tbuckley/cabot-search huggingface dataset:
Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial
Authors: P. Tynjala, P. Vahasalo, M. Tarkiainen, L. Kroger, K. Aalto, M. Malin, A. Putto-Laurila, V. Honkanen, P. Lahdenne
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent‑onset polyarticular JIA. <h3>Methods</h3> In a 54-week multicentre open-label clinical trial, 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4–15 years were randomly assigned into three treatment arms. The efficacy of infliximab plus methotrexate (TNF) was compared to that of two synthetic therapies: methotrexate alone (MTX) and DMARD methotrexate, sulphasalazine and hydroxychloroquine in combination (COMBO). Primary endpoint was American College of Rheumatology paediatric 75% improvement (ACR Pedi 75). Secondary endpoints were inactive disease and safety. <h3>Results</h3> In 59 patients, mean (±SE) age at baseline was 9.6±0.4 years, duration of JIA 1.9±0.2 months and number of active joints 18±1. ACR Pedi 75 was achieved in 100% (19/19) of patients receiving TNF, 65% (13/20) on COMBO (95% CI 44% to 86%) and 50% (10/20) on methotrexate (95% CI 28% to 72%) p&lt;0.0001. Thirteen patients receiving TNF (68%; 95% CI 47% to 89%) achieved inactive disease, whereas eight (40%; 95% CI 22% to 63%) on COMBO and five (25%; 95% CI 6% to 44%) on methotrexate did (p=0.002). Patients on TNF spent a mean 26 weeks (95% CI 18 to 34) with inactive disease, longer than did those receiving COMBO (13 weeks; 95% CI 6 to 20), or methotrexate (6 weeks; 95% CI 2 to 10). Serious adverse events were rare. <h3>Conclusion</h3> In early polyarticular JIA, targeting to achieve minimally active or inactive disease, infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone.
Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes
Authors: James G. Karras, Zihua Wang, Li Huo, Robert G. Howard, David A. Frank, Thomas L. Rothstein
Journal: The Journal of Experimental Medicine (1997)

Cytokine and growth factor receptor engagement leads to the rapid phosphorylation and activation of latent, cytosolic signal transducers and activators of transcription (STAT) proteins, which then translocate to the nucleus where they regulate transcriptional events from specific promoter sequences. STAT3 expression in particular has been associated with Abl, Src, and HTLV-1 transformation of normal cells. B-1 lymphocytes are self-renewing, CD5+ B cells that display a propensity for malignant transformation and are the normal counterpart to human chronic lymphocytic leukemias. Further, B-1 cells are characterized by aberrant intracellular signaling, including hyperresponsiveness to phorbol ester PKC agonists. Here we demonstrate that B-1 lymphocytes constitutively express nuclear activated STAT3, which is not expressed by unmanipulated conventional (B-2) lymphocytes. In contrast, STAT3 activation is induced in B-2 cells after antigen receptor engagement in a delayed fashion (after 3 h). Induction of STAT3 is inhibited by both the serine/threonine protein kinase inhibitor H-7 and the immunosuppressive drug rapamycin and requires de novo protein synthesis, demonstrating novel coupling between sIg and STAT proteins that differs from the classical paradigm for STAT induction by cytokine receptors. The inability of prolonged stimulation of conventional B-2 cells with anti-Ig, a treatment sufficient to induce CD5 expression, to result in sustained STAT3 activation suggests that STAT3 is a specific nuclear marker for B-1 cells. Thus, STAT3 may play a role in B cell antigen-specific signaling responses, and its constitutive activation is associated with a normal cell population exhibiting intrinsic proliferative behavior.
c-Myc Overexpression Causes Anaplasia in Medulloblastoma
Authors: Duncan Stearns, Aneeka Chaudhry, Ty W. Abel, Peter C. Burger, Chi V. Dang, Charles G. Eberhart
Journal: Cancer Research (2006)

