tbuckley/cabot-search huggingface dataset:
Dacarbazine and Outpatient Interleukin-2 in Treatment of Metastatic Malignant Melanoma: Phase II Southwest Oncology Group Trial
Authors: L. E. Flaherty, P.Y. Liu, W. S. Fletcher, J. W. Goodwin, S. P. Balcerzak, D. Daniels, R. L. Stephens, V. K. Sondak
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Dacarbazine and Outpatient Interleukin-2 in Treatment of Metastatic Malignant Melanoma: Phase II Southwest Oncology Group Trial Get access Lawrence E. Flaherty, Lawrence E. Flaherty * Wayne State University Medical CenterDetroit, Mich *Correspondence to : Lawrence E. Flaherty, M.D., Division of Hematology and Oncology, Wayne State University School of Medicine, P.O. Box 02188, Detroit, Ml 48202-0188. Search for other works by this author on: Oxford Academic PubMed Google Scholar P.Y. Liu, P.Y. Liu Southwest Oncology Group Statistical CenterSeattle, Wash Search for other works by this author on: Oxford Academic PubMed Google Scholar William S. Fletcher, William S. Fletcher Oregon Health Sciences UniversityPortland, Ore Search for other works by this author on: Oxford Academic PubMed Google Scholar John Wendall Goodwin, John Wendall Goodwin Ozarks Regional Community Clinical Oncology ProgramSpringfield, Mo. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stanley P. Balcerzak, Stanley P. Balcerzak Ohio State University Health CenterColumbus, Ohio Search for other works by this author on: Oxford Academic PubMed Google Scholar Danni Daniels, Danni Daniels Southwest Oncology Group Statistical CenterSeattle, Wash Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald L. Stephens, Ronald L. Stephens University of Kansas Medical Center, Kansas City, Kan Search for other works by this author on: Oxford Academic PubMed Google Scholar Vernon K. Sondak Vernon K. Sondak University of Michigan Medical CenterAnn Arbor, Mich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 11, 3 June 1992, Pages 893–894, https://doi.org/10.1093/jnci/84.11.893 Published: 03 June 1992 Article history Received: 03 February 1992 Revision received: 26 March 1992 Accepted: 01 April 1992 Published: 03 June 1992
Metastatic Lung Nodule Diagnosed on 18F-FDG PET/CT-Guided Fine Needle Aspiration in a Patient With Renal Cell Carcinoma
Authors: Kuruva Manohar, Anish Bhattacharya, Sameer Vyas, Pranab Dey, Arup Kumar Mandal, Mohammed Labeeb Abrar, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2012)

Computed tomography (CT)-guided fine-needle aspiration cytology is an essential procedure in establishing the malignant nature of either primary or metastatic lung nodules. However, false-negative findings may result from aspiration of low-cellular areas because true metabolic and cellular tumor volume cannot be identified by anatomic imaging alone. The authors describe a case of renal cell carcinoma with a lung nodule where the highly metabolic intratumoral area was demonstrated on FDG PET/CT, after which the PET/CT-guided fine-needle aspiration cytology established the malignant nature of the nodule.
Type A Behavior and Survival after Acute Myocardial Infarction
Authors: Robert B. Case, Stanley S. Heller, Nan B. Case, Arthur J. Moss
Journal: New England Journal of Medicine (1985)

To ascertain the influence of personality factors on the course of coronary artery disease, we measured Type A behavior in 516 patients within two weeks after an acute myocardial infarction, using the Jenkins Activity Survey questionnaire. Over a follow-up period of one to three years, there was no relation between the Type A score and total mortality, cardiac mortality, time to death for nonsurvivors, left ventricular ejection fraction, or duration of the stay in the coronary care unit. These negative findings were not changed by restricting the analyses to men below 61 years of age or by comparing extreme score categories. The contributions of behavioral, demographic, and cardiac physiologic factors to postinfarction mortality were also evaluated by multivariate survivorship analyses. The physiologic factors were the only ones that contributed a significant and independent mortality risk; the Type A score did not enter the survivorship model (relative risk, 0.8; 95 per cent confidence interval, 0.5 to 1.5). Thus, we found no relation between Type A behavior and the long-term outcome of acute myocardial infarction.
