: The Journal of Experimental Medicine (2004)

Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult.
Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins
Authors: N Rinaldi, M Schwarz-Eywill, D Weis, P Leppelmann-Jansen, M Lukoschek, U Keilholz, T F E Barth
Journal: Annals of the Rheumatic Diseases (1997)

To compare in vitro expression of beta 1, beta 3, and beta 4 integrins in normal fibroblast-like synoviocytes (FBS) and in FBS from rheumatoid arthritis (RA) synovium and to investigate the adhesion of normal FBS and RA-FBS to the integrin binding extracellular matrix (ECM) proteins: collagen type IV, fibronectin, laminin, and tenascin.Expression of integrin receptors of cultured FBS was detected by flow cytometry. Attachment of FBS to ECM proteins was quantified by adhesion assays. Inhibition studies were performed using monoclonal antibodies to the integrin subunits.Compared with normal FBS, RA-FBS showed increased expression of alpha 1 to alpha 6, beta 1, and beta 4 integrin subunits and enhanced binding of ECM proteins. Binding to ECM proteins was partly or completely blocked by an anti-beta 1 integrin antibody and antibodies to alpha 3, alpha 5, and alpha 6 integrin subunits. The blocking efficiency was significantly (P < 0.05) higher in RA-FBS than in normal FBS.The enhanced expression of the beta 1 integrin receptors on cultured RA-FBS correlated with increased attachment to ECM proteins. Adhesion of normal and RA-FBS to ECM proteins is mediated through beta 1 integrin receptors. Therefore, the tight binding of rheumatoid FBS to the matrix via beta 1 integrins might play a role in ECM remodelling in the rheumatoid process in vivo.
Countertransference Reactions to Violent Patients
Authors: JOHN R. LION, STEFAN A. PASTERNAK
Journal: American Journal of Psychiatry (1973)

Treating violent patients can evoke countertransference reactions of fear and anger in therapists that may interfere with effective management. The authors present six case reports in which countertransference reactions deleteriously affected the treatment outcome. They stress the importance of the physician's being aware of his fear and of how this fear may distort, by projection, his view of the patient as being dangerous.
Surgical and nonsurgical approaches to small-size nonsmall cell lung cancer
Authors: Dirk De Ruysscher, Kazuo Nakagawa, Hisao Asamura
Journal: European Respiratory Journal (2014)

Lobectomy and systematic nodal dissection are still the standard for small-size (&lt;3 cm) nonsmall cell lung cancer. There is growing interest in more parenchyma-sparing surgery, so-called sublobar resections (wedge resection or segmentectomy). Indeed, nonrandomised trials suggest that a segmentectomy may result in local control rates that are similar to lobectomy. Nonsurgical approaches, such as stereotactic ablative radiotherapy, consistently result in local control rates of ∼90% and survival rates that are comparable to lobectomy. Therefore, we are moving towards an era in which several therapeutic possibilities are available, that are probably equivalent from an oncological point of view. Further trials are needed to define the optimal therapy for individual patients.
Phenothiazine Deaths: A Critical Review
Authors: ROGER PEELE, IDELLA S. VON LOETZEN
Journal: American Journal of Psychiatry (1973)

To determine whether "phenothiazine death" is a valid entity, the authors examined case studies in the literature for other explanations of these sudden, unexpected, autopsy-negative deaths. The results of their comparisons of a large number of phenothiazine deaths and deaths due to lethal catatonia raise doubts as to the validity of phenothiazine death as an entity.
GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
Authors: Paul D P Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke L Fridley, Jonathan P Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C Larson, Honglin Song, Daniel C Tessier, François Bacot, Daniel Vincent, Julie M Cunningham, Joe Dennis, Ed Dicks, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M Armasu, Laura Baglietto, Elisa V Bandera, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise A Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Ian Campbell, Michael E Carney, Renato S Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda S Cook, Daniel W Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana Eccles, Robert Edwards, Arif B Ekici, Peter A Fasching, David Fenstermacher, James Flanagan, Yu-Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Qi Guo, Mari K Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Høgdall, Claus K Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly R Kalli, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne Krüger Kjaer, Gottfried E Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubiński, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara Olson, Irene Orlow, James Paul, Tanja Pejovic, Liisa M Pelttari, Jenny Permuth-Wey, Malcolm C Pike, Elizabeth M Poole, Xiaotao Qu, Harvey A Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Gianluca Severi, Hui Shen, Vijayalakshmi Shridhar, Xiao-Ou Shu, Weiva Sieh, Melissa C Southey, Paul Spellman, Kazuo Tajima, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Agnieszka Timorek, Shelley S Tworoger, Anne M van Altena, David van den Berg, Ignace Vergote, Robert A Vierkant, Allison F Vitonis, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Elisabeth Wik, Boris Winterhoff, Yin Ling Woo, Anna H Wu, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Marc T Goodman, Per Hall, Douglas F Easton, Celeste L Pearce, Andrew Berchuck, Georgia Chenevix-Trench, Edwin Iversen, Alvaro N A Monteiro, Simon A Gayther, Joellen M Schildkraut, Thomas A Sellers
Journal: Nature Genetics (2013)
Influence of obesity on the antilipolytic effect of insulin in isolated human fat cells obtained before and after glucose ingestion.
Authors: P Arner, J Bolinder, P Engfeldt, J Hellmér, J Ostman
Journal: Journal of Clinical Investigation (1984)

The antilipolytic effect of insulin was studied in 9 obese and 10 age- and sex-matched subjects of normal weight. Isolated fat cells were taken before and 1 h after an 100 g oral glucose load. Insulin inhibition of basal and isoprenaline-induced rates of lipolysis were determined by using a sensitive bioluminescent glycerol assay. When compared with the controls, the obese group showed a lower glucose tolerance, a higher insulin secretion, and a lower specific insulin receptor binding per adipocyte surface area, which would suggest an insulin-resistant state. Before oral glucose, however, the sensitivity of the antilipolytic effect of insulin was enhanced 10-fold in obesity (P less than 0.01), but the maximum antilipolytic effect was not altered. Glucose ingestion induced a 10-25-fold increase in insulin sensitivity (P less than 0.01) and a 10% but not significant increase in specific adipocyte insulin receptor binding in the nonobese group. In the obese group, however, neither the insulin binding nor the antilipolytic effect of the hormone was increased by oral glucose. After oral glucose, insulin sensitivity was similar in the two groups. The concentration of the hormone which produced a half maximum effect was about 1 microU/ml. Similar results were obtained with insulin inhibition of basal and isoprenaline-stimulated glycerol release. It is concluded that, after an overnight fast, the sensitivity of the antilipolytic effect of insulin is markedly enhanced in adipocytes of "insulin-glucose resistant" obese subjects, presumably because of alterations at postreceptor levels of insulin action. In obesity, the antilipolytic effect of insulin seems normal after glucose ingestion. Furthermore, in adipocytes of subjects of normal weight, oral glucose rapidly stimulates the sensitivity of the antilipolytic effect of insulin, apparently because of changes at postreceptor sites. This short-term regulation of insulin action following the ingestion of glucose does not seem to be present in obesity.