tbuckley/cabot-search huggingface dataset:
Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases.
Authors: A.J Farrell, D.R Blake, R.M Palmer, S Moncada
Journal: Annals of the Rheumatic Diseases (1992)

Cytokines induce nitric oxide synthesis by endothelial cells, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations in patients with RA and OA were significantly higher than in controls. In both disease groups synovial fluid nitrite was significantly higher than serum nitrite, implying nitric oxide synthesis by the synovium. Serum and synovial fluid nitrite concentrations in RA were also significantly higher than those in OA. These data show increased nitric oxide production in RA and OA and suggest a role for nitric oxide as an inflammatory mediator in rheumatic diseases.
P08 * INTRA-OPERATIVE MRI: THE ALDER HEY EXPERIENCE SO FAR
Authors: B. Zebian, V. Stagno, C. J. Parks, B. Pettorini, C. Mallucci, B. Pizer, L. Abernethy, S. Avula
Journal: Neuro-Oncology (2014)

INTRODUCTION: Intra-operative MRI (ioMRI) is increasingly being used by some neurosurgical units to ensure maximal tumour resection and therefore improved outcome. Its use has also extended to other non-oncological neurosurgical procedures. METHOD: We report our ioMRI experience in Alder Hey over a period of 53 months and compare the results with a historical cohort prior to the introduction of ioMRI specifically looking at the group of patients where complete surgical tumour resection was the desired outcome. RESULTS: ioMRI was used in 183 cases since its introduction at Alder Hey. Of these, 143 were debulkings / resections of tumours, 6 biopsies, 1 cyst drainage, 25 epilepsy cases, 7 craniofacial and 1 abscess drainage. Approximately 30% of patients underwent second-look surgery following ioMRI. None have required return to theatre for resection of residual disease. This compares to 14% in the historical cohort prior to availability of ioMRI. There was no increase in morbidity - infection or otherwise - directly attributable to ioMRI. CONCLUSION: The use of ioMRI has proven to be safe and effective at ensuring that the goals of surgery are met and has allowed for an improved service by reducing return to theatre rates.
Respiratory physiology: adaptations to high-level exercise
Authors: Donald C McKenzie
Journal: British Journal of Sports Medicine (2012)

Most exercise scientists would agree that the physiological determinants of peak endurance performance include the capacity to transport oxygen to the working muscle, diffusion from the muscle to the mitochondria, energy production and force generation, all influenced by signals from the central nervous system. In general, the capacity of the pulmonary system far exceeds the demands required for ventilation and gas exchange during exercise. Endurance training induces large and significant adaptations within the cardiovascular, musculoskeletal and haematological systems. However, the structural and functional properties of the lung and airways do not change in response to repetitive physical activity and, in elite athletes, the pulmonary system may become a limiting factor to exercise at sea level and altitude. As a consequence to this respiratory paradox, highly trained athletes may develop intrathoracic and extrathoracic obstruction, expiratory flow limitation, respiratory muscle fatigue and exercise-induced hypoxaemia. All of these maladaptations may influence performance.
Cytogenetics and molecular genetics of childhood brain tumors
Authors: J. A. Biegel
Journal: Neuro-Oncology (1999)

Considerable progress has been made toward improving survival for children with brain tumors, and yet there is still relatively little known regarding the molecular genetic events that contribute to tumor initiation or progression.Nonrandom patterns of chromosomal deletions in several types of childhood brain tumors suggest that the loss or inactivation of tumor suppressor genes are critical events in tumorigenesis.Deletions of chromosomal regions 10q, 11 and 17p, for example, are frequent events in medulloblastoma, whereas loss of a region within 22q11.2, which contains the INI1 gene, is involved in the development of atypical teratoid and rhabdoid tumors.A review of the cytogenetic and molecular genetic changes identied to date in childhood brain tumors will be presented.
The Thromboxane A <sub>2</sub> Receptor Antagonist S18886 Prevents Enhanced Atherogenesis Caused by Diabetes Mellitus
Authors: Adriana Zuccollo, Chaomei Shi, Roberto Mastroianni, Karlene A. Maitland-Toolan, Robert M. Weisbrod, Mengwei Zang, Shanqin Xu, Bingbing Jiang, Jennifer M. Oliver-Krasinski, Antonio J. Cayatte, Stefano Corda, Gilbert Lavielle, Tony J. Verbeuren, Richard A. Cohen
Journal: Circulation (2005)

