tbuckley/cabot-search huggingface dataset:
Past trauma and present functioning of patients attending a women's psychiatric clinic
Authors: E F Borins, P J Forsythe
Journal: American Journal of Psychiatry (1985)

A women's psychiatric clinic, incorporated within a university teaching general hospital and staffed entirely by women, was opened in March of 1980. The authors studied a sample of 100 women who came to the clinic and characterized them by demographic variables, psychiatric diagnoses, health problems, chronic illness, death in the family, and traumatic incidents. Death in the family before she was 18 was found to predict a woman's subsequent request for or completion of sterilization. Physical or sexual abuse was significantly related to abortion, and abortion and trauma were significantly correlated.Data were collected from the intake forms completed by 100 patients of a women's psychiatric clinic in order to characterize them by demographic variables, psychiatric diagnoses, health problems, chronic illness, death in the family, and traumatic incidents. Having postulated that the sample could be divided into specific groups according to the history of trauma, history of deaths in the family, and chronic illness in the patient and her family, an attempt was made to discover any relationship between such histories and the patient's current health problems. The existence of specific and different health issues and implications for the trauma group, the death group, and the chronic illness group was postulated. The only demographic characteristic that was significantly correlated with other variables was education. Women having no more than high school education were more likely to have experienced physical or sexual abuse than were those having postsecondary education. Members of the former group also were significantly more likely to have had an abortion. There was no statistically significant relationship between education level and other health or trauma variables. 49% of the sample had experienced the death of a family member. Of these, 25% had experienced at least 1 of these deaths before age 18. There was a small but significant correlation between death in the family and a personal history of chronic illness and 3 or more gynecological problems. There was a small statistical correlation between death in the family and a diagnosis of neurotic or adjustment disorder and finding of a high stress level. There was no statistical correlation between death in the family and abortion, there was a highly significant correlation between death in the family and request for or completion of sterilization. When the factor of physical and/or sexual abuse was examined separately, there was a significant correlation with abortion and a somewhat weaker correlation with sterilization. Abortion correlated very significant with 3 or more trauma factors; sterilization correlated also but at a less significant level than abortion.
Significance of FcγRIIIa-V158F Polymorphism—Letter
Authors: Janardan P. Pandey
Journal: Clinical Cancer Research (2016)

Cartron and colleagues in their commentary (CCR Translations) present an informative discussion of several putative host and tumor factors that may explain the conflicting reports of correlation between FcγRIIIa-V158F polymorphism and response to rituximab and other mAbs (1). To their list of possible variables influencing the outcome of mAb therapy, I would like to add the extensive genetic polymorphism in the Fc region of IgG. Most presentations on this topic have treated the constant region of human IgG as if it were naturally monomorphic. The constant region of IgG heavy chains is highly polymorphic with at least 18 testable specificities, γ marker (GM) allotypes, segregating at differing frequencies in different population groups (2).There are several mechanisms through which GM polymorphisms could contribute to the efficacy of mAbs. For instance, mAbs expressing different GM allotypes in the Fc region bind differentially to the neonatal Fc receptor (FcRn), thereby influencing the half-lives of infused mAbs (3). An mAb expressing the GM 1,3 haplotype has higher affinity to FcRn, and is transcytosed better, than the commercial mAbs expressing other allotypic combinations, including rituximab, which expresses GM 1,17 allotypes (3). Antibodies to GM allotypes could also contribute to the de novo and acquired resistance to mAb therapy. Most GM determinants are highly immunogenic. Thus, anti-allotype antibodies, generated through infusion of mAbs, allotype-incompatible blood transfusion, or preexisting because of maternal-fetal incompatibility, could reduce the effectiveness of infused mAbs. Through their epistatic interactions with the FcγRIIIa alleles expressed on natural killer cells, GM allotypes have been shown to contribute to the magnitude of antibody-dependent cellular cytotoxicity (ADCC), a leading mechanism underlying the clinical efficacy of mAb therapy (4, 5).There is another factor that could contribute to the inconsistent correlation between FcγRIIa-V158F polymorphism and the efficacy of mAb therapy. In addition to killing the tumor cells by engaging the Fc-mediated effector mechanisms, infused mAb “immunizes” the patients via the antigen-processing/presenting pathway and thus augments the endogenous antibody responses to the tumor antigen complexed with the mAb. These endogenous antibodies will express the patient's Fc (GM) genotype, whose affinity to the FcγR alleles might be different from that of the infused mAb, resulting in differences in the magnitude of ADCC and in the efficacy of mAb therapy.These mechanisms suggest that in the construction of mAbs and in the evaluation of their clinical efficacy, natural genetic variability in both FcγR and Fc (GM) should be taken into consideration.No potential conflicts of interest were disclosed.
A Family Reunion
Authors: Robert M. Bird, James F. Hammarsten, Richard A. Marshall, R. R. Robinson, Esther Beckner
Journal: New England Journal of Medicine (1957)

