tbuckley/cabot-search huggingface dataset:
Abstract 14023: Insulin-like Growth Factor-binding Protein 7 as a Biomarker of Diastolic Dysfunction and Functional Capacity: Results From the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction (RELAX) Trial
Authors: Parul U Gandhi, Margaret M Redfield, Horng H Chen, Susanna R Stevens, Kevin J Anstrom, Hanna K Gaggin, Marc J Semigran, James L Januzzi
Journal: Circulation (2015)

Introduction: Insulin-like growth factor-binding protein 7 (IGFBP7) was previously found to be associated with diastolic function in heart failure (HF) with reduced ejection fraction (EF), but it is unclear whether such associations exist in HF with preserved EF (HFpEF), where diastolic function is of pivotal importance. Hypotheses: Baseline (BL) and change (Δ) in IGFBP7 will be significantly associated and correlated with BL and Δ in diastolic indices as well as peak oxygen consumption (VO2 max ) in patients with HFpEF. IGFBP7 will decrease with sildenafil therapy. Methods: At BL and 6 months (6M), IGFBP7, imaging studies, and VO2 max were obtained and compared in 160 HFpEF patients randomized to sildenafil or placebo. Results: Patients with supramedian BL IGFBP7 concentrations (&gt;219 ng/mL) were more likely to be older, to have more congestion and worse renal function, and to have elevated concentrations of several emerging or established HF biomarkers including amino-terminal pro-B-type natriuretic peptide, cystatin C, and highly sensitive troponin (all P&lt;0.05). Higher BL IGFBP7 was correlated with indices of worse diastolic function, including higher E velocity (ρ=0.395, P&lt;0.001), E/e’ (ρ=0.398, P&lt;0.001), left atrial volume index (ρ=0.386, P&lt;0.001), right ventricular systolic pressure (RVSP; ρ=0.413, P&lt;0.001), and transmitral E/A (ρ=0.258, P=0.006). IGFBP7 was also inversely correlated with aortic distensability (ρ= -0.301, P=0.02). There was no association or correlation with measures of systolic function. Notably, in analyses adjusted for respective baseline variables, ΔIGFBP7 was significantly correlated with Δ in E (ρ=0.114), E/A (ρ=0.225), E/e’ (ρ=0.174), and RVSP (ρ=0.282; all P&lt;0.03). Elevated BL IGFBP7 was associated with lower BL VO2 max (13.2 versus 11.1 mL/min/kg; P&lt;0.001) and ΔIGFBP7 was inversely correlated with ΔVO2 max (ρ=-0.19, P=0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 6M in contrast to placebo-treated patients (median ΔIGFBP7 -1.5 versus +13.6 ng/mL; P&lt;0.001). Conclusions: In patients with HFpEF, concentrations of IGFBP7 have unique relationships with measures of diastolic dysfunction and VO2 max . Rise in IGFBP7 may reflect worsening diastology and deteriorating VO2 max .
Psychiatric residents' attitudes toward teaching
Authors: K E Callen, J M Roberts
Journal: American Journal of Psychiatry (1980)

The authors surveyed psychiatry residents in academic training programs to determine the amount of time they spent in teaching activities and to assess their attitudes toward teaching. They found that most residents spent from 1 to 2 hours per day teaching and felt they should do more. They tended to see themselves as capable teachers, and they valued traditional medical skills. They did not seem to value the use of audiovisual materials, written handouts, or self-instructional materials. Most of the residents had received no formal instruction designed to make them better teacher or direct feedback from faculty supervisors about their teaching skills.
Effect of the apoptosis signal ceramide (C6) on antitumor activity of chemotherapeutic agents in SCID mice
Authors: A. Nadeem, H. Wanebo, D. Shrayer, S. Hazelwood, M. Resnick
Journal: Journal of Clinical Oncology (2009)

