tbuckley/cabot-search huggingface dataset:
EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)
Authors: O Kowal-Bielecka, R Landewé, J Avouac, S Chwiesko, I Miniati, L Czirjak, P Clements, C Denton, D Farge, K Fligelstone, I Földvari, D E Furst, U Müller-Ladner, J Seibold, R M Silver, K Takehara, B Garay Toth, A Tyndall, G Valentini, F van den Hoogen, F Wigley, F Zulian, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2009)

Purpose: The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group (EUSTAR) was to develop evidence-based, consensus-derived recommendations for the treatment of SSc. Methods: To obtain and maintain a high level of intrinsic quality and comparability of this approach, EULAR standard operating procedures were followed. The task force comprised 18 SSc experts from Europe, the USA and Japan, two SSc patients and three fellows for literature research. The preliminary set of research questions concerning SSc treatment was provided by 74 EUSTAR centres. Results: Based on discussion of the clinical research evidence from published literature, and combining this with current expert opinion and clinical experience, 14 recommendations for the treatment of SSc were formulated. The final set includes the following recommendations: three on SSc-related digital vasculopathy (Raynaud’s phenomenon and ulcers); four on SSc-related pulmonary arterial hypertension; three on SSc-related gastrointestinal involvement; two on scleroderma renal crisis; one on SSc-related interstitial lung disease and one on skin involvement. Experts also formulated several questions for a future research agenda. Conclusions: Evidence-based, consensus-derived recommendations are useful for rheumatologists to help guide treatment for patients with SSc. These recommendations may also help to define directions for future clinical research in SSc.
Modeling Atrial Arrhythmias: Impact on Clinical Diagnosis and Therapies
Authors: V. Jacquemet, L. Kappenberger, C.S. Henriquez
Journal: IEEE Reviews in Biomedical Engineering (2008)

Atrial arrhythmias are the most frequent sustained rhythm disorders in humans and often lead to severe complications such as heart failure and stroke. Despite the important insights provided by animal models into the mechanisms of atrial arrhythmias, direct translation of experimental findings to new therapies in patients has not been straightforward. With the advances in computer technology, large-scale electroanatomical computer models of the atria that integrate information from the molecular to organ scale have reached a level of sophistication that they can be used to interpret the outcome of experimental and clinical studies and aid in the rational design of therapies. This paper reviews the state-of-the-art of computer models of the electrical dynamics of the atria and discusses the evolving role of simulation in assisting the clinical diagnosis and treatment of atrial arrhythmias.
Combined Inhibitory Effects of Curcumin and Phenethyl Isothiocyanate on the Growth of Human PC-3 Prostate Xenografts in Immunodeficient Mice
Authors: Tin Oo Khor, Young-Sam Keum, Wen Lin, Jung-Hwan Kim, Rong Hu, Guoxiang Shen, Changjiang Xu, Avanthika Gopalakrishnan, Bandaru Reddy, Xi Zheng, Allan H. Conney, Ah-Ng Tony Kong
Journal: Cancer Research (2006)