AN abundant literature exists concerning hereditary telangiectasia. The early descriptions were by Sutton (1864), Legg (1876), Rendou (1896), Osler (1901) and Weber (1907). The usual eponym associated with the disease includes the last three writers. Most of the articles in the literature concern case reports of only a few individuals in relatively small families.The present study of a large kindred having hereditary hemorrhagic telangiectasia was stimulated by a sixty-year-old man seen repeatedly in the Hospital and Clinics of the University of Oklahoma for recurrent bleeding episodes. He invited us to his annual family reunion, where approximately 200 kinsmen extended . . .
SURG-16PROGNOSTIC VALUE OF THE EXTENT OF RESECTION AND IDH1 MUTATION STATUS IN WHO GRADE II ASTROCYTOMAS
Authors: Christine Jungk, Moritz Scherer, Andreas Mock, David Capper, Alexander Radbruch, Andreas von Deimling, Christel Herold-Mende, Andreas Unterberg
Journal: Neuro-Oncology (2015)

INTRODUCTION: Current evidence supports a maximized extent of resection (EOR) in low-grade gliomas (LGG). However, conclusions were drawn in negligence of different histologic subtypes, underrating the fact that histology and molecular markers, like IDH1, per se confer divergent outcomes. We therefore evaluated the prognostic impact of extensive surgery in pure astrocytic LGGs stratified for IDH1. METHODS: From a consecutive series of 179 LGGs treated since 2004, we analyzed 46 pure astrocytomas with open tumor resection at 1st diagnosis. IDH1 mutation status was available for all patients. Pre-, early postoperative and follow-up tumor volumes were obtained from FLAIR images. Subgroup analysis for EOR ≥40% (n = 39) was performed. Analysis for overall (OS), progression-free (PFS), malignant progression-free survival (MPFS) and time to re-intervention (TTR) was conducted with uni- (uv) and multivariate (mv) regression models. RESULTS: A median final EOR of 90.4% (range 17.5 - 100%) was achieved at follow-up MRI, leaving a median residual tumor volume of 4.09cm3. EOR did not impact on OS but was significantly associated with PFS (HR 0.23; p = 0.04; uv) and TTR (HR = 0.23; p = 0.04; uv). IDH1 was the only independent prognosticator for OS (HR 0.04; p = 0.002; mv). After stratification for EOR ≥40%, initial and residual tumor volumes were both predictive of OS (HR >1, p < 0.01 and p < 0.05, respectively, uv), even after adjustment for IDH1. Significant associations of residual tumor with survival endpoints were exclusively found on follow-up but not on early postoperative MRI. CONCLUSION: After stratification for histology and IDH1, greater EOR delayed tumor progression and time to re-intervention. IDH1 was the strongest predictor of OS, potentially obscuring benefits of surgery. Our approach illustrates the diverse impact of biological and surgical factors upon outcome and highlights critical differences in prognostic value between early and late postoperative imaging. The need to strive for maximized resections in low-grade astrocytomas is underscored.
Abstract 311: Inhibition Of Matrix Metalloproteinase-13 Dependent Protease-activated Receptor-1 Activation Attenuates Fibrotic Signaling
Authors: Allison E Dixon, Fabrice Jaffre, Nigel Mackman, Burns C Blaxall
Journal: Circulation Research (2014)