e14642 Introduction: The ceramides are a major signaling pathway for apoptosis in cells undergoing stress or exposure to chemotherapy. We have demonstrated synergistic anti-tumor effects of combining C6 ceramide with paclitaxel, doxorubicin and cisplatin and are currently addressing the question; does C6 augment activity of all the major classes of drugs? Backround: Currently the in vivo anti-tumor effects of C6 with oxaliplatin and Gemcitabine. Methods: Invivo experiments SCID/Beige/Taconic male mice inoculated S.C. with 2X106 L3.6 pancreatic cells were treated 4 days post tumor implant with trice weekly (3x/wk) intraperitoneal (IP) injections of paclitaxel (P) 3.0 m/kg, oxaliplatin (OX) 2.5 mg/kg, cisplatin (CP) 2.5 mg/kg, Gemcitabine (Gem) 10 mg/kg with/without ceramide 10 mg/kg. Mice were observed for 6 weeks and were autopsied when near death. (All controls died by 3 rd week). Maximum tumor volume, tumor weight; body weight and survival were recorded. Results: Combination with C6 ceramide augmented the tumor reduction obtained by chemotherapy alone by 57% (while preserving body weight), and increased 6 week survival from 0% (Chemotherapy alone) to 60% with combined therapy. Mean survival was increased from 25 to 37 days. Although short term immunohistochemical studies suggested enhanced apoptosis and increased caspase 3 production by ceramide combinations it may actually be independent of capase activation and mitochondrial activation. Conclusions: Combination therapy with the apoptotic signal C6 ceramide significantly enhanced the anti-tumor effects of the anti microtubule, alkylating Paclitaxel a DNA interculating antibiotic (doxorubicin) the alkylating/DNA adducting agents (cisplatin, oxaliplatin) and an anti metabolite (gemcitabine) suggesting generation of broad based apoptotic signals which interact with major cancer drug classes (tested). No significant financial relationships to disclose.
Linear porokeratosis with multiple squamous cell carcinomas successfully treated by electrochemotherapy
Authors: M. Sommerlad, A. Lock, G. Moir, J. McGregor, R. Bull, R. Cerio, C. Harwood
Journal: British Journal of Dermatology (2016)

Porokeratosis is a clonal epidermal disorder of keratinization characterized by annular lesions with an atrophic centre and a hyperkeratotic edge. The cornoid lamella is the histopathological hallmark. Six clinical variants are recognized: porokeratosis of Mibelli; disseminated superficial porokeratosis; disseminated superficial actinic porokeratosis (DSAP); porokeratosis plantaris et palmaris disseminata; punctate porokeratosis and linear porokeratosis. Linear porokeratosis is the type most frequently associated with malignant transformation into squamous cell carcinoma (SCC). It is thought to represent a mosaic form of DSAP and has an incidence of less than 1 in 200 000; treatment options are limited. We describe a patient with systematized linear porokeratosis and multiple SCCs who was successfully treated with bleomycin electrochemotherapy (ECT), a form of intralesional chemotherapy. In view of their large number, the individual SCCs were treated with bleomycin ECT. One year post-treatment the patient remains tumour free. To our knowledge, this is the first case of multiple SCCs treated by ECT in the context of systematized linear porokeratosis. Our case highlights the challenges associated with diagnosing and managing this unusual form of porokeratosis.
Hypertensive Vascular Disease in Adolescence
Authors: Robert P. Masland, Felix P. Heald, Walter T. Goodale, J. Roswell Gallagher
Journal: New England Journal of Medicine (1956)

A MEDICAL clinic devoted to the care of adolescents affords an excellent opportunity to further knowledge of the natural history of hypertensive vascular disease. This report presents case material indicating that the presence of a persistently elevated blood pressure in an adolescent boy or girl is deserving of further study, whether or not there are accompanying symptoms. On the basis of experience in this clinic, we believe that a careful blood-pressure determination is an important part of the adolescent's examination.Elevation in blood pressure beyond the normal range in adolescence is not common. Various studies1 2 3 4 5 6 suggest that the normal range . . .
Social support: a genetic-epidemiologic analysis
Authors: K S Kendler
Journal: American Journal of Psychiatry (1997)

