tbuckley/cabot-search huggingface dataset:
Clinical factors, anticitrullinated peptide antibodies and MRI-detected subclinical inflammation in relation to progression from clinically suspect arthralgia to arthritis
Authors: Hanna W van Steenbergen, Lukas Mangnus, Monique Reijnierse, Tom W J Huizinga, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> Patients with clinically suspect arthralgia (CSA) have, according to their rheumatologists, an increased risk of rheumatoid arthritis (RA), but their actual outcome is unexplored. This longitudinal study investigated (1) progression from CSA to clinically detectable arthritis and (2) associations of clinical factors, serological factors (among which are anticitrullinated peptide antibodies (ACPAs)) and MRI-detected subclinical inflammation with arthritis development. <h3>Methods</h3> 150 patients with CSA were followed for ≥6 months. At baseline, clinical and serological data were collected and unilateral 1.5 T-MRI of metacarpophalangeal (MCP), wrist and metatarsophalangeal (MTP) joints was made. MRI scoring was done according to the RA MRI scoring system. Subclinical MRI inflammation was defined based on MRI results of 193 symptom-free persons. <h3>Results</h3> During follow-up (median=75 weeks, IQR=41–106 weeks), 30 patients developed clinical arthritis; 87% did so &lt;20 weeks after inclusion. In multivariable analyses, age, localisation of initial symptoms in small and large joints (compared with small joints only), C-reactive protein level, ACPA-positivity and subclinical MRI inflammation significantly associated with arthritis development; ACPA and MRI inflammation were most strongly associated (HR (95% CI) respectively, 6.43 (2.57 to 16.05) and 5.07 (1.77 to 14.50)). After 1-year follow-up, 31% of the patients with MRI inflammation and 71% of the ACPA-positive patients with MRI inflammation had progressed to arthritis. Forty-three per cent of the patients that developed arthritis within 1 year were ACPA-negative; 78% of them had subclinical MRI inflammation at baseline. When MRI inflammation was absent arthritis development was infrequent (6% in all patients with CSA and 3% in ACPA-negative patients with CSA). <h3>Conclusions</h3> Subclinical MRI inflammation precedes clinical arthritis with a few months. Subclinical MRI inflammation is, independent of other factors such as ACPA, associated with arthritis development.
Firearm Injuries and Gun Violence
Authors: Robert Steinbrook, Rachel J. Stern, Rita F. Redberg
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
COPD in farmers: what have we learnt?
Authors: Leslie Elliott, Susanna von Essen
Journal: European Respiratory Journal (2015)

Farming is a complex occupation, comprising a spectrum of activities that range from small-scale hobby farms to large-scale corporate farms. The activities, and thus the occupational exposures, on a farm are dictated by the type and size of the farm, as well as cultivation practices [1]. The farmers themselves are also diverse, living and working on farms alone or with family members or employees, working seasonally, or working at nonfarming occupations but returning home to farms that demand their labour. With heterogeneity on so many levels, it is no wonder that characterising exposures and identifying occupational hazards for agricultural workers has been daunting. Even more difficult has been measuring the burden of disease in farming populations when a specific hazard has been identified. Challenges in studying COPD prevalence in farmers: definition, diagnosis and choice of reference population <http://ow.ly/V3XUq>
The prosocial benefits of seeing purpose in life events: A case of cultural selection in action?
Authors: Konika Banerjee
Journal: Behavioral and Brain Sciences (2016)

Abstract Norenzayan et al. propose that religious beliefs with incidental prosocial effects propagated via a long-term process of cultural evolution. Applying their model, I explore a possible candidate target of cultural selection: the teleological view – often culturally elaborated as a belief in karma or fate – that life events occur to punish or reward individuals’ moral behavior.
Training and accreditation for the treatment of sexual disorders
Authors: J K Meyer
Journal: American Journal of Psychiatry (1976)

