tbuckley/cabot-search huggingface dataset:
On the Relation of the Argyll-Robertson Phenomenon to Syphilis
Authors: J. M. Clarke
Journal: BMJ (1903)

Later examination of the blood showed haemoglobln 12 per cent., leuo-cyteS 107,000, and red corpuscles 81s,000 per c.mm.At the necropsy the ribs, manubrium sterni, and nuaierous other bones showed green material in the medulla.The periosteum of the vertebrae, from the neck to the pelvis, was infiltrated with the same green material, as. was also the dura mater, the pericranium beneath the temporal muscle, the orbital cavities, the kidneys, the pancreas, and the glands just above the pancreas, the soft palate, tonsil, pharynx, mouth, and gums.The brain and spinal cord were healthy.Microscopically, the tumours con- sisted of large, round or oval-shaped cells, slightly larger than a white blood corpuscle, and containing often more than one nucleus, and occa- sionally a nucleolus.These cells were either embedded in an intercellular amorphous material of a very clear and transparent character or in a delicate network.At other times the tumour was interspersed with coarse bundles of connective tissue.In the midst of this granules with highly refractile properties were found lying in and be- tween the cells.
Patient Engagement Programs for Recognition and Initial Treatment of Depression in Primary Care
Authors: Richard L. Kravitz
Journal: JAMA (2013)

IMPORTANCEEncouraging primary care patients to address depression symptoms and care with clinicians could improve outcomes but may also result in unnecessary treatment.OBJECTIVE To determine whether a depression engagement video (DEV) or a tailored interactive multimedia computer program (IMCP) improves initial depression care compared with a control without increasing unnecessary antidepressant prescribing.DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial comparing DEV, IMCP, and control among 925 adult patients treated by 135 primary care clinicians (603 patients with depression and 322 patients without depression, defined by Patient Health Questionnaire-9 [PHQ-9] score) conducted from June 2010 through March 2012 at 7 primary care clinical sites in California. INTERVENTIONS DEV targeted to sex and income, an IMCP tailored to individual patient characteristics, and a sleep hygiene video (control).MAIN OUTCOMES AND MEASURES Among depressed patients, superiority assessment of the composite measure of patient-reported antidepressant drug recommendation, mental health referral, or both (primary outcome); depression at 12-week follow-up, measured by the PHQ-8 (secondary outcome).Among nondepressed patients, noninferiority assessment of clinician-and patient-reported antidepressant drug recommendation (primary outcomes) with a noninferiority margin of 3.5%.Analyses were cluster adjusted. RESULTSOf the 925 eligible patients, 867 were included in the primary analysis (depressed, 559; nondepressed, 308).Among depressed patients, rates of achieving the primary outcome were 17.5% for DEV, 26% for IMCP, and 16.3% for control (DEV vs control, 1.1 [95% CI, -6.7 to 8.9], P = .79;IMCP vs control, 9.9 [95% CI, 1.6 to 18.2], P = .02).There were no effects on PHQ-8 measured depression score at the 12-week follow-up: DEV vs control, -0.2 (95% CI, -1.2 to 0.8); IMCP vs control, 0.9 (95% CI, -0.1 to 1.9).Among nondepressed patients, clinician-reported antidepressant prescribing in the DEV and IMCP groups was noninferior to control (mean percentage point difference [PPD]: DEV vs control, -2.2 [90% CI, -8.0 to 3.49], P = .0499for noninferiority; IMCP vs control, -3.3 [90% CI, -9.1 to 2.4], P = .02for noninferiority); patient-reported antidepressant recommendation did not achieve noninferiority (mean PPD: DEV vs control, 0.9 [90% CI, -4.9 to 6.7], P = .23for noninferiority; IMCP vs control, 0.3 [90% CI, -5.1 to 5.7], P = .16for noninferiority). CONCLUSIONS AND RELEVANCEA tailored IMCP increased clinician recommendations for antidepressant drugs, a mental health referral, or both among depressed patients but had no effect on mental health at the 12-week follow-up.The possibility that the IMCP and DEV increased patient-reported clinician recommendations for an antidepressant drug among nondepressed patients could not be excluded.
MEK targeting in N-RAS mutated metastatic melanoma
Authors: Jaykumar Thumar, David Shahbazian, Saadia A Aziz, Lucia B Jilaveanu, Harriet M Kluger
Journal: Molecular Cancer (2014)