Social support is a widely used construct in the fields of mental health, sociology, and medicine and has typically been conceptualized as an environmental factor that influences the risk for dysfunction and disease. In this study a longitudinal twin design was used to clarify the etiology of social support.A 16-item social support inventory was administered at personal interview to a population-based sample of female twins twice, approximately 5 years apart. A twin measurement model-which permits an estimation of the etiologic role of genetic and environmental factors correcting for errors of measurement or short-term temporal fluctuations-was applied to these data.Six factors, which were moderately stable over time, were found: relative problems, friend problems, relative support, confidants, friend support, and social integration. The best-fitting twin measurement models indicated that genetic factors were of substantial etiologic significance for all six social support scales. Heritabilities of the stable component of social support ranged from 43% to 75%. Familial-environmental factors contributed to twin resemblance only for relative problems and relative support. No evidence was found for significant biases in the twin method.Measures of social support are moderately stable over time. When short-term fluctuations are corrected for, heritable factors are of substantial etiologic importance for social support as measured at personal interview. Treating social support solely as an environmental measure is probably incorrect. Through genetically influenced traits such as temperament, individuals play a substantial role in creating their own social environments.
129TiP: SAKK 16/14 – anti-PD-L1 antibody durvalumab (MEDI4736) in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). A multicenter single-arm phase II trial
Authors: S.I. Rothschild, A. Zippelius, S. Savic Prince, M. Gonzalez, W. Weder, A. Xyrafas, C. Rusterholz, M. Pless
Journal: Journal of Thoracic Oncology (2016)
The immunological impact of the RAF inhibitor BMS908662: Preclinical and early clinical experience in combination with CTLA-4 blockade.
Authors: Margaret Callahan, Gregg Masters, Jessica Katz, Valerie Russell, Ruth Ann Roman, Mary Montefusco, Shachi Vyas, Jianda Yuan, Taha Merghoub, Ashok Kumar Gupta, Jon Wigginton, Maria Jure-Kunkel, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2012)

2521 Background: Two new approaches to treat advanced melanoma have transformed the standard of care: the CTLA-4 blocking antibody, ipilimumab, and the targeted inhibitor of mutated BRAF, vemurafenib. These agents are mechanistically unique and combination therapy is a promising next step. We evaluated the combination of BMS908662 (662), a pan RAF inhibitor, with CTLA-4 blockade in preclinical studies and report first-in-human clinical experience with this combination. Methods: 1) We tested the impact of 662 on T cells in vitro, using cultured human T cells, and in vivo, using OT-1 transgenic mice. T cell activation and MAPK pathway signaling were assessed in parallel. 2) Preclinical studies measuring the anti-tumor activity of combination therapy were performed in CT-26 and SA1N tumor models. 3) Three pts with BRAF mutant stage IV melanoma were treated at MSKCC on CA206005, an IRB-approved protocol, receiving ipilimumab (3 mg/kg) and 662 (25 mg bid) (NCT01245556). Two pts consented to an IRB-approved protocol permitting immune monitoring. Results: 1) In vitro studies demonstrate that 662 can potentiate T cell activation after stimulation. This corresponds with increased MAPK pathway signaling, consistent with paradoxical activation of the MAPK pathway in wild type cells, a class effect of RAF inhibitors. In vivo, enhanced expansion of OT-1 cells after ovalbumin challenge was seen in mice treated with 662. T cell expansion was greatest in mice treated with a combination of CTLA-4 blockade and 662 (p&lt;0.05). 2) Both preclinical models demonstrate superior anti-tumor activity with combination therapy compared to monotherapy (p&lt;0.05). 3) All pts treated on protocol CA206005 tolerated combination therapy. New keratoacanthomas and SCCs, likely related to 662, were identified. One pt has an ongoing response at 10 mos (-85%), one had stable disease for 24 wks (-19%) and a third had disease progression. Enhanced MAPK signaling in PBMCs after treatment with 662 was detected ex vivo. Conclusions: RAF inhibitors may potentiate T cell activation in vitro and in vivo, offering one explanation for the enhanced anti-tumor activity seen in combination with CTLA-4 blockade in pre-clinical models.
Clinical and Chemical Diabetes in Offspring of Diabetic Couples
Authors: Charles B. Kahn, J. Stuart Soeldner, Ray E. Gleason, L. Rojas, Rafael A. Camerini-Davalos, Alexander Marble
Journal: New England Journal of Medicine (1969)