The field of "sex therapy" is not defined by specific, limited techniques. Rather, it encompasses a subspecialty based on an understanding of psychodynamics and psychological development but requiring additional skills from other branches of medicine. Despite its breadth and complexity, sex therapy training is unregulated, with the public lacking the protection afforded by standardized training programs or certification. The author outlines the scope of sex therapy as a psychiatric and medical subspecialty and delineates the necessary clinical skills for the physician-practitioner.
P0638 : Global epidemiology of hepatitis delta: First data from the hepatitis delta international network
Authors: S. Hardtke, Z. Abbas, S. Hamid, E. Ceausu, G.N. Dalekos, G. Niro, G. Corti, L.M. Pinheiro Borzacov, R. Parana, N.K. Gatselis, A. Motoc, P. Ingiliz, M. Muche, A. Wranke, M. Wöbse, C. Yurdaydin, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2015)
Abstract 18010: Induced Pluripotent Stem Cell-Based Modeling of Human NOTCH1 Mutations Reveals Novel Pathways Regulating Aortic Valve Disease
Authors: Christina V Theodoris, Mark P White, Molong Li, Lei Liu, Daniel He, Katherine S Pollard, Benoit G Bruneau, Deepak Srivastava
Journal: Circulation (2014)

In humans, NOTCH1 mutations result in congenital heart defects including valve malformations and severe valve calcification in adults. Valve calcification typically occurs on the aortic side of the valve leaflets that is not exposed to laminar shear stress, suggesting a protective role of flow sensed by the endothelial lining. To understand the mechanisms by which NOTCH1 mutations in endothelial cells (ECs) cause disease, we generated induced pluripotent stem cell (iPSC) lines from fibroblasts of four individuals from two families affected with aortic valve disease due to heterozygous non-sense mutations in NOTCH1. We differentiated control and mutant iPSC lines into ECs and exposed the ECs to either static or fluid shear stress conditions. NOTCH1 mRNA levels were decreased by ~50% in the NOTCH1+/- ECs under static or shear stress conditions. RNA-seq revealed that 165 genes were differentially expressed in static conditions and 193 genes responded abnormally to shear stress in NOTCH1+/- ECs compared to NOTCH1+/+ ECs. Differentially expressed genes included canonical NOTCH1 targets HRT2 and EFNB2 as well as novel targets involved in vascular development, inflammation, and endochondral ossification. Anti-calcific genes uniquely upregulated in shear stress were dysregulated in NOTCH1+/- ECs, indicating that they were unable to mount the normal protective response induced by shear stress in the valve. Generating isogenic NOTCH1+/+ and NOTCH1+/- cell lines using TALEN genome editing identified genes specifically dysregulated due to NOTCH1 heterozygosity rather than differentially expressed due to genetic background and showed rescue of this dysregulation in TALEN-corrected NOTCH1+/+ ECs. We have mapped the gene networks dysregulated in NOTCH1+/- ECs as determined by NOTCH1 ChIP-seq, differentially methylated regions of DNA, and genome-wide differences in the progression of activating and repressive chromatin states that begin to explain the mechanisms by which heterozygosity of a transcription factor leads to disease-specific changes. Determining the consequence of NOTCH1 heterozygous mutations in human patient-specific ECs will reveal novel mechanisms underlying aortic valve disease, leading to potential targets for intervention.
Depression in pregnancy
Authors: Simone N Vigod, Claire A Wilson, Louise M Howard
Journal: BMJ (2016)

#### What you need to know

Depression in pregnancy affects up to 10% of women, with higher rates in low and middle income countries, a rate only slightly lower than in the postpartum period.1 2 Yet, as few as 20% of pregnant women with depression receive adequate treatment.3 4 This is problematic because depression can profoundly affect a woman’s sense of wellbeing, relationships, and quality of life. Untreated or incompletely treated depression can also have adverse consequences for the offspring. Systematic reviews show an increase in markers of infant morbidity such as preterm birth, childhood emotional difficulties, behaviour problems, and, in some studies, poor cognitive development.5 6 Antenatal depression also is one of the strongest risk factors for postnatal depression, a condition linked to developmental problems in children.6 7 Severe depression can result in suicide, a major cause of maternal death.8 9 Perinatal suicides have been associated with lack of active treatment.10 Barriers to treatment include stigma, lack …
Serotonin synthesis inhibitors: A novel approach for managing gastrointestinal symptoms in carcinoid syndrome.
Authors: P. Brown, J. Jackson, K. Frazier, A. Turnage, E. Clark, D. Walke, Q. Yang, A. Main, J. Freiman, B. Zambrowicz
Journal: Journal of Clinical Oncology (2010)

