tbuckley/cabot-search huggingface dataset:
Abstract P5-15-06: Societal economics of the 21-gene Recurrence Score® in estrogen-receptor-positive early-stage breast cancer in Japan
Authors: H Yamauchi, C Nakagawa, S Yamashige, H Takei, H Yagata, A Yoshida, N Hayashi, J Hornberger, T Yu, R Chien, C Chao, C Yoshizawa, S Nakamura
Journal: Cancer Research (2012)

Abstract Background: Breast cancer incidence and breast-cancer mortality have been increasing in Japan. In estrogen-receptor-positive breast cancer, adding chemotherapy as adjuvant treatment is not definitive benefit for all women. Primary data on the clinical validity and decision impact of the 21-gene Recurrence Score for guiding the use of adjuvant chemotherapy has been studied among a Japanese population. Objective: The cost-effectiveness of the clinically validated 21-gene Recurrence Score for estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer (ESBC) was assessed from a Japanese societal perspective. Method: The proportion of patients with low, intermediate, and high risk of recurrence by the 21-gene Recurrence Score and the influence of the Recurrence Score on use of adjuvant chemotherapy were obtained in a study of 104 patients. A Markov model was used to track time until distant recurrence and time from distant recurrence to death. Effect of adjuvant chemotherapy based on 21-gene Recurrence Score was based on published clinical validation studies. Direct and indirect medical costs were obtained from the referral center. Utilities associated with progression and adverse events associated with chemotherapy were extracted from the literature. Sensitivity analyses were performed to assess the key drivers of cost-effectiveness and the robustness of the findings to variations in the input estimates. Results: Forty-eight percent of patients were identified by the 21-gene Recurrence Score as low-risk, 36% as intermediate-risk, and 16% as high-risk. In treatment decision by using the 21-gene Recurrence Score, chemotherapy use overall decreased by 19%, resulting in an average increase of 0.235 QALYs. Testing with the 21-gene Recurrence Score cost ¥350,000 per patient with ¥153,490 lower acute costs because fewer women were treated with adjuvant chemotherapy. Eighteen percent more women who were identified as high risk were recommended adjuvant chemotherapy, which results in longer progression-free survival. On average across all risk groups, cost of monitoring until recurrence per patient increased by ¥3,572 and costs associated with recurrence declined by ¥43,687. Use of the 21-gene Recurrence Score resulted in a net cost of ¥665,455 ($8,386) per QALY gained. Conclusions: The change in decisions resulting from use of the 21-gene Recurrence Score in women with estrogen-receptor-positive, lymph-node-negative, ESBC is projected to be societally cost-effective in Japan. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-06.
Histology, Anatomy, or Geography? Exome Sequencing Begins to Delineate Somatic Mutational Differences in Esophageal Cancer
Authors: Eric A. Collisson, Raymond J. Cho
Journal: Cancer Discovery (2012)

Esophageal carcinoma is composed of squamous cell and adenocarcinoma types, each with geographically distinct incidence. The earliest exome sequences in this disease begin to illuminate the genetic demarcations of these anatomically related cancers.
Employment practices in NHS trusts
Authors: S. Silcox
Journal: BMJ (1993)

injected temazepam tablets.Since temazepam is such a popular drug of misuse, I fear that injection of tablets will become more commonplace as liquid and gel filled capsules become harder to obtain.Injecting tablets is likely to be much more dangerous than injecting the liquid from capsules; injecting gel filled capsules is known to be dangerous.2Probably the only way to prevent misuse of temazepam is not to prescribe it in any formulation.
1243 PRECLINICAL CHARACTERIZATION OF NOVEL POTENT NON-NUCLEOSIDE NS5B PALM SITE INHIBITORS
Authors: P.A. Thompson, C.V. Tran, D.E. Murphy, A.X. Xiang, R.A. Patel, H. Hou, R.E. Showalter, X. Liao, J.R. Appleman, S.E. Webber
Journal: Journal of Hepatology (2011)
Who Needs Medicaid?
Authors: David E. Rogers, Robert J. Blendon, Thomas W. Moloney
Journal: New England Journal of Medicine (1982)

