tbuckley/cabot-search huggingface dataset:
Ophthalmic Neuro-Myology.
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
THU0046 Prevalence of vitamin D deficiency in rheumatoid arthritis patients: Association with anaemia of inflammation and effect of vitamin D supplementation
Authors: A. Abou-Raya, S. Abou-Raya, M. Helmii
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anaemia of inflammation (AI) and vitamin D deficiency can both contribute to significant morbidity in rheumatoid arthritis (RA) patients. The potential relationship between them remains poorly understood. A common feature of RA associated with AI is immune activation and production of inflammatory cytokines. In AI, proinflammatory cytokines affect iron metabolism. Vitamin D is recognized as having potent immunomodulatory properties that has prompted its potential use in autoimmune diseases including RA. <h3>Objectives</h3> To determine the prevalence of 25 hydroxyvitamin D deficiency in RA patients with AI and to assess the association between 25 hydroxyvitamin D and AI and the efficacy of vitamin D supplementation. <h3>Methods</h3> Eighty-five patients all fulfilling the ACR criteria for RA were enrolled in this 16-week randomized placebo-controlled study. Inclusion criteria included premenopausal women and men of the same body mass index and ethnicity having AI, that is, low circulating iron &lt;60μ/dl and no evidence of iron deficiency anaemia Tfr/log ferritin &lt;15. Vitamin D deficiency was defined as serum levels &lt;30ng/ml. Fifty-five healthy age-sex-BMI and ethnically matched controls were also recruited. Patients were randomized in a 1:1 ratio to receive either oral cholecalciferol 2000IU/day or placebo for 4 months together with standard RA treatment. Outcome measures included improvement of AI, inflammatory markers before and after vitamin D supplementation. Vitamin D levels were measured by Liaison immunoassay (normal 30-100ng/ml). Serum levels of proinflammatory cytokines IL-6 and TNF-alpha and acute phase reactants: hsCRP, ESR and fibrinogen and blood indices were measured at baseline and after vitamin D supplementation. <h3>Results</h3> The prevalence of vitamin D deficiency was 54% in RA patients with AI compared to 12% in the healthy controls, p=0.006. There was a significant positive correlation between vitamin D deficiency and AI, r =0.537; p=0.003. Following vitamin D supplementation a statistically significant improvement in the indices of AI occurred. Inflammatory markers and proinflammatory cytokines decreased significantly after vitamin D supplementation. <h3>Conclusions</h3> Vitamin D may attenuate inflammation and further studies to confirm whether vitamin D supplementation improves AI are needed. <h3>Disclosure of Interest</h3> None Declared
Commentary: Approaches to Environmental Exposure Assessment in Children
Authors: Virginia M. Weaver, Timothy J. Buckley, John D. Groopman
Journal: Environmental Health Perspectives (1998)

An improved understanding of the contribution made by environmental exposures to disease burden in children is essential, given current increasing rates of childhood illnesses such asthma and cancer.Children must be routinely included in environmental research.Exposure assessment, both external (e.g., air, water) and internal dose (e.g., biomarkers), is an integral component of such research.Biomarker measurement has some advantages that are unique in children.These include assessment of potentially increased absorption because of behaviors that differ from adults (i.e., hand-to-mouth activity); metabolite measurement, which can help identify age-related susceptibility differences; and improved assessment of dermal exposure, an important exposure route in children.Environmental exposure assessment in children will require adaption of techniques that are currently applied in adult studies as well as development of tools and validation of strategies that are unique for children.Designs that focus on parent-child study units provide adult comparison data and allow the parent to assist with more