tbuckley/cabot-search huggingface dataset:
Pulmonary Function in Convalescent Poliomyelitic Patients
Authors: Benjamin G. Ferris, James L. Whittenberger, John E. Affeldt
Journal: New England Journal of Medicine (1952)

THE severe poliomyelitis epidemics of recent years and the increasing success of treatment during the acute stages of respiratory failure have emphasized the need for more knowledge of the changes in pulmonary function during recovery from respiratory-muscle involvement. Such information would be of value in estimating a patient's progress, in formulating prognosis, and in assessing the effects of therapeutic procedures and the need for respiratory appliances.The degree of respiratory impairment in the acute phase of poliomyelitis varies markedly from patient to patient, and in convalescence all degrees of recovery occur (as in other types of neuromuscular paralysis). In the . . .
SP0137 Mirs in Activation of Myeloid Cells in RA
Authors: M. Kurowska-Stolarska
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The development of new treatments for rheumatoid arthritis (RA) is limited by our incomplete understanding of disease pathogenesis. Particularly, those pathways mediating disease onset, failed repair, and the development of treatment-refractory states are poorly understood. Myeloid cells (including dendritic cells, monocytes, macrophages) likely participate in such processes in RA. We recently discovered a novel epigenetic control mechanism of myeloid cells mediated via microRNA (miR) and obtained evidence for deregulation of this process in RA. We hypothesised that microRNAs controls transcriptional responses to growth and environmental factors of mononuclear myeloid cell subtypes and that its disregulation can contribute to the cause and perpetuation of arthritis. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6295
Choice of Therapy for Peripheral Arteriosclerosis
Authors: Edward A. Edwards
Journal: New England Journal of Medicine (1957)

AS surgical methods become available in the management of peripheral arteriosclerosis, the proper choice of treatment, for a particular problem encountered, becomes important. Such a choice necessitates an accurate appraisal of the pathology in the individual patient, and a knowledge of the results to be expected from various methods of treatment.Major surgery is justified only if life expectancy is adequate. The latest figures for the general population above forty years of age are impressively high (Table 1). How the general expectancy is affected by the presence of peripheral arteriosclerosis is not well documented. A study of 100 patients after . . .
SP0089 Pre-Clinical Proof for Dmoad Activity of FGF-18 (Sprifermin)
Authors: C. Ladel
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The aim of the investigations were to determine the efficacy of intra-articularly delivered test article rhFGF18 (Sprifermin) on human chondrocytes as well as in different animal models of OA and cartilage injuries. These studies intended to determine dosing, dosing regimen and potential clinical read-outs. <h3>Results</h3> Using human primary chondrocytes in-vitro the Mode-of-Action of Sprifermin was investigated. Different dosing regimens in-vitro demonstrated, that there is a phase of proliferation followed by a phase of differentiation with matrix synthesis. Intra-articular administration of Sprifermin to rats, dogs, rabbits and other species demonstrated disease modifying activity in all species tested. The therapeutic effective doses ranged from 1 to 100 µg/joint i.art administered in rats and dogs/rabbits, respectively. Therapeutic efficacy was demonstrated using histology, immunhistology and imaging as read-outs. The histopathology results indicate that Sprifermin had definite significant effects on improving the lesions of cartilage in all species tested. Anabolic effects – increased number of articular chondrocytes and formation of cartilage tissue - were seen after i.art. therapy and repair of cartilage lesion was demonstrable. The MRI data show increases in different structural measurements. s. <h3>Conclusions</h3> The results of this study demonstrate therapeutic efficacy of Sprifermin (rhFGF18)in several read-outs and confirm previous results in pre-clinical models concerning the pharmacological effects as well as the benefit of intra-articular injections of Sprifermin for treating OA. The translational design of the studies allows a direct translation and correlation to the clinical results. <h3>Disclosure of Interest</h3> C. Ladel Employee of: Employee of Merck KGaA
Book: Doctors Talking
Authors: N. Britten
Journal: BMJ (1999)