Gain of function mutations in B-RAF and N-RAS occur frequently in melanoma, leading to mitogen activating protein kinase (MAPK) pathway activation, and this pathway is the target of drugs in development. Our purpose was to study clinical characteristics of patients with mutations in this pathway and to determine activity of inhibitors of B-RAF and MEK in short term cultures grown from tumors of some of these patients. Clinical and pathologic data were collected retrospectively on melanoma patients tested for B-RAF and N-RAS mutations at the Yale Cancer Center and associations with survival were determined. We studied in vitro activity of the pan-RAF inhibitor, RAF265, and the MEK inhibitor, MEK162, in 22 melanoma short term cultures. We further characterized the effect of MEK inhibition on apoptosis and growth of melanoma cultures. In a cohort of 144 metastatic melanoma patients we found that patients with N-RAS mutant melanoma had a worse prognosis. These patients were more likely to have brain metastases at the time of presentation with metastatic disease than their N-RAS-wild-type counterparts. All N-RAS mutant melanoma cultures tested in our study (n = 7) were sensitive to MEK inhibition162. Exposure to MEK162 reduced ERK1/2 phosphorylation, and induced apoptosis. Clonogenic survival was significantly reduced in sensitive melanoma cell cultures. The prognosis of patients with melanoma expressing constitutively active N-RAS is poor, consistent with studies performed at other institutions. N-RAS mutant melanoma cultures appear to be particularly sensitive to MEK162, supporting ongoing clinical trials with MEK162 in N-RAS mutated melanoma.
A Simple Statistical Method for Estimating Type-II (Cluster-Specific) Functional Divergence of Protein Sequences
Authors: Xun Gu
Journal: Molecular Biology and Evolution (2006)

Predicting functional amino acid residues in silico is important for comparative genomics. In this paper, we focus on the issue of how to statistically identify cluster-specific amino acid residues that are related to the functional divergence after gene duplication. We approach this problem using a framework based on site-specific shift of amino acid property (type-II functional divergence), as opposed to site-specific shift of evolutionary rate (type-I functional divergence). An efficient statistical procedure is implemented to facilitate the development of phylogenomic database for cluster-specific residues of large-scale protein families. Our method has the following features: 1) statistical testing of the type-II functional divergence and 2) the site-specific Bayesian profile to measure how amino acid residues contribute to type-II (cluster-specific) functional divergence. Consequently, one may obtain the posterior probability for "functional" cluster-specific residues. Case studies are presented and indicate that radical cluster-specific residues are responsible for most of inferred type-II functional divergence, whereas conserved cluster-specific residues appear less than even those imperfect radical cluster-specific residues to this type of functional divergence.
Dipyridamole dilates large coronary arteries in conscious dogs.
Authors: T H Hintze, S F Vatner
Journal: Circulation (1983)

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.
Neointimal Hyperplasia After Arterial Injury Is Increased in a Rat Model of Non–Insulin-Dependent Diabetes Mellitus
Authors: Si-Hoon Park, Steven P. Marso, Zhongmin Zhou, Farhard Foroudi, Eric J. Topol, A. Michael Lincoff
Journal: Circulation (2001)

The key biological determinants that promote restenosis in the setting of diabetes have not been elucidated. There is no accepted animal model to study restenosis in diabetes.We evaluated 2 models of diabetes mellitus: (1) streptozotocin (STZ)-treated Sprague-Dawley rats (type I diabetes) versus regular Sprague-Dawley rats and (2) obese Zucker rats (type II diabetes) versus lean Zucker rats. Neointimal hyperplasia was assessed after carotid balloon injury at 21 days by computerized morphometry. There was no difference in neointimal area in the STZ-treated rats compared with controls, irrespective of insulin administration or dose of STZ. Neointimal area was increased >2-fold in obese Zucker rats compared with lean Zucker rats (0.21+/-0.06 versus 0.08+/-0.03 mm(2), P<0.01). The neointimal area was markedly increased in the obese Zucker rats 7 days after injury (0.058+/-0.024 versus 0.033+/-0.009 mm(2), P<0.05) and persisted through 21 days. In both obese and lean Zucker rats, cell proliferation peaked in the media at 3 days (118.66+/-84.28 versus 27.50+/-12.75 bromodeoxyuridine-labeled cells per cross section). In the intima, cell proliferation markedly increased beginning at day 3 and persisted through day 14 in the obese and lean Zucker rats (202.27+/-98.86 versus 35.71+/-20.54 bromodeoxyuridine-labeled cells at 7 days).The type II diabetic rat model, typifying insulin resistance, is associated with a propensity for neointima. The obese Zucker rat model may be an ideal diabetic model to further characterize the diabetic vascular response to injury.
Usefulness of transcutaneous Doppler jugular venous echo to predict pulmonary hypertension in COPD patients
Authors: W. Matsuyama, R. Ohkubo, K. Michizono, M. Abe, Y. Nakamura, M. Kawabata, M. Osame
Journal: European Respiratory Journal (2001)

