tbuckley/cabot-search huggingface dataset:
Estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using a minimal physiologic toxicokinetic model.
Authors: K Thomaseth, A Salvan
Journal: Environmental Health Perspectives (1998)

In this study we investigated estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on a minimal physiologic toxicokinetic model in humans. Our purpose was to obtain a mathematical tool for dose-response studies based on human data. We first simplified an existing model of TCDD kinetics in humans and estimated its parameters (i.e., liver elimination and background input of TCDD) using repeated measures of serum dioxin taken in Vietnam veterans (Ranch Hand data and data from an unexposed reference group). We carried out computer simulation and estimation of the model parameters both under a nonlinear weighted least-squares model (naive pooled data approach) and under a nonlinear mixed-effects model. The best parameter estimates were obtained with log-transformed data under a mixed-effects model: liver elimination parameter kf = 0.022 days-1 (95% confidence interval [CI] = 0.020, 0.024), and background input rate input = 0.1251 pg/kg/day (95% CI = 0.071, 0.179). The dioxin kinetic model and its estimated parameters were then used to provide dose estimates for a cohort of workers with exposure to TCDD at chemical plants in the United States. First, the model was used to estimate the rate of occupational intake of TCDD in a subset of the cohort consisting of 253 subjects for whom one measure of serum TCDD was available. A model of change in body-mass index over time was also identified for this subsample. The occupational exposure rate was estimated by linear regression using the above values of kinetic parameters and assuming an initial condition for serum TCDD of 7 ppt, i.e., the average level found in unexposed workers. The estimate of the occupational exposure parameter was 232.7 pg/kg/day (95% CI 192, 273). This value can be applied to the full cohort to obtain for each cohort member the time course of serum dioxin concentration from which exposure indices can be derived. Sensitivity coefficients to model parameters (background input, kf, occupational exposure, and the assumed TCDD concentration at hire) allow for a convenient recalculation of the serum TCDD curve and of the derived exposure indices for different assumed values of the model parameters.
Molecular Basis of Metastasis
Authors: Anne C. Chiang, Joan Massagué
Journal: New England Journal of Medicine (2008)

Metastases are the principal cause of death in patients with cancer. Recent advances bring hope that it will be possible to identify the molecules and processes involved in metastasis, and this new knowledge could lead to effective methods of preventing and treating metastases. This review describes the properties of cells that enable them to surmount physical boundaries, disseminate, and colonize a distant organ.
Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles
Authors: Supang Khondee, Emily F. Rabinsky, Scott R. Owens, Bishnu P. Joshi, Zhen Qiu, Xiyu Duan, Lili Zhao, Thomas D. Wang
Journal: Journal of Controlled Release (2014)
Sudden Death and Cardiovascular Collapse in Children With Restrictive Cardiomyopathy
Authors: Shannon M. Rivenes, Debra L. Kearney, E. O’Brian Smith, Jeffrey A. Towbin, Susan W. Denfield
Journal: Circulation (2000)

Background —Restrictive cardiomyopathy (RCM) is rare in children, and the prognosis is poor. In the present study, we evaluated all pediatric patients with RCM who were at our institution during a 31-year period to determine the clinical outcome and cause of death. Those who sustained sudden, unanticipated cardiac arrests were evaluated for risk factors that are predictive of sudden death. Methods and Results —Eighteen consecutive patients were reviewed. Presentation, clinical course, laboratory data, and histopathological evidence of ischemia were compared between patients with and without sudden death events. The results demonstrated that patients who were at risk for sudden death were girls with chest pain, syncope, or both at presentation and without congestive heart failure. Although not statistically significant for sudden death, Holter monitor evidence of ischemia predicted death within months. Histopathological evidence of acute or chronic ischemia was found in the majority of patients, with acute ischemia more common among those who sustained sudden death events. Conclusions —All children with RCM are at risk for ischemia-related complications and death, and some are at risk of sudden death. In the present study, patients at risk of sudden death appeared well and had no evidence of ongoing heart failure but often had signs or symptoms of ischemia characterized by chest pain, syncope, or both. ECGs and Holter monitors may be useful screening tools. The use of β-blockade, the placement of an implantable cardioverter-defibrillator, and preferential status 1A or B listing for cardiac transplantation are proposed for pediatric patients with RCM and evidence of ongoing ischemia.
The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre
Authors: C Datz, M Cramp, T Haas, O Dietze, H Nitschko, G Froesner, N Muss, F Sandhofer, W Vogel
Journal: Gut (1999)

