tbuckley/cabot-search huggingface dataset:
Is methadone too dangerous for opiate addiction?: Methadone is still needed in addiction treatments
Authors: Andrew Byrne, Richard Hallinan
Journal: BMJ (2006)

The nursing profession's coming of age The end of medicine as a professionEditor-Young describes the coming of age of the nursing profession. 1 All professions and occupations are human creations and therefore are subject to change.With the widening of roles of many professions, it becomes harder to define what a doctor can do that can't be done by an appropriately trained member of another profession.Perhaps major surgery and certifying cause of death are all that remains.With the increasing difficulty of getting junior doctors to do anything that may be regarded as work (rather than education) we doctors may be engineering the abolition of our profession, and we may move from distinct professions to practitioners from varied backgrounds being trained for a particular function.
Abstract 4929: Hypermethylation of tumor suppressor gene promoters in basal cell carcinoma
Authors: Tjinta Brinkhuizen, Manon van Engeland, Ariënne van Marion, Maurice van Steensel
Journal: Cancer Research (2010)

Abstract Background Basal-cell carcinoma (BCC) is the most frequent malignancy in Caucasians, with increasing incidence. Overactivity of the Sonic Hedgehog pathway is implicated in BCC etiology, however recent literature suggests that BCC carcinogenesis may be more complex. Silencing of tumor suppressor genes by promoter hypermethylation, influenced by hypoxia, results in deregulation of cancer-related pathways. Since BCC arises in a hypoxic micro-environment, we assumed that epigenetic modifications may play a major part in BCC tumorigenesis. In this pilot we investigated promoter hypermethylation of tumor suppressor genes selected for their possible involvement in BCC. Eventually, knowledge of epigenetic modifications in BCC may impact diagnosis, classification, and treatment. Methods DNA was isolated from 33 formalin fixed paraffin-embedded BCC of 3 different histological subtypes. Marked tumor tissue was macroscopically scraped from slides and collected. CpG island methylation status of 10 promoter regions was analysed by methylation-specific PCR on sodium bisulfite-treated DNA. Data were compared with 36 normal skin tissue samples. All data were analysed with SPSS version 17.0. We used the Pearson Chi-Square test. Statistical significance was defined as a p-value ≤0.05. Results DNA methylation levels of the examined candidate gene promoters in tumor tissue compared to normal skin tissue were significantly higher for the following genes: APC 100% vs. 47,1% (p&amp;lt;0,001); sFRP5 93,9% vs. 42,4% (p&amp;lt;0,001); SHH 90,9% vs. 50,0% (p&amp;lt; 0,001) and 81,8% vs. 56,3% (p= 0,029) for CylD. In addition, the PTCH1 promoter showed a tendency to hypermethylation. The remaining promoters of sFRP1, sFRP2, sFRP4, TSC1 and RASSF1A showed no hypermethylation. Conclusions From our preliminary data we conclude that in BCC, promoters of several tumor suppressor genes, which may normally inhibit BCC growth, show aberrant methylation resulting in silencing of these genes. As a consequence, signalling pathways implicated in cancerous growth such as the SHH-, WNT- and NFκB- routes may be affected. Our data provide evidence that epigenetic modifications may play a role in BCC tumorigenesis. Genome-wide analyses will be our next step to screen for more relevant genes and to chart the full extent of genomic methylation changes in BCC. This entirely new approach may lead to new insights into development and treatment of BCC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4929.
Mitochondrial CB1 receptors regulate neuronal energy metabolism
Authors: Giovanni Bénard, Federico Massa, Nagore Puente, Joana Lourenço, Luigi Bellocchio, Edgar Soria-Gómez, Isabel Matias, Anna Delamarre, Mathilde Metna-Laurent, Astrid Cannich, Etienne Hebert-Chatelain, Christophe Mulle, Silvia Ortega-Gutiérrez, Mar Martín-Fontecha, Matthias Klugmann, Stephan Guggenhuber, Beat Lutz, Jürg Gertsch, Francis Chaouloff, María Luz López-Rodríguez, Pedro Grandes, Rodrigue Rossignol, Giovanni Marsicano
Journal: Nature Neuroscience (2012)
The Calciferol Requirements of Patients with Surgical Hypoparathyroidism
Authors: ANTHONY W. IRELAND
Journal: Annals of Internal Medicine (1968)