Pulmonary hypertension is an important factor that determines the prognosis of chronic obstructive pulmonary disease (COPD) patients. Echocardiography is a noninvasive and useful bedside method for measurement of pulmonary artery pressure. However, this method is sometimes difficult because of the overinflated lungs in COPD patients. This study attempted to estimate pulmonary hypertension in COPD patients using transcutaneous Doppler jugular vein flow velocity recording. The mean pulmonary artery pressure (MPAP) of 64 COPD patients was examined using cardiac catheterization. The right jugular vein flow velocity was measured within 24 h using transcutaneous Doppler echo, after which the ratio of diastolic flow (Df) and systemic flow (Sf) velocity was calculated. Subsequently, the statistical correlation of MPAP and the Df/Sf ratio was examined. MPAP was also measured using standard cardiac echo methods and the results were compared. The Df/Sf velocity ratio showed significant correlation with MPAP in COPD patients (r=0.844, p&lt;0.0001). The sensitivity was 71.4%, and the specificity 95.3% (cut-off ratio=1.0). Jugular venous Doppler echo could be performed in all patients while other cardiac echo methods could not be performed in all patients. The specificity of the methods used was higher than other cardiac echo methods. Transcutaneous jugular vein flow velocity measurement may be applicable to bedside prediction of pulmonary hypertension in chronic obstructive pulmonary disease patients.
Uric Acid and Incident Kidney Disease in the Community
Authors: Daniel E. Weiner, Hocine Tighiouart, Essam F. Elsayed, John L. Griffith, Deeb N. Salem, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2008)

Uric acid may mediate aspects of the relationship between hypertension and kidney disease via renal vasoconstriction and systemic hypertension. To investigate the relationship between uric acid and subsequent reduced kidney function, limited-access data of 13,338 participants with intact kidney function in two community-based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular Health Study, were pooled. Mean baseline serum uric acid was 5.9 +/- 1.5 mg/dl, mean baseline serum creatinine was 0.9 +/- 0.2 mg/dl, and mean baseline estimated GFR was 90.4 +/- 19.4 ml/min/1.73 m(2). During 8.5 +/- 0.9 yr of follow-up, 712 (5.6%) had incident kidney disease defined by GFR decrease (>or=15 ml/min/1.73 m(2) with final GFR <60 ml/min/1.73 m(2)), while 302 (2.3%) individuals had incident kidney disease defined by creatinine increase (>or=0.4 mg/dl with final serum creatinine >1.4 mg/dl in men and 1.2 mg/dl in women). In GFR- and creatinine-based logistic regression models, baseline uric acid level was associated with increased risk for incident kidney disease (odds ratio 1.07 [95% confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21] per 1-mg/dl increase in uric acid, respectively), after adjustment for age, gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin, hematocrit, baseline kidney function and cohort; therefore, elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population.
National Trends in Outpatient Psychotherapy
Authors: Mark Olfson, Steven C. Marcus
Journal: American Journal of Psychiatry (2010)

