tbuckley/cabot-search huggingface dataset:
Amygdala and Nucleus Accumbens Activation to Emotional Facial Expressions in Children and Adolescents at Risk for Major Depression
Authors: Christopher S Monk, Rachel G Klein, Eva H Telzer, Elizabeth A Schroth, Salvatore Mannuzza, John L Moulton, Mary Guardino, Carrie L Masten, Erin B McClure-Tone, Stephen Fromm, R James Blair, Daniel S Pine, Monique Ernst
Journal: American Journal of Psychiatry (2007)

Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions.Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconstrained (passive viewing) and constrained (rate nose width on face, rate subjective fear while viewing face).When attention was unconstrained, high-risk subjects showed greater amygdala and nucleus accumbens activation to fearful faces and lower nucleus accumbens activation to happy faces (small volume corrected for the amygdala and nucleus accumbens). No group differences emerged in amygdala or nucleus accumbens activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than in the low-risk group.Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression. Constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for major depression.
Physician-Assisted Suicide
Authors: Lois Snyder, Daniel P. Sulmasy
Journal: Annals of Internal Medicine (2001)

Medical professional codes have long prohibited physician involvement in assisting a patient's suicide. However, despite ethical and legal prohibitions, calls for the liberalization of this ban have grown in recent years. The medical profession should articulate its views on the arguments for and against changes in public policy and decide whether changes are prudent. In addressing such a contentious issue, physicians, policymakers, and society must fully consider the needs of patients, the vulnerability of particular patient groups, issues of trust and professionalism, and the complexities of end-of-life health care. Physician-assisted suicide is prominent among the issues that define our professional norms and codes of ethics. The American College of Physicians-American Society of Internal Medicine (ACP-ASIM) does not support the legalization of physician-assisted suicide. The routine practice of physician-assisted suicide raises serious ethical and other concerns. Legalization would undermine the patient-physician relationship and the trust necessary to sustain it; alter the medical profession's role in society; and endanger the value our society places on life, especially on the lives of disabled, incompetent, and vulnerable individuals. The ACP-ASIM remains thoroughly committed to improving care for patients at the end of life.
Sex-Dependent Attenuation of Plaque Growth After Treatment With Bone Marrow Mononuclear Cells
Authors: Wendy D. Nelson, Andrey G. Zenovich, Harald C. Ott, Craig Stolen, Gabriel J. Caron, Angela Panoskaltsis-Mortari, Samuel A. Barnes, Xiangrong Xin, Doris A. Taylor
Journal: Circulation Research (2007)

There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE(-/-)) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE(-/-) mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE(-/-) recipients significantly decreased plaque formation (P<0.001). This reparative response univariately correlated with increased CD34(+) (P=0.02), CD45(+) (P=0.0001), and AC133(+)/CD34(+) (P=0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31(+)/CD45(low) cells. In a multivariate analysis, BM-AC133(+)/CD34(+) and BM-CD45(+) percentage counts correlated with a lower plaque burden (P<0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation (r=-0.86, P=0.0004). In untreated apoE(-/-) mice of either sex, BM-AC133(+)/CD34(+) cells rose initially and then fell as plaque accumulated; however, BM-AC133(+)/CD34(+) percentages were higher in females at all times (P<or=0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE(-/-) mice; this reparative response correlated with the upregulation of BM-AC133(+)/CD34(+) and CD45(+) cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE(-/-) mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted.
Imaging Tumors with an Albumin-Binding Fab, a Novel Tumor-Targeting Agent
Authors: Mark S. Dennis, Hongkui Jin, Debra Dugger, Renhui Yang, Leanne McFarland, Annie Ogasawara, Simon Williams, Mary J. Cole, Sarajane Ross, Ralph Schwall
Journal: Cancer Research (2007)