AB0431 The Effect of Tocilizumab on Bone Mineral Density in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis
Authors: K. Kume, K. Amano, S. Yamada, T. Kanazawa, H. Ohta, K. Hatta, K. Amano, N. Kuwaba
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with systemic bone loss.[1-3] Rheumatologists should have strategies to prevent bone loss in RA patients.[4] Interleukin-6 (IL-6) is a major cytokine involved in the pathology of RA, and may also promote osteoporosis.[5,6] Tocilizumab (TCZ) is an IL-6 receptor inhibitor, which is highly effective in the treatment of RA.[7,8] Several reports have suggested that tumor necrosis factor (TNF) inhibitors prevent bone loss;[9,10] however, there is no evidence that TCZ affects bone mineral density (BMD). <h3>Objectives</h3> To analyze the effects of therapy with tocilizumab (TCZ), an anti-interleukin-6 receptor antibody on the bone mineral density (BMD) of the lumbar spine and femoral neck in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Eighty-six patients with active RA (indicated by a 28-joint disease activity score ESR &gt;3.2) despite treatment with methotrexate (MTX) 12mg per week were included in this open label prospective study and started on TCZ (8 mg/kg every 4 weeks). All patients used a stable dosage of MTX, and were not allowed to use steroids or bisphosphonates during the study period. The BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry at baseline and 52 weeks after initiating TCZ. <h3>Results</h3> Seventy-eight patients completed this study. The BMD of the lumbar spine and femoral neck remained stable after 1 year of TCZ treatment. In 33 patients who had osteopenia at baseline, there was a significant increase in the BMD of the lumbar spine (0.022±0.042; P&lt;0.05) and femoral neck (0.024±0.0245; P&lt;0.05). <h3>Conclusions</h3> TCZ affects the BMD in patients who had active RA despite treatment with MTX. The BMD of the lumbar spine and femoral neck in patients with normal BMD at baseline was stable. TCZ increased the BMD of patients who had osteopenia at baseline. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1088
OP0111 Mechanism of New Bone Formation in Ankylosing Spondylitis: the Role of IL-32 in Osteoblast Differentiation
Authors: S. Hong, E.-J. Lee, Y.J. Kim, B.S. Koo, E.-J. Chang, E.-J. Lee, W.J. Seo, J. Oh, T.-H. Kim, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic inflammatory arthritis characterized by bony overgrowth. It has been suggested that erosive bone destruction, followed by repair with ossification, leads to new bone formation. However, little is known about the molecular mechanisms underlying proliferative bone formation in AS. Previously, we have reported that IL-32 could affect bone physiology via osteoclast activation. <h3>Objectives</h3> To investigate the role of IL-32 on osteoblast differentiation and its association with new bone formation in AS. <h3>Methods</h3> The concentration and expression levels of IL-32 and TNF-α were evaluated in the synovial fluid and tissue from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA) by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. To address whether IL-32 affects bone formation <i>in vivo</i>, we examined osteoblast differentiation from calvarial cells of IL-32 transgenic (Tg) mice and also the bone volume in these mice. To elucidate the mechanism of IL-32 effect on osteoblastogenesis, osteoblast regulators including DKK1, BMPRII, BMP2 and LRP5 were assayed in the IL-32 Tg mice. To determine the role of IL-32 in the interaction of osteoblasts and osteoclasts, the expression of RANKL and OPG was measured with or without IL-32 treatment in human primary osteoblasts. <h3>Results</h3> The levels of IL-32 were significantly higher in the synovial fluid of AS patients compared with RA or OA patients. In addition, the expression of IL-32 in AS synovia was increased compared to that in RA or OA synovia. The differentiation of osteoblasts from calvarial cells was more robust and rapid in IL-32 Tg mice than in wild-type mice. Micro-CT analysis further revealed that IL-32 Tg mice, particularly males, have a higher bone volume than wild-type mice. The levels of DKK-1, a negative regulator of Wnt signaling, were decreased in IL-32 Tg mice during osteoblast differentiation. In addition, after IL-32 stimulation, DKK-1 expression was significantly decreased in osteoblast precursor cells from mice and also in human osteoblasts. Furthermore, the expression of RANKL, but not OPG, was enhanced by the stimulation with IL-32, leading to a higher expression ratio of RANKL to OPG. <h3>Conclusions</h3> These results indicate that IL-32 is significantly highly expressed in AS and may enhance osteoblast differentiation via its inhibitory effects on DKK-1. Therefore, IL-32 might have a role in osteoproliferation and is a potential biomarker to predict new bone formation in AS. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2857
483 IL28B POLYMORPHISM IS ASSOCIATED WITH NECROINFLAMMATORY ACTIVITY AND ADVANCED FIBROSIS IN PATIENTS INFECTED WITH CHRONIC HEPATITIS DUE TO GENOTYPE NON-1 HCV
Authors: S.H. Um, Y.J. Park, S.Y. Yim, J.Y. Jeong, H.S. Lee, H.J. Chun, C.D. Kim, H.S. Ryu
Journal: Journal of Hepatology (2013)
1237 THE GENETIC BACKGROUND DIFFERENTIALLY AFFECTS HEPATIC NECRO-INFLAMMATION IN RESPONSE TO CCL2 IN A MURINE MODEL OF STEATOHEPATITIS
Authors: S. Galastri, E. Zamara, S. Milani, E. Novo, A. Provenzano, S. Sutti, I. Locatelli, E. Vivoli, E. Albano, M. Parola, F. Marra
Journal: Journal of Hepatology (2012)
