tbuckley/cabot-search huggingface dataset:
Etanercept: therapeutic use in patients with rheumatoid arthritis
Authors: L. Garrison, N. D McDonnell
Journal: Annals of the Rheumatic Diseases (1999)

Tumour necrosis factor (TNF) plays a central part in the pathophysiology of rheumatoid arthritis (RA). TNF initiates signal transduction by interacting with surface bound TNF receptors. Soluble tumour necrosis factor receptors (sTNFRs) act as natural inhibitors of TNF activity. Etanercept, recombinant p75 sTNFR:Fc fusion protein, has received approval from the US Food and Drug Administration for patients with RA and juvenile RA (JRA) who have failed treatment with at least one other drug. Etanercept has demonstrated excellent safety and efficacy in large scale, randomised, double blind, placebo controlled trials of patients with RA and JRA who are refractory to other disease modifying anti-rheumatic drugs. The therapeutic effects mediated by etanercept are rapid and sustained. Combining etanercept with methotrexate was found to be safe and more effective than treatment with methotrexate alone in the treatment of RA. These clinical findings demonstrate that etanercept can result in symptomatic improvement in patients with RA and JRA. Etanercept is an important new addition to the treatment of these diseases.
Increased Submandibular Gland Uptake on Thyroid Scintigraphy Due to Wharton's Duct Stone
Authors: MICHAEL S. KIPPER, LINDA D. KROHN
Journal: Clinical Nuclear Medicine (1996)

Multiple causes of extrathyroidal accumulation of radioiodine have been reported. The results of an 81-year-old woman's scan showed unilateral submandibular concentration secondary to a stone obstructing Wharton's duct. The scan had been ordered to assess thyromegaly. The serendipitous combination of scintiscan findings and clinical symptoms prompted further evaluation and surgical removal of the occlusive stone. A potential false-positive interpretation was avoided because of a careful patient history as well as physical examination of the submandibular regions. Salivary duct occlusion must be added to the list of causes of extrathyroidal accumulation of radioiodine.
ATAXIA OF CENTRAL ORIGIN APPEARING IN CHILDHOOD.
Authors: ARTHUR WILLARD FAIRBANKS
Journal: JAMA (1905)

This paper is a brief consideration of a form of central nervous disease previously described under the titles of hereditary ataxia, cerebellar ataxia, and not infrequently under the heading of Friedreich's disease. It varies, in certain particulars, however, as we shall see, from the usual conception of what should constitute the affection bearing Friedreich's name. In view of its relative rarity, the number of cases of this affection coming under the observation of any single observer is naturally small. The clinical characteristics of this affection stated briefly are: Muscular inco-ordination commencing usually in childhood, and, as a rule, first affecting the muscles of the lower extremities, thence extending to the upper extremities, and to the muscles of the trunk, head, larynx, tongue and eyes; slowness of muscular response to volitional impulse; swaying, unsteady gait; slow, hesitating or deliberate speech, sometimes of nasal character and occasionally explosive; nystagmus; oscillation or tremor
Pain at the base of the thumb
Authors: D. R. Dickson, C. C. L. Dickson, R. Farnell
Journal: BMJ (2015)

#### The bottom line A woman in her 60s presents with progressive pain at the base of her thumb, which is exacerbated by writing, lifting pans, and turning door handles. Osteoarthritis at the base of the thumb (the carpometacarpal joint) is common, usually idiopathic, and mostly affects postmenopausal women. The joint is subjected to considerable forces, particularly during pinching and gripping, making it prone to osteoarthritis. Take a focused pain history: ### Alternative or concomitant diagnoses to consider
Why We Don't Spend Enough on Public Health
Authors: David Hemenway
Journal: New England Journal of Medicine (2010)

The field of public health has long been the poor relation of medicine. Medicine — in which most resources are used to help cure individual patients after they have become sick or injured or to help manage already-existing chronic conditions — is flashy, its master practitioners and innovators lionized, and its accomplishments widely celebrated. In contrast, public health — in which most resources are focused on trying to keep something bad from happening in the first place — is seemingly mundane, its efforts and prime movers often all but invisible.Medicine is primarily a private good — the patient receives . . .
885. AAV-Mediated Gene Transfer of Constitutively and Pharmacologically-Activated Glial Cell-Derived Neurotrophic Factor Receptor To Inhibit Retinal Degeneration
Authors: Mariacarmela Allocca, Umberto Di Vicino, Luciano Domenici, Victor M. Rivera, Alberto Auricchio
Journal: Molecular Therapy (2006)

