tbuckley/cabot-search huggingface dataset:
Frequency of Provider Contact After FDA Advisory on Risk of Pediatric Suicidality With SSRIs
Authors: Elaine H. Morrato, Anne M. Libby, Heather D. Orton, Frank V. deGruy, David A. Brent, Richard Allen, Robert J. Valuck
Journal: American Journal of Psychiatry (2007)

Objective: The Food and Drug Administration (FDA) issued a public health advisory in October 2003 on the risk of suicide in pediatric patients taking antidepressants and advised maintaining "close supervision" of such patients. In this study, the authors compared trends in the frequency of provider contacts for patients with depression before and after the advisory was issued. Method: Retrospective cohorts of children (N=27,370) and adults (N=193,151) with new episodes of depression treated with antidepressants were created from a national claims database of managed care plans (1998–2005). Two standards were used in measuring patient monitoring: the Health Plan Employer Data and Information Set (HEDIS) quality-of-care criterion calling for three contacts in 3 months and the FDA-recommended contact schedule totaling seven visits in 3 months. Time-series models compared postadvisory trends to the expected trend based on preadvisory measures. Results: Less than 5% of all patients met FDA contact recommendations before the advisory, and the rate did not change after the advisory. A greater proportion of patients met the HEDIS contact criterion before the advisory (60% for children and 40% for adults), and the rate did not change after the advisory. A greater proportion of pediatric patients seen by a psychiatrist (80%) met the HEDIS criterion than those seen by a pediatrician (60%) or a non-pediatrician primary care physician (54%), and than adults seen by a psychiatrist (65%) or a primary care physician (37%). The proportions of pediatric patients who met the FDA recommendations did not differ by specialty. Conclusions: Contrary to expectations, the frequency of visits by patients with new episodes of depression treated with antidepressants did not increase after the October 2003 FDA advisory was issued.
Evidence of altered structural and secretory glycoconjugates in the jejunal mucosa of patients with gluten sensitive enteropathy and subtotal villous atrophy.
Authors: M Vecchi, G Torgano, R de Franchis, S Tronconi, D Agape, G Ronchi
Journal: Gut (1989)

The pattern of lectin histochemistry in formalin fixed, paraffin embedded normal jejunal and subtotal villous atrophy specimens from patients with gluten sensitive enteropathy were compared. There was no significant difference in the binding pattern of five lectins (Arachis hypogaea, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris and Triticum vulgaris) between normal and abnormal specimens. There were significant changes in the binding pattern of three lectins (Dolichos biflorus, Ulex europaeus, Ricinus communis), with special reference to goblet cells staining. These changes were present in all the specimens studied, regardless of the clinical diagnosis of dermatitis herpetiformis or coeliac disease. Dolichos biflorus reactive goblet cells were significantly decreased (p less than 0.001) in abnormal tissue and confined to the luminal edge of the mucosa. Strong reactivity of goblet cells in abnormal tissue was recorded with Ricinus communis and Ulex europaeus, lectins that bind to few or no goblet cells in normal tissue. These findings show that modifications of structural and secretory glycoconjugates occur in the jejunal mucosa of patients with gluten sensitive enteropathy.
Nephrogenesis Is Induced by Partial Nephrectomy in the Elasmobranch Leucoraja erinacea
Authors: Marlies Elger, Hartmut Hentschel, Jennifer Litteral, Maren Wellner, Torsten Kirsch, Friedrich C. Luft, Hermann Haller
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The mammalian kidney responds to partial nephrectomy with glomerular and tubular hypertrophy, but without renal regeneration. In contrast, renal regeneration in lower vertebrates is known to occur. Understanding the underlying mechanisms of renal regeneration is highly important; however, a serviceable animal model has not been developed. A neonephrogenic zone has been identified in the European lesser spotted dogfish, Scyliorhinus caniculus (Hentschel H. Am J Anat 190: 309–333, 1991), as well as in the spiny dogfish Squalus acanthias and the little skate, Leucoraja erinacea. The zone features the production of new nephrons complete with a countercurrent system. To analyze this nephrogenic region of elasmobranch fish further, a renal reduction model was established. The neonephrogenic zone in the adult kidney of the little skate resembles the embryonic metanephric kidney and contains stem cell-like mesenchymal cells, tips of the branching collecting duct system, and outgrowth of the arterial system. Four stages of nephron development were analyzed by serial sections and defined: stage I, aggregated mesenchymal cells; stage II, S-shaped body-like structure with high-prismatic epithelial cells; stage III, segmental nephron segregation; stage IV, functioning nephron. The stages were analyzed after partial nephrectomy. In addition, cell proliferation was assessed by incorporation of bromo-deoxyuridine (BrdU). New nephrons developed in animals undergoing partial nephrectomy. Growth was greatly stimulated in the nephrogenic zone, both in the remnant tissue and in the contralateral kidney within 10 wk. Mesenchymal cell aggregates increased significantly per renal cross-section compared with controls (stage I, 0.64 ± 0.28 versus 0.27 ± 0.25; P < 0.005; n = 10 animals per group). The same was the case for S-shaped body-like cysts (stage II, 0.24 ± 0.19 versus 0.08 ± 0.09; P < 0.02). Cellular proliferation in the neonephrogenic zone of the contralateral kidney was also greatly enhanced (14.42 ± 3.26 versus 2.64 ± 1.08 BrdU-positive cells per cross-section, P < 0.001). It is concluded that the skate possesses a nephrogenic zone containing stem cell-like mesenchymal cells during its entire life. Partial nephrectomy induces renal growth by accelerating nephrogenesis. This unique model may facilitate understanding renal regeneration. E-mail: [email protected] or [email protected].
Adverse Childhood Experiences and Child Health in Early Adolescence
Authors: Emalee G. Flaherty, Richard Thompson, Howard Dubowitz, Elizabeth M. Harvey, Diana J. English, Laura J. Proctor, Desmond K. Runyan
Journal: JAMA Pediatrics (2013)