complex study designs.Use of equipment that is sized appropriately for children, such as small air pumps and badge monitors, is also important.When biomarkers are used, biologic specimens that can be obtained noninvasively are preferable.Although the current need is primarily for small focused studies to address specific questions and optimize research tools, the future will require establishment of large prospective cohorts.Urban children are an important study cohort because of relatively high morbidity observed in the urban environment.Finally, examples of completed or possible future studies utilizing these techniques are discussed for specific exposures such as benzene, environmental tobacco smoke, aflatoxin,
EFFECTS OF EVOLOCUMAB (AMG 145) TREATMENT ON VITAMIN E LEVELS: RESULTS FROM THE 52-WEEK PHASE 3 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED DESCARTES STUDY
Authors: Dirk Blom, Maria Laura Monsalvo, Kate Tsirtsonis, Scott Wasserman, Robert Scott, Eli Roth
Journal: Journal of the American College of Cardiology (2015)
AB0574 Evaluation of the efficacy of tocilizumab toward the patients with active rheumatoid arthritis of nagasaki prefecture, japan
Authors: S.-Y. Kawashiri, Y. Ueki, K. Migita, N. Matsuoka, A. Mizokami, M. Mine, K. Fujikawa, T. Aramaki, H. Nakamura, K. Eguchi, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab (TCZ) is a humanized anti-interleukin 6 receptor (IL-6R) monoclonal antibody and it was approved in Japan as an antirheumatic drugs in 2008. Evidence of the efficacy of TCZ in real-world RA patients is still few as compared with tumour necrosis factor (TNF) inhibitors. <h3>Objectives</h3> We have tried to evaluate the efficacy of TCZ in patients with RA during the 3 years after an approval in 2008 at Nagasaki prefecture, Japan. <h3>Methods</h3> One hundred fifty-two RA patients at Nagasaki prefecture, Japan, who has received 8 mg/kg of TCZ every 4 weeks during 3 years, were consecutively enrolled in this study. Ninety-nine patients had evaluable data for 1 year at present. We have focused on the efficacy of TCZ in the present study trying to evaluate the clinical response of disease activity score (DAS) 28, simplified disease activity index (SDAI), clinical disease activity index (CDAI), Boolean approach and Health Assessment Questionnaire (HAQ) by last observation carried forward (LOCF) methodology toward these 99 patients, respectively. <h3>Results</h3> The mean age, disease duration and clinical disease activity at baseline were 58 years-old, 11 years, DAS28-ESR: 5.5, SDAI: 28.7 and CDAI: 25.5, respectively. Fifty-nine percent of the patients had received TNF inhibitors before introduction of TCZ. Although most of the patients were active as well as established disease at baseline, the continuation rate at 1 year was superior as 81.1%. A rate of clinical remission at 1 year of DAS28-ESR, SDAI, CDAI and Boolean-based definition was 49.5%, 17.2%, 13.1% and 13.1%, respectively. There was a clear relation of the rate of clinical remission with shorter disease duration (less than 2 years) or no previous history of TNF inhibitors. Furthermore, low HAQ at baseline was the only variable to be associated with CDAI remission (OR [95% CI]: 0.34 [0.09-0.88], p=0.06) and HAQ remission (OR [95% CI]: 0.17 [0.03-0.50], p&lt;0.01) at 1 year defined by logistic regression analysis. <h3>Conclusions</h3> The present study shows an excellent therapeutic efficacy as well as the characterisitic of patients being achieved in remission by TCZ in the real-world clinical practice. <h3>References</h3> Kawashiri SY, et al. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline. Mod Rheumatol. 2011;21:370-4. Kawashiri SY, et al. Disease activity score 28 may overestimate the remission induction of rheumatoid arthritis patients treated with tocilizumab: comparison with the remission by the clinical disease activity index. Mod Rheumatol. 2011;21:365-9. <h3>Disclosure of Interest</h3> None Declared
PTU-156 Dietary response in coeliac disease should be assessed by repeat duodenal biopsy
