tbuckley/cabot-search huggingface dataset:
The Serum Digitalis Concentration — Does It Diagnose Digitalis Toxicity?
Authors: Joseph A. Ingelfinger, Peter Goldman
Journal: New England Journal of Medicine (1976)

We propose that an investigation of the serum digitalis concentration as a test for digitalis toxicity should (1) study patients with similar toxic manifestations, (2) obtain control concentrations from nontoxic patients with symptoms suggesting toxicity, (3) define criteria for toxicity and nontoxicity, (4) select representative patients, (5) describe the study population and (6) analyze how much diagnostic information the serum digitalis concentration provides that cannot be inferred from other observations. To determine if available evidence validates the digitalis concentration as a test for toxicity 27 reports were reviewed. No investigation employed symptomatic controls. Of five studies most consistent with points 1–5 only three demonstrated higher mean serum digitalis concentrations in toxic patients. Whether knowledge of the digitalis concentrations was diagnostically more useful than knowledge of the digitalis dosage, renal function, serum potassium concentration and cardiac status was not determined in any study. The usefulness of the serum digitalis concentration as a test for digitalis toxicity is therefore not established. (N Engl J Med 294:867–870, 1976)
Almost a quarter of Royal College fellows say their hospitals cannot deliver continuity of care
Authors: N. Hawkes
Journal: BMJ (2012)

Radical changes are needed in the way hospitals are organised and run, the Royal College of Physicians’ Future Hospital Commission is likely to recommend when it reports next year.

At a meeting at the college on 17 July to report progress, Tim Evans, academic vice president, said that work so far had identified that hospitals were under substantial stress, often providing a disjointed service to patients with a lack of compassion and continuity of care.

A survey of the college’s fellows had shown many concerns, ranging from worries about their hospital’s ability to deliver …
Occurrence of bcl-2 Oncogene Translocation With Increased Frequency in the Peripheral Blood of Heavy Smokers
Authors: D. A. Bell, Y. Liu, G. A. Cortopassi
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Occurrence of bcl-2 Oncogene Translocation With Increased Frequency in the Peripheral Blood of Heavy Smokers Get access Douglas A. Bell, Douglas A. Bell Affiliations of authors:Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle ParkN.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Yafei Liu, Yafei Liu Cortopassi, Department of Molecular Pharmacology and Toxicology, University of Southern CaliforniaLos Angeles Search for other works by this author on: Oxford Academic PubMed Google Scholar Gino A. Cortopassi Gino A. Cortopassi Cortopassi, Department of Molecular Pharmacology and Toxicology, University of Southern CaliforniaLos Angeles Correspondence to: Gino A. Cortopassi, Ph.D., Department of Molecular Pharmacology and Toxicology, University of Southern California. 1985 Zonal Ave., Los Angeles, CA 90033. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Pages 223–224, https://doi.org/10.1093/jnci/87.3.223 Published: 01 February 1995
Endoscopic mucosal resection and endoscopic submucosal dissection in the West – too many concerns and caveats?
Authors: H. Neuhaus
Journal: Endoscopy (2010)

Local treatment of early gastrointestinal neoplasia promises to be curative and superior to surgery in terms of organ preservation, safety, duration of hospitalization, and cost-effectiveness. Prerequisites for a local approach are that these advantages outweigh the risk of lymph node metastases and recurrence of neoplasia. In addition the procedure-related morbidity and mortality should be low.
Hyponatremia and Inappropriate Secretion of Vasopressin (Antidiuretic Hormone) in Patients with Hypopituitarism
Authors: Wolfgang Oelkers
Journal: New England Journal of Medicine (1989)