The natural history of hepatitis C virus (HCV) infection is variable and factors determining the course of the illness are unclear.To determine the natural course of HCV infection in a well characterised group of patients 18 years after an epidemic outbreak of non-A, non-B hepatitis at a plasmapheresis centre.Between 1994 and 1996, 20 of 30 affected individuals were studied. HCV infection was confirmed using second and third generation ELISA test kits. HCV RNA was detected by a polymerase chain reaction (PCR) method and HCV genotyping was performed by analysing amplicons from the conserved 5'-non-translated region generated by nested PCR. Thirty two liver biopsies were carried out in 14 patients.HCV antibodies were detected in all subjects. Eighteen patients had abnormal liver enzymes and 17 were HCV RNA positive, all of whom were infected with genotype 1a. Ninety per cent of this cohort showed evidence of chronic HCV infection with 50% having progressive liver disease and 20% cirrhosis 18 years after acute onset of non-A, non-B hepatitis. Considerable variation in disease outcome occurred between individuals and no correlation with clinical features of the acute illness was found.Variability in the consequences of HCV infection in cases infected with the same virus suggests that host factors are important in determining disease outcome. The factors which determine differences in the natural history of the disease still remain to be elucidated.
Ablation of painful metastatic bone tumors: A systematic review
Authors: Gianpaolo Carrafiello, Domenico Laganà, Carlo Pellegrino, Monica Mangini, Federico Fontana, Filippo Piacentino, Chiara Recaldini, Francesca Rovera, Gianlorenzo Dionigi, Luigi Boni, Carlo Fugazzola
Journal: International Journal of Surgery (2008)
Oxygen dissociation curves in children with anemia and malignant disease
Authors: Robert S. Festa, Toshio Asakura
Journal: American Journal of Hematology (1979)

Abstract Two automatic apparatuses utilizing a dual wavelength spectrophotometer were used to perform oxygen dissociation curves on microsamples of blood. The method provides a complete print‐out of an oxygen dissociation curve in 15–20 min and the P 50 values obtained in normal individuals agree closely with those obtained by classical methods. These apparatuses were used to measure oxygen affinity, ie P 50 , in anemic children with malignant disease prior to treatment and in children undergoing therapy. Red cell 2,3‐DPG levels were also measured. In patients with anemia at the time of diagnosis and prior to therapy, the P 50 values and 2,3‐DPG levels were elevated as is usual in other types of anemia. However, when oxygen affinity and 2,3‐DPG levels were measured in anemic patients receiving treatment, three types of response to anemia were noted: 1) increased P 50 and 2,3‐DPG; 2) normal or low P 50 and 2,3‐DPG, and; 3) normal or low P 50 with increased 2,3‐DPG. Patients who adapted poorly to anemia during treatment had usually received prior intensive chemotherapy and transfusion therapy, and their pattern of red cell glycolytic intermediates was consistent with a red cell population with an increased cell age. The failure of some patients to respond to anemia with a decrease in oxygen affinity has implications in regards to the hemoglobin level at which they should be transfused.
Undergraduate medical education. Core curriculum should remain flexible.
Authors: K G Alberti, P H Baylis
Journal: BMJ (1993)

become the overriding aim of medical education, but it must recognise that some students will seek a medical degree as entry to a variety of activities related to health, including research, education, business, and public service.In such a future how will we define core and protect students' opportunity to exercise independent thought in approaching the complexities of medicine?A core of essential knowledge and skills relevant to medical practice undoubtedly exists and can be identified, but at what cost and to what purpose?In my view, which is coloured by my recent experience as dean of health sciences at McMaster University, medical schools should have confidence in students' ability to discern appropriate learning objectives and to pursue these in a self directed fashion.Judgment of students' qualification for licensure should be separated as much as possible from assessment of academic performance so as to maximise opportunities for personal and intellectual development during medical education.Endorsement of the core and options model without strict limitations on the definition of core will perpetuate a content driven, professorially controlled system of medical education unworthy of Britain's earlier traditions of leadership.The times demand a more aggressive commitment to innovation in the interests of both the public and the profession.
New Focus Placed on von Willebrand Disease
Authors: Rebecca Voelker
Journal: JAMA (1997)