Faced by a worsening economy and a powerful public mandate to decrease taxes and non-defense government expenditures, many are calling for additional cuts in spending for Medicaid-a large, not very popular program that pays for the medical care of many of the nation's poor. Available evidence suggests that Medicaid has been far more valuable than is commonly realized: It serves a broad cross-section of the American people, its adoption coincides with major improvements in the health of Americans, and its costs per recipient are about the same as the costs of care per person for all Americans of similar age. Not widely recognized is the program's importance to the financial well-being (if not the very survival) of any major teaching hospitals and the majority of nursing homes in this country. Public and professional awareness of the accomplishments of this program may be a crucial factor in determining whether the cuts will spare many of the gains in access to medical care that have been made during the past two decades. If we do not wish to reduce needed medical services to the poor, health-care institutions and health professionals will have to cooperate with each other and with the government in developing less costly ways of delivering high-quality care.
HAZARD FROM LID OF SCREENED BED
Authors: Greta B. Millikan
Journal: JAMA (1930)

To the Editor:  —I have recently passed through the bitterest experience of my life in losing a year old grandchild. She was strangled by catching her head under the lid of a screened bed. The need of an automatic lid fastener for such beds is imperative, and I have taken every means I can think of to urge this point. I have written to manufacturers of beds and to child specialists, and I am now writing you hoping that it may be possible to publish at least a word of caution in your journal. The need of anautomaticfastener seems to me very great—one which would securely fasten the lid whether the nurse remembered it or not.
Intravenous fluid therapy in adult inpatients
Authors: P. Frost
Journal: BMJ (2015)

Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses <i>α</i>-, <i>β</i>-, and <i>γ</i>-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1<i>β</i> expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1<i>β</i> expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1<i>β</i> mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1<i>α</i> in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1<i>α</i>-knockout (NOS1<i>α</i>KO) mice. Compared with control mice, mice with macula densa–specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (<i>P</i>&lt;0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (<i>P</i>&lt;0.01) fed a high-salt diet. These results indicate that NOS1<i>β</i> is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.
Cutaneous vasculitis and IgA glomerulonephritis in ankylosing spondylitis.
Authors: C Beauvais, G Kaplan, B Mougenot, C Michel, E Marinho
Journal: Annals of the Rheumatic Diseases (1993)

Two patients with ankylosing spondylitis were found to have IgA nephropathy and leucocytoclastic cutaneous vasculitis. Immunofluorescence showed perivascular deposition of IgA in the skin of one patient and in the mesangium of both patients. Such an association has been reported only once before. This supports the concept of abnormal IgA immune stimulation in the pathogenesis of ankylosing spondylitis.
GMC advises doctors on seeking consent
Authors: L. Beecham
Journal: BMJ (1999)

The UK General Medical Council (GMC) has issued advice for doctors on seeking patients“ consent.

The new guidance, prepared by the GMC's standards committee, discusses the ethical issues that doctors should consider before, during, and after obtaining the consent of patients to investigation, treatment, screening, and research.

The publication points out that the amount of information patients …
Physicians' attitudes to four common problems: hypertension, atrial fibrillation, transient ischaemic attacks, and angina pectoris.
Authors: C A Bucknall, G K Morris, J R Mitchell
Journal: BMJ (1986)

A questionnaire was completed by 341 senior physicians on their attitudes to four common cardiovascular problems. Their replies showed that uncertainty about the end point for diastolic blood pressure still prevails and that their approach to the management of hypertension of differing severity in men and women of varying ages stems more from personal belief than from the results of clinical trials. Unless patients with atrial fibrillation also had mitral valve disease anticoagulation was not thought to be necessary, thereby making it ethically possible to carry out a trial of anticoagulants in stroke prevention on patients with atrial fibrillation but no valvular disease. The physicians9 suggestions for very active management in transient ischaemic attacks extended beyond the evidence available to them, whereas their approach to the use of coronary arteriography closely reflected the results of clinical trials. These findings may indicate that recent cardiovascular trials that have provided definitive results have had more impact than earlier inadequate studies.
Colitis of Long Duration
Authors: Edward H. Eliscu
Journal: JAMA (1968)