Child maltreatment and other adverse childhood experiences, especially when recent and ongoing, affect adolescent health. Efforts to intervene and prevent adverse childhood exposures should begin early in life but continue throughout childhood and adolescence.To examine the relationship between previous adverse childhood experiences and somatic concerns and health problems in early adolescence, as well as the role of the timing of adverse exposures.Prospective analysis of the Longitudinal Studies of Child Abuse and Neglect interview and questionnaire data when target children were 4, 6, 8, 12, and 14 years old.Children with reported or at risk for maltreatment in the South, East, Midwest, Northwest, and Southwest United States Longitudinal Studies of Child Abuse and Neglect sites.A total of 933 children who completed an interview at age 14 years, including health outcomes.Eight categories of adversity (psychological maltreatment, physical abuse, sexual abuse, neglect, caregiver's substance use/alcohol abuse, caregiver's depressive symptoms, caregiver treated violently, and criminal behavior in the household) experienced during the first 6 years of life, the second 6 years of life, the most recent 2 years, and overall adversity.Child health problems including poor health, illness requiring a doctor, somatic concerns, and any health problem at age 14 years.More than 90% of the youth had experienced an adverse childhood event by age 14 years. There was a graded relationship between adverse childhood exposures and any health problem, while 2 and 3 or more adverse exposures were associated with somatic concerns. Recent adversity appeared to uniquely predict poor health, somatic concerns, and any health problem.Childhood adversities, particularly recent adversities, already show an impact on health outcomes by early adolescence. Increased efforts to prevent and mitigate these experiences may improve the health outcome for adolescents and adults.
neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.
Authors: I L Andrulis, S B Bull, M E Blackstein, D Sutherland, C Mak, S Sidlofsky, K P Pritzker, R W Hartwick, W Hanna, L Lickley, R Wilkinson, A Qizilbash, U Ambus, M Lipa, H Weizel, A Katz, M Baida, S Mariz, G Stoik, P Dacamara, D Strongitharm, W Geddie, D McCready
Journal: Journal of Clinical Oncology (1998)

