tbuckley/cabot-search huggingface dataset:
Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas
Authors: Kathleen R. Lamborn, W. K. Alfred Yung, Susan M. Chang, Patrick Y. Wen, Timothy F. Cloughesy, Lisa M. DeAngelis, H. Ian Robins, Frank S. Lieberman, Howard A. Fine, Karen L. Fink, Larry Junck, Lauren Abrey, Mark R. Gilbert, Minesh Mehta, John G. Kuhn, Kenneth D. Aldape, Janelle Hibberts, Pamela M. Peterson, Michael D. Prados
Journal: Neuro-Oncology (2008)

The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials.
Abstract 2033: Protection of quiescent fibroblasts from proteasome inhibition-mediated proteotoxicity
Authors: Aster Legesse-Miller, Irene Raitman, Erin M. Haley, Albert Liao, Lova L. Sun, David J. Wang, Johanna M.S. Lemons, Eric J. Suh, Elizabeth L. Johnson, Benjamin A. Laund, Hilary A. Coller
Journal: Cancer Research (2012)

Abstract Objectives: The aim of this study is to investigate quiescence-related resistance to proteasome-inhibition mediated proteotoxicity, and its regulatory mechanisms. Introduction: Quiescence, the reversible arrest of cellular proliferation, is critical for normal cellular development and tissue maintenance. Moreover, while proteasome inhibitors (PIs) are used to treat specific cancers, it has been shown that subsets of cells within a tumor, through quiescence, avoid PI-induced apoptosis and survive. Thus, deciphering the mechanisms through which quiescent cells resist proteasome inhibition is of basic and clinical relevance. Methods: Proliferating and quiescent primary human fibroblasts were used as a model system to study the effects of PIs (MG132, epoxomycin and Bortezomib). Flow cytometry, Western blots, microscopy and microarrays were used to identify specific pathways activated by proliferating and quiescent fibroblasts in response to proteasome inhibition. Results: We found that the proteasome-inhibited quiescent fibroblasts maintain viability while proliferating fibroblasts rapidly undergo apoptosis. We further found that proteasome-inhibited proliferating and quiescent fibroblasts up-regulate multiple protective pathways, including authophagy, chaperones and antioxidants, and evidence no observable difference in proteasome-mediated degradation pathway activity. However, we found that in proliferating fibroblasts, proteasome inhibition leads to increased reactive oxygen species (ROS), peri-nuclear protein aggresomes, and apoptotic cell death. By comparison, proteasome-inhibited quiescent cells display selective up-regulation of MnSOD (a ROS detoxifying enzyme), dispersed protein aggregates, and less apoptotic cell death. Knockdown of p62/SQSTM1 (a protein important for aggresome formation) or treatment with an antioxidant N-acetylcysteine results in reduced aggresome formation and decreased apoptosis in response to proteasome inhibition. Moreover, inhibition of autophagy sensitizes serum-starved quiescent cells to proteasome inhibition induced apoptosis. This suggests that multiple mechanisms, including autophagy, ROS detoxification and differential subcellular trafficking of ubiquitinated proteins are implicated in quiescence-related resistance to PI-induced apoptosis. These results point to possible strategies for improving the effectiveness of PIs in cancer treatment. 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 2033. doi:1538-7445.AM2012-2033
Products of arachidonic acid metabolism and the effects of cyclooxygenase inhibition on ongoing cutaneous allergic reactions in human beings☆☆☆★★★
Authors: Paul C. Atkins, Burton Zweiman, Bruce Littman, Charles Presti, Carolyn von Allmen, Anne Moskovitz, J.D. Eskra
Journal: Journal of Allergy and Clinical Immunology (1995)
Psychomotor Performance and Counterregulatory Responses During Mild Hypoglycemia in Healthy Volunteers
Authors: Anthony B Stevens, William R McKane, Patrick M Bell, Paul Bell, David J King, John R Hayes
Journal: Diabetes Care (1989)