Earlier studies using prostate cancer cells in culture showed that phenethyl isothiocyanate (PEITC) and curcumin have significant chemopreventive and possibly chemotherapeutic effects. However, their in vivo effects are still lacking. Hence, this study was undertaken to determine the possible in vivo efficacy of prostate cancer-prevention as well as cancer-therapeutic treatment by PEITC and curcumin alone or in combination. We evaluated the effects on tumor growth in vivo, using NCr immunodeficient (nu/nu) mice bearing s.c. xenografts of PC-3 human prostate cancer cells. Molecular biomarkers representing proliferation and apoptosis were determined. Continued i.p. injection of curcumin or PEITC (6 and 5 mumol; thrice a week for 28 days), beginning a day before tumor implantation significantly retarded the growth of PC-3 xenografts. Combination of i.p. administration of PEITC (2.5 mumol) and curcumin (3 mumol) showed stronger growth-inhibitory effects. Next, we evaluated the cancer-therapeutic potential of curcumin and PEITC in mice with well-established tumors, and the results showed that PEITC or curcumin alone had little effect, whereas combination of curcumin and PEITC significantly reduced the growth of PC-3 xenografts. Immunohistochemistry staining and Western blot analysis revealed that the inhibition of Akt and nuclear factor-kappaB signaling pathways could contribute to the inhibition of cell proliferation and induction of apoptosis. Taken together, our results show that PEITC and curcumin alone or in combination possess significant cancer-preventive activities in the PC-3 prostate tumor xenografts. Furthermore, we found that combination of PEITC and curcumin could be effective in the cancer-therapeutic treatment of prostate cancers.
Phase I Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients
Authors: Ezra E.W. Cohen, Kehua Wu, Christine Hartford, Masha Kocherginsky, Kimberly Napoli Eaton, Yuanyuan Zha, Anitha Nallari, Michael L. Maitland, Kammi Fox-Kay, Kristin Moshier, Larry House, Jacqueline Ramirez, Samir D. Undevia, Gini F. Fleming, Thomas F. Gajewski, Mark J. Ratain
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Nevertheless, sirolimus is readily available, has been well studied in organ transplant patients, and shows efficacy in several preclinical cancer models. Experimental Design: Three simultaneously conducted phase I studies in advanced cancer patients used an adaptive escalation design to find the dose of oral, weekly sirolimus alone or in combination with either ketoconazole or grapefruit juice that achieves similar blood concentrations as its intravenously administered and approved prodrug, temsirolimus. In addition, the effect of sirolimus on inhibition of p70S6 kinase phosphorylation in peripheral T cells was determined. Results: Collectively, the three studies enrolled 138 subjects. The most commonly observed toxicities were hyperglycemia, hyperlipidemia, and lymphopenia in 52%, 43%, and 41% of subjects, respectively. The target sirolimus area under the concentration curve (AUC) of 3,810 ng-h/mL was achieved at sirolimus doses of 90, 16, and 25 mg in the sirolimus alone, sirolimus plus ketoconazole, and sirolimus plus grapefruit juice studies, respectively. Ketoconazole and grapefruit juice increased sirolimus AUC approximately 500% and 350%, respectively. Inhibition of p70 S6 kinase phosphorylation was observed at all doses of sirolimus and correlated with blood concentrations. One partial response was observed in a patient with epithelioid hemangioendothelioma. Conclusion: Sirolimus can be feasibly administered orally, once weekly with a similar toxicity and pharmacokinetic profile compared with other mTOR inhibitors and warrants further evaluation in studies of its comparative effectiveness relative to recently approved sirolimus analogs. Clin Cancer Res; 18(17); 4785–93. ©2012 AACR.
Intratracheal administration of dry powdered low-molecular-weight chitosan/siRNA complexes suppressed gene expression in the airway, alveoli, and metastatic tumors in murine lung
Authors: Daisuke Ihara, Noboru Hattori, Hirokazu Okamoto, Nobuoki Kohno
Journal: European Respiratory Journal (2013)

Introduction; There is an increasing number of efforts to deliver small interfering RNA (siRNA) to lung. Although many different formulations with siRNA have been optimized in in vitro studies, only a few have been reported successful in vivo.  Objectives; As a carrier of siRNA, we chose low-molecular-weight chitosan (LMWC) and succeeded in producing dry powder of LMWC/siRNA complexes. In the present study, we tried to determine whether intratracheal administration of dry powdered LMWC/siRNA complexes suppressed gene expression in murine lung.  Methods; Dry powdered LMWC/siRNA targeting green fluorescent protein (GFP-siRNA) and Lewis lung carcinoma cells stably expressing GFP (LLC-GFP) were prepared. Dry powder of LMWC/GFP-siRNA complexes was intratracheally administered to GFP transgenic mice and the C57BL/6 mice injected with LLC-GFP cells through tail vein. The fluorescence in the lung tissue sections was analyzed with a BIOREVO fluorescence microscope (BZ-9000; KEYENCE, Japan).  Results; Intratracheal administration of LMWC/GFP-siRNA complexes was found to suppress the fluorescence level of bronchial epithelium and alveoli in the lung of GFP transgenic mice. It was also effective at reducing the fluorescence level in metastatic lung tumors consisting of LLC-GFP cells.  Conclusion; The results of the present study suggest that LMWC is an effective carrier for siRNA delivery to the lung, and powdered LMWC/siRNA complexes may become a promising tool to knock-down a specific gene expression in various lung diseases.
Methods of deriving EULAR/ACR recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis
Authors: T Karonitsch, D Aletaha, M Boers, S Bombardieri, B Combe, M Dougados, P Emery, D Felson, J Gomez-Reino, E Keystone, T K Kvien, E Martin-Mola, M Matucci-Cerinic, P Richards, P van Riel, J Siegel, J S Smolen, T Sokka, D van der Heijde, R van Vollenhoven, M Ward, G Wells, A Zink, R Landewe
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). <h3>Methods:</h3> After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. <h3>Results:</h3> The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The “patient-reported symptom state” (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. <h3>Conclusions:</h3> The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.
Patterns of exercise-related inflammatory response in sickle cell trait carriers
Authors: Julien Tripette, Philippe Connes, Mona Hedreville, Maryse Etienne-Julan, Laurent Marlin, Olivier Hue, Marie-Dominique Hardy-Dessources
Journal: British Journal of Sports Medicine (2008)