S18886 is an orally active thromboxane A2 (TXA2) receptor (TP) antagonist in clinical development for use in secondary prevention of thrombotic events in cardiovascular disease. We previously showed that S18886 inhibits atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice by a mechanism independent of platelet-derived TXA2. Atherosclerosis is accelerated by diabetes and is associated with increased TXA(2) and other eicosanoids that stimulate TP. The purpose of this study was to determine whether S18886 lessens the enhanced atherogenesis in diabetic apoE(-/-) mice.Diabetes mellitus was induced in apoE(-/-) mice with streptozotocin and was treated or not with S18886 (5 mg.kg(-1).d(-1)). After 6 weeks, aortic lesion area was increased >4-fold by diabetes in apoE(-/-) mice, associated with similar increases in serum glucose and cholesterol. S18886 largely prevented the diabetes-related increase in lesion area without affecting the hyperglycemia or hypercholesterolemia. S18886 prevented deterioration of endothelial function and endothelial nitric oxide synthase expression, as well as increases in intimal markers of inflammation associated with diabetes. In human aortic endothelial cells in culture, S18886 also prevented the induction of vascular cell adhesion molecule-1 and prevented the decrease in endothelial nitric oxide synthase expression caused by high glucose.The TP antagonist inhibits inflammation and accelerated atherogenesis caused by diabetes, most likely by counteracting effects on endothelial function and adhesion molecule expression of eicosanoids stimulated by the diabetic milieu.
Equilibrium between Host and Cancer Caused by Effector T Cells Killing Tumor Stroma
Authors: Bin Zhang, Yi Zhang, Natalie A. Bowerman, Andrea Schietinger, Yang-Xin Fu, David M. Kranz, Donald A. Rowley, Hans Schreiber
Journal: Cancer Research (2008)

Abstract The growth of solid tumors depends on tumor stroma. A single adoptive transfer of CD8+ CTLs that recognize tumor antigen–loaded stromal cells, but not the cancer cells because of MHC restriction, caused long-term inhibition of tumor growth. T cells persisted and continuously destroyed CD11b+ myeloid-derived, F4/80+ or Gr1+ stromal cells during homeostasis between host and cancer. Using high-affinity T-cell receptor tetramers, we found that both subpopulations of stromal cells captured tumor antigen from surrounding cancer cells. Epitopes on the captured antigen made these cells targets for antigen-specific T cells. These myeloid stromal cells are immunosuppressive, proangiogenic, and phagocytic. Elimination of these myeloid cells allowed T cells to remain active, prevented neovascularization, and prevented tumor resorption so that tumor size remained stationary. These findings show the effectiveness of adoptive CTL therapy directed against tumor stroma and open a new avenue for cancer treatments. [Cancer Res 2008;68(5):1563–71]
Controversies About the Psychotherapy of Schizophrenia
Authors: JOHN G. GUNDERSON
Journal: American Journal of Psychiatry (1973)

The author discusses the current controversies over the psychotherapeutic treatment of schizophrenics that have come out of an NIMH program involving experienced clinicians. The controversies concern where to focus content, what techniques to employ, and what theories can be derived from intensive psychotherapy with schizophrenic patients. He concludes that studies of interactional variables and greater communication among clinicians are required to facilitate an understanding of what the therapeutic effects of such psychotherapy may be.
The Role of Maintenance Therapy in the Treatment of Multiple Myeloma
Authors: Ashraf Z. Badros
Journal: Journal of the National Comprehensive Cancer Network (2010)

Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades, without evidence of clear benefit until recently. Chemotherapy maintenance offers no benefit after conventional or high-dose treatment. Interferon-based maintenance is associated with minimal improvements in clinical outcomes, but is poorly tolerated. Results of corticosteroid maintenance studies have been conflicting; at least one randomized trial showed improved survival with prednisone maintenance after conventional chemotherapy. The role of the novel agents thalidomide, lenalidomide, and bortezomib as maintenance is emerging. Most reported maintenance studies have evaluated thalidomide, alone or in combination with a corticosteroid. Several of these studies suggest that thalidomide-based maintenance prolongs overall survival after autologous stem cell transplantation. Important questions that have not yet been resolved include the optimal dose and duration of thalidomide, whether clinical benefit depends on response to induction therapy and risk for relapse, and whether reported benefits are caused by cytoreduction or eradication of minimal residual disease, especially with bortezomib maintenance. Ongoing randomized trials are evaluating lenalidomide and bortezomib maintenance therapies to better define the role of these drugs as maintenance in multiple myeloma.
Possible Determinants of Aggression
Authors: A. Lange
Journal: Psychotherapy and Psychosomatics (1972)

Some determinants of aggression have been discussed. First of all, it was shown that contrary to thinking of the last decades frustration could not simply be held as a major determinant of aggressive behavior. In several experiments frustration led to inhibition instead to an increase of aggression. Following this, the fenomenon of aggression was considered in terms of learning theory. Two sorts of primary reinforcers (intrinsical and extrinsical) were distinguished from secondary reinforcers of aggression. By means of this reinforcement-model a link could be established between several kinds of aggression like frustration aggression, instrumental aggression and obedient aggression.
Proposal for the Use of Progression-Free Survival in Unblinded Randomized Trials
Authors: Boris Freidlin, Edward L. Korn, Sally Hunsberger, Robert Gray, Scott Saxman, Jo Anne Zujewski
Journal: Journal of Clinical Oncology (2007)

Progression-free survival is an attractive end point for clinical trials when an overall survival end point may be confounded by additional treatments administered after progression. When a trial is performed in an unblinded manner, however, there is the potential for bias between the treatment arms because of the subjective aspects of the progression end point. We discuss the magnitude of this potential bias and suggest methods for lessening it. We propose the carrying forward of any progression information to two designated time points for the statistical analysis for trials that are not blinded. This proposal, possibly combined with central review of progression scans for these two time points, essentially eliminates any bias, with little risk of major efficiency loss compared with using the reported progression times.
Services for neurological conditions are still poor, says National Audit Office:
Authors: Jacqui Wise
Journal: BMJ (2015)

Progress in achieving better services and outcomes for people with neurological conditions in England has been poor, a report from the National Audit Office concludes.1

In 2012 the Public Accounts Committee set out how services should be improved to achieve better outcomes for people with neurological conditions.2 3 But the audit office’s report said that progress on three of the committee’s recommendations has been poor, moderate on two, and good on one.

Many neurological conditions severely affect quality of life and …
Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction
Authors: Dirk Westermann, Mario Kasner, Paul Steendijk, Frank Spillmann, Alexander Riad, Kerstin Weitmann, Wolfgang Hoffmann, Wolfgang Poller, Matthias Pauschinger, Heinz-Peter Schultheiss, Carsten Tschöpe
Journal: Circulation (2008)

Background— Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and during atrial pacing and handgrip exercise. Methods and Results— Patients with HFNEF (n=70) and patients without heart failure symptoms (n=20) were enrolled. Pressure-volume loops were measured with a conductance catheter during basal conditions, handgrip exercise, and atrial pacing with 120 bpm to analyze diastolic and systolic left ventricular function. During transient preload reduction, the diastolic stiffness constant was measured directly. Diastolic function with increased stiffness was significantly impaired in patients with HFNEF during basal conditions. This was associated with increased end-diastolic pressures during handgrip exercise and with decreased stroke volume and a leftward shift of pressure-volume loops during atrial pacing. Conclusions— Increased left ventricular stiffness contributed to increased end-diastolic pressure during handgrip exercise and decreased stroke volume during atrial pacing in patients with HFNEF. These data suggest that left ventricular stiffness modulates cardiac function in HFNEF patients and suggests that diastolic dysfunction with increased stiffness is a target for treating HFNEF.
Superior Protection against Malaria and Melanoma Metastases by a C-glycoside Analogue of the Natural Killer T Cell Ligand α-Galactosylceramide
Authors: John Schmieg, Guangli Yang, Richard W. Franck, Moriya Tsuji
Journal: The Journal of Experimental Medicine (2003)