A total of 678 glucose tolerance tests (oral glucose, cortisone-primed oral glucose, intravenous glucose and intravenous tolbutamide tests) were performed upon 155 of 274 offspring from 80 conjugal diabetic parents. The diabetic status of the untested offspring was determined by communication with parent or sibling. Administration of multiple tests (of various types) or repeated oral glucose tolerance tests detected a higher frequency of chemical diabetes than that obtained after a single test. The overall frequency of chemical diabetes (41 to 62 per cent, depending on the age and weight of the offspring) was considerably higher than that of overt diabetes (8.8 per cent). The oral glucose tolerance test appeared to be as sensitive as any other glucose tolerance test in detecting chemical diabetes. In such persons, many of whom were nonobese teen-agers and young adults, abnormal tests were frequently followed by one or more normal tests, as were normal tests followed by abnormal tests in no predictable sequence.
A phase II evaluation of bevacizumab in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group (GOG) Study
Authors: C. Aghajanian, M. W. Sill, K. Darcy, B. Greer, D. S. McMeekin, P. G. Rose, J. Rotmensch, M. N. Barnes, P. Hanjani, K. Leslie
Journal: Journal of Clinical Oncology (2009)

5531 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor, has demonstrated clinical benefit in multiple tumor types. This is the first report of the activity of bevacizumab in patients with recurrent or persistent endometrial cancer (EMC). Methods: Eligible patients had persistent or recurrent EMC after receiving 1–2 prior cytotoxic regimens, measurable disease, and GOG performance status &lt; 2. Treatment consisted of BV 15 mg/kg IV q 3 weeks until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at 6 months, objective response rate, and toxicity by NCI CTCAE v3.0. The clinical trial was carried out in a flexible 2-stage group sequential design intended to detect either cytostatic or cytotoxic activity. Sample sizes were targeted to limit the probability of designating ineffective regimens as being active 10% with at least 90% statistical power. Clinically significant improvements were 20% increases in the proportion responding or surviving progression-free at 6 months over historical controls. Results: From March 2006 to January 2008, 56 patients were enrolled. Two were excluded due to a second primary and one due to inadequate pathology; thus, the sample included 53 patients. Median age was 62 (range 44–84) years, and prior treatment consisted of 1 or 2 regimens in 33 and 20 patients, respectively. Twenty-eight patients (52.8%) had prior radiation. Early results showed 8/53 (15.1%) response rate, with 1 complete response and 7 partial responses; and 19/53 (35.8%) of patients progression free at 6 months with 2 patients pending at the time of data analysis. Median PFS was 4.2 months. Median Overall survival (OS) was 10.5 months. The following grade 3 or 4 toxicities were observed: anemia (1 grade 3), cardiovascular (4 grade 3), constitutional (2 grade 3), hemorrhage (1 grade 3), hepatic (1 grade 3), musculoskeletal (2 grade 3), metabolic (1 grade 3, 1 grade 4), neurologic (1 grade 3), pain (4 grade 3), and vascular (1 grade 3, 1 grade 4). Conclusions: BV appears to have single agent activity in women with recurrent or persistent EMC and warrants further investigation. No significant financial relationships to disclose.
Familial Male Pseudohermaphroditism without Gynecomastia Due to Deficient Testicular 17-Ketosteroid Reductase Activity
Authors: James R. Givens, Winfred L. Wiser, Robert L. Summitt, Irwin J. Kerber, Richard N. Andersen, Donald E. Pittaway, Stewart A. Fish
Journal: New England Journal of Medicine (1974)