Authors: G Corbett, L Sharkey, E Currie, J Lee, N Sweeney, J Woodward
Journal: Gut (2012)

<h3>Introduction</h3> Therapeutic goals in coeliac disease (CD) are poorly defined. Emerging evidence reports worse outcomes with lack of mucosal recovery, suggesting histological normalisation as the aim of treatment. However, few centres routinely re-biopsy and many clinicians depend on serology or symptoms for follow-up. This retrospective study evaluates the role of the follow-up biopsy compared to serology in treated coeliacs and is the largest study of paired biopsies reported. <h3>Methods</h3> Details of patients attending the Addenbrookes Adult CD Clinic are entered onto a database. Patients undergo repeat duodenal biopsy 9–12 months after commencing dietary therapy. Serum Anti-TTG antibodies and total IgA are measured at clinic visits. From the database of around 600 adult patients (30% male, 70% female, average age at diagnosis 48 and 44 yrs respectively) follow-up biopsy results were available for 433 patients and compared using a paired t-test. <h3>Results</h3> Paired initial and follow-up biopsies were available for 368/433 patients (no information about index biopsy in 65). 239 (65%) were re-biopsied within 12 months, 311 (85%) within 24 months. The proportion achieving normalisation of duodenal mucosa (Marsh 0) at 12 months, 12–24 months or after 24 months is 27%, 25% (p=0.61) and 25% (p=0.1) respectively. Those without villous atrophy (VA) (Marsh 0, 1 or 2) is 58%, 58% (p=0.98) and 52% (p=0.24) respectively. Excluding the 2.5% of patients with IgA deficiency, 13% of patients had negative anti-TTG antibody titres at the time of diagnostic biopsy. In the group of patients with positive serology at first biopsy, only 43% with VA on follow-up biopsy were positive for anti-TTG antibodies. Conversely, 13% without VA on follow-up had positive serology. The sensitivity, positive predictive and negative predictive values for serology compared to biopsy at follow-up are 43.4%, 68.8% and 70.5% respectively. <h3>Conclusion</h3> Response to diet in CD might be monitored by symptoms, serology or histology. Many patients diagnosed in adulthood report minimal or no symptoms at diagnosis and this is therefore not a credible marker of response. Here we show that: Anti-TTG antibody serology has a sensitivity of 87% at diagnosis Anti-TTG serology has a poor sensitivity (43%) on follow-up and is therefore unreliable Histological response rates are not increased after 1 year on diet Approximately 28% of patients achieve normal duodenal mucosa, 58% show no or minimal signs of coeliac disease on follow-up biopsy. We suggest that follow-up biopsy on diet is the only reliable form of assessing response to treatment, and that the proportion of patients achieving histological response could be used as a means of auditing quality of care in coeliac clinics. <h3>Competing interests</h3> None declared.
CD3−CD4+ cells with a Th2-like pattern of cytokine production in the peripheral blood of a patient with cutaneous T cell lymphoma
Authors: D Brugnoni, P Airò, C Tosoni, M Taglietti, F Lodi-Rizzini, P Calzavara-Pinton, C Leali, R Cattaneo
Journal: Leukemia (1997)
Presence of Bound Immunoglobulins and Complement in the Myocardium in Acute Rheumatic Fever
Authors: Melvin H. Kaplan, Robert Bolande, Louis Rakita, John Blair
Journal: New England Journal of Medicine (1964)

RECENT evidence has supported the concept that the Group A streptococcus possesses antigens immunologically related to human heart tissue1 2 3 and that crossreactive autoimmunity to heart may be stimulated in certain persons after streptococcal infection.4 It has been observed further that such crossreactive autoantibodies are associated with both the poststreptococcal state and rheumatic heart disease.4 Consistent with the possible role of autoimmunity in the pathogenesis of rheumatic fever are the additional observations of focal deposits of bound gamma globulin in the myocardium of 18 per cent of 100 biopsies of the rheumatic atrial appendage studied,5 and of extensive and massive deposition . . .