Severe hyponatremia occurs in some patients with untreated hypopituitarism, but it is not known whether such hyponatremia is caused by the hypersecretion of vasopressin (antidiuretic hormone). This report describes severe, symptomatic hyponatremia in five women 59 to 83 years old (serum sodium, 111 to 118 mmol per liter) who presented with hypopituitarism (which had been previously undiagnosed in four). Plasma vasopressin was inappropriately high (1.3 to 25.8 pmol per liter [1.4 to 28 ng per liter]) in relation to plasma osmolality (236 to 260 mOsm per kilogram of body weight). All five patients had normal renal function and no signs of dehydration or volume depletion. The hyponatremia was resolved within a few days after the institution of hydrocortisone therapy, after infusion of normotonic or hypertonic saline had been found to be less effective. When four of the patients were later restudied while receiving maintenance hydrocortisone treatment, the relation between plasma vasopressin and osmolality was normal. We conclude that ACTH deficiency may cause the syndrome of inappropriate secretion of antidiuretic hormone. The beneficial effect of hydrocortisone is probably exerted through the suppression of vasopressin secretion. (N Engl J Med 1989;321:492–6.)
A1.11 A20 controls activation of STAT1, but has no effect on STAT3: Implications for development of enthesitis
Authors: K De Wilde, A Martens, J Coudenys, K Debusschere, E Verheugen, F Windels, R Beyaert, G van Loo, D Elewaut
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> A20 is a negative regulator of NF-kB with potent anti-inflammatory properties. SNPs in A20 have been associated with a variety of IMIDs, including RA, psoriasis and PsA. Cell specific deletion of A20 results in a myriad of inflammatory disorders: for&nbsp;example, myeloid deletion results in polyarthritis but epidermal loss rather leads to psoriatic like lesions. Our goal was to delineate the underlying mechanisms and earliest phases leading to joint inflammation in A20 myeloid deficient mice. <h3>Materials and methods</h3> We used mice with a myeloid specific deficiency of A20 (A20<sup>myelKO</sup> mice using LysM-cre). This model is IL-6 dependent, but TNF independent. We isolated BMDMs from A20<sup>myelKO</sup> and wildtype mice and stimulated them with IL-6 or IFN-γ. qPCR and western blot analysis were performed to study whether A20 has an effect on the activation of the JAK-STAT pathway. Transfection experiments were conducted on HEK293T cells&nbsp;to examine which part of A20 is responsible for this effect. <i>In vivo</i> experiments with a JAK-STAT inhibitor (tofacitinib) were performed: A20<sup>myelKO</sup> mice were divided into 2 groups: a tofacitinib and a placebo group. Mice were treated bidaily&nbsp;with respectively 50mg/kg tofacitinib orplacebo. <h3>Results</h3> In the earliest phase of disease, inflammation was markedly confined to enthesial sites. We also found that A20 has a marked suppressive effect in myeloid cells on the expression of STAT1, but not STAT3 induced genes. Western blot showed that A20 has an inhibitory effect on STAT1, but not STAT3 phosphorylation. Reporter assays confirmed these findings and highlighted&nbsp;that this effect is probably due to ZnF motif 4 and 7, rather than to the OTU domain. We therefore assessed the role of JAK-STAT inhibition <i>in vivo</i> and found significantly lower clinical scores and significantly less inflammation of the synovio-entheseal complex in tofacitinib compared to placebo treated mice. <h3>Conclusions</h3> Our data reveal a novel interplay between myeloid cells and tissue resident cells at entheseal sites that relies on A20. In the absence of A20, STAT1 but not STAT3 signalling is engaged leading to activation of a marked STAT1 dependent inflammation. Interestingly, the effects of JAK-STAT are operating independently from TNF.
Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon
Authors: Jay H. Hoofnagle, Kevin D. Mullen, D. Brian Jones, Vinod Rustgi, Adrian Di Bisceglie, Marion Peters, Jeanne G. Waggoner, Yoon Park, E. Anthony Jones
Journal: New England Journal of Medicine (1986)

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.
Fatal Hematoma during Treatment with Adjusted-Dose Subcutaneous Heparin Therapy
Authors: Andreas Gabel, Stefan Müller
Journal: New England Journal of Medicine (1999)

To the Editor: Subcutaneous heparin therapy for atrial fibrillation, deep-vein thrombosis, unstable coronary syndromes, or ischemic cerebral attacks may be an alternative to intravenous treatment, if there are contraindications to oral anticoagulants and mobilization of the patient or discharge from the hospital is desired. Unfortunately, few studies support this practice. With the method of adjusted-dose treatment with heparin, the drug is given subcutaneously, and the partial-thromboplastin time is monitored. Daily adjustment of the dose can result in effective prolongation of the partial-thromboplastin time. The same prophylactic effect is expected with the adjusted-dose method as with the well-studied intravenous use of . . .
Deficiency of a Granulocyte-Membrane Glycoprotein (gp150) in a Boy with Recurrent Bacterial Infections
Authors: M. Amin Arnaout, Jane Pitt, Harvey J. Cohen, Julian Melamed, Fred S. Rosen, Harvey R. Colten
Journal: New England Journal of Medicine (1982)