Heart failure (HF) is the leading cause of morbidity and mortality in the United States and is characterized by progressive myocardial fibrosis, pathologic remodeling and deteriorating cardiac function. Cardiac fibroblasts (CF) are largely responsible for the secretion of ECM proteins as well as cytokines and growth factors in the heart. Upon injury or pathologic stimulation, CF transition to a myofibroblast phenotype, leading to excess production of ECM proteins and pro-inflammatory cytokines. Previous studies in our lab have indicated a role for protease-activated receptor-1 (PAR-1), the most highly expressed GPCR on CF, in pathologic cardiac remodeling. In particular, we reported the novel cleavage of PAR-1 via matrix metalloproteinase-13 (MMP-13) and cardioprotective effects of MMP-13 inhibition in an acute model of HF. Therefore, we hypothesize that MMP-13 plays an important role in cardiac remodeling through activation of PAR-1, particularly in the pathologic transition of CF to myofibroblasts. To investigate this hypothesis, RNA was collected from hearts of mice infused with isoproterenol (ISO) for 7 days and concurrently treated with a specific MMP-13 inhibitor, WAY170523, or vehicle. To evaluate the effect of WAY170523, we used qRT-PCR to measure changes in the expression of fibrotic markers, COL1a1, COL3a1, and TGF-β. Inhibition of MMP-13 with WAY170523 attenuated expression of these genes compared to vehicle treated animals. We previously reported that stimulation of CF and cardiomyocytes with MMP-13 induces phosphorylation of ERK1/2, a member of the MAPK family known to play a role in cardiac hypertrophy, and treatment with a direct PAR-1 antagonist decreased the activation of ERK1/2. We have found that ERK1/2 phosphorylation is directly attenuated following inhibition of MMP-13 with WAY170523. Overall, these data suggest a role for MMP-13 dependent PAR-1 activation in pathologic myofibroblast transition and a potential therapeutic role for MMP-13 inhibition, possibly through its inhibition of ERK1/2 phosphorylation. Treatment with WAY170523 also attenuates markers of fibrosis in vivo, indicating a potential salutary role for MMP-13 inhibition in the treatment of HF.
Skin Lesions in Melanoma and Kaposi’s Sarcoma
Authors: Farid Fata, Ayoub Mirza, Albert Bernath
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.5.1415 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11870189 Skin Lesions in Melanoma and Kaposi’s Sarcoma Case 3. Familial Classic Mediterranean Kaposi's Sarcoma Farid FataxFarid FataSearch for articles by this author , Ayoub MirzaxAyoub MirzaSearch for articles by this author , Albert BernathxAlbert BernathSearch for articles by this author Show More Geisinger Medical Center, Danville, PA https://doi.org/10.1200/JCO.2002.20.5.1415 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Demonstration of Effective Antitumor Immunity in an Autochthonous Host Bearing Primary Colon Tumors Induced by 1,2-Dimethylhydrazine Dihydrochloride&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: B R Bansal, R Mark, J Mobini, J E Rhoads, S C Bansal
Journal: JNCI Journal of the National Cancer Institute (1979)

The role of host defense mechanisms in preventing the development of subclinical tumors into invasive tumors in an autochithonous host was studied in a model of rat colon carcinoma induced by 1,2-dimethylhydrazine dihydrochloride (DMH). Multiple gastrointestinal (GI) tumors were induced in inbred WF female rats exposed to DMH. In vitro and in vivo data suggested that the excision of the "first" GI tumor induced specific antitumor immune responses. After a complete excision of the first GI tumor, only 2 additional GI tumors were observed in 10 rats, whereas 13 and 12 additional GI tumors in 10 and 9 rats, respectively, were observed if the first GI tumor was left in situ or permitted to grow in an isolated segment of the colon. Furthermore, immunosuppression with antithymocyte globulin decreased the effectiveness of antitumor immunity induced by the immunizing first GI tumor. These experiments supported the view that an effective antitumor immunity is induced against successive tumors of an organ after a complete excision of a tumor originating in the same organ. The results of these experiments are discussed in relation to the observations of multiple primary neoplasms in humans.
Data on diabetes care should be used to identify poorly performing CCGs, say MPs
Authors: Susan Mayor
Journal: BMJ (2016)

By April 2016 information gathered from GPs in England on how they care for patients with diabetes should be used to identify clinical commissioning groups (CCGs) that are performing below the national average, an MPs’ report has recommended.1

The House of Commons Public Accounts Committee, which scrutinises public spending, has called for “significant action” to reduce variations in diabetes care and outcomes in across the country.