Dr. Edward H. Eliscu: The patient is a 50-year-old white woman who for 30 years had experienced malaise, fever, vomiting, and non-bloody diarrhea which was recently associated with weakness. The past medical history and the family history were noncontributory. Physical examination revealed a pale woman in no distress. Abdominal examination showed nothing remarkable. Laboratory studies revealed a hemoglobin level of 10 gm/100 cc, white blood cell count of 22,000, and a temperature of 101 F (38.3 C). Results of the guaiac test on the stool on several occasions gave 2+ values and on several occasions were not positive. Sigmoidoscopy was performed and the findings were said to be characteristic of ulcerative colitis. The stool examination revealed a few pus cells and culture produced<i>Escherichia coli</i>. The patient was treated with intravenous fluid and improved. Since her first episode in 1937, she had regulated her diet, eliminating roughage and spicy foods,
Regulation of Glucose-Transporter Function
Authors: Mary A Kasanicki, Paul F Pilch
Journal: Diabetes Care (1990)

Glucose transport in mammals is mediated by a multigene family whose expression can be highly tissue specific. All cells express at least one transporter isoform in a constitutive fashion, because a certain level of glucose uptake is an absolute necessity, regardless of influences by various regulatory factors. The level of the constitutive transporter, usually the erythroid glucosetransporter isoform, can be regulated by environmental factors, e.g., nutrition and transformation. Certain cells express unique transporter isoforms, the quantitatively most important of which is the muscle-adipocyte glucose-transporter isoform that functions in response to insulin to clear most of the blood glucose after a meal. The available data suggest that the major insulin target tissues are uniquely able to produce this transporter isoform, sequester it in a unique organelle, and bring it to the cell surface in response to insulin. This insulin response is dramatically different from that seen in various fibroblastic cells, quantitatively and qalitatively, and suggests the expression in adipose tissue and muscle of a multigene program that defines the insulin-stimulated glucose transport of relevance to organismal glucose homeostasis.
Dexamethasone did not reduce mortality or neurologic sequelae in bacterial meningitis
Authors: Fred A. Zar
Journal: Annals of Internal Medicine (2010)

ACP Journal Club17 August 2010Dexamethasone did not reduce mortality or neurologic sequelae in bacterial meningitisFred A. Zar, MD, FACPFred A. Zar, MD, FACPUniversity of Illinois at Chicago, Chicago, Illinois, USA (F.A.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-4-201008170-02010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source Citationvan de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurol. 2010;9:254-63. https://pubmed.ncbi.nlm.nih.gov/20138011Clinical Impact RatingsEmergency Med: Hospitalists: Infectious Disease: Neurology: References1 Lebel MH, Freij BJ, Syrogiannopoulos GA, et al. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. N Engl J Med. 1988;319:964-71. [PMID: 3047581] Google Scholar2 Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med. 1991;324:1525-31. [PMID: 2027357] Google Scholar3 van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids in acute bacterial meningitis. Cochrane Database Syst Rev. 2003;(3):CD004405. [PMID: 12918010] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Illinois at Chicago, Chicago, Illinois, USA (F.A.Z.)This article was published at Annals.org on 3 August 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 August 2010Volume 153, Issue 4Page: JC2-10KeywordsAge groupsBacterial meningitisHearingInfectious diseasesLife expectancyMeningitisNeurologySurvival analysis ePublished: 17 August 2010 Issue Published: 17 August 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Methods for evaluating the effects of environmental chemicals on human sperm production.
Authors: A J Wyrobek
Journal: Environmental Health Perspectives (1983)