FOR MANY patients, the heavy menstrual periods, frequent nosebleeds, and ease in bruising seem normal. They likely have a sister or mother who also has heavy periods. Or a father or brother with nosebleeds or bleeding gums. "Because others in the family have it, they just think this is life," said Anne Dilley, PhD, an epidemiologist in the Hematologic Diseases Branch of the Centers for Disease Control and Prevention (CDC) in Atlanta, Ga. Dilley is among a group of researchers, clinicians, and advocates who want to assure patients that excessive bleeding and bruising don't have to be a way of life. They're trying to focus more attention on the often unrecognized von Willebrand disease, an autosomal disorder characterized by mucous membrane bleeding. As Dilley embarks on the last phase of the first large-scale epidemiologic study examining the prevalence of the bleeding disorder in women, the Food and Drug Administration (FDA)
Hematologic Malignancies With Extramedullary Spread of Disease
Authors: Matthew Olnes, Patricia Alli, Amy Freedman, Martin Auster, Rodrigo Erlich
Journal: Journal of Clinical Oncology (2003)

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.2003.04.188 Journal of Clinical Oncology - published online before print November 1, 2016 PMID: 12721270 Hematologic Malignancies With Extramedullary Spread of Disease Case 3. Extra-Nodal Hodgkin’s Disease Presenting as Rapidly Progressive Liver Failure Matthew OlnesxMatthew OlnesSearch for articles by this author , Patricia AllixPatricia AlliSearch for articles by this author , Amy FreedmanxAmy FreedmanSearch for articles by this author , Martin AusterxMartin AusterSearch for articles by this author , Rodrigo ErlichxRodrigo ErlichSearch for articles by this author Show More Johns Hopkins Bayview Medical Center, Baltimore, MD https://doi.org/10.1200/JCO.2003.04.188 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Wenckebach and Mobitz Type II A-V Block Due to Block Within the His Bundle and Bundle Branches
Authors: ONKAR S. NARULA, PHILIP SAMET
Journal: Circulation (1970)

Fourteen patients with conduction defects were analyzed by using bundle of His (BH) recordings. The BH electrograms were validated by BH and right atrial pacing (AP). In 12 patients with Mobitz type II A-V block, failure in impulse transmission for the dropped beats was localized distal to the recording site of the BH. Three of these 12 patients showed normal QRS complexes. In two of these three, the QRS complexes remained unchanged during intermittent periods of complete heart block (CHB), and thus represent His bundle rhythm with subsidiary pacemaker arising above the bifurcation of the BH. The A-H time in this group of 12 patients ranged from 60 to 160 msec and the H-V time ranged from 40 to 90 msec. At any atrial rate (NSR or AP) conduction time through the A-V node (A-H), and His-Purkinje system (H-V) remained constant. With increasing atrial (A) rates during AP, the number of impulses blocked distal to the BH increased. At high AP rates Wenckebach phenomenon between A and BH occurred concomitantly with block distal to the BH. Of the two additional patients studied, the one with Wenckebach type 2° A-V block during NSR and a narrow QRS complex had the delay localized between two recorded and validated BH potentials ("split" BH). The other patient, with 1:1 A-V conduction during NSR and left bundle-branch block, developed Wenckebach cycles during AP at 110 beats/min. The progressive delay in the P-R interval was localized in the His-Purkinje system (HPS) probably in the right bundle. Our data support the clinical observations that Mobitz II A-V blocks are associated with bilateral bundle-branch block as well as with BH lesions. The ECG is of limited value in the localization of the delays occurring at two sites simultaneously: namely, in the A-V node and the HPS. Furthermore, demonstration of the Wenckebach cycles within the HPS (BH or either bundle branch), which cannot be determined from the surface ECG, has important clinical implications.
P51 DESUMOYLATION OF HYPOXIA INDUCIBLE FACTOR (HIF)-2a BY SENP1 IS INVOLVED IN HPPCn-ENHANCED SORAFENIB RESISTANCE UNDER HYPOXIA IN HEPATOCELLULAR CARCINOMA
Authors: B. Zhu, S.-S. Lin, P.-F. Liu, Y.-F. Li, H.-Y. Gao, Z.-Y. Su, H.-Y. Sun, L.-S. Wang, C.-P. Cui
Journal: Journal of Hepatology (2014)
G Protein–Coupled Receptor 30 (GPR30) Mediates Gene Expression Changes and Growth Response to 17β-Estradiol and Selective GPR30 Ligand G-1 in Ovarian Cancer Cells
Authors: Lidia Albanito, Antonio Madeo, Rosamaria Lappano, Adele Vivacqua, Vittoria Rago, Amalia Carpino, Tudor I. Oprea, Eric R. Prossnitz, Anna Maria Musti, Sebastiano Andò, Marcello Maggiolini
Journal: Cancer Research (2007)