Abstract Both anaplasia and increased c-myc gene expression have been shown to be negative prognostic indicators for survival in medulloblastoma patients. myc gene amplification has been identified in many large cell/anaplastic medulloblastoma, but no causative link between c-myc and anaplastic changes has been established. To address this, we stably overexpressed c-myc in two medulloblastoma cell lines, DAOY and UW228, and examined the changes in growth characteristics. When analyzed in vitro, cell lines with increased levels of c-myc had higher rates of growth and apoptosis as well as significantly improved ability to form colonies in soft agar compared with control. When injected s.c. into nu/nu mice, flank xenograft tumors with high levels of c-myc in DAOY cell line background were 75% larger than those derived from control. Overexpression of c-myc was required for tumor formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors was severely anaplastic, with large areas of necrosis/apoptosis, increased nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role in inducing anaplasia in medulloblastoma. Because anaplastic changes are often observed in recurrent medulloblastoma, we propose that c-myc dysregulation is involved in the progression of these malignant embryonal neoplasms. (Cancer Res 2006; 66(2): 673-81)
Family-based association analysis of β2-adrenergic receptor polymorphisms in the childhood asthma management program
Authors: Edwin K. Silverman, David J. Kwiatkowski, Jody S. Sylvia, Ross Lazarus, Jeffrey M. Drazen, Christoph Lange, Nan M. Laird, Scott T. Weiss
Journal: Journal of Allergy and Clinical Immunology (2003)
Improved Arterial Oxygenation with Biologically Variable or Fractal Ventilation Using Low Tidal Volumes in a Porcine Model of Acute Respiratory Distress Syndrome
Authors: ABDULAZIZ BOKER, M. RUTH GRAHAM, KEITH R. WALLEY, BRUCE M. McMANUS, LINDA G. GIRLING, ELIZABETH WALKER, GERALD R. LEFEVRE, W.ALAN C. MUTCH
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We compared biologically variable ventilation (V˙ bv; n = 9) with control mode ventilation (V˙ c; n = 8) at low tidal volume (Vt)—initial 6 ml/kg—in a porcine model of acute respiratory distress syndrome (ARDS). Hemodynamics, respiratory gases, airway pressures, and Vt data were measured. Static P-V curves were generated at 5 h. Interleukin (IL)-8 and IL-10 were measured in serum and tracheal aspirate. By 5 h, higher PaO2 (173 ± 30 mm Hg versus 119 ± 23 mm Hg; mean ± SD; p < 0.0001 group × time interaction [G × T]), lower shunt fraction (6 ± 1% versus 9 ± 3%; p = 0.0026, G × T) at lower peak airway pressure (21 ± 2 versus 24 ± 1 cm H2O; p = 0.0342; G × T) occurred with V˙ bv. IL-8 concentrations in tracheal aspirate and wet:dry weight ratios were inversely related; p = 0.011. With V˙ c, IL-8 concentrations were 3.75-fold greater at wet:dry weight ratio of 10. IL-10 concentrations did not differ between groups. In both groups, ventilation was on the linear portion of the P-V curve. With V˙ bv, Vt variability demonstrated an inverse power law indicating fractal behavior. In this model of ARDS, V˙ bv improved PaO2 at lower peak airway pressure and IL-8 levels compared with V˙ c.
Dysregulated Renin–Angiotensin–Aldosterone System Contributes to Pulmonary Arterial Hypertension
Authors: Frances S. de Man, Ly Tu, M. Louis Handoko, Silvia Rain, Gerrina Ruiter, Charlène François, Ingrid Schalij, Peter Dorfmüller, Gérald Simonneau, Elie Fadel, Frederic Perros, Anco Boonstra, Piet E. Postmus, Jolanda van der Velden, Anton Vonk-Noordegraaf, Marc Humbert, Saadia Eddahibi, Christophe Guignabert
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Patients with idiopathic pulmonary arterial hypertension (iPAH) often have a low cardiac output. To compensate, neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are up-regulated, but this may have long-term negative effects on the progression of iPAH.
Relationship of Enhanced Norepinephrine Activity During Memory Consolidation to Enhanced Long-Term Memory in Humans
Authors: Steven M Southwick, Michael Davis, Beverly Horner, Larry Cahill, Charles A Morgan, Paul E Gold, J Douglas Bremner, Dennis C Charney
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The purpose of this study was to investigate the effect of enhanced noradrenergic activity on memory consolidation in humans. METHOD: Thirty healthy subjects (21 men and nine women) viewed a series of 12 slides that depicted an emotionally arousing story. Five minutes after viewing the slides, subjects received either intravenous yohimbine or intravenous placebo in a double-blind randomized fashion. Multiple blood samples were drawn for determining plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG). One week later subjects took a surprise memory test for the slides. RESULTS: There was no significant difference in memory score between yohimbine and placebo groups. Linear regression revealed a significant effect of MHPG on memory score for the group as a whole (subjects who had received yohimbine and those who had received placebo) and for the placebo group alone. CONCLUSIONS: These findings strengthen support for the hypothesis that enhanced memory for emotionally arousing events in humans depends critically on postlearning adrenergic modulation.
Motivational Deficits and Cognitive Test Performance in Schizophrenia
Authors: Gagan Fervaha, Konstantine K. Zakzanis, George Foussias, Ariel Graff-Guerrero, Ofer Agid, Gary Remington
Journal: JAMA Psychiatry (2014)