AB0992 Indirect Assessment of Amyloid A Deposits in Various Organs – A New Approach of Histological Diagnosis Based on A Postmortem Clinicopathologic Study of 161 Rheumatoid Arthritis Patients
Authors: M. Bély, Ά. Apáthy
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Amyloidosis is a progressive cumulative process, in its early stage only a few structures in some organs are affected, and in later stages of the disease increasingly more may be involved (1). <h3>Objectives</h3> The aim of this study was to determine the amount of amyloid deposits in various organs of rheumatoid arthritis (RA) patients afflicted with amyloidosis at death. <h3>Methods</h3> Systemic AA amyloidosis (AAa) was located in 34 (21.1%) of 161 RA patients. The existence of amyloid A deposits in various organs was determined histologically. The extent of amyloid A deposition was evaluated by semi-quantitative visual estimation on a 0 to 3 plus scale, based on the number of involved blood vessels and tissue structures per light microscopic field (x40 objective of an Olympus BX51). <h3>Results</h3> Amyloid A protein deposition does not begin at the same time in various organs, but subsequently the amount of deposited amyloid A protein is increasing simultaneously in all investigated organs. The amounts of deposited amyloid A protein are different, but the proportion of deposits in various organs is constant and independent of the stage of amyloidosis (Fig. 1). <h3>Conclusions</h3> Amyloid A deposition starts in the most frequently involved structures and organs (1). Amyloid A deposition started earlier in the kidneys and in the heart than in the liver or lungs. The amount of deposited amyloid A varied in various organs, but in later stages of amyloidosis the proportion of deposits did not change; the ratios were constant, independent of the stage of the disease. The constant relationship between amyloid A deposits in various organs allows an estimate of deposited amyloid in not investigated organs as well. For example, actual amounts of amyloid A in the kidneys may indirectly indicate the extent of amyloid A deposition in the heart, liver, lungs etc. Detection of amyloid deposits in an organ may allow the estimation of amyloid deposits in other organs. This indirect correlation may be of clinical significance. <h3>References</h3> Bély M, Apáthy Άgnes: Clinical Pathology of rheumatoid arthritis: Cause of death, lethal complications and associated diseases in rheumatoid arthritis. First English edition. Published by Akadémiai Kiadό, Member of Wolters Kluwer Group. Budapest 2012 http://www.akkrt.hu <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1229
The US Office for Human Research Protections' judgment of the SUPPORT trial seems entirely reasonable
Authors: P. D. P. Pharoah
Journal: BMJ (2013)

There has been substantial criticism of the investigation of the Office for Human Research Protections (OHRP) of the US Department of Health and Human Services into the informed consent process used when newborn infants were enrolled in the SUPPORT trial.1 2 3 4 The OHRP stated that the lead investigators were “in violation of the regulatory requirements for informed consent, stemming from …
A Randomized Clinical Trial of the Noninvasive and Invasive Approaches to Drug Therapy of Ventricular Tachycardia
Authors: L. Brent Mitchell, Henry J. Duff, Dante E. Manyari, D. George Wyse
Journal: New England Journal of Medicine (1987)

There is controversy over whether therapy to prevent ventricular tachyarrhythmias should be selected noninvasively (by trying drugs and monitoring the patient electrocardiographically) or invasively (by selecting a drug that prevents induction of the arrhythmia by programmed stimulation). We randomly assigned 57 patients with symptomatic and demonstrable ventricular tachyarrhythmias to therapy selected either noninvasively or invasively. The tachyarrhythmias involved were sustained ventricular tachycardia (35 patients), nonsustained ventricular tachycardia with hypotension (15 patients), and ventricular fibrillation (7 patients). The noninvasive approach sought reduction of ventricular premature beats by more than 80 percent and of couplets by more than 90 percent, with elimination of three or more successive ventricular beats on ambulatory monitoring and exercise testing. The invasive approach sought to prevent the induction of five or more repetitive beats by programmed stimulation. The noninvasive approach required fewer drug trials (3.2±1.8 [mean ±SD] vs. 5.5±2.8, P<0.001) and fewer hospital days (20±15 vs. 33±24, P = 0.01) and identified a therapy predicted to be effective for more patients than did the invasive approach (29 of 29 vs. 15 of 28, P<0.001). When a predicted effective therapy was not found, amiodarone was prescribed despite persisting inducibility of ventricular tachycardia. Patients randomly assigned to the noninvasive approach had more symptomatic recurrences of tachyarrhythmia than those treated by the invasive approach (two-year actuarial probabilities of 0.50±0.10 vs. 0.20±0.08, P = 0.02). Similar differences were observed when amiodarone recipients were excluded. There were only three deaths from recurrent ventricular tachyarrhythmias — two in the group whose treatment was selected noninvasively and one in the group whose treatment was selected invasively (not significant). We conclude that therapy selected by the invasive approach prevents recurrences of ventricular tachyarrhythmias better than that selected by the noninvasive approach. (N Engl J Med 1987; 317:1681–7.)