Sperm tests provide a direct and effective way of identifying chemical agents that induce spermatogenic damage in man. Four human sperm tests are available: sperm count, motility, morphology (seminal cytology) and the Y-body test. These sperm tests have numerous advantages over other approaches for assessing spermatogenic damage, and they have already been used to assess the effects of at least 85 different occupational, environmental, and drug-related chemical exposures. When carefully controlled, seminal cytology appears to be statistically more sensitive than the other human sperm tests and should be considered an integral part of semen analysis when assessing induced spermatogenic damage. Human sperm studies have complex requirements and, before sampling, careful consideration should be given to exposure details, group size and makeup, as well as animal and human data that indicate spermatogenic effects. Several study designs are possible and should include questionnaires covering medical and reproductive histories as well as known confounding factors. Animal sperm tests, such as the mouse morphology test, may be used to identify the toxic components of a complex mixture. Animal tests may also help assess the chemical effects on fertility and reproductive outcome in cases when human data are incomplete. Further efforts are needed in these areas to develop improved human sperm tests sensitive to induced spermatogenic damage, to develop improved animal models of induced spermatogenic damage, to understand the relationships among sperm changes, fertility, and reproductive outcome, and to develop sperm tests with express mutational end points.
Abstract 390: Expression of the actin-binding protein Anillin is a prognostic biomarker for primary ER positive breast cancer.
Authors: Kristina Magnusson, Gabriela Gremel, Fredrik Pontén, Karin Jirström
Journal: Cancer Research (2013)

Abstract Identification of novel prognostic and predictive factors is important for individualizing prognosis and treatment for cancer patients. The present study aimed at examining the potential prognostic value of Anillin (ANLN) expression in breast cancer. ANLN, an actin-binding protein required for cytokinesis, was discovered using the Human Protein Atlas as being differentially expressed in breast cancer and, thus, a potential prognostic biomarker. The purpose of the Human Protein Atlas project (www.proteinatlas.org) is to generate validated antibodies towards the entire human proteome and to use these antibodies for protein profiling in normal tissues and cancer cells. The freely available Human Protein Atlas provides an opportunity to use antibody-based proteomics as a high-throughput strategy to discover novel cancer biomarkers of potential clinical relevance. ANLN has been shown to be up-regulated in several human tumor types including lung, renal and pancreatic tumors. For the purpose of the current study, tissue microarrays with tumor samples from three independent breast cancer cohorts were analyzed by immunohistochemistry (IHC). SiRNA mediated ANLN knockdown of breast cancer cell lines followed by western blot or IHC on cytospin was done for antibody validation. Cell viability assay and cell cycle assay was used to study the function of ANLN knocked breast cancer cells. The majority of breast tumors displayed moderate to strong nuclear positivity in slightly varying fractions, generally below 25%. High nuclear fraction of ANLN was associated with large tumor size, high histological grade, high proliferation and estrogen receptor (ER) negativity. Furthermore, high nuclear expression of ANLN was significantly associated with poor prognosis for patients with ER positive breast tumors in all three cohorts. SiRNA mediated ANLN knockdown was found to induce low cell viability for ER positive breast cancer cells but not for ER negative breast cancer cells. In addition, cell cycle studies showed that ANLN knockdown yielded a shift to G2/M phase, in both ER positive and ER negative breast cancer cells. In conclusion, our results strongly suggest that ANLN can be used as a prognostic biomarker for ER positive breast cancer patients. Citation Format: Kristina Magnusson, Gabriela Gremel, Fredrik Pontén, Karin Jirström. Expression of the actin-binding protein Anillin is a prognostic biomarker for primary ER positive breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 390. doi:10.1158/1538-7445.AM2013-390
AN IMMUNOLOGIC STUDY OF TWO METABOLICALLY ACTIVE PEPTIDES FROM THE ANTERIOR PITUITARY GLAND
Authors: Henry Friesen, Minoru Irie, Richard J. Barrett
Journal: The Journal of Experimental Medicine (1962)