Cardiopulmonary Resuscitation by Chest Compression Alone or with Mouth-to-Mouth Ventilation
Authors: Alfred Hallstrom, Leonard Cobb, Elise Johnson, Michael Copass
Journal: New England Journal of Medicine (2000)

Despite extensive training of citizens of Seattle in cardiopulmonary resuscitation (CPR), bystanders do not perform CPR in almost half of witnessed cardiac arrests. Instructions in chest compression plus mouth-to-mouth ventilation given by dispatchers over the telephone can require 2.4 minutes. In experimental studies, chest compression alone is associated with survival rates similar to those with chest compression plus mouth-to-mouth ventilation. We conducted a randomized study to compare CPR by chest compression alone with CPR by chest compression plus mouth-to-mouth ventilation.
Abstract 1674: Two phase study of KCNJ1 polymorphisms, calcium, magnesium and colorectal adenoma risk, results from the Tennessee Colorectal Polyp Study
Authors: Xiangzhu Zhu, Martha J. Shrubsole, Reid M. Ness, Qiuyin Cai, Jirong Long, Zhi Chen, Xinqing Deng, Walter E. Smalley, Todd Edwards, Wei Zheng, Qi Dai
Journal: Cancer Research (2012)

Abstract Background: Previous studies generated inconsistent results on the associations between intakes of calcium and magnesium with risk of colorectal adenoma and cancer. It is possible that some of the inconsistency is due to a modifying effect by genetic polymorphisms involved in calcium and magnesium homeostasis. The KCNJ1 gene encodes the Inward-rectifier potassium channel (ROMK). ROMK plays an essential role in the homeostasis of potassium, which is critical for the reabsorption of calcium and magnesium. Objectives: We hypothesize that common variants in KCNJ1 may modify the associations between intakes of calcium and/or magnesium and risk of colorectal adenoma risk. Methods: Included were participants of the Tennessee Colorectal Polyp Study (TCPS), a colonoscopy-based case control study conducted in Nashville, TN. In the phase I study, genotyping was performed using the Affymetrix Human Mapping 500K array set in 958 colorectal adenoma cases and 909 controls and 13 tagging single-nucleotide polymorphisms (SNPs) in the KCNJ1 gene were evaluated. SNPs identified as significant in phase I were genotyped in phase II in an independent set (860 cases and 3083 controls). Results: In phase I, 1 tagging SNP was significantly associated with adenoma risk and 8 SNPs were interacted significantly with calcium or magnesium intake in risk of colorectal adenoma. In phase II, only 1 of the 9 SNPs significantly interacted with calcium and magnesium intakes in relation to colorectal adenoma although the genotype per se was not directly associated with the risk. In combined analysis, the p value for the interaction between the SNP and calcium intake was 0.00015 and it remained statistically significant after Bonferroni correction for multiple comparisons. In stratified analyses by levels of calcium and magnesium (above or below RDA levels), we found adenoma risk significantly increased for those who with at least 1 variant allele and whose intake levels of calcium and magnesium were below the RDA levels, with ORs (95% CI) of 1.35 (1.10, 1.67) and 1.43 (1.08, 1.89) respectively, compared to those who did not possess the variant allele. The corresponding ORs (95% CI) increased to 1.84 (1.33, 2.53) and 2.30 (1.53, 3.46), respectively, multiple adenomas versus controls. Conclusions: In this two-stage analysis, we found no overall association of adenoma with KCNJ1 genotype. However, common KCNJ1 variants significantly interacted with intakes of calcium and magnesium in risk of colorectal adenoma, particular for multiple adenomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1674. doi:1538-7445.AM2012-1674
Abstract 3902: Development of Aurora A inhibitors with <i>ortho</i>-halophenyl substituted pyrimidines: Unusual potency, SAR and X-ray crystallography studies.