Objective To clarify whether sickle cell trait (SCT) carriers (SCT group) present a specific postexercise inflammatory response to repeated and strenuous exercise. Design The patterns of inflammatory markers in response to repeated heavy exercise were investigated in SCT carriers (SCT group: eight men, 20.0±0.7 years) and subjects with normal haemoglobin (CONT group: seven men, 20.6±0.7 years). The exercise consisted of three successive maximal ramp exercise tests, interspaced with 10 min of recovery, and accomplished at room temperature. Blood was sampled at rest (T R ), at the end of each of the three tests (T 1 , T 2 , T 3 ) and during the immediate (T 1 h , T 2 h ) and late (T 24 h , T 48 h ) recovery periods. Standard haematological parameters and plasma levels of cytokines (TNFα, IL-6) and adhesion molecules: soluble L- and P-selectins (sL-selectin, sP-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1) were measured. Results In both groups, the three successive maximal exercise bouts prompted an inflammatory response (ie, white blood cells and IL-6 levels increased in response to exercise). sICAM-1 and sVCAM-1 levels did not change during or after exercise and presented no difference between groups. However, during exercise, sL-selectin and sP-selectin kinetics differed between groups: sL-selectin increased earlier in the SCT group than in the CONT group, and sP-selectin statistically increased only in the SCT group. Conclusion Although the data do not indicate an extended exercise inflammatory response in SCT carriers, a specific activation of the L- and P-selectins was observed. Further studies are needed to determine whether the selectins' changes are evidence of greater risk for SCT carriers during physical exercise in specific conditions or an indication of a protective mechanism mediated by the shedding process of adhesion molecules.
Preclinical Evaluation of New and Highly Potent Analogues of Octreotide for Predictive Imaging and Targeted Radiotherapy
Authors: Mihaela Ginj, Jianhua Chen, Martin A. Walter, Veronique Eltschinger, Jean Claude Reubi, Helmut R. Maecke
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Molecular imaging and targeted radiotherapy are emerging fields in nuclear oncology. Five human somatostatin receptors (hsstr1-hsstr5) are known to be overexpressed to some degree on various tumors, sstr2 being the most important one. Clinically used somatostatin based radiopeptides target exclusively sstr2. The aim of this study was to develop novel analogues with a broader sstr profile for diagnostic (positron emission tomography and single-photon emission computed tomography) and radiotherapeutic applications. Experimental Design: The following promising structures emerged from a parallel synthetic approach: [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA0),1-Nal3,Thr8]-octreotide (1, DOTA-NOC-ATE) and [DOTA0,BzThi3,Thr8]-octreotide (2, DOTA-BOC-ATE). The conjugates were labeled with cold and radioactive 111In. Pharmacologic properties were compared with [111In-DOTA,Tyr3]-octreotide ([111In-DOTA]-TOC). Results: The receptor affinity profile showed high affinity of both peptides to hsstr2, hsstr3, and hsstr5 and some intermediate affinity to hsstr4, whereas [111In-DOTA]-TOC shows affinity only to sstr2. The internalization is fast in sstr2 expressing AR4-2J and in transfected sstr3 expressing human embryonic kidney 293 cells. Both radiopeptides internalize much more efficiently than [111In-DOTA]-TOC. Animal biodistribution studies showed very high and specific uptake of [111In]-1 and [111In]-2 in s.c. implanted AR4-2J tumors (Lewis rats) and in somatostatin receptor expressing normal tissues. The uptake was at least 2-fold higher in these tissues and in the tumor compared with [111In-DOTA]-TOC. In addition, the kidney uptake was significantly lower for both radiopeptides. Conclusions: These data suggest that the novel radiopeptides are superior to [111In/90Y-DOTA]-TOC and show great promise for the clinical application in the imaging of somatostatin receptor–positive tumors and their targeted radiotherapy.
Sacroiliac joint abnormalities in paraplegics.
Authors: M A Khan, I Kushner, A A Freehafer
Journal: Annals of the Rheumatic Diseases (1979)

We studied 186 paraplegic patients to clarify the pathogenesis of the sacroiliac (SI) joint abnormalities reported in these patients. Partial or complete fusion of SI joints was noted in 47 patients (25%), and milder degrees of abnormalities of these joints were present in 27 patients (15%). The abnormalities differed from those seen in ankylosing spondylitis and were found more commonly in patients with high levels of cord injury. It is likely that trunk mobility is necessary to maintain integrity of SI joint and that absence of such mobility compromises SI joint structure in many paraplegics.
Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial
Authors: Stéphane Haïk, Gabriella Marcon, Alain Mallet, Mauro Tettamanti, Arlette Welaratne, Giorgio Giaccone, Shohreh Azimi, Vladimiro Pietrini, Jean-Roch Fabreguettes, Daniele Imperiale, Pierre Cesaro, Carlo Buffa, Christophe Aucan, Ugo Lucca, Laurène Peckeu, Silvia Suardi, Christine Tranchant, Inga Zerr, Caroline Houillier, Veronica Redaelli, Hervé Vespignani, Angela Campanella, François Sellal, Anna Krasnianski, Danielle Seilhean, Uta Heinemann, Frédéric Sedel, Mara Canovi, Marco Gobbi, Giuseppe Di Fede, Jean-Louis Laplanche, Maurizio Pocchiari, Mario Salmona, Gianluigi Forloni, Jean-Philippe Brandel, Fabrizio Tagliavini
Journal: The Lancet Neurology (2014)
Different Genetic Background of Schizophrenia Spectrum Psychoses: A Twin Study
Authors: Ernst Franzek, Helmut Beckmann
Journal: American Journal of Psychiatry (1998)