<h3>Importance</h3> Motivational and cognitive deficits are core features of schizophrenia, both closely linked with functional outcomes. Although poor effort and decreased motivation are known to affect performance on cognitive tests, the extent of this relationship is unclear in patients with schizophrenia. <h3>Objective</h3> To evaluate the association between intrinsic motivation and cognitive test performance in patients with schizophrenia. <h3>Design, Setting, and Participants</h3> Cross-sectional and 6-month prospective follow-up study performed at 57 sites in the United States, including academic and community medical treatment centers, participating in the Clinical Antipsychotic Trials of Intervention Effectiveness study. The primary sample included 431 stable patients with a<i>DSM-IV</i>diagnosis of schizophrenia currently receiving a stable medication regimen. <h3>Interventions</h3> Cognitive performance and intrinsic motivation were evaluated using a comprehensive neuropsychological test battery and a derived measure from the Heinrichs-Carpenter Quality of Life Scale, respectively. Symptom severity and functional status were also assessed. <h3>Main Outcomes and Measures</h3> The primary outcome variable was global neurocognition. Individual domains of cognition were also evaluated for their association with motivation. <h3>Results</h3> Level of intrinsic motivation was significantly and positively correlated with global cognitive test performance, a relationship that held for each domain of cognition evaluated (correlation range, 0.20-0.34;<i>P</i> &lt; .001). This association was found to be reliable after statistically accounting for positive, negative, depressive, and overall symptom severity (<i>P</i> &lt; .05) and after accounting for community functioning (<i>P</i> &lt; .001). The relationship between motivation and cognitive performance also remained significant after controlling for antipsychotic dose (<i>P</i> &lt; .05). Prospective increase in motivation during the 6-month follow-up was also found to be significantly related to improvement in global cognitive performance (<i>P</i> &lt; .05). <h3>Conclusions and Relevance</h3> The present findings provide strong support for a robust and reliable relationship between motivation and cognitive performance and suggest that test performance is not purely a measure of ability. Future studies assessing cognition in patients with schizophrenia should consider potential moderating variables such as effort and motivation. Implications for the assessment and interpretation of cognitive impairment based on neuropsychological test measures in schizophrenia are discussed, especially in the case of clinical trials for cognition-enhancing treatments. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00014001
Skull With Two Fruits
Journal: JAMA (2002)

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
Points: Spinal disease presenting as acute abdominal pain
Authors: D V M. Jones
Journal: BMJ (1983)