Authors: Harshani R. Lawrence, Mathew P. Martin, Yunting Luo, Roberta Pireddu, Harsukh Gevariya, Sevil Ozcan, Jin-Yi Zhu, Mercedes Rodriguez, Roy Elias, Hua Yang, Said M. Sebti, Ernst Schonbrunn, Nicholas J. Lawrence
Journal: Cancer Research (2012)

Abstract The Aurora kinases are a family of serine-threonine kinases that play an important role in the regulation of cell division. The three members of the Aurora family Aurora A, B and C share a high degree of structural homology in their kinase domain but each kinase plays a different role in the control of mitosis. Aurora A and B have received the most attention to date as anticancer targets. Detailed studies have shown Aurora A and B are over expressed in a variety of cancers and are implicated in many aspects of tumor development. Aurora A is frequently over-expressed in tumors and cancer cell lines and has characteristics of an oncogene. Aurora B is also over expressed in many cancer types but does not have oncogenic properties. Aurora B plays important roles in M phase to ensure correct chromosome-microtubule alignment and attachment and chromosomal cytokinesis. Therefore, inhibition of Aurora kinase A and B is emerging as target-based therapy in cancer treatment. From our previous work HLM-8598 was identified from an in-house chemical library as a potent and highly selective inhibitor for Aurora A (IC50 value of 0.073 ± 0.002 μM) over Aurora B (IC50 = 5.4 ± 1.8 μM). X-ray crystallography studies of HLM-8598 bound to Aurora A confirmed HLM-8598 is a type-1 kinase inhibitor that interacts with the ATP binding site of the enzyme. The HLM-8598 bound to Aurora A structure-assisted synthesis of new analogs with IC50 &amp;lt; 2.5 nM affinity. We will present the synthesis of new analogs that contain an ortho-halogen substituted phenyl moiety, structure activity relationship studies as a part of our efforts to identify unusually potent Aurora A kinase inhibitors. We will discuss the use of kinase structural elements to rationally guide compound synthesis and improve design strategy. The in vitro and in vivo activities of ortho-halogen phenyl substituted pyrimidines will be presented as unusually potent Aurora A inhibitors and potential anti-cancer agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3902. doi:1538-7445.AM2012-3902
Cancer clinical trials in the 21st century: the need for a paradigm shift in design, conduct, and support.
Authors: MJ Piccart, B Philippe
Journal: Cancer Research (2009)

Abstract Abstract #ES-1 Over the last fifteen years, more than 45,000 women with early disease were randomized to taxane versus non-taxane regimens across 26 separate trials. Although collective results from 21 first-generation studies involving more than 36,000 women suggest that the addition of a taxane modestly improves anthracycline therapy, we are still uncertain of which subgroups of patients benefit from taxanes. The shortcomings of this enormous international effort provide many important lessons for the design, conduct, and support of clinical trials in the 21st century. Our growing understanding of the molecular heterogeneity of breast cancer dictates that this “one size fits all” approach to adjuvant therapy is now obsolete. Past efforts to investigate emerging therapies have suffered by the inclusion of women with endocrine responsive, luminal low proliferative disease, who enjoy a favourable long-term outcome in the absence of any adjuvant systemic therapy. Even when a clearly defined population has been defined, such as HER2 positive disease for adjuvant trastuzumab, there has been substantial duplication of efforts by individual co-operative groups. As a result, we remain uncertain of the optimal duration and schedule of adjuvant trastuzumab administration. Post-registration trials testing shorter duration trastuzumab regimens require greater numbers of participants to demonstrate non-inferiority and are now being conducted with considerable opportunity cost. Future registration studies will require careful upfront selection of secondary trials designed to address specific, non-overlapping questions of clinical importance. New-generation trials must mandate prospective collection of biospecimens and integrate cutting-edge technologies as early barometers of efficacy to accelerate the trajectory of novel agents to the clinic with the parallel development of therapeutic biomarkers that can be used to individually tailor treatment. Such a paradigm shift will require a new partnership between investigators, patients, and industry with a unified global commitment to reshape the framework of clinical trials, so that further progress can be made in the fight against breast cancer in the 21st century. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr ES-1.