Association with albumin as a means to improve biodistribution and tumor deposition of a Fab was investigated using AB.Fab4D5, a bifunctional molecule derived from trastuzumab (HERCEPTIN) capable of binding albumin and tumor antigen HER2 (erbB2) simultaneously. AB.Fab4D5 was compared with trastuzumab and a trastuzumab-derived Fab (Fab4D5) for the ability to target tumors overexpressing HER2 in mouse mammary tumor virus/HER2 allograft models. Biodistribution was monitored using intravital microscopy, histology, and integrated single-photon emission computed tomography/computed tomography analysis. Fab4D5 tumor deposition was characterized by rapid but transient appearance in tumor at 2 h with little retention, followed by rapid accumulation in kidney by 6 h. Trastuzumab was slow to accumulate in tumors and slow to clear from normal tissues, although significant tumor deposition was achieved by 24 h. In contrast, AB.Fab4D5 was observed at 2 h in tumor and its presence was sustained beyond 24 h similar to trastuzumab. Intravital microscopy revealed that at peak tumor accumulation, tumor cell staining by AB.Fab4D5 was more uniform than for Fab4D5 or trastuzumab. Similar tumor deposition was achieved for both AB.Fab4D5 and trastuzumab at 48 h (35.9 +/- 1.8% and 38.2 +/- 3.1% injected dose/g); however, AB.Fab4D5 targeted tumors more rapidly and quickly cleared from blood, leading to a lower overall normal tissue exposure. Importantly, unlike Fab4D5, AB.Fab4D5 did not accumulate in kidney, suggesting that association with albumin leads to an altered route of clearance and metabolism. Rapid targeting, excellent tumor deposition and retention, coupled with high tumor to blood ratios may make AB.Fab an exceptional molecule for imaging and cancer therapy.
Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group
Authors: J Avouac, J Fransen, UA Walker, V Riccieri, V Smith, C Muller, I Miniati, IH Tarner, S Bellando Randone, M Cutolo, Y Allanore, O Distler, G Valentini, L Czirjak, U Müller-Ladner, DE Furst, A Tyndall, M Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2010)

Objective To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc). Methods A list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores. Results Physicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting. Conclusion The three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.
Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA2LEN taskforce position paper
Authors: I. Baiardini, F. Braido, C. Bindslev-Jensen, P. J. Bousquet, Z. Brzoza, G. W. Canonica, E. Compalati, A. Fiocchi, W. Fokkens, R. Gerth van Wijk, A. Giménez-Arnau, K. Godse, C. Grattan, J. J. Grob, S. La Grutta, D. Kalogeromitros, E. Kocatürk, C. Lombardi, A. Mota-Pinto, E. Ridolo, S. S. Saini, M. Sanchez-Borges, G. E. Senna, I. Terreehorst, A. Todo Bom, E. Toubi, J. Bousquet, T. Zuberbier, M. Maurer
Journal: Allergy (2011)

To cite this article: Baiardini I, Braido F, Bindslev-Jensen C, Bousquet PJ, Brzoza Z, Canonica GW, Compalati E, Fiocchi A, Fokkens W, Gerth van Wijk R, Giménez-Arnau A, Godse K, Grattan C, Grob JJ, La Grutta S, Kalogeromitros D, Kocatürk E, Lombardi C, Mota-Pinto A, Ridolo E, Saini SS, Sanchez-Borges M, Senna GE, Terreehorst I, Todo Bom A, Toubi E, Bousquet J, Zuberbier T, Maurer M. Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA2LEN taskforce position paper. Allergy 2011; 66: 840–844. Abstract The aim of this Global Allergy and Asthma European Network (GA2LEN) consensus report is to provide recommendations and suggestions for assessing patient-reported outcomes (PROs) including health-related quality of life in patients with urticaria. We recommend that PROs should be used both in clinical trials and routine practice for the evaluation of urticaria patients. We suggest that PROs should be considered as the primary outcome of future clinical trials. Two validated and disease-specific instruments for assessing PROs are available, the urticaria activity score (for symptoms) and the chronic urticaria questionnaire on quality of life CU-Q2oL. This latter tool, CU-Q2oL, is available in many languages and should be preferred, where available, over more generic instruments for assessing urticaria-specific effects on quality of life. CU-Q2oL is only suited for the investigation of patients with chronic spontaneous urticaria. Similar instruments for other forms of urticaria have yet to be developed and validated. Also, tools for assessing other chronic spontaneous urticaria PROs besides quality of life and symptoms are needed.
Activation of Pro-Apoptotic Cascade by Dopamine in Renal Epithelial Cells is Fully Dependent on Hydrogen Peroxide Generation by Monoamine Oxidases
Authors: Pascale Bianchi, Marie-Hélène Séguélas, Angelo Parini, Claudie Cambon
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Dopamine plays a critical role in regulation of different renal functions, including glomerular filtration, renin secretion, and sodium excretion. Recent studies have shown that some of the dopamine effects in the proximal tubule may involve hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) generation by the catecholamine-degrading enzyme monoamine oxidases (MAO). The present study is an investigation of the potential role of H<sub>2</sub>O<sub>2</sub> generated by MAO during dopamine degradation in apoptosis of proximal tubule cells. Dopamine concentrations between 50 and 200 μM induced apoptosis of rat proximal tubule and monoamine oxidase B-transfected HEK 293 cells (+73% compared with untreated cells) but not in wild-type HEK 293 cell lacking monoamine oxidases. Apoptosis of proximal tubule cells was preceded by an increase in the ratio of Bax/Bcl2 proteins, the release of mitochondrial cytochrome c, caspase-3 activation, and DNA fragmentation. All these events required dopamine internalization into the cells, its metabolism by MAO, and H<sub>2</sub>O<sub>2</sub> production, as they were prevented by the dopamine uptake inhibitor GBR-12909, the irreversible MAO inhibitor pargyline, or the antioxidant N-acetylcysteine. These results show that, in renal proximal tubule cells, dopamine induces oxidative stress, activation of pro-apoptotic cascade, and cell apoptosis exclusively by mechanisms involving H<sub>2</sub>O<sub>2</sub> production by monoamine oxidases. E-mail: parini@toulouse.inserm.fr
A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina
Authors: Cindy L Grines, Matthew W Watkins, John J Mahmarian, Ami E Iskandrian, Jeffrey J Rade, Pran Marrott, Craig Pratt, Neal Kleiman
Journal: Journal of the American College of Cardiology (2003)
After the Dust Settles
Authors: Samuel Vaisrub
Journal: JAMA (1977)