Investigation of the basis for increased susceptibility to infection with pyogenic organisms in an eight-year-old boy revealed a defect in receptor coupled polymorphonuclear-leukocyte functions. For example, phagocytosis of opsonized oil red O particles or particles coated with immunoglobulin, superoxide generation, and degranulation induced by opsonized zymosan were decreased. This defect in receptor-coupled function was not due to decreased receptor–ligand binding or to impaired superoxide generation or degranulation when these effects were elicited by soluble stimuli. The defect appeared to be associated with the absence of a normal granulocyte-surface-membrane glycoprotein with an approximate molecular weight of 150,000 daltons (gp150). This glycoprotein was present in reduced amounts (approximately 50 per cent of normal) in the granulocytes from each of the patient's parents, suggesting a genetic basis for its deficiency. (N Engl J Med. 1982; 306:693–9.)
CLINICAL OUTCOMES OF PERCUTANEOUS MITRAL VALVE REPAIR WITH MITRACLIP SYSTEM FOR FUNCTIONAL MR WITH END-STAGE HEART FAILURE
Authors: Yukiko Mizutani, Shunsuke Kubo, Song Guangyuan, Yoshifumi Nakajima, Krissada Meemook, Jonah Solaiman Tehrani, Chidinma Dinneya, Asma Hussaini, Mamoo Nakamura, Robert Siegel, Alfredo Trento, Saibal Kar
Journal: Journal of the American College of Cardiology (2016)
Likelihood of Unemployed Smokers vs Nonsmokers Attaining Reemployment in a One-Year Observational Study
Authors: Judith J. Prochaska, Anne K. Michalek, Catherine Brown-Johnson, Eric J. Daza, Michael Baiocchi, Nicole Anzai, Amy Rogers, Mia Grigg, Amy Chieng
Journal: JAMA Internal Medicine (2016)

Studies in the United States and Europe have found higher smoking prevalence among unemployed job seekers relative to employed workers. While consistent, the extant epidemiologic investigations of smoking and work status have been cross-sectional, leaving it underdetermined whether tobacco use is a cause or effect of unemployment.To examine differences in reemployment by smoking status in a 12-month period.An observational 2-group study was conducted from September 10, 2013, to August 15, 2015, in employment service settings in the San Francisco Bay Area (California). Participants were 131 daily smokers and 120 nonsmokers, all of whom were unemployed job seekers. Owing to the study's observational design, a propensity score analysis was conducted using inverse probability weighting with trimmed observations. Including covariates of time out of work, age, education, race/ethnicity, and perceived health status as predictors of smoking status.Reemployment at 12-month follow-up.Of the 251 study participants, 165 (65.7) were men, with a mean (SD) age of 48 (11) years; 96 participants were white (38.2%), 90 were black (35.9%), 24 were Hispanic (9.6%), 18 were Asian (7.2%), and 23 were multiracial or other race (9.2%); 78 had a college degree (31.1%), 99 were unstably housed (39.4%), 70 lacked reliable transportation (27.9%), 52 had a criminal history (20.7%), and 72 had received prior treatment for alcohol or drug use (28.7%). Smokers consumed a mean (SD) of 13.5 (8.2) cigarettes per day at baseline. At 12-month follow-up (217 participants retained [86.5%]), 60 of 108 nonsmokers (55.6%) were reemployed compared with 29 of 109 smokers (26.6%) (unadjusted risk difference, 0.29; 95% CI, 0.15-0.42). With 6% of analysis sample observations trimmed, the estimated risk difference indicated that nonsmokers were 30% (95% CI, 12%-48%) more likely on average to be reemployed at 1 year relative to smokers. Results of a sensitivity analysis with additional covariates of sex, stable housing, reliable transportation, criminal history, and prior treatment for alcohol or drug use (25.3% of observations trimmed) reduced the difference in employment attributed to smoking status to 24% (95% CI, 7%-39%), which was still a significant difference. Among those reemployed at 1 year, the average hourly wage for smokers was significantly lower (mean [SD], $15.10 [$4.68]) than for nonsmokers (mean [SD], $20.27 [$10.54]; F(1,86) = 6.50, P = .01).To our knowledge, this is the first study to prospectively track reemployment success by smoking status. Smokers had a lower likelihood of reemployment at 1 year and were paid significantly less than nonsmokers when reemployed. Treatment of tobacco use in unemployment service settings is worth testing for increasing reemployment success and financial well-being.
OPTIMIZACIÓN DE LA LIMPIEZA INTESTINAL EN CÁPSULA ENDOSCOPICA DE INTESTINO DELGADO
Authors: M Duran Rigueira, A Orive Calzada, S Torres Burgos, M Navajas Laboa, M Aguirresarobe Gil de San Vicente, XXL Bridet, M López López, A Hernández Martín, A Bernal Martínez, J Cabriada Nuño
Journal: Endoscopy (2010)