e13543 Background: Carcinoid syndrome (CS) occurs when metastatic carcinoid tumors secrete large amounts of serotonin (5-HT) and other bioactive substances into systemic circulation causing a variety of symptoms, including GI symptoms such as profound diarrhea. Reduction in 5-HT production by the tumor would be expected to improve symptoms in patients with CS. We therefore have examined the utility of inhibiting tryptophan hydroxylase (TPH), the enzyme that catalyzes the rate-limiting step in the synthesis of 5-HT, as a strategy to reduce 5-HT production in vivo with the goal of developing a new therapeutic approach to CS. The ability of LX1031 and LX1032, two novel TPH inhibitors to reduce 5-HT production was determined in clinical trials. Methods: Single and multiple ascending dose studies with LX1031 and LX1032 were conducted in normal volunteers. In addition, a 28-day study was conducted with the locally acting TPH inhibitor LX1031 in patients with non-constipating IBS. In the IBS study, multiple measures of GI symptoms were recorded daily along with a weekly global assessment. In all studies, blood and urine was collected for measurement of 5-HT and 5-HIAA, biomarkers of 5-HT production. Results: In normal volunteers LX1032 significantly reduced 5-HT production in a dose-dependent manner. Both LX1031 and LX1032 gave a 50-60% decrease in 24-hour urinary 5-HIAA after 14 days of 1000 mg QID and 500 mg TID, respectively, compared to placebo. In IBS patients, LX1031 produced a similar dose-dependent reduction in 5-HT production, and in the high dose arm demonstrated statistically significant improvements in parameters of global relief and stool consistency that correlated with the decrease in 5-HT production. Conclusions: These results demonstrate that TPH inhibitors, such as LX1032 and the locally acting LX1031, can significantly reduce 5-HT production in normal subjects at well-tolerated dose levels. In patients with IBS, administration of LX1031 was shown to lower 5-HT production and improve clinical GI symptoms. These results indicate that inhibiting serotonin synthesis via TPH inhibition is a viable new strategy for the symptomatic treatment of patients with carcinoid syndrome. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lexicon Pharmaceuticals, Inc. Lexicon Pharmaceuticals, Inc. No significant financial relationships to disclose.
An open-label extension study to evaluate safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC)
Authors: R. E. Hawkins, S. J. Hong, A. Ulys, J. Rolski, B. Hong, C. Sternberg
Journal: Journal of Clinical Oncology (2009)