Objective: The authors investigated recent trends in the use of outpatient psychotherapy in the United States. Method: Service use data from two representative surveys of the U.S. general population, the 1998 (N=22,953) and 2007 (N=29,370) Medical Expenditure Panel Surveys, were analyzed, focusing on individuals who made more than one outpatient psychotherapy visit during that calendar year. The authors computed rates of any psychotherapy use; percentages of persons treated for mental health conditions with only psychotherapy, only psychotropic medication, or their combination; the mean number of psychotherapy visits of persons receiving psychotherapy; and psychotherapy expenditures. Results: The percentage of persons using outpatient psychotherapy was 3.37% in 1998 and 3.18% in 2007 (adjusted odds ratio=0.95, 95% CI=0.82−1.09). Among individuals receiving outpatient mental health care, use of only psychotherapy (15.9% and 10.5% in 1998 and 2007, respectively; adjusted odds ratio=0.66, 95% CI=0.48−0.90) as well as psychotherapy and psychotropic medication together (40.0% and 32.1%; adjusted odds ratio=0.73, 95% CI=0.59−0.90) declined while use of only psychotropic medication increased (44.1% and 57.4%; adjusted odds ratio=1.63, 95% CI=1.32−2.00). Declines occurred in annual psychotherapy visits per psychotherapy patient (mean values, 9.7 and 7.9; adjusted β=−1.53, p<0.0001), mean expenditure per psychotherapy visit ($122.80 and $94.59; β=28.21, p<0.0001), and total national psychotherapy expenditures ($10.94 and $7.17 billion; z=2.61, p=0.009). Conclusions: During the decade from 1998 to 2007, the percentage of the general population who used psychotherapy remained stable. Over the same period, however, psychotherapy assumed a less prominent role in outpatient mental health care as a large and increasing proportion of mental health outpatients received psychotropic medication without psychotherapy.
Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion
Authors: John L. Johnson, David Jamil Hadad, Reynaldo Dietze, Ethel Leonor Noia Maciel, Barrett Sewali, Phineas Gitta, Alphonse Okwera, Roy D. Mugerwa, Mary Rose Alcaneses, Maria Imelda Quelapio, Thelma E. Tupasi, Libby Horter, Sara M. Debanne, Kathleen D. Eisenach, W. Henry Boom
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.Objectives: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months.Methods: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment.Measurements and Main Results: Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01–0.10).Conclusion: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.
Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque
Authors: Joshua C Bis, Maryam Kavousi, Nora Franceschini, Aaron Isaacs, Gonçalo R Abecasis, Ulf Schminke, Wendy S Post, Albert V Smith, L Adrienne Cupples, Hugh S Markus, Reinhold Schmidt, Jennifer E Huffman, Terho Lehtimäki, Jens Baumert, Thomas Münzel, Susan R Heckbert, Abbas Dehghan, Kari North, Ben Oostra, Steve Bevan, Eva-Maria Stoegerer, Caroline Hayward, Olli Raitakari, Christa Meisinger, Arne Schillert, Serena Sanna, Henry Völzke, Yu-Ching Cheng, Bolli Thorsson, Caroline S Fox, Kenneth Rice, Fernando Rivadeneira, Vijay Nambi, Eran Halperin, Katja E Petrovic, Leena Peltonen, H Erich Wichmann, Renate B Schnabel, Marcus Dörr, Afshin Parsa, Thor Aspelund, Serkalem Demissie, Sekar Kathiresan, Muredach P Reilly, Kent Taylor, Andre Uitterlinden, David J Couper, Matthias Sitzer, Mika Kähönen, Thomas Illig, Philipp S Wild, Marco Orru, Jan Lüdemann, Alan R Shuldiner, Gudny Eiriksdottir, Charles C White, Jerome I Rotter, Albert Hofman, Jochen Seissler, Tanja Zeller, Gianluca Usala, Florian Ernst, Lenore J Launer, Ralph B D'Agostino, Daniel H O'Leary, Christie Ballantyne, Joachim Thiery, Andreas Ziegler, Edward G Lakatta, Ravi Kumar Chilukoti, Tamara B Harris, Philip A Wolf, Bruce M Psaty, Joseph F Polak, Xia Li, Wolfgang Rathmann, Manuela Uda, Eric Boerwinkle, Norman Klopp, Helena Schmidt, James F Wilson, Jorma Viikari, Wolfgang Koenig, Stefan Blankenberg, Anne B Newman, Jacqueline Witteman, Gerardo Heiss, Cornelia van Duijn, Angelo Scuteri, Georg Homuth, Braxton D Mitchell, Vilmundur Gudnason, Christopher J O'Donnell
Journal: Nature Genetics (2011)
Osteitis and synovitis, but not bone erosion, is associated with proteoglycan loss and microstructure damage in the cartilage of patients with rheumatoid arthritis
Authors: Barbara Herz, Andreas Albrecht, Matthias Englbrecht, Götz H Welsch, Michael Uder, Nina Renner, Philipp Schlechtweg, Dominik Paul, Lars Lauer, Klaus Engelke, Rolf Janka, Jürgen Rech, Georg Schett, Stephanie Finzel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To investigate the relation between anatomic changes of the synovium, the bone, the bone marrow and the cartilage to biochemical properties of the cartilage in patients with rheumatoid arthritis (RA). <h3>Methods</h3> 33 patients with RA received 3-T MRI scans of the metacarpophalangeal joints. Two independent methods, (A) the delayed gadolinium enhanced MRI of the cartilage (dGEMRIC, T2-mapping), which was used to assess the biochemical properties of the cartilage; (B) synovitis, osteitis and bone erosions were quantified according to the RA MRI scoring (RAMRIS) method and cartilage thickness (CT), interbone joint space (IBJS, distance between proximal and distal bone surface) and intercartilage joint space (ICJS, distance between proximal and distal cartilage surface) were measured. <h3>Results</h3> Biochemical changes of the cartilage, corresponding to low dGEMRIC and high T2 values, were more likely to be seen in joints with decreased IBJS and ICJS as well as decreased CT. For instance, dGEMRIC was directly correlated to the IBJS (p=0.001) and ICJS (p=0.001), whereas T2 mapping was inversely correlated to IBJS and ICJS (both p=0.017). Moreover, the degree of osteitis, and to some extent synovitis, was correlated to biochemical cartilage changes as measured by dGEMRIC (p=0.003) or the T2 mapping (p=0.013). By contrast, bone erosions did not correlate to the degree of biochemical cartilage changes. <h3>Discussion</h3> These data support the concept that synovitis and osteitis may be two main triggers for cartilage damage. Thus, the actual inflammatory state of a joint, but not so much the degree of bone erosion, appears to influence cartilage properties in RA.