The effect of mild hypoglycemia on psychomotor performance and counterregulatory responses was studied among 12 healthy volunteers. Each volunteer received two modified hyperinsulinemic glucose clamps. One morning, plasma glucose was held constant at euglycemic levels (4.9 mM) for 95 min, and another morning, it was lowered over 35 min and then held constant at hypoglycemic levels (3.4 mM) for 60 min. A battery of psychomotor tests and a questionnaire assessing hypoglycemic symptoms were administered before and repeated during the last 30 min of each clamp. The questionnaire and three selected psychomotor tests were also administered repetitively during the 1st h of each clamp. During the hypoglycemic studies, a rise was seen in plasma epinephrine and pancreatic polypeptide at 45 min. An increase in symptom scores was first recorded at 50 min during the hypoglycemic studies [median 4 (range 0–13) vs. 2 (5-6), P &amp;lt; .05]. Performance was impaired on two psychomotor tests included in the battery. One was the trail making test on fine motor performance (–19.3 ± 4.2 targets/min, mean ± SE vs. 1.2 ± 4.8 targets/min, P &amp;lt; .05), and the other was the digitsymbol substitution (DSS) test on information processing and memory (18 ± 3 vs. 29 ± 4 symbols/min, P &amp;lt; .03). Of the tests administered during the 1st h, performance was impaired on the DSS. Thi impairment became significant at 45 min (14 ± 4 vs. 22 ± 4 symbols/min, P &amp;lt; .005). In conclusion, mild hypoglycemia selectively impairs psychomotor performance in healthy volunteers but not before the onset of glucose counterregulation and warning symptoms.
Consultation with the Police: An Example of Community Psychiatry Practice
Authors: ALAN M. ELKINS, GEORGE O. PAPANEK
Journal: American Journal of Psychiatry (1966)

A part of the psychiatrist's potential contribution as consultant to community agents lies in his special skills in understanding the subtleties of communication among individuals and groups. The author's consultation with the local police in a predominantly Puerto Rican area helped to open the channels of communication between patrolmen and the local population and thus to ease the tensions which threatened community progress.
Predictors of treatment delay in patients with acute myocardial infarction undergoing primary angioplasty: An analysis from the CADILLAC trial
Authors: Mark A. Turco, Martin Fahy, Roxana A. Mehran, Alexandra Lansky, Cindy L. Grines, James E. Tcheng, Eulogio Garcia, Giulio Guagliumi, David A. Cox, Thomas D. Stuckey, Dawn E. Shaddinger, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2003)
Five million deaths despite royal college's warning 40 years ago
Authors: K. Burke
Journal: BMJ (2002)

Exactly 40 years after the Royal College of Physicians warned the public that smoking causes lung cancer, the college is pressing the UK government to end “ministerial indifference and inaction” over a habit that has killed millions of Britons.

The college is calling for more investment in smoking cessation clinics and mass media public education to cut the number of people smoking by 1% every year—more than double the current rate.

In his foreword to a commemorative booklet launched on Thursday, the Royal …
Oral protein energy supplements for children with cystic fibrosis: CALICO multicentre randomised controlled trial
Authors: Vanessa J Poustie, Jayne E Russell, Ruth M Watling, Deborah Ashby, Rosalind L Smyth
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To determine whether oral protein energy supplements, used long term in children with cystic fibrosis who are moderately malnourished, improve nutritional and other outcomes. <b>Design</b> Multicentre randomised controlled trial.<b>Setting</b> Seven specialist paediatric cystic fibrosis centres and their associated shared care clinics and seven smaller paediatric cystic fibrosis clinics. <b>Participants</b> 102 children with cystic fibrosis, aged between 2 and 15 years, who were moderately malnourished. <b>Interventions</b> Oral protein energy supplements in addition to usual dietary advice compared with dietary advice alone, for 12 months. <b>Main outcome measure</b> Change in body mass index centile over one year. <b>Results</b> Use of supplements was not associated with a change in body mass index centile (mean difference 2.99 centile points, 95% confidence interval −2.70 to 8.68) or other nutritional and spirometric outcomes in this group of children. <b>Conclusions</b> Long term use of oral protein energy supplements did not result in an improvement in nutritional status or other clinical outcomes in children with cystic fibrosis who were moderately malnourished. Oral protein energy supplements should not be regarded as an essential part of the management of this group of children. <b>Trial registration</b> ISRCTN: 95744468.
INTRAPERITONEAL USE OF DEXTROSE IN TREATMENT OF DISEASES OF CHILDREN
Authors: HEYWORTH N. SANFORD
Journal: JAMA (1928)

When an infant suffers from a severe nutritional disturbance there is often a deficiency of food and water. Water is lost as a result of diarrhea and evaporation from the lungs, and food is not assimilated for obvious reasons. The indication for the treatment of these infants with severe nutritional disorders is, therefore, to supply the lacking elements. Food and water must be given.  Vomiting often hampers the giving of water by mouth. Hypodermoclysis is painful and its possibilities are limited. Fluids administered by rectum are not retained, and the small veins make intravenous injections impracticable. Blackfan and Maxcy 1 first advocated intraperitoneal injections as a means of supplying the desired fluid. The method of intraperitoneal injections is a practical one, when it is not possible to give enough fluid by mouth on account of vomiting and diarrhea. Much larger amounts of fluid may be given intraperitoneally than intravenously or
Iodoform as a Local Application
Authors: W. Cottle
Journal: BMJ (1878)