Abstract To evaluate possible 17-ketosteroid reductase deficiency, we studied two sisters with primary amenorrhea, hirsutism, clitoral enlargement and a 46,XY karyotype, who lacked breast development. Plasma luteinizing hormone, follicle-stimulating hormone and urinary 17-ketosteroids were elevated in both subjects. Plasma Δ4-androstenedione was seven to nine times greater than normal, whereas plasma testosterone was low or in the low-normal male range. Spermatic venous plasma of Case 2 contained increased amounts of Δ4-androstenedione and estrone and subnormal amounts of testosterone and estradiol, findings consistent with testicular 17-ketosteroid reductase deficiency. In vitro incubation of testicular tissue of Case 2 confirmed a partial defect in testicular 17-ketosteroid reductase activity and documented increased 3β-hydroxysteroid dehydrogenase activity. Failure of breast development was probably due to lower estrogen levels than in previously reported cases. We conclude that testicular 17-ketostero...
149P: The role of CTCs and cfDNA for diagnosis and monitoring of EGFR mutations in advanced NSCLC patients
Authors: S. Calabuig-Fariñas, E. Jantus Lewintre, C. Mayo-De-Las-Casas, A. Blasco Cordellat, M.A. Molina-Vila, R. Rosell, C. Camps
Journal: Journal of Thoracic Oncology (2016)
Hepatitis C Virus, Human Herpesvirus 8, and the Development of Plasma-Cell Leukemia
Authors: Sylvie Hermouet, Isabelle Corre, Michelle Gassin, Edith Bigot-Corbel, Claudia A. Sutton, James W. Casey
Journal: New England Journal of Medicine (2003)

To the Editor: The role of hepatitis C virus (HCV) and human herpesvirus 8 (HHV-8), two B-cell–tropic viruses, in B-cell proliferation1 is illustrated by the following unusual case of plasma-cell leukemia. In 1995, a 32-year-old man with a history of hepatitis A virus and HCV infection but who tested negative for hepatitis B virus and human immunodeficiency virus was admitted to the hospital with septic shock, bilateral pneumonia, and hepatosplenomegaly. The hemoglobin level was 8.9 g per deciliter; the white-cell count was 26.6×109 per liter with 50 percent plasmablasts (Figure 1A), 41 percent neutrophils, 7 percent lymphocytes, and 2 percent . . .
Substantial Variability in Biopsy Practice Patterns Among Gastroenterologists for Suspected Eosinophilic Gastrointestinal Disorders
Authors: Evan S. Dellon, Margaret H. Collins, Peter A. Bonis, John Leung, Kelley E. Capocelli, Ranjan Dohil, Gary W. Falk, Glenn T. Furuta, Calies Menard-Katcher, Sandeep K. Gupta, Ikuo Hirano, Girish S. Hiremath, Amir F. Kagalwalla, Barry K. Wershil, Chris A. Liacouras, Amanda B. Muir, Vincent A. Mukkada, Philip E. Putnam, Alain M. Schoepfer, Alex Straumann, John M. Wo, Guang-Yu Yang, Marc E. Rothenberg, Nirmala Gonsalves
Journal: Clinical Gastroenterology and Hepatology (2016)
Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin Lineage
Authors: Julia Lichtnekert, Natalya V. Kaverina, Diana G. Eng, Kenneth W. Gross, J. Nathan Kutz, Jeffrey W. Pippin, Stuart J. Shankland
Journal: Journal of the American Society of Nephrology (2016)

Because adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP + CoRL and, within these glomeruli, more RFP + CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP + CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells ( α 8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.