Prevention of Postoperative Hematoma by the Use of the Compression Suture
Authors: Radford C. Tanzer
Journal: New England Journal of Medicine (1956)

POSTOPERATIVE hematoma, a complication apt to occur in wounds of more mobile areas or in fields requiring the undermining of covering structures, can be minimized by attention to the all-important factors of hemostasis and the elimination of dead space. The latter can be controlled in most cases by the observation of well tried principles; layer-to-layer closure; imbrication of layers; filling of dead space by rotated muscle or skin-fat flaps from adjacent borders; introduction of space-filling materials such as bone, cartilage and inorganic substances; and use of pressure dressings combined with immobilization.Occasionally, however, one encounters situations in which conventional methods . . .
AB0156 Increased Soluble Semaphorin 4D in Rheumatoid Arthritis
Authors: Y. Yoshida, A. Ogata, T. Tomita, S. Kang, T. Hirano, Y. Shima, M. Narazaki, T. Tanaka, A. Kumanogoh
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune and inflammatory disorder of joints, which characterized with periarticular bone resorption. Recently cross-disciplinary field osteoimmunology was established because of reciprocal interactions between the immune and skeletal systems. To date, it is well known that inflammatory cytokines such as IL-6 and TNF stimulate bone resorption directly or through RANKL pathway. Recently semaphorins are thought to be new players in osteoimmunology. Sema4D that is produced by osteoclasts inhibits osteoblastgenesis and Sema3A that is produced by osteoblasts inhibits osteoclastgenesis. We previously reported Sema4D activate not only B cells, but also macrophage/monocytes, and induce proinflammatory cytokine production. These findings suggest that Sema4D plays an important role in the pathogenesis of RA and become a promising therapeutic target of RA. <h3>Objectives</h3> To investigate the role of Sema4D in RA patients. <h3>Methods</h3> The soluble Sema4D levels in sera and synovial fluid from patients with RA and osteoarthritis (OA) were measured by ELISA. Synovial fluid cells and peripheral blood cells from patients with RA were analyzed by flow cytometry. Sema4D expression of synovium were also observed by histological and immunohistochemical methods. <h3>Results</h3> Serum levels of soluble Sema4D were increased in RA in comparison to healthy individuals (11.1±8.5 ng/ml and 5.7±2.7 ng/ml, respectively; p&lt;0.0001). Serum levels of soluble Sema4D in OA and other diseases were slightly increased but it9s not significant. In synovial fluid, soluble Sema4D were detected similarly in sera of RA (11.8±7.0 ng/ml). In contrast, Sema4D was not detected in synovial fluid of OA. The levels of serum soluble Sema4D was correlated with disease activities of RA such as DAS28 (r=0.383, p&lt;0.01), CRP (r=0.346, p&lt;0.01), rheumatoid factor (r=0.328, p&lt;0.01), and urinary deoxypyridinoline (r=0.318, p&lt;0.05). The change of serum soluble Sema4D was correlated with the change of DAS28 in RA patients treated with bologics. The infiltrations of Sema4D expressing cells were observed in RA synovium. Compared to healthy individuals, the cell surface expression of sema4D was decreased in CD3+ cells and CD14+ cells in peripheral blood and synovial fluids of RA patients. The treatment with ADAMTS14, which is upregulated in RA patients reduce the expression of cell surface Same4D. In addition soluble Sema4D stimulates IL-6 and TNF-alpha production from PBMC. <h3>Conclusions</h3> Soluble Sema4D was shown to be elevated in RA and is derived from T cells and monocytes in peripheral blood and synovial fluid by shedding from cell surface. Increased soluble Sema4D may play an important role in immune activation and bone resorpotion in RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3513
Antinuclear Antibody Induced by Procainamide
Authors: Stephen E. Blomgren, John J. Condemi, Margaret C. Bignall, John H. Vaughan
Journal: New England Journal of Medicine (1969)

Sixteen patients were followed prospectively for the possible development of the lupus syndrome while being treated for cardiac arrhythmias with conventional doses of procainamide hydrochloride. In eight antinuclear antibody developed. Two of the eight had positive slide reactions with nucleoprotein-coated latex particles. In one of these two rheumatoid factor (anti-IgG) activity in low titer also developed. Another two of the eight showed symptoms consistent with the lupus syndrome. The high percentage of patients in this study in whom antinuclear antibody developed suggests that the lupus response appearing in patients treated with procainamide is not restricted to the small proportion of the population that may have a genetic predisposition to idiopathic lupus erythematosus.