Retinitis pigmentosa (RP) is a group of inherited retinal degenerations for which no treatment is available. Despite their high genetic heterogeneity, common mechanisms like apoptosis are responsible for photoreceptor cell death. Various molecules with neurotrophic activity are being evaluated for treatment of RP in animal models. Delivery of Glial Cell-Derived Neurotrophic Factor (GDNF), either as a recombinant protein or by retinal gene transfer results in photoreceptor protection in genetic models of RP. The GDNF receptor is a complex including both GFR-α and Ret, which is endowed with tyrosine kinase activity and is expressed on photoreceptor outer segments as well as in other retinal cell types. It is therefore unclear whether GDNF neuroprotective effect is exerted directly on photoreceptors. To assess GDNF neuroprotective mechanism and to test a potential therapeutic strategy to regulate its neurotrophic activity, we have developed adeno-associated viral vectors (AAV) expressing either a constitutively activated (RetMen2A) or a pharmacologically-activated chimeric Ret receptor (Fv2Ret). Fv2Ret homodimerization, trans-phosphorylation and activation are induced by administration of the small dimerizer drug AP20187. RetMen2A and Fv2Ret expression in the retina transduced with AAV 2/5 vectors is restricted to photoreceptors by the human rhodopsin promoter. Following subretinal administration of AAV2/5 vectors in Balb/c mice, we show recombinant Ret expression and phosphorylation which is constitutive and robust in the case of RetMen2A and dependent upon AP20187 administration, albeit at low levels, in the case of Fv2Ret. No functional or morphological protection from light-damage was observed following AAV mediated gene transfer of either Ret molecule suggesting that photoreceptors might not be the direct target of GDNF neuroprotective effect in light-induced retinal degeneration.
Homology, neurogenetic imprecision, and lesional complexity
Authors: Ralph-Axel M&uuml;ller
Journal: Behavioral and Brain Sciences (1999)

The two commentaries appear supportive of the target article. Ujhelyi's commentary can be complemented with recent evidence supporting continuity of language and cognitive evolution in hominids. Gow &amp; Rodkin's caveats regarding “pathonormal inference” and the single-case methodology are discussed from a developmental neurobiological perspective. Early structural brain lesion and developmental disorders can serve as pathological models of normal neurofunctional variability resulting from neurodevelopmental imprecision. A final point concerns the advantages of integrating multiple structural and functional imaging modalities in neuropsychological studies.
Bioterrorism and compulsory vaccination: Author's reply
Authors: Tom Jefferson
Journal: BMJ (2004)

EDITOR—Winkenwerder and Grabenstein question the scientific basis of my editorial. I repeat my statement that the only available field evidence in humans comes from a badly reported 1950s trial of a vaccine similar to adsorbed anthrax vaccine (AVA). This vaccine was probably effective against cutaneous anthrax but the researchers specifically concluded that no such claims could be made regarding …
Transjugular intrahepatic portosystemic shunt: Short-term and long-term effects on hepatic and systemic hemodynamics in patients with Cirrhosis
Authors: Erich Lotterer, Arthur Wengert, Wolfgang E. Fleig
Journal: Hepatology (1999)

The aim of this prospective, nonrandomized study was to assess the short– and long–term effects of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic and systemic hemodynamics and on gastroesophageal collateral flow in patients with cirrhosis and failure of chronic sclerotherapy. Cardiac output (CO), free and wedged pulmonary artery pressure (FPAP and WPAP) systemic vascular resistance (SVR) azygos venous blood flow (AzVBF), and the relative (portal minus vena cava) pressure in the portal vein (rel.PP) were determined immediately before, 30 minutes, 1 week, 3 months, and 1 year after TIPS implantation in 21 patients with alcoholic and biliary cirrhosis with repeated bleeding from esophageal varices despite chronic sclerotherapy. TIPS was inserted when patients were in a stable hemodynamic condition. Palmaz stents were dilated to a 10–mm to 14–mm diameter until gastroesophageal collaterals were no longer visible on direct splenoportography. Relative portal pressure decreased from 21 ± 5 mm Hg to 11 ± 5 mm Hg 30 minutes after the procedure ( P &lt; .001). CO increased from 7.1 ± 1.5 L/min at baseline to 8.9 ± 2.0 L/min ( P &lt; .005) at 30 minutes, 8.2 ± 2.0 L/min ( P &lt; .01) at 1 week, and 8.0 ± 2.0 L/min ( P &lt; .01) at 3 months after TIPS, and returned to 7.2 ± 1.3 L/min (ns) after 1 year. Before TIPS, SVR was 990 ± 285 dyne · sec · cm -5 and decreased to 856 ± 252 dyne · sec · cm -5 ( P &lt; .05) and 866 ± 267 dyne · sec · cm -5 P &lt; .05) at 30 minutes and 1 week after the procedure, and increased again to 903 ± 208 dyne · sec · cm -5 (s) and 1,016 ± 260 dyne · sec · cm -5 (ns) at 3 months and 1 year, respectively. AzVBF continuously decreased from 474 ± 138 mL/min before TIPS to 335 ± 116 mL/min, 289 ± 147 mL/min, 318 ± 157 mL/min, and 250 ± 104 mL/min (all P &lt; .005) at 30 minutes, 1 week, 3 months, and 1 year after TIPS. Portal decompression after TIPS is associated with a significant increase of CO for at least 3 months, which is only partly explained by a transient decrease of SVR. After 1 year, CO had returned to baseline levels. Despite an immediate decrease in portal pressure, the reduction of blood flow through gastroesophageal collaterals is delayed and not complete before 1 year after TIPS. In contrast to previous short–term observations, TIPS does not seem to cause long–term aggravation of the hyperkinetic circulation in patients with cirrhosis.
The Rag2–Il2rb–Dmd– Mouse: a Novel Dystrophic and Immunodeficient Model to Assess Innovating Therapeutic Strategies for Muscular Dystrophies
Authors: Denis Vallese, Elisa Negroni, Stéphanie Duguez, Arnaud Ferry, Capucine Trollet, Ahmed Aamiri, Christian AJ Vosshenrich, Ernst-Martin Füchtbauer, James P Di Santo, Libero Vitiello, Gillian Butler-Browne, Vincent Mouly
Journal: Molecular Therapy (2013)