α-Galactosylceramide (α-GalCer) is a glycolipid that stimulates natural killer T cells to produce both T helper (Th) 1 and Th2 cytokines. This property enables α-GalCer to ameliorate a wide variety of infectious, neoplastic, and autoimmune diseases; however, its effectiveness against any one disease is limited by the opposing activities of the induced Th1 and Th2 cytokines. Here, we report that a synthetic C-glycoside analogue of α-GalCer, α-C-galactosylceramide (α-C-GalCer), acts as natural killer T cell ligand in vivo, and stimulates an enhanced Th1-type response in mice. In two disease models requiring Th1-type responses for control, namely malaria and melanoma metastases, α-C-GalCer exhibited a 1,000-fold more potent antimalaria activity and a 100-fold more potent antimetastatic activity than α-GalCer. Moreover, α-C-GalCer consistently stimulated prolonged production of the Th1 cytokines interferon-γ and interleukin (IL)-12, and decreased production of the Th2 cytokine IL-4 compared with α-GalCer. Finally, α-C-GalCer's enhanced therapeutic activity required the presence of IL-12, which was needed to stimulate natural killer cells for optimal interferon-γ production, but did not affect IL-4. Overall, our results suggest that α-C-GalCer may one day be an excellent therapeutic option for diseases resolved by Th1-type responses.
Proadrenomedullin NH2-Terminal 20 Peptide Is a Potent Angiogenic Factor, and Its Inhibition Results in Reduction of Tumor Growth
Authors: Alfredo Martínez, Enrique Zudaire, Sergio Portal-Núñez, Liliana Guédez, Steven K. Libutti, William G. Stetler-Stevenson, Frank Cuttitta
Journal: Cancer Research (2004)

We have found through ex vivo and in vivo angiogenesis models that the adrenomedullin gene-related peptide, proadrenomedullin NH2-terminal 20 peptide (PAMP), exhibits a potent angiogenic potential at femtomolar concentrations, whereas classic angiogenic factors such as vascular endothelial growth factor and adrenomedullin mediate a comparable effect at nanomolar concentrations. We found that human microvascular endothelial cells express PAMP receptors and respond to exogenous addition of PAMP by increasing migration and cord formation. Exposure of endothelial cells to PAMP increases gene expression of other angiogenic factors such as adrenomedullin, vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor C. In addition, the peptide fragment PAMP(12-20) inhibits tumor cell-induced angiogenesis in vivo and reduces tumor growth in xenograft models. Together, our data demonstrate PAMP to be an extremely potent angiogenic factor and implicate this peptide as an attractive molecular target for angiogenesis-based antitumor therapy.
Thyroid Transcription Factor-1 Inhibits Transforming Growth Factor-β–Mediated Epithelial-to-Mesenchymal Transition in Lung Adenocarcinoma Cells
Authors: Roy-Akira Saito, Tetsuro Watabe, Kana Horiguchi, Tadashi Kohyama, Masao Saitoh, Takahide Nagase, Kohei Miyazono
Journal: Cancer Research (2009)