PURPOSE It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified &gt; or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.
Brain Dopamine D <sub>1</sub> Receptors in Twins Discordant for Schizophrenia
Authors: Jussi Hirvonen, Theo G.M. van Erp, Jukka Huttunen, Sargo Aalto, Kjell Någren, Matti Huttunen, Jouko Lönnqvist, Jaakko Kaprio, Tyrone D. Cannon, Jarmo Hietala
Journal: American Journal of Psychiatry (2006)

Objective: It has been suggested that deficits in higher-order cognitive functions serve as intermediate phenotypic indicators of genetic vulnerability to schizophrenia. The dopamine hypothesis of schizophrenia postulates that insufficiency of dopamine transmission in the prefrontal cortex contributes to the cognitive deficits observed in patients with the disease, and there is robust empirical evidence for a central role of prefrontal cortex dopamine D 1 receptors in working memory functions. Method: The authors examined the genetic and nongenetic effects on D 1 receptor binding in schizophrenia by studying monozygotic and dizygotic twin pairs discordant for schizophrenia as well as healthy comparison twins using positron emission tomography (PET) and the D 1 receptor antagonist ligand [ 11 C]SCH 23390. Performance on neuropsychological tests sensitive to frontal lobe functioning was evaluated. Results: High D 1 receptor density in the medial prefrontal cortex, superior temporal gyrus, and heteromodal association cortex (angular gyrus) was associated with increasing genetic risk for schizophrenia (comparison twins < unaffected dizygotic co-twins < unaffected monozygotic co-twins). Medicated schizophrenia patients demonstrated a widespread reduction in D 1 receptor binding when compared with the unaffected co-twin, and higher doses of antipsychotics were associated with lower D 1 receptor binding in the frontotemporal regions. Conclusions: This study demonstrated an association between genetic risk for schizophrenia and alterations in cortical D 1 receptor binding, an observation that has implications for future studies of the molecular genetics of schizophrenia. In addition, the data indicate a widespread reduction of D 1 receptor binding in medicated schizophrenia patients, supporting a link between antipsychotic drug action and dopamine D 1 receptor down-regulation.
Studies on the Coumarin Anticoagulant Drugs: Interaction of Human Plasma Albumin and Warfarin Sodium*
Authors: Robert A. O'Reilly
Journal: Journal of Clinical Investigation (1967)

In studies by continuous flow electrophoresis the coumarin anticoagulant drug warfarin sodium was found to be bound solely to the albumin fraction of the plasma proteins. The interaction was studied in detail by equilibrium dialysis of solutions of crystalline human plasma albumin and warfarin sodium. Analysis of the data showed that albumin possesses a single strong binding site for warfarin with an association constant of 154,000 at 3° C and secondary classes of several sites with a much lower affinity. The free energy of binding for the first anion determined at 3° and 37° C was -6.54 and -7.01 kcal per mole, respectively. The standard enthalpy change for the interaction was -3.48 kcal per mole, and the entropy change was +11.2 U.
Proteomics of the Heart
Authors: Emma McGregor, Michael J. Dunn
Journal: Circulation Research (2006)

Heart diseases resulting in heart failure are among the leading causes of morbidity and mortality in developed countries. Underlying molecular causes of cardiac dysfunction in most heart diseases are still largely unknown but are expected to result from causal alterations in gene and protein expression. Proteomic technology now allows us to examine global alterations in protein expression in the diseased heart and can provide new insights into cellular mechanisms involved in cardiac dysfunction. The majority of proteomic investigations still use 2D gel electrophoresis (2-DE) with immobilized pH gradients to separate the proteins in a sample and combine this with mass spectrometry (MS) technologies to identify proteins. In spite of the development of novel gel-free technologies, 2-DE remains the only technique that can be routinely applied to parallel quantitative expression profiling of large sets of complex protein mixtures such as whole cell lysates. It can resolve >5000 proteins simultaneously (approximately 2000 proteins routinely) and can detect <1 ng of protein per spot. Furthermore, 2-DE delivers a map of intact proteins, which reflects changes in protein expression level, isoforms, or post-translational modifications. The use of proteomics to investigate heart disease should result in the generation of new diagnostic and therapeutic markers. In this article, we review the current status of proteomic technologies, describing the 2-DE proteomics workflow, with an overview of protein identification by MS and how these technologies are being applied to studies of human heart disease.
Atypical lipoma of the lung.
Authors: K Matsuba, T Saito, K Ando, T Shirakusa
Journal: Thorax (1991)