Hellen Matthews, John Bain Scottish Cultural Press, £7.95, pp 126 ISBN 1 84017 030 1 Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Resistance to the health reforms of the 1990s has taken many forms, but among general practitioners a recurrent theme has been the threat to personal care and the doctor-patient relationship. Matthews and Bain have set out to show us what it means to be a family doctor in Scotland, in the words of 11 general practitioners practising in a variety of settings. These chatty interview accounts of general practice in deprived inner cities, … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
FIVE-YEAR STENT-RELATED AND PATIENT-RELATED OUTCOMES IN PATIENTS WITH AND WITHOUT DIABETES: FROM THE SORT OUT IV TRIAL
Authors: Lisette Okkels Jensen, Michael Maeng, Per Thayssen, Jan Ravkilde, Lars Krusell, Knud Hansen, Anne Kaltoft, Henrik Hansen, Anders Junker, Anton Villadsen, Klara Berencsi, Evald Christiansen, Jens Lassen
Journal: Journal of the American College of Cardiology (2015)
A4
Authors: Michael A. Cawthon, Michael F. Hartshorne, Stephen R. Bunker, Robert D. Karl, John M. Bauman, William H. Howard, William K. Love
Journal: Clinical Nuclear Medicine (1984)

Cawthon, Michael A.; Hartshorne, Michael F.; Bunker, Stephen R.; Karl, Robert D. Jr.; Bauman, John M.; Howard, William H. III; Love, William K. Author Information
Abstract PL04-03: Targeting the hedgehog pathway in meduloblastoma and basal cell carcinoma
Authors: Frederic J. de Sauvage
Journal: Cancer Research (2011)

Abstract The hedgehog (Hh) pathway is an ancient signaling cascade that directs patterning in most animals and is crucial for proper development. While Hh signaling is very active during embryogenesis, it remains relatively quiet in adult life. However, aberrant reactivation of the pathway in adult tissues can lead to the development of cancer. Hh pathway activation in tumors such as basal cell carcinoma (BCC) and medulloblastoma is the result of inactivating mutations in PATCHED (PTCH) or activating SMOOTHENED (SMO) mutations. Targeting the Hh pathway with small molecule antagonists therefore provides a new therapeutic opportunity for the treatment of these tumor types. GDC-0449, an oral Hedgehog (Hh) pathway inhibitor, was tested in a first-in-human, first-in-class, phase I study in BCC patients. Strong antitumor activity was observed in patients with locally advanced and metastatic BCC, thereby highlighting the potential benefit of inhibiting aberrant Hh signaling in tumors where the pathway is mutated. While most BCC tumors display Hh pathway activity, only a subset of medulloblastoma tumors are caused by mutations in the Hh pathway. Early evidence of clinical benefit of GDC-0449 in a medulloblastoma patient selected for Hh pathway activity was demonstrated. However, as is the case for most targeted therapies used in cancer, mechanisms of resistance to Hedgehog pathway inhibitors have started to emerge in man and mouse models, highlighting the importance of this pathway for these tumors. Characterization of various resistance mechanisms such as SMO mutations or amplification of downstream pathway components suggests potential for therapeutic strategies for the treatment of HPI resistant tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr PL04-03. doi:10.1158/1538-7445.AM2011-PL04-03
Abstract 5297: The caHUB biospecimen pre-analytical variables program.
Authors: Latarsha Carithers, Jim Vaught
Journal: Cancer Research (2013)

Abstract The Cancer Human Biobank is an infrastructure that the Biorepositories and Biospecimen Research Branch of the Cancer Diagnosis Program at NCI uses to carry out highly specialized tissue collections to support biospecimen research programs. Specifically, the caHUB Biospecimen Pre-analytical Variables Program collects data on how variables in tissue collection, handling, storing and shipping standard operating procedures affect downstream analysis. Phase one of this program will assess variations in formalin fixation procedures. This will include examining the effects of (i) time delay to the start of tissue fixation after resection and (ii) overall tissue formalin fixation time on the signal of key proteomic markers used for diagnostic treatment that will be assessed by immunohistochemistry. Future phases of this study will address a variety of pre-analytical variables and alternate analysis platforms. The results of this project will be used to determine best practices for molecular preservation and lead to the development of evidence-based protocols for optimal collection, processing, and storage of biospecimens. Citation Format: Latarsha Carithers, Jim Vaught. The caHUB biospecimen pre-analytical variables program. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5297. doi:10.1158/1538-7445.AM2013-5297
Methotrexate for the Treatment of Crohn's Disease
Authors: Brian G. Feagan, James Rochon, Richard N. Fedorak, E. Jan Irvine, Gary Wild, Lloyd Sutherland, A. Hillary Steinhart, Gordon R. Greenberg, Richard Gillies, Marybeth Hopkins, Stephen B. Hanauer, John W.D. McDonald
Journal: New England Journal of Medicine (1995)

Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful.
AB0919 A Look at LÖFgren Syndrome: 80 Cases in Two Universitary Hospitals: Table 1
Authors: B. Segura, S. Holgado, L. Mateo-Soria, M. Martínez-Morillo, A. Riveros-Frutos, J.M. Pego-Reigosa, M. Carnicero-Iglesias, S. Rodriguez-Muguruza, X. Tena-Marsà, A. Olivé-Marqués
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Löfgren9s syndrome is a common form of sarcoidosis in the Mediterranean region. Characterized by bilateral hilar lymphadenopathy, erythema nodosum and arthritis,usually symmetrical and predominate in lower extremities. <h3>Objectives</h3> To describe the clinical characteristics, treatment and outcome of a series of patients diagnosed with Löfgren syndrome. <h3>Methods</h3> Retrospective design (1984–2013) multicenter (2 university hospitals) with a total catchment area of 1,015,000 inhabitants. Löfgren syndrome was defined as the association of erythema nodosum and/or ankle arthritis and bilateral hilar lymphadenopathy in chest radiography. Exclusion criteria:presence of some other granulomatous disease. <h3>Results</h3> 80 patients were diagnosed: 29 men and 51 women (mean age: 42.3). The mean follow-up was 54 months. 48 (60%) had the classic triad of the disease; 18 (22.5%) hilar adenopathy and arthritis,13 (16.7%) hilar adenopathy and erythema nodosum. In one case the diagnosis was casual. Ocular manifestations occurred in 11 patients with the most common xerophthalmia. 28 patients had fever, 18 fatigue and 4 significant weight loss. All had abnormalities in the study of the chest and were classified in the stage I-II. Pulmonary function tests were perfomed in 55 patients,was pathological in 6. In laboratory tests it was seen: normocytic normochromic anemia in 26 patients (32.5%), lymphopenia in 6 (7.5%), bicytopenia in 4 (5%), hypercalcemia in 4 and hypercalciuria in 1.T he ESR was determined in 78 patients with a mean of 52.4±37.2 mm/hour. The tuberculin test was positive in 6 cases. In these patients, active tuberculosis disease is excluded. 39 biopsies were performed: 23 transbronchial, 11 skin, 3 lymph node, 2 muscular and 1 of lower lid. Were available for pathologic confirmation of sarcoidosis in 28 cases (35%). It was nonspecific in 11 patients. NSAID treatment was performed in 54 patients and glucocorticoids in 33. The remission in the first 2 years after diagnosis was observed in 87.5% of cases. 14 patients relapsed: 7 performed glucocorticoids, 3 NSAIDs and 4 had not received treatment. Table 1 shows the main characteristics of the patients compared to the most important series in the literature. <h3>Conclusions</h3> Löfgren9s syndrome is a common clinical form of sarcoidosis in the Mediterranean area. Should be suspected in the presence of erythema nodosum or periarticular swelling ankles. The clinical and radiological pattern can obviate biopsy. The prognosis is good and recurrence scarce. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2955
SAT0437 Mediterranean Fever Gene: Evaluation of Clinical Presentations in Turkish Children
Authors: E. Comak, S. C. Dogan, A. Uslu Gokceoglu, I. Keser, R. Artan, A. Yilmaz, T. Bilgen, E. Sayar, A. İslek, M. Koyun, S. Akman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is an inherited autosomal recessive disorder, caused by MEditerranean FeVer gene (MEFV) mutations. Recent studies suggest that MEFV gene mutations may be related to some clinical situations and rheumatologic diseases other than FMF. <h3>Objectives</h3> The purpose of the present study was to review the clinical findings and demographic features of children with MEFV gene mutations. <h3>Methods</h3> The medical records of patients with MEFV mutations who were analyzed between 2003 and 2012 in the department of Medical Biology at Akdeniz University, Antalya, Turkey were reviewed retrospectively. Each sample was screened for the mutations located in exon 2 and exon 10 of the MEFV gene by direct sequencing. <h3>Results</h3> A total of 559 children, 264 girls (47.2 %), with a mean age of 8.22±4.64 years (1-18 years) were included. 72 patients (12.9%) had parental consanguinity and 198 (35.4%) had a family history of FMF in first-degree relatives. 