Introducción: En ocasiones, la calidad de las imágenes obtenidas con el estudio mediante Cápsula Endoscópica, no es adecuada por mala preparación.
Abstract 1945: Inhibition of PTK6 kinase activity reduces proliferation and migration of tumor cells
Authors: Yan Wang, Michael Malkowski, Weihong Jin, David Belanger, Hongbo Zeng, Patrick J. Curran, M. Arshad Siddiqui, Hua Miao, Gerald W. Shipps, Judith Hailey, Eugene Maxwell, Donna Carr, Cynthia Seidel-Dugan
Journal: Cancer Research (2011)

Abstract Protein kinase 6 (PTK6) is a member of the Frk family of non-receptor tyrosine kinase that is overexpressed in several types of cancers with the highest overexpression observed in breast tumors. PTK6 shows sequence homology to the src tyrosine kinase family. Its functional domains, including a SH3, a SH2 and a kinase domain, are arranged similarly with src family kinases although PTK6 lacks a myristoylation domain. We have identified a potent small molecule PTK6 kinase inhibitor from kinase cross screens that inhibits PTK6 autophosphorylation and phosphorylation of its substrate Sam68, a member of the KH domain containing RNA binding proteins. In cell culture, the compound inhibited proliferation, soft agar growth and migration of tumor cells. The compound inhibited soft agar growth of breast tumor cells more potently than dasatinib. A specific PTK6 kinase inhibitor may provide a novel approach to inhibit the growth of selected tumors, sensitize the response of the tumor cells to other chemotherapeutics and prevent/inhibit metastasis of cancer in a wide range of cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1945. doi:10.1158/1538-7445.AM2011-1945
Abstract 1637: The MEK/Erk pathway is required for PC3 cell survival following FdUMP[10] treatment
Authors: Evan Gomes, Jamie Jennings-Gee, William H. Gmeiner
Journal: Cancer Research (2010)

Abstract We have demonstrated that the novel polymeric fluoropyrimidine (FP) antitumor agent FdUMP[10] is efficacious towards prostate tumor (PC3) xenografts at well-tolerated doses while 5-fluorouracil (5FU) is not efficacious. FdUMP[10] treatment of PC3 cells results in complete inhibition of thymidylate synthase and S-phase arrest with generation of extensive DNA double-strand breaks as detected from γH2AX phosphorylation. S-phase arrest was confirmed by Western blots evaluating cyclin expression. In addition, we show that although cell-cycle arrested, FdUMP[10]-treated PC3 cells are not quiescent as indicated by extensive levels of DNA synthesis. The elevated DNA synthesis levels are likely indicative of futile repair. Although approximately 90% of cells are non-viable as assessed by a clonogenic assay, only about 30% of cells undergo apoptosis as assessed by Annexin V+ cells. The observation that FdUMP[10] treatment resulted in potent anti-tumor activity with minimal induction of apoptotic events lead us to assess to what extent activation of cell survival pathways inhibited cell death. The phosphoinositide 3-kinase PI3K/Akt and the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinases (MEK/ERK1/2) signal transduction pathways play critical roles in mammalian cell survival and have been shown to be activated in various cancers. Previous studies have shown that inhibition of PI3K/Akt or MEK/ERK1/2 can each enhance the effectiveness of cytotoxic chemotherapy. Our results show that FdUMP[10] treatment reduced phosphorylated Akt levels suggesting FdUMP[10] treatment inactivates the PI3K/Akt pro-survival pathway. However, inhibition of PI3K/Akt with LY294002 alone promoted a significant loss in the clonogenic capacity of PC3 cells independent of FdUMP[10] treatment while co-treatment did not provide an enhanced therapeutic effect. In contrast to these findings, inhibition of the MEK/ERK1/2 pathway with U0126 showed a significant decrease in viability only in combination with FdUMP[10] treatment. Here, we demonstrate that the potent effects of FdUMP[10]-induced cytotoxicity towards prostate cancer cells may be exacerbated by impairment of the MEK/ERK1/2 but not the PI3K/Akt cell survival pathway. Altogether, our studies suggest advanced prostate cancer may be amenable to treatment with FdUMP[10] in combination with inhibitors of MAPK signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1637.
635 HIV VIRAL LOAD INDEPENDENTLY PREDICTS SURVIVAL IN HIVINFECTED PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC)
Authors: T.Y. Chen, M.B. Badshah, M. Ventura, B. Mínguez, M. Harris, M.K. Jain, T. Harout, B. Conway, J.A. Aberg, N. Bräu
Journal: Journal of Hepatology (2013)
IMPACT OF REQUIREMENT FOR TRANSFUSION ON COST OF CARE, LENGTH OF STAY AND IN-HOSPITAL MORTALITY IN TRANSCATHETER MITRAL VALVE REPAIR: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Ronak Bhimani, Badal Thakkar, Dipen Khanpara, Parth Bhatt, Achint Patel, Nileshkumar Patel, Abhishek Deshmukh, Apurva Badheka
Journal: Journal of the American College of Cardiology (2016)
Botryoid White-Cell Nuclei
Authors: Edward Chew, Surender Juneja
Journal: New England Journal of Medicine (2013)