OP0223 Increased TH17 Cell Frequency and Poor Clinical Outcome in Rheumatoid Arthritis Are Associated with A Genetic Variant in the IL-4R Gene, Rs1805010
Authors: J. Leipe, M. Schramm, I. Prots, H. Schulze-Koops, A. Skapenko
Journal: Annals of the Rheumatic Diseases (2014)

Background The minor allele of the interleukin-4 receptor ( IL4R ) gene single nucleotide polymorphism (SNP), I50V (rs1805010), confers impaired IL-4 signaling and has been associated with an aggressive destructive course of rheumatoid arthritis (RA). IL-4 inhibits the development of Th17 cells, a cell population recently identified to be prominent in RA patients and to associate with cartilage and bone destruction. Objectives Here, we investigated whether the I50V IL4R SNP modulates Th17 cell development and, hence, subsequent clinical outcome in RA. Methods Patients with early, active RA (n=90; DAS28 4.6±1.1) and controls (healthy subjects, [n=24], osteoarthritis patients [OA, n=15]) were genotyped. To assess the inhibitory effect of IL-4 on Th17 cell development, we primed CD4 T cells from all patient and control genotype groups for 72 h in the presence or absence of IL-4 and determined Th17 cell frequencies. Further, in all groups, IL-17, IL-22 serum levels were assessed by ELISA, and Th17 cell frequencies were analyzed ex vivo and after activation by flow cytometry. Clinical and radiographic data were collected and evaluated at baseline and one year after disease onset. Results Gentotyping revealed that 26% of the patients were homozygous for the major allele of I50V IL4R SNP (I50/I50), 60% were heterozygous (I50/V50), and 14% were homozygous for the minor allele (V50/V50). RA patients homozygous for the minor allele (V50/V50) demonstrated significantly higher clinical activity associated with the presence of erosions after one year of follow-up as compared to the other patients. The inhibitory effect of IL-4 on Th17 development in those V50/V50 patients with the impaired IL-4R signaling was significantly less prominent or even absent. Accordingly, frequencies of Th17 cells were significantly increased in the V50/V50 group of RA patients correlating with high disease activity. Those patients demonstrated consistently higher IL-17 and IL-22 serum levels as compared to I50/I50 or I50/V50 RA patients, and controls. Conclusions The data indicate that the minor allele of I50V IL4R SNP (V50/V50) contributes to increased Th17 cell frequency, enhanced clinical activity and accelerated radiographic progression in RA by rendering CD4 T cells from RA patients insensitive to the attenuating effect of IL-4 on Th17 cell development. Here, we provide a potential genetic basis for the Th17 cell-driven inflammatory process underlying early RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6028
LONGITUDINAL STUDY ON INDEPENDENT AND JOINT EFFECT OF BRACHIAL-ANKLE PULSE WAVE VELOCITY AND BLOOD PRESSURE CONTROL ON INCIDENT STROKE IN HYPERTENSIVE PATIENTS
Authors: Yun Song, Benjamin Xu, Richard Xu, Renee Tung, Eric Frank, Wayne Tromble, Tong Fu, Weiyi Zhang, Fangfang Fan, Yan Zhang, Li Jianping, Bao Huihui, Xiaoshu Cheng, Genfu Tang, Binyan Wang, Yundai Chen, Tianlun Yang, Ningling Sun, Xiaoying Li, Lianyou Zhao, Fan Fan Hou, Junbo Ge, Qiang Dong, Yingxian Sun, Yong Huo
Journal: Journal of the American College of Cardiology (2016)