5110 Background: The efficacy and safety of pazopanib (paz), a multikinase angiogenesis inhibitor, was evaluated in a randomized, double-blind placebo-controlled phase III study (VEG105192), in treatment-naïve and cytokine-pretreated patients (pts) with advanced RCC. Pts with progressive disease (PD) on placebo had the option to receive paz 800 mg QD via an extension study (VEG107769). Methods: Pts with ECOG PS ≤ 2, adequate organ function and no other systemic anticancer treatment since PD on VEG105192 were eligible. The primary endpoint was safety. Secondary endpoints included response rate (RR) per RECIST and progression-free survival (PFS). RR was described along with 95% confidence intervals (CIs). PFS was summarized descriptively using Kaplan-Meier estimates for the median, quartiles and PFS rates at 6, 12, and 18 mo along with approximate 95% CIs. Results: 70 placebo pts were enrolled (+ 1 paz pt as an exemption due to symptom improvement). 34 pts (48%) were treatment-naïve and 37 (52%) were cytokine pretreated (at baseline in VEG105192). Median age was 59 y (25–80); baseline ECOG PS 0 (32%), 1 (52%), and 2 (14%). Median time from randomization to placebo in VEG105192 to start of paz treatment on VEG107769 was 6.4 mo (1–18 mo). At VEG107769 clinical cut-off (May 08), 21 (30%) pts had died, 40 (56%) pts had discontinued paz, and 31 (44%) pts were still on paz. Median exposure to paz was 5.7 mo. Most pts died or discontinued paz due to PD. The majority of adverse events (AEs) were Gr 1/2. Gr 3/4 AEs were experienced by 21%/7% of pts. The most common AEs were hypertension (46%; 4% Gr 3/4), hair color changes (39%; 0% Gr 3/4), diarrhea (38%; 1% Gr 3/4), anorexia (24%; 1% Gr 3/4), and nausea (24%; 0% Gr 3/4). Two pts had fatal AEs: sudden death and gastrointestinal hemorrhage. The most common Gr 3 chemistry laboratory abnormalities were hyponatremia (7%) and elevated ALT (7%) and AST (6%); no Gr 4. RR was 32.4% (95% CI: 21.5, 43.3); median PFS was 8.3 mo (95% CI: 6.1, 11.4 mo). Conclusions: Patients with advanced RCC who developed PD on placebo in a phase III study subsequently achieved clinical benefit from paz treatment in this extension study. These findings support the continued evaluation of paz in advanced RCC. [Table: see text]
FRI0334 The Effect of Urate-Lowering Therapy on the Radiographic Changes in Patients With Gout
Authors: Y.H. Eun, S. Lee, E.-J. Park, J. Hwang, J. Lee, H.-S. Cha, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> The aim of this study was to investigate the radiographic changes in patients with gout in association with the control of serum uric acid level. <h3>Methods</h3> A retrospective observational study in a single tertiary medical center was performed. Sixty one patients who had at least one erosive change on baseline radiography or tophus on physical examination were included. Follow up radiography was taken at least 5 years apart from baseline radiograph. The primary endpoint was the changes in the radiographic damage scores based on modified Sharp/van der Heijde (mSvH) score in association with the control of serum uric acid level during the study period. Patients were divided by three groups which consist of improved, no change, aggravated patients for subgroup analysis. The changes in the size of soft tissue density in radiograph were also measured. <h3>Results</h3> The mean age was 55±13 years and 60 (98%) patients were male. Disease duration was 11±7 years and mean serum uric acid level was 8.8±1.9 mg/dL at baseline. Follow up duration between two radiographies was 10.8±3.6 years. All patients were receiving urate-lowering therapy. The change in the mean mSvH score between baseline and follow visit was not statistically significant (6.77 vs. 6.69, respectively). The number of patient in improved, no change, aggravated groups was 22, 14, and 25 and the mean baseline plain radiographic damage score was 12.1, 4.85, and 3.7 respectively. As expected, the change in damage scores was positively correlated to AUC of uric acid level (r=0.32, p=0.01). The patients with longer disease duration at baseline were more likely to have improvement in the follow up radiograph. (r=0.46, p=0.004). In subgroup analysis, only the baseline radiographic damage score was significantly different from each other. In improved group, the change of damage scores was negatively associated with disease duration at baseline (r=0.48, p=0.024). <h3>Conclusions</h3> Our study demonstrated that radiographic damage in gout may be reversible to some extent and that the magnitude of improvement depends on the degree of serum uric acid control. <h3>Disclosure of Interest</h3> None declared
A5.12 Systemic bone loss is correlated with rat arthritis severity
Authors: G Courbon, L Vico, H Marotte
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Joint inflammation and periarticular bone loss are hallmarks of rheumatoid arthritis (RA). In RA patients, systemic bone loss increases bone fracture risk. Dual-energy X-ray absorptiometry (DXA) assesses bone mineral density (BMD) in daily practice to partially estimate fracture risk. Rat adjuvant-induced arthritis (AIA) analysis already improved erosion mechanism knowledge. We explored in this model the putative correlation between systemic bone loss and arthritis severity in this model. <h3>Materials and methods</h3> We divided 20 female Lewis rats in control (CTRL, n = 10) and AIA groups (n = 10). Rat AIA was induced by <i>Mycobacterium butyricum</i> injection at day 0. Arthritis was monitored by several parameters, including articular index (AI), defined from 0 for no joint inflammation to 4 for extended oedema and erythema of ankle. After rat sacrifice at day 17, BMD was assessed by DXA densitometer. For each animal, right ankle, tibia, and second lumbar vertebra (LV2) were measured. Region of interest (ROI) was reproducibly defined. BMD values were mean of two distinct analyses, including ROI reset. We performed non-parametrical statistics, including Spearman correlation "r" coefficient. <h3>Results</h3> At day&nbsp;17 post-arthritis induction, ankle BMD was lower in AIA than CTRL rats (-22%;&nbsp;p &lt; 0.001). BMD<sub>tibia</sub> and BMD<sub>LV2</sub> were also decreased in AIA group (-15% and -14% respectively; p &lt; 0.001 for both). BMD reduction was higher in ankles than in tibia and LV2 sites (p &lt; 0.05). BMD<sub>ankle</sub> values were correlated with BMD<sub>tibia</sub> values (r = 0.79; p &lt; 0.001) and with BMD<sub>LV2</sub> values (r = 0.77; p &lt; 0.001). Systemic bone loss in AIA correlated with inflammation (BMD<sub>ankle</sub> and AI: r&nbsp;=&nbsp;-0.91, p &lt; 0.001. BMD<sub>tibia</sub> and AI: r&nbsp;=&nbsp;-0.82, p &lt; 0.001. BMD<sub>LV2</sub> and AI: r&nbsp;=&nbsp;-0.83, p &lt; 0.001). <h3>Conclusions</h3> Arthritis-induced bone loss mainly affects the arthritic joint. But, in addition, a systemic bone loss is present in AIA model, including tibia and LV2 sites, like in RA. Moreover, inflammation is predictable of local but also systemic bone loss. Bone loss in AIA model mimics RA bone loss regarding as local as systemic physiopathologic effects. A better understanding of bone loss mechanisms in this animal model would improve our knowledge of systemic mechanisms and pathologic bone loss in humans.
Probable Clonal Origin of Neurofibrosarcoma in a Patient With Hereditary Neurofibromatosis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J M Friedman, P J Fialkow, C L Greene, M N Weinberg
Journal: JNCI Journal of the National Cancer Institute (1982)