Abstract Estrogens play a crucial role in the development of ovarian tumors; however, the signal transduction pathways involved in hormone action are still poorly defined. The orphan G protein–coupled receptor 30 (GPR30) mediates the nongenomic signaling of 17β-estradiol (E2) in a variety of estrogen-sensitive cancer cells through activation of the epidermal growth factor receptor (EGFR) pathway. Whether estrogen receptor α (ERα) also contributes to GPR30/EGFR signaling is less understood. Here, we show that, in ERα-positive BG-1 ovarian cancer cells, both E2 and the GPR30-selective ligand G-1 induced c-fos expression and estrogen-responsive element (ERE)-independent activity of a c-fos reporter gene, whereas only E2 stimulated an ERE-responsive reporter gene, indicating that GPR30 signaling does not activate ERα-mediated transcription. Similarly, both ligands up-regulated cyclin D1, cyclin E, and cyclin A, whereas only E2 enhanced progesterone receptor expression. Moreover, both GPR30 and ERα expression are required for c-fos stimulation and extracellular signal-regulated kinase (ERK) activation in response to either E2 or G-1. Inhibition of the EGFR transduction pathway inhibited c-fos stimulation and ERK activation by either ligand, suggesting that in ovarian cancer cells GPR30/EGFR signaling relays on ERα expression. Interestingly, we show that both GPR30 and ERα expression along with active EGFR signaling are required for E2-stimulated and G-1–stimulated proliferation of ovarian cancer cells. Because G-1 was able to induce both c-fos expression and proliferation in the ERα-negative/GPR30-positive SKBR3 breast cancer cells, the requirement for ERα expression in GPR30/EGFR signaling may depend on the specific cellular context of different tumor types. [Cancer Res 2007;67(4):1859–66]
Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome
Authors: Antonio Torrelo, Sapna Patel, Isabel Colmenero, Dolores Gurbindo, Francisco Lendínez, Angela Hernández, Juan Carlos López-Robledillo, Ali Dadban, Luis Requena, Amy S. Paller
Journal: Journal of the American Academy of Dermatology (2010)
Points from Letters: Manpower Needs in Nigeria
Authors: J. S. Dodge
Journal: BMJ (1966)

BRmsH 1603practitioners now do significant maternity work.Extra payments are to be made for the elderly on our lists.The elderly are not by any means the source of extra work for the family practitioner.Some of us would say that the mental invalid is much more time- consuming when treated and followed up properly, and there is no incentive at present for us to do this work.Service in pursuance of public policy is to attract extra payment.This is fair enough in vaccination, cervical smears, etc., but surely in a "health" service we should be encouraged to set time aside for routine physical check-ups as part of a full preventive service-including even preventive psychiatry.In incentive payments we have at last an effective means of guiding the future direc- tion and quality of family care.Let us hope that they will be used in a forward-looking way to improve service, and not as a means of simply placating present discontent.-Iam, etc., Dundee.
A PILLOW AT THE FOOT OF THE BED AFTER ABDOMINAL OPERATIONS
Authors: Thomas S. Cullen
Journal: JAMA (1923)

That continued disuse of the muscles is followed by a certain amount of atrophy and flabbiness is well known to all of us, and nowhere can we find a better example than in the legs after the patient has lain in bed some weeks. For many years I have often made it a practice, unless there were contraindications, to order a pillow placed at the foot of the bed a few days after an operation. This pillow can be pushed down between the lower end of the mattress and the foot of the bed, or be firmly fastened to the latter. The patient is instructed to use this pillow much as one would use a punching bag, and, in addition, the pillow also acts as a fixed point enabling him to push himself up gently in the bed. The frequent punching of the pillow in large measure prevents the muscles
Agr2 Mediates Paracrine Effects on Stromal Fibroblasts That Promote Invasion by Gastric Signet-Ring Carcinoma Cells
Authors: Tadahiro Tsuji, Rika Satoyoshi, Namiko Aiba, Takanori Kubo, Kazuyoshi Yanagihara, Daichi Maeda, Akiteru Goto, Kazuo Ishikawa, Masakazu Yashiro, Masamitsu Tanaka
Journal: Cancer Research (2014)