Thirty patients with surgical hypoparathyroidism are presented. All received vitamin D therapy in the form of calciferol. Biochemical control, as defined by arbitrary criteria, was achieved in only nine patients for a total period of 26 patient-years. The mean controlling dose of calciferol was 2.12 mg/day; the mean dose producing hypercalcemia in 16 patients was 3.28 mg/day. No patient was controlled on less than 1.25 mg/day, and only two patients were controlled on a calciferol dose of 1.25 mg/day. Every patient receiving calciferol doses greater than 2.50 mg/day became hypercalcemic. A mechanism is suggested for the proximity between "controlling" and "intoxicating" doses of calciferol in hypoparathyroidism. The documented periods of hypercalcemia lasted 1 to 6 weeks after withdrawal of calciferol. No significant differences were found between the calciferol requirements of euthyroid and hypothyroid patients.
Stimulation of amphibian gastroduodenal bicarbonate secretion by sucralfate and aluminium: role of local prostaglandin metabolism.
Authors: J R Crampton, L C Gibbons, W D Rees
Journal: Gut (1988)

The present studies were designed to explore the possible mode of protective and ulcer healing actions of sucralfate by examining its effect on gastroduodenal bicarbonate secretion by isolated amphibian mucosa. Luminal sucralfate (0.5 g/l) significantly increased bicarbonate secretion by fundic and antral mucosa without influencing transmucosal potential difference. Significant stimulation of duodenal bicarbonate secretion occurred only at 1.0 g/l without change in potential difference. Aluminium, a component of sucralfate, produced similar increases in bicarbonate secretion, while the sucrose and sulphate components were without effect. Pretreatment of mucosae with the cyclooxygenase inhibitor, indomethacin (10 5M) did not abolish the secretory response to sucralfate or aluminium. The results suggest that stimulation of gastroduodenal bicarbonate secretion, possibly by the aluminium moiety of sucralfate, may play a role in its protective and ulcer healing actions.
Anogenital Cutaneous Lesions
Authors: Robert R. Kierland
Journal: JAMA (1968)

You know, or should know, what a great pleasure it is for me to be with you today. To be chosen by colleagues to be chairman of the Section on Dermatology of the American Medical Association is a high honor and one that is appreciated most deeply. With the chairmanship go the honors; it should be emphasized, however, that the secretary, J. Fred Mullins, MD, with his capable assistant secretary E. Richard Harrell, MD, actually does all of the work. My only task is to address you, my friends and fellow dermatologists, and at first glance this would appear to be a simple procedure or task. Choosing a subject, however, that would be of interest to most, and of help to all, is not easy and is a task to which I have devoted some hours of thinking. I am not a philosopher, my research days are behind me, and
Extent of the acute phase response in fulminant hepatic failure.
Authors: S Izumi, R D Hughes, P G Langley, J R Pernambuco, R Williams
Journal: Gut (1994)

The extent of the acute phase response and the relation between acute phase proteins and cytokines in plasma was investigated in 50 patients with fulminant hepatic failure. On admission, C reactive protein was significantly higher in fulminant hepatic failure (median: 12.4 micrograms/ml, range:0.2-112 micrograms/ml) than in 20 controls (median: 0.8 microgram/ml, range: 0.3-2.9 micrograms/ml, p &lt; 0.001). Serial measurements showed that plasma C reactive protein increased daily after admission until day 5, the end of the study period. alpha 1-Antitrypsin (AAT) (median: 69.1%, range: 27.5-124%) and fibrinogen (median: 1.10 g/l, range: 0-2.82 g/l) were significantly lower in fulminant hepatic failure on admission than in controls (AAT: median: 126%, range: 75.4-149%; fibrinogen: median 2.48 g/l, range: 1.82-3.39 g/l, p &lt; 0.001) and did not change subsequently. Both AAT and fibrinogen were maintained at significantly higher concentrations in survivors than in those who did not. Bacterial infection occurred in 23 patients during the course of fulminant hepatic failure, but did not influence the concentrations of these three proteins. Interleukin 6 was significantly higher in fulminant hepatic failure (median: 21.2 pg/ml, range: 0-871 pg/ml) than in controls (median: 2.4 pg/ml, range: 1.5-8.2 pg/ml, p &lt; 0.001). There was a significant correlation between interleukin 6 and the C reactive protein concentrations in patients with viral hepatitis on admission and in all patients 48 hours later, consistent with other evidence that interleukin 6 stimulates synthesis of this acute phase protein.
A Dose–Response Study of Arsenic Exposure and Global Methylation of Peripheral Blood Mononuclear Cell DNA in Bangladeshi Adults
Authors: Megan M. Niedzwiecki, Megan N. Hall, Xinhua Liu, Julie Oka, Kristin N. Harper, Vesna Slavkovich, Vesna Ilievski, Diane Levy, Alexander van Geen, Jacob L. Mey, Shafiul Alam, Abu B. Siddique, Faruque Parvez, Joseph H. Graziano, Mary V. Gamble
Journal: Environmental Health Perspectives (2013)

Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation.The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water.Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation.Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures.These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications.
Primary Malignant Melanoma of the Oesophagus
Authors: W. Roesch, H.G. Rohner
Journal: Endoscopy (1984)

Primary malignant melanoma of the oesophagus is a rare tumour, whereas metastatic disease originating from melanomas is occasionally encountered in the upper GI-tract. Two cases of endoscopically diagnosed primary esophageal melanomas are presented which were treated by surgery and radiotherapy combined with immunostimulation, respectively.
Effect of left ventricular systolic pressure increase on ventricular arrhythmogenicity in old canine myocardial infarction
Authors: K. Yano, O. Hano, T. Hirata, Y. Matsumoto, M. Hirata, T. Mitsuoka
Journal: Cardiovascular Research (1992)

The aim was to examine the effect of an increase in left ventricular systolic pressure (LVSP) on ventricular arrhythmogenicity in old canine myocardial infarction.Fourteen mongrel dogs of either sex weighing 11 to 15 kg were used. Studies were performed 28 d after creation of myocardial infarction by ligation of the anterior descending coronary artery. Electrical induction of ventricular arrhythmia and determinations of effective refractory period (ERP) and local intraventricular conduction delay (LIVCD) were performed using the extrastimulus technique with a cycle length of 300 ms in the normal and infarcted zones of the left ventricle. Heterogeneity of ERP (delta ERP) was determined as a difference between the longest and shortest ERP values in each site. LVSP was raised by constriction of the ascending aorta in a stepwise fashion (control, level A, level B).Incidence of electrically induced ventricular arrhythmia was increased from 28.6% at control level of LVSP [130.7(SEM 7.3) mm Hg] to 42.9% at level A [190.9(6.0) mm Hg] and to 64.3% (p < 0.05) at level B [243.3(4.0) mm Hg]. delta ERP and LIVCD were greater in the infarct zone than in the normal zone at each level of LVSP (p < 0.001). delta ERP in the infarct zone increased from 18.9(4.3) ms at control level of LVSP to 20.7(6.8) ms at level A, and to 27.1(8.1) ms at level B (p < 0.001). LIVCD in the infarct zone also increased from 22.9(6.2) ms at control level of LVSP to 26.8(4.9) ms at level A (p < 0.001), and to 36.1(6.0) ms at level B (p < 0.001). delta ERP and LIVCD in the normal zone were only slightly raised by increasing the LVSP. delta ERP and LIVCD in the infarct zone were closely correlated with incidence of electrically induced ventricular arrhythmia.Increasing the LVSP enhances ventricular arrhythmogenicity and pre-existing electrophysiologic abnormalities of the heart in the presence of old myocardial infarction. Thus a rise in LVSP from any cause in the old myocardial infarction can be a trigger of life threatening ventricular arrhythmias.
Intra-Arterial Barbiturate Injection in a Drug Addict
Authors: ITAMAR KOTT
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The damaging effects of intra-arterial barbiturate injections were first described by Van der Post in 1942. Until recently the vast majority of cases had been related to the administration of anesthetics. However, the marked increase of parenteral drug usage by addicts has today resulted in the presentation of this problem at the hospital emergency unit.<sup>1</sup> <h3>Report of a Case.—</h3> The patient was a 23-year-old addict who had been injecting heroin and other drugs for five years. On the day of hospitalization he had introduced 75 mg of secobarbital dissolved in water into his right wrist. He immediately experienced burning pain in the right hand, which became swollen and mottled within ten minutes. Within two hours his hand was markedly swollen, cyanotic, and anesthetized. Numerous similar self-administered injections had occurred uneventfully in the past, but on this occasion the injection inadvertently went into the radial artery instead
Sustainable health services are crucial to reducing NHS's carbon footprint, conference hears
Authors: M. Limb
Journal: BMJ (2014)