Peptides I and II, two metabolically active peptides from porcine pituitary glands, stimulated antibody production in rabbits. The antiserum obtained had antibodies which interacted with peptides I and II from porcine pituitaries, peptides I and II from human pituitaries, and fraction H prepared by Rudman from hog pituitaries. None of the other pituitary preparations tested showed any interaction with peptides I and II. All three preparations stimulated the release of free fatty acids from rabbit adipose tissue in vitro. Antiserum inhibited this biological action to a different extent in each of the three preparations. Following an intravenous injection of peptides I and II there was a rapid rise in the plasma concentration of free fatty acids in rabbits. Injection of antiserum together with peptides I and II failed to block the rapid increase in free fatty acids. However, an injection of at least ten times the minimal amount of peptides I and II which raised the plasma free fatty acid concentration produced no increase in a rabbit with a high antibody titer to these peptides.
Deficiency of Asparagine Synthetase Causes Congenital Microcephaly and a Progressive Form of Encephalopathy
Authors: Elizabeth K. Ruzzo, José-Mario Capo-Chichi, Bruria Ben-Zeev, David Chitayat, Hanqian Mao, Andrea L. Pappas, Yuki Hitomi, Yi-Fan Lu, Xiaodi Yao, Fadi F. Hamdan, Kimberly Pelak, Haike Reznik-Wolf, Ifat Bar-Joseph, Danit Oz-Levi, Dorit Lev, Tally Lerman-Sagie, Esther Leshinsky-Silver, Yair Anikster, Edna Ben-Asher, Tsviya Olender, Laurence Colleaux, Jean-Claude Décarie, Susan Blaser, Brenda Banwell, Rasesh B. Joshi, Xiao-Ping He, Lysanne Patry, Rachel J. Silver, Sylvia Dobrzeniecka, Mohammad S. Islam, Abul Hasnat, Mark E. Samuels, Dipendra K. Aryal, Ramona M. Rodriguiz, Yong-hui Jiang, William C. Wetsel, James O. McNamara, Guy A. Rouleau, Debra L. Silver, Doron Lancet, Elon Pras, Grant A. Mitchell, Jacques L. Michaud, David B. Goldstein
Journal: Neuron (2013)
Ethanol and development of disease and injury to tha alimentary tract.
Authors: E L Krawitt
Journal: Environmental Health Perspectives (1977)

Effects of ethanol on the gastrointestinal tract are reviewed, and an overview of possible mechanisms of ethanol damage to the alimentary tract is presented. Ethanol toxicity most commonly results in metabsorption. Mechanisms contributing to ethanol-induced calcium malabsorption are considered in detail as a prototype for problems encountered in evaluating effects of toxicants on intestinal function. Effects at the local level in the intestine must be differentiated from systemic effects. The mechanism of suppression of calcium absorption by chronic ethanol ingestion differs from that produced by acute administration. Effects of acute administration appear to be due to local mucosal damage and are reversed in 18 hr. Such damage is not present with chronic administration, which affects only duodenal transport. Treatment with vitamin D and its metabolites does not reverse the inhibition of calcium transport. The overall findings suggest that ethanol inhibition of calcium transport is mediated at the intestinal level, probably affecting vitamid D independent mechanisms.
Jeffrey Robert Clyne
Authors: J M. Walker
Journal: BMJ (2004)

Former general practitioner Salford and director of occupational medicine Manchester Airport (b Manchester 1930; q Manchester 1954; MBE, JP, FRCGP), d 14 February 2004.​2004.




Figure 1




After his military service Jeffrey joined a general practice in Salford in 1957. He was involved in the diabetes clinic at Salford Royal Hospital and played a part in its research. Following retirement from general practice in 1987 Jeffrey developed an interest in occupational medicine, eventually being appointed director of occupational medicine at Manchester Airport. His interests included music, travelling abroad, and the appreciation of fine wines. He leaves a wife, Pearl; five children; and 10 grandchildren.