known ocean.And this estimate of human powers, I thought should be a bar against the indulgence of all those envyings and heartburnings that too often embitter the professional career.And then, if I followed them into the recesses of their study, I learnt that know- ledge not only fills but purifies the understanding; that, in their com- muning with Nature, their minds had insensibly imbibed her influences; that their industry, like hers, was calm, unobtrusive, and incessant-an instinct rather than an effort, and its reward the gratitude of mankind.If their lives were chequered with the good dnd evil of our lot, I saw that they sustained the trials of prosperity with honour, and the sharp strokes of adversity with dignity.The con- sciousness of duties discharged, and the occupations of their career, alleviated private griefs; while the contemplation of the serenity and steadfastness of Nature prepared the heart for those higher and nobler thoughts without which there is indeed no repose."Let me add, we have reason to know that such thoughts were enter- tained by both, and consequently that it may be said of both- " They rest from their labours, and their works do follow them.
NI-82 * DIFFUSION AND CONVENTIONAL MR IMAGING GENOMIC BIOMARKER SIGNATURE FOR EGFR MUTATION IDENTIFICATION IN GLIOBLASTOMA
Authors: E. Wassal, P. Zinn, R. Colen
Journal: Neuro-Oncology (2014)

PURPOSE: To create a diffusion and conventional MR imaging biomarker signature in order to identify those Glioblastoma (GBM) patients with EGFR mutation status. EGFR is the cell-surface receptor for members of the epidermal growth factor family(EGF-family)of extracellular protein ligands,a subfamily of receptor tyrosine kinases. EGFR gene expression is present in 40% of GBM patients.Identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR.Thus,a non-invasive imaging surrogate that predicts EGFR mutation status will help stratify patients into therapy and clinical trials. MATERIALS AND METHODS: We identified 80 treatment-naïve patients from TCGA who had both gene and microRNA expression profiles including the EGFR mutation status and pretreatment MRI from The Cancer Imaging Archive (TCIA). Qualitative VASARI imaging features for these 80 patients were assessed by 3 independent neuroradiologists and consensus was reached. Quantitative volumetric analysis was done in the 3D Slicer software 3.6 using segmentation module.Fluid Attenuated Inversion Recovery (FLAIR)was used for segmentation of the edema and post-contrast T1 weighted imaging(T1W1)for segmentation of enhancement and necrosis.Diffusion was analyzed in Olea Sphere 2.3 and Conventional FLAIR/post- contrast T1WI was registered to DWI/ADC maps. ADC, FLAIR, T1 Gadolinium enhancement values were measured using the ROI based method, in the perilesional edema/non-enhancing tumor and the enhancing tumor zones, dividing the perilesional edema/non-enhancing tumor into 3 zones each of 1 cm width, 3 ROI measurements were taken from each zone. Each quantitative feature was correlated to EGFR mutation status to create the imaging biomarker signature predictive of EGFR mutation status. Survival analysis was done in all cases. RESULTS: A diffusion and conventional MR imaging biomarker signature was created that predicted EGFR mutation status. CONCLUSIONS: EGFR mutation status plays an important role in predictive and prognostic stratification of patients with GBM. The identification of a non-invasive biomarker signature as a surrogate for EGFR mutation can help stratify patients in specific therapy and predict response to therapy.
A radiation hybrid map of 506 STS markers spanning human chromosome 11
Authors: M.R. James, C.W. Richard, J.-J. Schott, C. Yousry, K. Clark, J. Bell, J.D. Terwilliger, J. Kazan, C. Dubay, A. Vignal, M. Agrapart, T. Imai, Y. Nakamura, M. Polymeropoulos, J. Weissenbach, D.R. Cox, G.M. Lathrop
Journal: Nature Genetics (1994)
The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase.
Authors: A R Amin, P E Di Cesare, P Vyas, M Attur, E Tzeng, T R Billiar, S A Stuchin, S B Abramson
Journal: The Journal of Experimental Medicine (1995)