Since its last report on diabetes in 2012 the committee noted some progress in improving outcomes for people with diabetes. But significant variations exist in the routine care and support patients receive, and the number of patients with complications …
Mitigating Meal-Related Glycemic Excursions in an Insulin-Sparing Manner During Closed-Loop Insulin Delivery: The Beneficial Effects of Adjunctive Pramlintide and Liraglutide
Authors: Jennifer L. Sherr, Neha S. Patel, Camille I. Michaud, Miladys M. Palau-Collazo, Michelle A. Van Name, William V. Tamborlane, Eda Cengiz, Lori R. Carria, Eileen M. Tichy, Stuart A. Weinzimer
Journal: Diabetes Care (2016)

OBJECTIVE Closed-loop (CL) insulin delivery effectively maintains glucose overnight but struggles when challenged with meals. Use of single-day, 30-μg/meal pramlintide lowers meal excursions during CL. We sought to further elucidate the potential benefits of adjunctive agents after 3–4 weeks of outpatient dose titration. RESEARCH DESIGN AND METHODS Two CL studies were conducted: one evaluating adjunctive pramlintide and the other liraglutide. Ten subjects (age 16–23 years; A1C 7.2 ± 0.6% [55 ± 6.6 mmol/mol]) completed two 24-h sessions: one on CL alone and one on CL plus 60-μg pramlintide (CL + P), after a 3–4-week outpatient dose escalation. Eleven subjects (age 18–27 years; A1C 7.5 ± 0.9% [58 ± 9.8 mmol/mol]) were studied before and after treatment with 1.8 mg liraglutide (CL + L) after a similar 3–4-week dose escalation period. Timing and content of meals during CL were identical within experiments; meals were not announced. RESULTS Pramlintide delayed the time to peak plasma glucose (PG) excursion (CL 1.6 ± 0.5 h vs. CL + P 2.6 ± 0.9 h, P &amp;lt; 0.001) with concomitant blunting of peak postprandial increments in PG (P &amp;lt; 0.0001) and reductions in postmeal incremental PG area under the curve (AUC) (P = 0.0002). CL + L also led to reductions in PG excursions (P = 0.05) and incremental PG AUC (P = 0.004), with a 28% reduction in prandial insulin delivery. Outpatient liraglutide therapy led to a weight loss of 3.2 ± 1.8 kg, with a 26% reduction in total daily insulin dose. CONCLUSIONS Adjunctive pramlintide and liraglutide treatment mitigated postprandial hyperglycemia during CL control; liraglutide demonstrated the additional benefit of weight loss in an insulin-sparing manner. Further investigations of these and other adjunctive agents in long-term outpatient CL studies are needed.
John Evans (1814–1897)
Authors: Frank A. Traylor, David H. Watkins
Journal: New England Journal of Medicine (1963)

IT is said of the young John Evans that he intended during his lifetime to build a city, found a college, govern one of the states of the union, go to the United States Senate, amass a fortune and achieve great fame. Much of this, and more, this extraordinary man accomplished in the course of his career.He was born on March 9, 1814, on a farm in Ohio, of strict Quaker parents. Despite his father's strong desire for him to manage the family store John enrolled in Lynn Medical College, Cincinnati, in 1836, graduating in 1838. Receiving a pony, . . .
Preventing esophageal stricture after endoscopic submucosal dissection: steroid injection and shielding with polyglycolic acid sheets and fibrin glue
Authors: Yosuke Kataoka, Yosuke Tsuji, Yoshiki Sakaguchi, Shinya Kodashima, Nobutake Yamamichi, Mitsuhiro Fujishiro, Kazuhiko Koike
Journal: Endoscopy (2015)