Thyroid transcription factor-1 (TTF-1) is expressed in lung cancer, but its functional roles remain unexplored. TTF-1 gene amplification has been discovered in a part of lung adenocarcinomas, and its action as a lineage-specific oncogene is highlighted. Epithelial-to-mesenchymal transition (EMT) is a crucial event for cancer cells to acquire invasive and metastatic phenotypes and can be elicited by transforming growth factor-beta (TGF-beta). Mesenchymal-to-epithelial transition (MET) is the inverse process of EMT; however, signals that induce MET are largely unknown. Here, we report a novel functional aspect of TTF-1 that inhibits TGF-beta-mediated EMT and restores epithelial phenotype in lung adenocarcinoma cells. This effect was accompanied by down-regulation of TGF-beta target genes, including presumed regulators of EMT, such as Snail and Slug. Moreover, silencing of TTF-1 enhanced TGF-beta-mediated EMT. Thus, TTF-1 can exert a tumor-suppressive effect with abrogation of cellular response to TGF-beta and attenuated invasive capacity. We further revealed that TTF-1 down-regulates TGF-beta2 production in A549 cells and that TGF-beta conversely decreases endogenous TTF-1 expression, suggesting that enhancement of autocrine TGF-beta signaling accelerates the decrease of TTF-1 expression and vice versa. These findings delineate potential links between TTF-1 and TGF-beta signaling in lung cancer progression through regulation of EMT and MET and suggest that modulation of TTF-1 expression can be a novel therapeutic strategy for treatment of lung adenocarcinoma.
Clinical characteristics of fatalities due to influenza A (H1N1) virus in Mexico
Authors: G. Fajardo-Dolci, R. Gutierrez-Vega, H. Arboleya-Casanova, A. Villalobos, K. S. Wilson, S. G. Garcia, J. Sotelo, J. A. Cordova Villalobos, C. Diaz-Olavarrieta
Journal: Thorax (2010)

<h3>Background</h3> Mexico has experienced a disproportionate mortality burden due to the influenza A(HIN1) pandemic. A study was undertaken to investigate the sociodemographic and clinical characteristics of the first 100 patients who died from confirmed influenza A(H1N1). <h3>Methods</h3> A clinical evaluation was made of the first 100 consecutive deaths of confirmed cases between 10 April and 28 May 2009 reported by the Federal Ministry of Health. Statistical analysis included disease frequencies and descriptive comparisons with national health data. <h3>Results</h3> Most patients (60%) were aged 30–79 years, 53% were female and 40% were residents of Mexico City. On admission, 50% had one or more chronic medical conditions including metabolic syndrome (40%), cardiovascular disease (21%), diabetes (20%), hypertension (20%) and respiratory disease (8%). 38% of women and 26% of men were obese based on body mass index). The main clinical symptoms were fever (84%), cough (85%), dyspnoea (75%) and myalgia (30%). The frequency of all chronic diseases was higher in this sample than in the national statistics. Most (82%) developed symptoms before the Mexican government issued the influenza alert (24 April). Median hospital stay prior to death was 4 days (range 0–58). <h3>Conclusions</h3> Patients, mostly young adults, who died from A(HIN1) influenza had a high frequency of one or more chronic diseases upon admission. Most died shortly after the health authorities initiated national influenza control measures.
Otitis Media: The Spectrum of Middle Ear Inflammation
Authors: G S Giebink, P G Quie
Journal: Annual Review of Medicine (1978)

Otitis media is characterized by a broad range of pathophysiologic events occurring within the middle ear. Only recently have these events been defi ned by terminology acceptable to both clinicians and researchers ( 1). All middle ear effusions appear to result from inflammation of the middle ear cleft. Acute suppurative (purulent) otitis and chronic nonsuppurative (serous and mucoid) otitis have been described. Combinations, such as mucopurulent and sero­ purulent otitis, also occur. Prior to the development of sensitive diagnostic tools, such as the pneumatic otoscope and tympanometer, diagnosis of otitis media was based largely on the presence of an inflammed tympanic membrane and/or on the presence of otorrhea. Thus, until recently we have primarily detected acute otitis media only, and it is mostly from this experience that the natural history of otitis media has been studied. This review describes the (a) incidence, (b) pathogenesis, (c) diagnosis, (d) management, and (e) compli­ cations of acute and chronic otitis media.
The significance of persistent ST elevation versus early resolution of ST segment elevation after primary PTCA
Authors: Shlomi Matetzky, Maxim Novikov, Luis Gruberg, Dov Freimark, Micha Feinberg, Dan Elian, Ilya Novikov, Elio Di Segni, Oren Agranat, Yedael Har-Zahav, Babeth Rabinowitz, Elieser Kaplinsky, Hanoch Hod
Journal: Journal of the American College of Cardiology (1999)