503diagnosis and several more had raised blood pressure on admission to hospital.'In our series a low blood pressure or low pulse pressure was unusual, even in cases of severe aortic stenosis, although the pulse waveform was almost always abnormal.We believe that the coexistence of aortic stenosis and hyper- tension ismore than chance and it may be that raised systemic pressure accelerates wear of the aortic valve, especially if it is congenitally bicuspid.
Epidemiology of the injuries of the locomotor system in elite volleyball players
Authors: R Aido, M Massada, N Leitão, C Magalhães, N Puga
Journal: British Journal of Sports Medicine (2011)

Background The epidemiological study is an important tool in the understanding and development of any medical field. In Sports Medicine highlights their importance in the development of preventive strategies with the ultimate goal of protecting and enhancing the performance of athletes. Objective This observational study has the aim to identify the prevalence, incidence, aetiology, severity and anatomical location of injuries of the locomotor system occurred in volleyball elite players. Setting, participants and methods 20 Portuguese volleyball players from the senior national team, with mean age of 24.29 years and 11.14 years of average sports volleyball, were evaluated during 4 months. All the injuries were recorded and reported with their clinical diagnosis. Results During the study, 55 injuries were detected with an incidence rate of 6.11 injuries per athlete per 1000 h of sporting activity. An higher incidence of injuries was observed during games when compared with the training sessions (10.11 vs 5.56). The 55 lesions were diagnosed in 18 athletes (90.00%) who comprised the study, noting the prevalence of overuse injuries (72.73%). The anatomical segment most affected was the lower limb (45.54%). Lower limb anatomic area with highest number of injuries was the knee and leg (27.27%). Muscular injuries (38.18%) and tendinopathys (34.54%) were the most frequent injuries reported. There was a predominance of lesions in the dominant member (64.86%). In eight players (40.00%) recurrence of previous injuries was diagnosed. The greatest number of lesions was considered of mild (58.18%) or moderate (34.54%) severity. The analysis between the injuries and the athlete's position stated that the opposites were the most affected players. The first month of sport activity was the period with more injuries recorded. Conclusions The results reported in this study show a predominance of overuse and recurrent injuries in elite volleyball athletes. These finding are consistent with previously conducted epidemiological records.
Neurobehavioral Effects of Dental Amalgam in Children
Authors: Timothy A DeRouen, Michael D Martin, Brian G Leroux, Brenda D Townes, James S Woods, Jorge Leitão, Alexandre Castro-Caldas, Henrique Luis, Mario Bernardo, Gail Rosenbaum, Isabel P Martins
Journal: JAMA (2006)