The authors report on a systematic twin study of index twins suffering from schizophrenia spectrum psychoses. Using different diagnostic systems, they examined twin concordance, family history, and the frequency and severity of the birth complications of 22 monozygotic and 23 dizygotic twin pairs.All twins in the region of Lower Franconia, Germany, born after 1930 and hospitalized for psychiatric disease were ascertained. The zygosity diagnoses were based on molecular genetic methodology and a zygosity questionnaire. Two psychiatrists, working independently, formulated diagnoses according to DSM-III-R criteria and Leonhard's nosology.There were substantially different concordance rates with regard to diagnostic subgroups, and monozygotic concordance was significantly higher than dizygotic concordance in only two of the following five subgroups (subgroups 1 and 3): 1) strict schizophrenia according to DSM-III-R: monozygotic, 85.7%, dizygotic, 25.0%; 2) schizophreniform, schizoaffective, and delusional (paranoid) disorders and psychotic disorder not otherwise specified according to DSM-III-R: monozygotic, 47.1%, dizygotic, 30.8%; 3) unsystematic schizophrenia according to Leonhard: monozygotic, 88.9%, dizygotic, 25.0%; 4) systematic schizophrenia according to Leonhard: monozygotic pairs lacking, dizygotic, 0%; 5) cycloid psychoses according to Leonhard: monozygotic, 38.5%, dizygotic, 36.4%. In the case of cycloid psychoses and conditions less prominent in DSM-III-R schizophreniform, schizoaffective, and delusional (paranoid) disorders and psychotic disorder not otherwise specified, the affected twins had suffered significantly more severe birth complications than their healthy partners. Not one of the 37 monozygotic twins was diagnosed as having systematic schizophrenia, whereas six of the 25 dizygotic index twins received this diagnosis.The results of the study suggest that schizophrenia spectrum psychoses may consist of clinically and etiologically heterogeneous subgroups with different genetic backgrounds.
Prolapse of the Urethra in Young Girls
Authors: H. H. F. Barns
Journal: BMJ (1953)

Prolapse of the Urethra in Young GirlsProlapse of the urethral mucosa in the adult woman is well recognized, but it is not so well appreciated that the condition occurs in young girls.Keefe (1917), in a study of the recorded cases, found that 60% of the patients were children, 28% were women over 40 years of age, and the remaining 12% were between 15 and 40 years of age.
Breast Cancer DNA Methylation Profiles in Cancer Cells and Tumor Stroma: Association with HER-2/neu Status in Primary Breast Cancer
Authors: Heidi Fiegl, Simone Millinger, Georg Goebel, Elisabeth Müller-Holzner, Christian Marth, Peter W. Laird, Martin Widschwendter
Journal: Cancer Research (2006)

Abstract The HER-2/neu gene is amplified and overexpressed in 20% to 30% of invasive breast carcinomas and is associated with increased metastatic potential and less tamoxifen sensitivity. We generated the DNA methylation profiles of 143 human breast tumors and found significant differences in HER-2/neu expression and DNA methylation of five genes. For three of these five genes [PGR (coding for the progesterone receptor), HSD17B4 (coding for type 4 17-β-hydroxysteroid dehydrogenase, an enzyme that mainly degrades active 17-β-estradiol into inactive metabolites), and CDH13 (coding for H-cadherin)] a higher prevalence of DNA methylation in HER-2/neu-positive cancers was confirmed in an independent set of microdissected primary breast cancers. DNA methylation was not only present in cancer cells but also in the tumor stroma fraction. Of the isolated fractions in HER-2/neu-positive versus -negative cancers, 27.1% versus 10.5%, respectively, showed DNA methylation of the five genes (P = 0.011, Fisher's exact test). In Her-2++/+++ breast cancers, HSD17B4 mRNA expression was inversely associated with HSD17B4 methylation (P = 0.04). These data support the view that in addition to HER-2/neu-associated signaling, epigenetic changes in cancer as well as in tumor stroma cells might attribute to the specific biological features of HER-2/neu-positive cancers. (Cancer Res 2006; 66(1): 29-33)