An “integrated” national strategy to promote sustainable services across England’s health, public health, and social care system has been launched.

Senior health and local government figures said that the plan would help organisations to deal with deep social and financial problems and to build community resilience to cope with climate change.

The strategy was launched on 29 January in London by the Sustainable Development Unit, which is funded by NHS England and Public Health England.1

It is not backed by extra funding, but it encourages organisations and their staff to develop sustainable care and business models that use resources more effectively to improve people’s health and create a healthier environment.

But David Nicholson, the NHS’s chief executive, said that more investment in outpatient care would be needed to enable people to look after their own health, as this was …
CALR-mutated essential thrombocythemia evolving to chronic myeloid leukemia with coexistent CALR mutation and BCR-ABL translocation
Authors: Irina Bonzheim, Barbara Mankel, Peter Klapthor, Janine Schmidt, Tanja Hinrichsen, Oliver Wachter, Falko Fend, Leticia Quintanilla-Martinez
Journal: Blood (2015)
Book Review Understanding Health Care Reform By Theodore R. Marmor. 288 pp. New Haven, Conn., Yale University Press, 1994. $35 (cloth); $14 (paper). 0-300-05878-0 (cloth); 0-300-05879-9 (paper). Medicine's Dilemmas: Infinite Needs versus Finite Resources By William L. Kissick. 240 pp., illustrated. New Haven, Conn., Yale University Press, 1994. $25 (cloth); $12 (paper). 0-300-05964-7 (cloth)
Authors: Steffie Woolhandler, David U. Himmelstein
Journal: New England Journal of Medicine (1994)
COX-2 Inhibitors — A Lesson in Unexpected Problems
Authors: Jeffrey M. Drazen
Journal: New England Journal of Medicine (2005)

This issue of the Journal contains three articles about the adverse cardiovascular effects of agents that selectively inhibit one form of prostaglandin endoperoxide synthase, commonly known as cyclooxygenase-2 (COX-2).13 This is part of a long bench-to-bedside story with an adverse outcome that was not widely anticipated at its start. Unfortunately, as the evidence began to suggest unexpected toxicity of this group of agents, the same zeal that had driven the clinical investigation to show their gastrointestinal safety was not evidenced by studies designed to show their cardiovascular safety.In 1987, evidence emerged4 that there were probably two enzymes — . . .
The challenge of preventing environmentally related disease in young children: community-based research in New York City.
Authors: Frederica P Perera, Susan M Illman, Patrick L Kinney, Robin M Whyatt, Elizabeth A Kelvin, Peggy Shepard, David Evans, Mindy Fullilove, Jean Ford, Rachel L Miller, Ilan H Meyer, Virginia A Rauh
Journal: Environmental Health Perspectives (2002)

Rates of developmental and respiratory diseases are disproportionately high in underserved, minority populations such as those in New York City's Washington Heights, Harlem, and the South Bronx. Blacks and Latinos in these neighborhoods represent high risk groups for asthma, adverse birth outcomes, impaired development, and some types of cancer. The Columbia Center for Children's Environmental Health in Washington Heights uses molecular epidemiologic methods to study the health effects of urban indoor and outdoor air pollutants on children, prenatally and postnatally, in a cohort of over 500 African-American and Dominican (originally from the Dominican Republic) mothers and newborns. Extensive data are collected to determine exposures to particulate matter < 2.5 microm in aerodynamic diameter (PM(2.5)), polycyclic aromatic hydrocarbons (PAHs), diesel exhaust particulate (DEP), nitrogen oxide, nonpersistent pesticides, home allergens (dust mite, mouse, cockroach), environmental tobacco smoke (ETS), and lead and other metals. Biomarkers, air sampling, and clinical assessments are used to study the effects of these exposures on children's increased risk for allergic sensitization, asthma and other respiratory disorders, impairment of neurocognitive and behavioral development, and potential cancer risk. The center conducts its research and community education in collaboration with 10 community-based health and environmental advocacy organizations. This unique academic-community partnership helps to guide the center's research so that it is most relevant to the context of the low-income, minority neighborhoods in which the cohort resides, and information is delivered back to these communities in meaningful ways. In turn, communities become better equipped to relay environmental health concerns to policy makers. In this paper we describe the center's research and its academic-community partnership and present some preliminary findings.
Surgeons in the United States
Authors: Lowell Brown
Journal: JAMA (1977)