179 patients (32%) were homozygous, 87 (%15.6) were compound heterozygous and 289 (%51.7) heterozygous for the MEFV gene. Four patients (0.7%) had complex allele mutations (M694V/M694V-E148Q in 3 patients, M694I- E148Q/ E148Q in one patient). Patiens were classified according to final diagnosis as FMF in 334 patients (59.7%), juvenil idiopathic arthritis in 29 (5.2%), Henoch-Schonlein purpura in 25 (4.5%), polyarteritis nodosa in 2 (0.4%), celiac disease in 6 (1.1%), Chron’s disease in 3 (0.5%), Behçet disease in 2(0.4%) and uveitis in 2 (0.4%). 36 patients (6.44%) were classified as normal as they did not have any specific complaints, 12 of whom had homozygous, 21 heterozygous and 3 compound heterozygous for MEFV gene. 132 (23.6%) heterozygous mutation carriers may suffer from a mild or incomplete form of FMF, also called ‘FMF-like’ disease. But none of them not have accurrate FMF diagnosis. <h3>Conclusions</h3> These data suggest that mutations of the MEFV gene may present with varied distinct clinical presentations, other than FMF. And also clinicians should be aware of higher rate of homozygous or compound heterozygous MEFV mutations identified by chance, such as during family screenings, in individuals who do not present with typical manifestations of FMF especially in countries where FMF is frequent. <h3>Disclosure of Interest</h3> None Declared
A1.22 IL-22 Drives the initiation and augmentation of TH17-dependent experimental arthritis
Authors: Debbie M Roeleveld, Renoud J Marijnissen, Wim B van den Berg, Marije I Koenders
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that leads to progressive destruction of cartilage and bone. IL-22 and IL-22-producing T helper cells are elevated in RA patients, suggesting a role for this cytokine in the pathogenesis of this disease. Interestingly, IL-22 is a dual cytokine with both proinflammatory and anti-inflammatory properties, and therefore its exact role in RA pathology requires further investigation. <h3>Objectives</h3> The aim of this study was to explore the role of IL-22 in the initiation and augmentation of a spontaneous model of experimental arthritis by using gene knockout mice and neutralizing antibodies for IL-22. In addition, we aimed to determine the influence of IL-22 on T cell subsets and cytokines in our mouse model. <h3>Methods</h3> IL-1Ra-deficient mice develop spontaneous arthritis due to excess IL-1 signalling, and we previously demonstrated the importance of IL-17 and Th17 cells in this model (Koenders, Arthritis Rheum 2008). To investigate the role of IL-22 in this Th17-dependent arthritis model, we compared IL-1Ra<sup>-/-</sup> x IL-22<sup>WT</sup> mice to mice lacking both IL-1Ra and IL-22. Joint swelling was scored weekly, and mice were sacrificed at the age of fifteen weeks. In addition, IL-1Ra-deficient mice were treated for 4 weeks with anti-IL-22 neutralizing antibodies after the onset of arthritis to inhibit disease progression. <h3>Results</h3> IL-1Ra-/- mice also deficient for IL-22 showed reduced incidence of arthritis, as well as reduced joint swelling and bone erosion. In addition, Th1, Th17, and regulatory T cell numbers were decreased in spleen and lymph nodes of mice lacking IL-22. Furthermore, IL-1Ra-deficient mice treated with anti-IL-22 antibodies after the clinical onset of arthritis showed reduced progression on inflammation and significant inhibition on bone erosion. This indicates that not only the onset but also the progression of arthritis is dependent on IL-22. Interestingly, reduced IL-17 serum levels were found after IL-22 blocking, suggesting a not previously observed feedback loop of IL-22 on Th17 cells. <h3>Conclusion</h3> These findings suggest that the Th17 cytokine IL-22 plays an important role both in initiation and augmentation of experimental arthritis, and might therefore be an interesting new target in RA treatment.
Abstract 1692: SR16388 impairs protein homeostasis and induces autophagy in diverse human cancer cell lines.
Authors: Lidia C. Sambucetti, Wei Zhou, Joy Calaoagan, Laurie Kara, Xiaohe Liu, Barbara Sato, Steve Samuelson, Nathan Collins, Keith Laderoute
Journal: Cancer Research (2013)