A neurofibroma, a fibroma, a primary neurofibrosarcoma, and four neurofibrosarcoma metastases from a woman with hereditary neurofibromatosis who was heterozygous (GdB/GdA- ) for the X-linked enzyme glucose-6-phosphate dehydrogenase were studied to determine the number of cells from which the tumors developed. Both enzyme types were observed in the benign tumors in proportions similar to those present in seven different normal tissues studied. These findings indicated that the benign tumors arose from many cells. In marked contrast, only type A activity was detected in the primary neurofibrosarcoma and in all of the metastases. Two or more steps probably were involved in the development of neurofibrosarcoma in this patient: the inherited genetic mutation producing neurofibromatosis and a rare event or combination of events that permitted a single cell to undergo malignant proliferation.
Evidence for a Colon Chalone
Authors: John C. Houck, K. Kanagalingam, Steven L. Kaufman, Geoffrey Sunshine
Journal: JNCI Journal of the National Cancer Institute (1976)

The molecular weight fractions of 10,000-50,000 daltons prepared from "used" medium obtained during cultivation of human colon carcinoma cells (SW-48) in vitro inhibited the proliferation and DNA synthesis of these cells. Fractions exceeding 50,000 daltons were not inhibitory; those less than 10,000 daltons were cytotoxic. The inhibitory fraction did not affect either proliferation of human fibroblasts or transformation of human lymphocytes in vitro. Similar fractions from the colon mucosa of other species inhibited the proliferation of SW-48 cells, whereas extracts of dog jejunum or lung did not. This mitotic inhibition was completely reversible and could be destroyed by preincubation with trypsin. Therefore, colon cells appear to contain a cell- (but not species) specific, endogenous mitotic inhibitor or chalone.
Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease
Authors: Daniel Weintraub, Claire Chiang, Hyungjin Myra Kim, Jayne Wilkinson, Connie Marras, Barbara Stanislawski, Eugenia Mamikonyan, Helen C. Kales
Journal: JAMA Neurology (2016)

As many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown.
Quantitative Perfusion Scintigraphy (QPS) or the Anatomic Segment Method (ASM) for estimating Postoperative Pulmonary Function (PF) in patients treated for non-small cel lung cancer (NSCLC): a retrospective comparison
Authors: Tom Holvoet, Eric Derom, Jan Van Meerbeeck
Journal: Journal of Thoracic Oncology (2009)
Abstract 14440: Impaired Myocardial Blood Flow is Associated With Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy -Perfusion Study on Cardiac Magnetic Resonance Imaging
Authors: Daisuke Tezuka, Masahiro Terashima, Go Haraguchi, Mitsuaki Isobe
Journal: Circulation (2013)

Introduction: Hypertrophic cardiomyopathy (HCM) generally shows ischemic signs, which is partially attributed to the disorder of myocardial perfusion. Recently, cardiac magnetic resonance imaging (...