Current revelations about millions of unnecessary operations and thousands of resulting deaths must make a surgeon wonder whether he is, in fact, a member of a secret terrorist group. Suspicious glances from patients, sometimes even from members of his own family, must generate self-doubt. Did he perhaps bypass the rigid surveillance of the tissue committee or peer review board to wield the scalpel wantonly? Was it necessary to remove Mrs X's gallbladder only because she had recurrent gallstone colic? Could not Mr Y have done without a hemorrhoidectomy? Did Ms Z really need plastic repair for her Cyranoesque nose? After all, people got along with these miseries, however painfully and precariously, before the age of modern surgery. Would it not be safer to palliate rather than operate? Why invite suspicions and angry accusations?  The storm of the Report on Unnecessary Surgery by the Subcommittee on Oversight and Investigation is still
Total Marrow Irradiation: A New Ablative Regimen as Part of Tandem Autologous Stem Cell Transplantation for Patients with Multiple Myeloma
Authors: George Somlo, Ricardo Spielberger, Paul Frankel, Chatchada Karanes, Amrita Krishnan, Pablo Parker, Leslie Popplewell, Firoozeh Sahebi, Neil Kogut, David Snyder, An Liu, Timothy Schultheiss, Stephen Forman, Jeffrey Y. C. Wong
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To establish feasibility, maximum tolerated dose (MTD), and potential efficacy of ablative dose total marrow irradiation (TMI) delivered by helical tomotherapy in patients with multiple myeloma (MM). Experimental Design: Patients with responding or stable MM received tandem autologous stem cell transplants, first with melphalan 200 mg/m2, and 60 days or later with TMI. TMI doses were to be escalated from 1,000 cGy by increments of 200 cGy. All patients received thalidomide and dexamethasone maintenance. Results: Twenty-two of 25 enrolled patients (79%) received tandem autologous stem cell transplantation (TASCT): TMI was administered at a median of 63.5 days (44–119) after melphalan. Dose-limiting toxicities at level 5 (1,800 cGy) included reversible grade 3 pneumonitis, congestive heart failure, and enteritis (1), and grade 3 hypotension (1). The estimated median radiation dose to normal organs was 11% to 81% of the prescribed marrow dose. Late toxicities included reversible enteritis (1), and lower extremity deep venous thrombosis during maintenance therapy (2). The complete and very good partial response rates were 55% and 27% following TASCT and maintenance therapy. At a median of 35 months of follow-up (21–50+ months), progression-free and overall survival for all patients were 49% (95% CI, 0.27–0.71) and 82% (0.67–1.00). Conclusion: Ablative dose TMI as part of TASCT is feasible, and the complete response rate is encouraging. Careful monitoring of late toxicities is needed. Further assessment of this modality is justified at the 1,600 cGy MTD level in MM patients who are candidates for ASCT. Clin Cancer Res; 17(1); 174–82. ©2010 AACR.
T-cell lymphoma: the real thing
Authors: P G ISAACSON
Journal: Gut (1999)

See article on page 662 

It is altogether appropriate that the gut should possess efficient immunological defences given the interface between its antigen-rich contents and the permeable mucosa. More than that, however, the gut is an important immunological organ in its own right. In this respect, the gut mucosa contains more lymphocytes than all other organs of the immune system combined. It is estimated that in humans a metre of intestine contains 1010 lymphocytes, which is almost equivalent to the number contained in the spleen.1 In the light of this quantitative difference and the fact that intestinal lymphoid tissues are subject to constant immunostimulation, it might be expected that a larger proportion of lymphomas would arise from the intestine than the peripheral lymphoid system but, curiously, the contrary is true. Although the gastrointestinal tract is the commonest site of extra-nodal lymphoma in Western countries, only 10% of lymphomas overall arise there.2 There are, however, significant differences in the types of lymphoma that arise in the gut compared with the peripheral lymphoid tissues. Thus, both Hodgkin’s disease and …
Estimating Pediatric Glomerular Filtration Rates in the Era of Chronic Kidney Disease Staging
Authors: Andre Mattman, Shaun Eintracht, Thomas Mock, Geraldine Schick, David W. Seccombe, Robert Morrison Hurley, Colin Thomas White
Journal: Journal of the American Society of Nephrology (2005)