Agr2 is a disulfide isomerase residing in the endoplasmic reticulum (ER), which physiologically regulates protein folding and mediates resistance to ER stress. Agr2 is overexpressed in adenocarcinomas of various organs, where it participates in neoplastic transformation and metastasis, therefore acts as a pro-oncogenic protein. Besides its normal localization in the ER, Agr2 is also found in the serum and urine of cancer patients, although the physiological significance of extracellular Agr2 is poorly understood. In this study, we demonstrated that extracellular Agr2 can activate stromal fibroblasts and promote fibroblast-associated cancer invasion in gastric signet-ring cell carcinoma (SRCC), where Agr2 is highly expressed. Agr2 secreted from SRCC cells was incorporated by the surrounding gastric fibroblasts and promoted invasion by these cells. In turn, activated fibroblasts coordinated the invasive behavior of fibroblasts and cancer cells. Our findings suggested that Agr2 drives progression of gastric SRCC by exerting paracrine effects on fibroblasts in the tumor microenvironment, acting also to increase the growth and resistance of SRCC cells to oxidative and hypoxic stress as cell autonomous effects.
Disentangling separate effects
Authors: Jane Smith
Journal: BMJ (2006)

A cartoon by the American cartoonist Sidney Harris has one white-coated researcher saying to another: “Find out who set up this experiment. It seems that half of the patients were given a placebo and the other half were given a different placebo.” In this week's BMJ we bring you that experiment.

On p 391 Ted Kaptchuk and colleagues report their randomised trial of two “placebo treatments.” They wanted to see whether a sham acupuncture needle had a greater placebo effect than an inert pill in patients with persistent arm pain. The patients were randomised to …
ABC of Medical Computing: THE INTERNET
Authors: A. Millman, N. Lee, K. Kealy
Journal: BMJ (1995)

The Internet is a huge network of computers that spans the globe. It originated in the late 1960s from an American military project which was intended to provide reliable communications in the event of a nuclear war. The network started with just four computers but grew rapidly over the next few years. An estimated 40 million computers are now connected to it, and this number is growing by about 10% each year. Although access was originally restricted to government departments and organisations such as universities, the Internet has recently been opened up to everybody. It is now used by people and organisations from all walks of life including commercial organisations, university departments, hospitals, and medical schools, as well as agrowing number of individual users dialling in from home.



The Internet is best regarded as a framework which allows the free exchange of information between computers. With new services and users connecting to the network every day, it is becoming increasingly valuable as an information resource and communications superhighway. Among other things, it is now possible to access thousands of databases at universities and other research centres all over the world, read electronic journals, view and buy products from numerous companies, exchange news and views on a wide range of specialist subjects, and send virtually instantaneous electronic mail to any organisation, company, or individual connected to the internet.

### Services available on theInternet

Accessing the Internet is very easy. You need a computer and a modem connected to a telephone line, and you will also need to contact an Internet service provider who will supply you with suitable software to load on to your computer, an Internet telephone number and password, an email address, and access to a help desk. Good software will store the telephone number of …
SUNLIGHT AND SKIN CANCER IN KENYA
Authors: FRANK PIERS
Journal: British Journal of Dermatology (1948)

Journal Article SUNLIGHT AND SKIN CANCER IN KENYA Get access FRANK PIERS, M.D., L.R.C.P., L.R.C.S. FRANK PIERS, M.D., L.R.C.P., L.R.C.S. Nairobi, Kenya Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 60, Issue 10, 1 October 1948, Pages 319–332, https://doi.org/10.1111/j.1365-2133.1948.tb10933.x Published: 01 October 1948
Characteristics of genetic epidemiology and genetic models for vitiligo
Authors: Xue-Jun Zhang, Jiang-Bo Liu, Jin-Ping Gui, Ming Li, Quan-Geng Xiong, Hong-Bo Wu, Jin-Xian Li, Sen Yang, Hong-Yan Wang, Min Gao, Jie Yang, Qing Yang
Journal: Journal of the American Academy of Dermatology (2004)