The development of innovative therapeutic strategies for muscular dystrophies, particularly cell-based approaches, is still a developing field. Although positive results have been obtained in animal models, they have rarely been confirmed in patients and resulted in very limited clinical improvements, suggesting some specificity in humans. These findings emphasized the need for an appropriate animal model (i.e., immunodeficient and dystrophic) to investigate in vivo the behavior of transplanted human myogenic stem cells. We report a new model, the Rag2–Il2rb–Dmd– mouse, which lacks T, B, and NK cells, and also carries a mutant Dmd allele that prevents the production of any dystrophin isoform. The dystrophic features of this new model are comparable with those of the classically used mdx mouse, but with the total absence of any revertant dystrophin positive fiber. We show that Rag2–Il2rb–Dmd– mice allow long-term xenografts of human myogenic cells. Altogether, our findings indicate that the Rag2–Il2rb–Dmd– mouse represents an ideal model to gain further insights into the behavior of human myogenic stem cells in a dystrophic context, and can be used to assess innovative therapeutic strategies for muscular dystrophies. The development of innovative therapeutic strategies for muscular dystrophies, particularly cell-based approaches, is still a developing field. Although positive results have been obtained in animal models, they have rarely been confirmed in patients and resulted in very limited clinical improvements, suggesting some specificity in humans. These findings emphasized the need for an appropriate animal model (i.e., immunodeficient and dystrophic) to investigate in vivo the behavior of transplanted human myogenic stem cells. We report a new model, the Rag2–Il2rb–Dmd– mouse, which lacks T, B, and NK cells, and also carries a mutant Dmd allele that prevents the production of any dystrophin isoform. The dystrophic features of this new model are comparable with those of the classically used mdx mouse, but with the total absence of any revertant dystrophin positive fiber. We show that Rag2–Il2rb–Dmd– mice allow long-term xenografts of human myogenic cells. Altogether, our findings indicate that the Rag2–Il2rb–Dmd– mouse represents an ideal model to gain further insights into the behavior of human myogenic stem cells in a dystrophic context, and can be used to assess innovative therapeutic strategies for muscular dystrophies.
P3-07-17: Optimal Number of Sentinel Lymph Nodes That Could Avoid Completion of Axillary Lymph Node Dissection in Operable Breast Cancer.
Authors: RJ Salmon, Ricke Y de, MC Falcou
Journal: Cancer Research (2011)