A 26-year-old man was found unresponsive at work. When examined at the hospital, he had a temperature of 41.9°C, a heart rate of 150 bpm, unrecordable blood pressure, and a score of 4 on the Glasgow Coma Scale.
P60 Pre-treatment IP-10 concentrations are associated with a sustained virological response in HIV/HCV co-infected patients
Authors: D. Joshi, M. Bruce, A. Suddle, C. Taylor, I. Carey, K. Agarwal
Journal: Gut (2011)

<h3>Introduction</h3> Treatment of chronic HCV (cHCV) in HIV positive patients with pegylated interferon (PEG-IFN) and ribavirin (RIB) is associated with poorer treatment outcomes and an increased side effect profile. Strong immune T helper type 1 responses towards HCV determine outcome of infection. Interferon γ inducible protein 10 (IP-10) has been shown to correlate with treatment response in cHCV mono-infection but limited data are available for HIV co-infected patients. <h3>Aim</h3> To investigate whether pre-treatment plasma levels of cytokines/chemokines differ between HIV/HCV co-infected and HCV mono-infected patients and whether they can predict response to PEG-IFN and RIB therapy. <h3>Method</h3> Pre-treatment plasma samples were studied in HIV positive patients co-infected with cHCV and HIV negative cHCV patients. Plasma levels of IFN-γ, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10 and IP-10 (all pg/ml) were measured by ELISA. Patients were matched according to genotype, fibrosis stage and age. All patients were treated with PEG-IFN α 2a and weight based RIB for 24 weeks or 48 weeks according to genotype. All patients were previously treatment naive. Virological response was divided into SVR, non-response (NR) and responder relapse (RR). All results are presented as medians. <h3>Results</h3> 37 HIV positive patients (CD4 count 495 cells/ml, undetectable HIV viral load in 86%) co-infected with HCV ([HCV viral load (VL) 1.68E6 IU/ml, 54% genotype 1, 7 (19%) patients with advanced fibrosis on biopsy (Ishak F&gt;5)] were divided according virological response [n=23 SVR (62%), n=7 RR, n=7 NR]. 35 HIV negative patients with cHCV [HCV VL 2.12E6, 64% genotype 1, 5 (14%) patients with advanced fibrosis (Ishak F&gt;5) were also divided according to virological response [n=23 SVR (66%), n=7 RR, n=6 NR]. Irrespective of HIV status, IP-10 (62 vs 105, p=0.006) and IL-6 (4 vs 7, p=0.03) levels were lower at baseline in patients who achieved an SVR. Baseline IP-10 (92 vs 49, p=0.009) and IL-8 (39 vs 22, p=0.01) were higher in the HIV positive group but the concentrations of IFN-γ, IL-2, IL-4, IL-6, IL-10 were similar between the two groups. In HIV positive patients baseline IP-10 concentrations were lower in those who achieved a SVR (84 vs 107 p=0.02) and also differed according to treatment response (SVR, 84 vs RR, 124 vs NR, 107 p=0.03). <h3>Conclusion</h3> In our cohort IP-10 acted as a robust predictor of SVR among HIV/HCV co-infected and HCV mono-infected patients. IP-10 could serve as a pre-treatment biomarker to help identify patients who will achieve a SVR.