With the use of information from a database of pediatric patients with concomitant nuclear GFR and serum creatinine (Cr), estimated GFR equations were derived on the basis of local laboratory methods and population. These formulas then were compared with those recommended by the National Kidney Foundation for estimating GFR in children. For this, their ability to estimate accurately an individual's true GFR and chronic kidney disease stage, identify patients whose true GFR was <60 ml/min per 1.73 m(2), and to identify correctly deterioration in an individual's GFR over time was compared. Next, two methods to estimate GFR in children without the use of height or weight were developed. The first was a height- and weight-independent formula; the second was a novel approach using the Schwartz formula and calculating a Cr cutoff based on age-based estimates of height and GFR level of interest, i.e., <60 ml/min per 1.73 m(2). Our results suggest that if local laboratory constants are derived and a height is known, then the Schwartz formula offers the most accuracy with least mathematical complexity to perform in the clinical setting. If height is not available but the local laboratory constants have been derived, then the British Columbia's Children's Hospital 2 formula is of value; however, in the setting of estimating pediatric renal function in the outpatient laboratory, where neither of these factors is commonly known, an approach whereby a Cr cutoff for a GFR of interest is developed is suggested. Provided are Cr levels that are based on a reference method of Cr measurement to facilitate this approach for the clinician.
Intracellular Ca <sup>2+</sup> , Intercellular Electrical Coupling, and Mechanical Activity in Ischemic Rabbit Papillary Muscle
Authors: Lukas R.C. Dekker, Jan W.T. Fiolet, Ed VanBavel, Ruben Coronel, Tobias Opthof, Jos A.E. Spaan, Michiel J. Janse
Journal: Circulation Research (1996)

During myocardial ischemia, electrical uncoupling and contracture herald irreversible damage. In the present study, we tested the hypothesis that an increase of intracellular Ca 2+ is an important factor initiating these events. Therefore, we simultaneously determined tissue resistance, mechanical activity, pH o , and intracellular Ca 2+ (with the fluorescent indicator indo 1, Molecular Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia. In a fourth experimental group, intracellular Ca 2+ was increased under nonischemic conditions by perfusing with 0.1 mmol/L ionomycin and 0.1 μmol/L gramicidin. Ca 2+ transients and contractions rapidly disappeared after the induction of ischemia. In the control group, diastolic Ca 2+ began to rise after 12.6±1.3 minutes of ischemia; uncoupling, after 14.5±1.2 minutes of ischemia; and contracture, after 12.6±1.5 minutes of ischemia (mean±SEM). Preconditioning significantly postponed Ca 2+ rise, uncoupling, and contracture (21.5±4.0, 24.0±4.1, and 23.0±5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate significantly advanced these events (1.9±0.7, 3.6±0.9, and 1.9±0.2 minutes of ischemia, respectively). In all groups, the onset of uncoupling always followed the start of Ca 2+ rise, whereas the start of contracture was not different from the rise in Ca 2+ . Perfusion with ionomycin and gramicidin permitted estimation of a threshold [Ca 2+ ] for electrical uncoupling of 685±85 nmol/L. In conclusion, the rise in intracellular Ca 2+ is the main trigger for cellular uncoupling during ischemia. Contracture is closely associated with the increase of intracellular Ca 2+ during ischemia.
Dentition, Diet, Tobacco, and Alcohol in the Epidemiology of Oral Cancer 2
Authors: Saxon Graham, Hari Dayal, Thomas Rohrer, Mya Swanson, Harry Sultz, Donald Shedd, Stuart Fischman
Journal: JNCI Journal of the National Cancer Institute (1977)

Interview and dental examination data were gathered on 584 males with cancer of the oral cavity and on 1,222 control patients with nonneoplastic diseases at Roswell Park Memorial Institute, Buffalo, New York. No dietary characteristics distinguished cancer patients from controls. However, a higher risk of developing oral cancer was associated with heavy smoking, heavy drinking, and poor dentition. When controlled for the other factors, each factor carried a higher risk. Moreover, heavy smokers and heavy drinkers with poor dentition and males with all three traits had a substantially higher risk than would have been expected, if the traits were considered additively. The risk for males with all three traits was 7.7 times that of men with none of these traits.