Postoperative stricture after endoscopic submucosal dissection (ESD) for esophageal neoplasms is a major complication; Ono et al. have reported that stricture occurs in 90 % of cases in which the circumferential extent of a lesion comprises more than two-thirds of the esophagus [1]. Several methods for preventing stricture, such as endoscopic balloon dilation (EBD), intralesional steroid injection, and oral steroid therapy, have previously been reported, but each method has its own drawbacks.
Safety and Efficacy Of Rituximab In adult’s Immune Thrombocytopenia (ITP) : Results After One-Year Of Follow-Up In 252 Patients From The Prospective French ITP-Ritux Registry
Authors: Mehdi Khellaf, Olivier Fain, Louis Terriou, Jean-François Viallard, Stéphane Cheze, roudot-Thoraval Françoise, Mohamed Hamidou, Borhane Slama, Sylvain Audia, Nicolas Schleinitz, Manuel Cliquennois, Guillaume le Guenno, Caroline Bonmati, France Teillet, Olivier Lambotte, Gwenola Maigne, Lionel Galicier, Arnaud Hot, Francois Lefrere, Daniel Adoue, Dominique Bordessoule, Xavier Delbrel, Didier Bouscary, Jean-Yves Cahn, Alaa Ghali, Denis Verrot, Alain Delmer, Patrick Jego, Julie Magnant, Anne-Laure Buchdahl, Bruno Royer, Sophie Rosenstingl, Jean-Marc Durand, Philippe Bierling, Marc Michel, Bertrand Godeau
Journal: Blood (2013)
In vitro activity of novel KIT/PDGFRA switch pocket kinase inhibitors against mutations associated with drug-resistant GI stromal tumors.
Authors: M. C. Heinrich, S. Wise, M. Hood, B. Smith, M. Kaufman, W. Lu, Y. Wang, D. Griffith, D. Flynn, J. A. Fletcher
Journal: Journal of Clinical Oncology (2010)

10007 Background: Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or PDGFRA kinases, which are targets of imatinib (IM) or sunitinib (SU). Resistance to IM or SU is commonly due to the acquisition of secondary mutations that markedly reduce the potency of kinase inhibitors. Both IM and SU bind to the KIT/PDGFRA ATP binding pocket. KIT and PDGFRA kinases possess negative and positive regulatory domains that modulate kinase activity by competitive binding into the switch pocket domain. Switch pocket kinase inhibitors (SPKIs) occupy this pocket and block enzymatic activity. We developed SPKIs with low nanomolar potency against wild-type KIT/PDGFRA kinases. Methods: We tested the activity of three SPKIs (DP-2976, DP-3636, DP-4444) in enzymatic assays using various wild-type and recombinant KIT kinases. In addition, a panel of kinase mutants was biochemically profiled for sensitivity to these SPKIs using several cell line models, including GIST cell lines derived from imatinib-resistant tumor clones. Results: All three SPKIs were very potent (5-10 nM IC50) against wild-type KIT and PDGFRA. In addition, these compounds maintained their potency against representative GIST-associated drug resistance mutations (V654A, T670I, D816H, D816V). DP-2976 and DP-3636 were also potent against the pan drug-resistant PDGFRA D842V mutation with IC50s of 50 and 20 nM, respectively. To confirm these observations in a GIST cellular context, we tested the relative potency of these compounds against two previously described IM-resistant GIST cell lines (exon 11 + V654A, exon 11 + D820A). All three compounds were significantly more potent than IM or SU for both cell lines. These results also correlated with enhanced inhibition of downstream signaling pathways, cellular proliferation and survival. Conclusions: DP-2976, DP-3636, and DP-4444 have markedly superior in vitro potency compared with IM or SU against a panel of GIST-relevant mutant kinases. Based on these results, we hypothesize that these compounds might have useful clinical activity against drug- resistant GIST. Further preclinical studies are indicated to develop these compounds for human clinical studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Deciphera Deciphera, MolecularMD Novartis Novartis
Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper
Authors: K. Brockow, W. Aberer, M. Atanaskovic-Markovic, S. Bavbek, A. Bircher, B. Bilo, M. Blanca, P. Bonadonna, G. Burbach, G. Calogiuri, C. Caruso, G. Celik, J. Cernadas, A. Chiriac, P. Demoly, J. N. G. Oude Elberink, J. Fernandez, E. Gomes, L. H. Garvey, J. Gooi, M. Gotua, M. Grosber, P. Kauppi, V. Kvedariene, J. J. Laguna, J.S. Makowska, H. Mosbech, A. Nakonechna, N. G. Papadopolous, J. Ring, A. Romano, H. Rockmann, R. Sargur, L. Sedlackova, S. Sigurdardottir, B. Schnyder, T. Storaas, M. Torres, M. Zidarn, I. Terreehorst
Journal: Allergy (2016)

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.