Abstract Background Axillary lymph node dissection (ALND) has been the standard of care for breast cancer patients with sentinel lymph node (SLN) metastasis. It is now under discussion since the publications of ACOZOG Z0011 and NSABP-32. The 1–3% rate of axillary recurrence is very low in these studies, whereas the rate of additional nodal metastasis after the completion of ALND varies from 15% to 35%. The purpose of this study was to determine the optimal number of nodes to be removed in order to obtain an axilla free of disease after initial surgery. Patients and methods: 4928 consecutive patients treated for breast cancer ≤ 2 cm with primary breast surgery with SNB between 2000 and 2009 were reviewed from the Institut Curie breast cancer prospective database. 1165 patients with a positive SLN (macrometastasis, micrometastasis and isolated tumor cells) underwent ALND. The proportion of patients with positive ALND was analysed according to the total number of sentinel lymph nodes biopsied. Results were compared with Chi-square test for qualitative variables and with Kruskal-Wallis for quantitative variables. Results: Among the 1165 patients, 308 (26.4%) had a positive ALND. Among them, 81.1% of patients had a macrometastasis in the SLN versus 45.6% in the 857 patients with negative ALND (p&amp;lt;0.0001); 10.8% had a micrometastasis versus 31.4% (p&amp;lt;0.001) and 8.1% of patients had isolated tumor cells in the SLN versus 23% (p&amp;lt;0.001). The proportion of patients with positive ALND decreased with the number of sentinel nodes removed (Figure 1), independently of the number of positive SLN. Among the 1165 patients, the rate of patients with 5 nodes removed or more and with residual disease in the axilla was &amp;lt; 1% (n=11). Those patients could have avoided completion ALND, representing 3.6% of the total positive ALND that would have been neglected. Conclusions: We showed that patients with positive SLN have a very low risk (&amp;lt;1%) of residual disease in the axilla when 5 nodes or more have been removed. This number which is a major component of nomograms, could be used as a threshold to avoid completion ALND. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-17.
Long-Term Safety and Efficacy of Percutaneous Coronary Intervention With Stenting and Coronary Artery Bypass Surgery for Multivessel Coronary Artery Disease
Authors: Joost Daemen, Eric Boersma, Marcus Flather, Jean Booth, Rod Stables, Alfredo Rodriguez, Gaston Rodriguez-Granillo, Whady A. Hueb, Pedro A. Lemos, Patrick W. Serruys
Journal: Circulation (2008)

Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups.We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P=0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease.In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.
Application of Pediatric and Adult Guidelines for Treatment of Lipid Levels Among US Adolescents Transitioning to Young Adulthood
Authors: Holly C. Gooding, Angie Mae Rodday, John B. Wong, Matthew W. Gillman, Donald M. Lloyd-Jones, Laurel K. Leslie, Sarah D. de Ferranti
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Health care practitioners who care for adolescents transitioning to adulthood often face incongruent recommendations from pediatric and adult guidelines for treatment of lipid levels. <h3>Objective</h3> To compare the proportion of young people aged 17 to 21 years who meet criteria for pharmacologic treatment of elevated low-density lipoprotein cholesterol (LDL-C) levels under pediatric vs adult guidelines. <h3>Design, Setting, and Participants</h3> We performed a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) population. Surveys were administered from January 1, 1999, through December 31, 2012, and the analysis was performed from June through December 2014. Participants included 6338 individuals aged 17 to 21 years in the United States. <h3>Main Outcomes and Measures</h3> To estimate the number and proportion of individuals aged 17 to 21 years in the NHANES population who were eligible for statin therapy, we applied treatment algorithms from the 2011 Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents of the National Heart, Lung, and Blood Institute and the 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association. After imputing missing data and applying NHANES sampling weights, we extrapolated the results to 20.4 million noninstitutionalized young people aged 17 to 21 years living in the United States. <h3>Results</h3> Of the 6338 young people aged 17 to 21 years in the NHANES population, 2.5% (95% CI, 1.8%-3.2%) would qualify for statin treatment under the pediatric guidelines compared with 0.4% (95% CI, 0.1%-0.8%) under the adult guidelines. Participants who met pediatric criteria had lower mean (SD) LDL-C levels (167.3 [3.8] vs 210.0 [7.1] mg/dL) but higher proportions of other cardiovascular risk factors, including hypertension (10.8% vs 8.4%), smoking (55.0% vs 23.9%), and obesity (67.7% vs 18.2%) compared with those who met the adult guidelines. Extrapolating to the US population of individuals aged 17 to 21 years represented by the NHANES sample, 483 500 (95% CI, 482 100-484 800) young people would be eligible for treatment of LDL-C levels if the pediatric guidelines were applied compared with only 78 200 (95% CI, 77 600-78 700) if the adult guidelines were applied. <h3>Conclusions and Relevance</h3> Application of pediatric vs adult guidelines for lipid levels, which consider additional cardiovascular risk factors beyond age and LDL-C concentration, might result in statin treatment for more than 400 000 additional adolescents and young adults.
Plasma Homocysteine as a Risk Factor for Vascular Disease
Authors: Ian M. Graham
Journal: JAMA (1997)

<h3>Context.</h3> —Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. <h3>Objective.</h3> —To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. <h3>Design.</h3> —Case-control study. <h3>Setting.</h3> —Nineteen centers in 9 European countries. <h3>Patients.</h3> —A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. <h3>Measurements.</h3> —Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. <h3>Results.</h3> —The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of atrisk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. <h3>Conclusions.</h3> —An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.