Abstract SR16388 is a novel amino steroid that targets estrogen-binding proteins including genomic estrogen receptors (ERs). Preclinical studies have demonstrated that SR16388 is a well-tolerated, orally active compound with compelling properties as an experimental antitumor agent: SR16388 has been demonstrated to 1) inhibit the proliferation and viability of diverse human cancer cell lines in vitro; 2) have antiangiogenic activity in vivo; and 3) reduce the growth of human tumor xenografts in mice. SR16388, which binds to and potently inhibits ERα and ERβ in breast cancer cells, also inhibits the widely expressed orphan nuclear receptor ERRα that has been implicated in the development of various human malignancies. ERRα is thought to regulate tumor cell energy metabolism associated with energy stress within solid tumor microenvironments. We have been exploring potential mechanisms that could explain SR16388’s broad anti-proliferative effects toward human tumor cell lines with different genotypes and tissues of origin. In these studies, we observed that SR16388 can initiate a cell-cycle arrest at G1 or G2 and ultimately cause cytotoxicity (e.g., by apoptosis) even in cells that do not express ERs or ERRα. We recently observed that SR16388 can induce persistent macroautophagy (autophagy) in diverse tumor cells, including cells from hematopoietic malignancies (e.g., multiple myeloma/MM cells) in addition to carcinomas such as prostate and breast cancers. We demonstrated induction of autophagy by using established assays (e.g., LC3I/II processing; fluorescent reporters for acidic vacuole formation; long-lived protein degradation). Here we present results demonstrating that SR16388 can rapidly and potently induce autophagy in cultures of MM cells (U266, RPMI-8226) and PC3 prostate cancer cells. Induction of autophagy in PC3 cells, in particular, was detected in tumor xenografts as early as 3 hours after dosing of mice with a therapeutic dose level of SR16388. We will present data supporting the hypothesis that SR16388 exerts its anti-proliferative and anti-tumor effects in part through the induction of stress pathways modulated by perturbations of protein homeostasis. These effects could yield therapeutic benefits that derive from targets within solid tumor microenvironments. Citation Format: Lidia C. Sambucetti, Wei Zhou, Joy Calaoagan, Laurie Kara, Xiaohe Liu, Barbara Sato, Steve Samuelson, Nathan Collins, Keith Laderoute. SR16388 impairs protein homeostasis and induces autophagy in diverse human cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1692. doi:10.1158/1538-7445.AM2013-1692
TCT-218 Clinical benefit of Multi-detector computed tomography for percutaneous coronary intervention in Chronic Total Occlusions: TACCTO prospective randomized trial
Authors: Beatriz Vaquerizo, Antonio Barros, Sandra Pujadas, Ester Bajo, DARLENE ESTRADA-YÁNEZ, Helena Tizón, Marcelo Jimenez, Faustino Miranda-Guardiola, Ruben Leta, Juan Cinca, Antonio Serra
Journal: Journal of the American College of Cardiology (2014)
Abstract 1856: A KRAS-variant as a putative biomarker of ovarian cancer risk
Authors: Joanne B. Weidhaas, Frank Slack
Journal: Cancer Research (2010)

Abstract Purpose: Ovarian cancer is the single most deadly form of women's cancer, largely due to a lack of known risk factors or genetic markers. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. We investigated the association of a single nucleotide variant (rs61764370), referred to as the KRAS-variant, that disrupts a let-7 microRNA binding site in the KRAS oncogene 1, and ovarian cancer risk. Methods: Specimens were obtained from non-selected ovarian cancer patients in three independent cohorts (n = 457) and two independent ovarian case-control studies. Specimens from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 58) and their family members were also collected. Findings: The KRAS-variant is found in greater than 29% of non-selected ovarian cancer cases and is a marker for a significant increased risk of developing ovarian cancer by case control analysis (OR = 2.46, CI = 1.14-5.29, p = .020, n = 201). This was validated in a second independent ovarian case-control (n = 630). The KRAS-variant was also identified in 60% of HBOC patients without BRCA1 or BRCA2 mutations (n = 25, p &amp;lt; 0.001), previously considered uninformative, as well as in their family members with cancer. Interpretation: These findings support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS-variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1856.