An unusual endobronchial lipoma characterised by pleomorphic, multinucleated giant cells admixed with mature adipose cells developed in a 52 year old woman, arising from the right middle lobe bronchus. Lobectomy was performed and the postoperative course was uneventful.
Synergy between the ectoenzymes CD39 and CD73 contributes to adenosinergic immunosuppression in human malignant gliomas
Authors: Shuo Xu, Qian-Qian Shao, Jin-Tang Sun, Ning Yang, Qi Xie, Dong-Hai Wang, Qi-Bing Huang, Bin Huang, Xin-Yu Wang, Xin-Gang Li, Xun Qu
Journal: Neuro-Oncology (2013)

The importance of ectoenzymes CD39 and CD73 in mediating adenosinergic immunosuppression has been recognized, but their roles in human malignant glioma–associated immunosuppression remain largely unknown. In this study, the ectoenzyme characteristics of malignant glioma cells and infiltrating CD4+ T lymphocytes isolated from newly diagnosed malignant glioma patients were investigated. The ectoenzyme activities of both cell populations were determined by nucleotide hydrolysis assay. The immunosuppressive property of the CD39-CD73 synergic effect was evaluated via responder T-cell proliferation assay. We observed that CD39−CD73+ glioma cells and infiltrating CD4+CD39highCD73low T lymphocytes exhibited 2 distinct but complementary ectoenzyme phenotypes, which were further verified by enzyme activity assay. The nucleotide hydrolysis cascade was incomplete unless CD39 derived from T lymphocytes and CD73 collaborated synergistically. We demonstrated that increased suppression of responder CD4+ T-cell proliferation suppression was induced by CD4+CD39+ T cells in the presence of CD73+ glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. In addition, survival analysis suggested that CD73 downregulation was a positive prognostic factor related to the extended disease-free survival of glioblastoma patients. Our data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4+CD39+ T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.
A COMPARATIVE TRIAL OF ECT AND TOFRĀNIL
Authors: E. M. BRUCE, N. CRONE, G. FITZPATRICK, S. J. FREWIN, A. GILLIS, C. F. LASCELLES, L. J. LEVENE, H. MERSKEY
Journal: American Journal of Psychiatry (1960)

The proportion of patients who improved during the first month of treatment was higher in the group given ECT but over 60% of those given Tofrānil showed a good response in that time, perhaps justifying the view that Tofrānil may often serve as a substitute for ECT.
Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Authors: Charles E. Geyer, John Forster, Deborah Lindquist, Stephen Chan, C. Gilles Romieu, Tadeusz Pienkowski, Agnieszka Jagiello-Gruszfeld, John Crown, Arlene Chan, Bella Kaufman, Dimosthenis Skarlos, Mario Campone, Neville Davidson, Mark Berger, Cristina Oliva, Stephen D. Rubin, Steven Stein, David Cameron
Journal: New England Journal of Medicine (2006)

Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2, also referred to as HER2/neu) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy. In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients.Women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab were randomly assigned to receive either combination therapy (lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle) or monotherapy (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle). The primary end point was time to progression, based on an evaluation by independent reviewers under blinded conditions.The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events.Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572 [ClinicalTrials.gov].).
Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification, and sustained expression of an exogenous gene in vivo.
Authors: M Kitamura, S Taylor, R Unwin, S Burton, F Shimizu, L G Fine
Journal: Journal of Clinical Investigation (1994)

To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.
Reversibility of airways obstruction in bronchiectasis.
Authors: S G Nogrady, W V Evans, B H Davies
Journal: Thorax (1978)

Patients with airways obstruction and bronchiectasis were investigated for features of allergic disease and for reversibility of airways obstruction in respinse to inhaled and intravenous salbutamol. There was a 26% increase in PEFR and a 16% increase in FEV1 after inhaled salbutamol, and the response to the intravenous drug was not significantly better than that to the inhaled. Those patients who responded to bronchodilators could not be identified by clinical or immunological features.