Dental (silver) amalgam is a widely used restorative material containing 50% elemental mercury that emits small amounts of mercury vapor. No randomized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure.To assess the safety of dental amalgam restorations in children.A randomized clinical trial in which children requiring dental restorative treatment were randomized to either amalgam for posterior restorations or resin composite instead of amalgam. Enrollment commenced February 1997, with annual follow-up for 7 years concluding in July 2005.A total of 507 children in Lisbon, Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth, no previous exposure to amalgam, urinary mercury level <10 microg/L, blood lead level <15 microg/dL, Comprehensive Test of Nonverbal Intelligence IQ > or =67, and with no interfering health conditions.Routine, standard-of-care dental treatment, with one group receiving amalgam restorations for posterior lesions (n = 253) and the other group receiving resin composite restorations instead of amalgam (n = 254).Neurobehavioral assessments of memory, attention/concentration, and motor/visuomotor domains, as well as nerve conduction velocities.During the 7-year trial period, children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam group and 21.3 (median, 18) restored in the composite group. Baseline mean creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group and 1.9 microg/g in the composite group, but during follow-up were 1.0 to 1.5 microg/g higher in the amalgam group than in the composite group (P<.001). There were no statistically significant differences in measures of memory, attention, visuomotor function, or nerve conduction velocities (average z scores were very similar, near zero) for the amalgam and composite groups over all 7 years of follow-up, with no statistically significant differences observed at any time point (P values from .29 to .91). Starting at 5 years after initial treatment, the need for additional restorative treatment was approximately 50% higher in the composite group.In this study, children who received dental restorative treatment with amalgam did not, on average, have statistically significant differences in neurobehavioral assessments or in nerve conduction velocity when compared with children who received resin composite materials without amalgam. These findings, combined with the trend of higher treatment need later among those receiving composite, suggest that amalgam should remain a viable dental restorative option for children.clinicaltrials.gov Identifier: NCT00066118.
Lower Incidence of Colorectal Cancer and Later Age of Disease Onset in 27 Families With Pathogenic <i>MSH6</i> Germline Mutations Compared With Families With <i>MLH1</i> or <i>MSH2</i> Mutations: The German Hereditary Nonpolyposis Colorectal Cancer Consortium
Authors: Jens Plaschke, Christoph Engel, Stefan Krüger, Elke Holinski-Feder, Constanze Pagenstecher, Elisabeth Mangold, Gabriela Moeslein, Karsten Schulmann, Johannes Gebert, Magnus von Knebel Doeberitz, Josef Rüschoff, Markus Loeffler, Hans K. Schackert
Journal: Journal of Clinical Oncology (2004)

The aim of the study was the analysis of the involvement and phenotypic manifestations of MSH6 germline mutations in families suspected of hereditary nonpolyposis colorectal cancer (HNPCC).Patients were preselected among 706 families by microsatellite instability, immunohistochemistry, and/or exclusion of MLH1 or MSH2 mutations and were subjected to MSH6 mutation analysis. Clinical and molecular data of MSH6 mutation families were compared with data from families with MLH1 and MSH2 mutations.We identified 27 families with 24 different pathogenic MSH6 germline mutations, representing 3.8% of the total of the families, and 14.7% of all families with DNA mismatch repair (MMR) gene mutations (n = 183). The median age of onset of colorectal cancer in putative mutation carriers was 10 years higher for MSH6 (54 years; 95% CI, 51 to 56) compared with MLH1 and MSH2 (44 years; 95% CI, 43 to 45; log-rank test, P = .0038). Relative to other malignant tumors, colorectal cancer was less frequent in MSH6 families compared with MLH1 and MSH2 families (Fisher's exact test, P < .001). In contrast, the frequency of non-HNPCC-associated tumors was increased (Fisher's exact test, P < .001).Later age of disease onset and lower incidence of colorectal cancer may contribute to a lower proportion of identified MSH6 mutations in families suspected of HNPCC. However, in approximately half of these families, at least one patient developed colorectal or endometrial cancer in the fourth decade of life. Therefore, a surveillance program as stringent as that for families with MLH1 or MSH2 mutations is recommended.
Etiology of Type I Diabetes Mellitus: Heterogeneity and Immunological Events Leading to Clinical Onset
Authors: D. Doniach, G. F. Bottazzo, M. R. C. Path, A. G. Cudworth
Journal: Annual Review of Medicine (1983)

Type I diabetes is a heterogeneous disorder and the causes of pancreatic beta-cell destruction are unknown. In 1-2% of all cases, viruses (e.g. coxsackie, rubella, mumps, or beta-cell poisons) have been implicated. Twin studies suggest at most 50% of genetic predisposition. In this review we describe the autoimmune components which, in association with inheritance of HLA-haplotypes in susceptible families, allow the future selection of predisposed sibs for possible preventive therapy to retard loss of insulin secretion. The known association of the endocrine autoimmune organ-specific disorders in 10% of Type I diabetics is the extreme expression of the other main genetic ingredient in the development of insulitis in this disease, irrespective of the triggering environmental components. In this “polyendocrine” subgroup and in the “juvenile-onset” cases there is a prolonged latency period during which pancreatic autoimmunity markers are present before clinical expression of the disease.