Classically, osteoarthritis (OA) has been considered a noninflammatory disease. However, the detection of selected inflammatory mediators in osteoarthritic fluid, in the absence of significant inflammatory cell infiltrate, is increasingly appreciated. We sought to identify the inflammatory component in human OA-affected cartilage that may be involved in cartilage damage/destruction. Using Western blot analysis and an antibody to the conserved region of nitric oxide synthase (NOS), we have observed up-regulation of NOS, one of the "key players" of inflammation, in chondrocytes of OA-affected patients. Remarkably, none of the cartilage samples examined from normal joints demonstrated detectable amounts of this NOS. Western blot analysis using the same alpha-NOS antibody indicated that this NOS from OA-affected cartilage (OA-NOS) was larger in size than (and distinct from) transfected human hepatocyte or murine inducible NOS (iNOS) (150 versus 133 kD) and similar in size to neuronal constitutive NOS (ncNOS). Antibodies specific for iNOS showed binding to murine and human iNOS but not to OA-NOS, endothelial constitutive NOS, or ncNOS. Antibodies specific for ncNOS bound to ncNOS and also to OA-NOS, but not to murine or human iNOS or endothelial constitutive NOS. Incubation of OA cartilage in serum-free medium resulted in spontaneous release, for up to 72 h, of substantial amounts of nitrite (up to approximately 80 microM/100 mg wet tissue), which could be inhibited by at least 80% with various inhibitors of iNOS, including inhibitors of protein synthesis and transcription factor NF-kappa B, but which (unlike murine macrophage iNOS) was not sensitive to hydrocortisone or TGF-beta. Exposure of OA-affected cartilage to interleukin 1 beta, tumor necrosis factor-alpha, and lipopolysaccharide resulted in approximately 20-50% augmentation of nitrite accumulation, which was also sensitive to cycloheximide and pyrrolidine dithiocarbamate. Hence, our data indicate that OA-NOS (based on immunoreactivity and molecular weight) is similar to ncNOS and that it releases nitric oxide, which may contribute to the inflammation and pathogenesis of cartilage destruction in OA.
Is appendicitis familial?
Authors: N Andersson, H Griffiths, J Murphy, J Roll, A Serenyi, I Swann, A Cockcroft, J Myers, A St Leger
Journal: BMJ (1979)

A family history of appendicectomy was sought in two groups of children admitted to Llandough Hospital over sixteen months. The study group consisted of 29 children with histologically confirmed acute appendicitis, while the control group consisted of 29 children admitted for reasons unrelated to abdominal pain. A history of appendicectomy was elicited in first-degree relatives--that is, siblings and parents of 20 of the children in the study group and of four of the controls--a statistically significant difference. The results obtained from this study suggest that a familial predisposition to appendicitis exists.
IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection
Authors: Martin Lagging, Ana I. Romero, Johan Westin, Gunnar Norkrans, Amar P. Dhillon, Jean-Michel Pawlotsky, Stefan Zeuzem, Michael von Wagner, Francesco Negro, Solko W. Schalm, Bart L. Haagmans, Carlo Ferrari, Gabriele Missale, Avidan U. Neumann, Elke Verheij-Hart, Kristoffer Hellstrand
Journal: Hepatology (2006)

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.
Caring for the Uninsured and Underinsured
Authors: Adam O. Goldstein, Laura Enyedi, Marlene Calderon, Jeff Babb, Scott Bennett
Journal: JAMA (1991)

<h3>To the Editor.—</h3> Access to health care is a significant problem for millions of Americans, particularly for those who are poor, homeless, lack health insurance, and are unemployed. Proposed comprehensive solutions to health care access problems, including mandated employer-based health insurance, health insurance risk pools, and universal health insurance programs, may take several years of public and private debate before they are finally enacted.<sup>1-3</sup> In the meantime, physicians have an obligation to provide a portion of their professional time to serving those without the resources to pay.<sup>4</sup>Many physicians dedicate substantial portions of their efforts to providing such free care, acting as role models for their peers as well as for those still in medical training.<sup>5</sup>However, the extent to which the academic medical profession and its educational processes support such efforts is unknown. The current study was designed to assess the commitments of US medical schools
Swedish and American Psychiatry: A Comparative View
Authors: JORDAN H. LACHMAN
Journal: American Journal of Psychiatry (1970)

A service of the government, Swedish psychiatry is more a part of traditional somatic medicine than in America, and the psychiatrist's role is more that of a symptom remover than a problem solver. Having missed the era of individual, dynamic psychotherapy. Sweden is working out its mental health problems in a social and community perspective.
An unusual case of sarcoidosis in an adult patient with sickle cell disease: Management with methotrexate and low dose of steroid
Authors: Letizia Delmonte, Alberto Zamo, Maurizio Cantini, Lucia de Franceschi
Journal: American Journal of Hematology (2012)

An unusual case of sarcoidosis in an adult patient with sickle cell disease: Management with methotrexate and low dose of steroidTo the editor: Sarcoidosis is a multisystem disease, which pathogenesis is still only partially known.The prevalence of sarcoidosis is largely different depending on race and ethnicity [1].The association of sarcoidosis and sickle cell disease (SCD) has been reported in few cases [2].In June 2011, a 52-year-old-man with sickle/b-thalassemia in a care of our service