<h3>To the Editor.—</h3> As a general surgeon in a community hospital, I would like to comment on the article "Surgeons in the United States: Activities, Output and Income," by Walter W. Hauck, Jr, PhD, et al (236:1864, 1976), wherein the authors conclude that the operative work loads of surgeons are, in general, too low. As background, it is interesting that of the six co-authors commenting on the practice of my specialty, only one is a physician, and he, Osler L. Peterson, MD, is apparently not a practicing surgeon. Also, as seems customary in such studies, it emanates from an institution, Harvard Medical School in this instance, where only one form of surgical practice is known—that of the so-called teaching institution with a surgical residency training program and a university affiliation. The thing that troubles me about this article and others of a similar nature is that no effort is made
Busulfan, cyclophosphamide, and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma
Authors: Christopher R. Cogle, Jan S. Moreb, Helen L. Leather, Katarzyna J. Finiewicz, Shahab A. Khan, Vijay S. Reddy, John R. Wingard
Journal: American Journal of Hematology (2003)

Abstract Autologous stem cell transplantation (ASCT) has enabled the use of high‐dose alkylating agents either as a single agent or in combination with other cytotoxic agents and/or total body irradiation (TBI) for the treatment of multiple myeloma. Despite improved complete remission rates, relapse and regimen‐related toxicities remain challenging. In an effort to increase event‐free survival and decrease the high incidence of regimen‐related toxicity, we have studied the use of etoposide in combination with reduced‐dose busulfan and cyclophosphamide as a conditioning regimen for ASCT in a group of 26 patients with advanced multiple myeloma. Median follow‐up for the group was 30 months. There was no early treatment‐related mortality. The main toxicity was mucositis. Otherwise, there was 1 case of reversible, clinically diagnosed hepatic veno‐occlusive disease. Post‐engraftment, 10 patients (38%) achieved CR, 15 (58%) patients achieved PR or SD, and 1 patient developed progressive disease (4%). Five patients in PR and 1 with progressive disease before transplant attained a CR post‐transplant. The median times for event‐free survival and overall survival after transplantation were 24 and 43 months, respectively. In conclusion, conditioning with busulfan, cyclophosphamide, and etoposide followed by ASCT is a safe regimen with comparable effectiveness to other previously used preparative regimens, thus providing another approach of non‐TBI containing high‐dose chemotherapy for patients with multiple myeloma. Am. J. Hematol. 73:169–175, 2003. © 2003 Wiley‐Liss, Inc.
X-RAY FUSED MAGNETIC RESONANCE IMAGING GUIDED INTRAPERICARDIAL DELIVERY OF XENOGENIC MESENCHYMAL STEM CELLS IN SWINE
Authors: Yingli Fu, Nicole Azene, Tina Ehtiati, Aaron Flammang, Wesley Gilson, Judy Cook, Kathleen Gabrielson, Clifford Weiss, Jeff Bulte, Peter Johnston, Dara Kraitchman
Journal: Journal of the American College of Cardiology (2012)
Pfizer criticised over delay in admitting drug's problems
Authors: Jeanne Lenzer
Journal: BMJ (2004)

Pfizer delayed announcing negative data about its painkiller valdecoxib (Bextra), Curt Furberg, a member of the US Food and Drug Administration's Data Safety and Risk Management Advisory Committee, told the BMJ this week. When the company eventually presented its data to the FDA, it also left out important details, Dr Furberg alleges.

Pfizer stood to gain by …