tbuckley/cabot-search huggingface dataset:
Abstract 4212: Prevention of estrogen-induced breast cancer by antioxidants: Role of N-quinone oxidoreductase 1 (NQO1)
Authors: Hari K. Bhat, Bhupendra Singh
Journal: Cancer Research (2011)

Abstract The importance of estrogens in the etiology of breast cancer is widely recognized. However, the exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. The objective of the current study was to characterize the role of NQO1 in the prevention of estrogen-induced DNA damage and mammary tumorigenesis by antioxidants vitamin C or butylated hydroxyanisole (BHA). NQO1 converts 17β-estradiol (E2)-quinones back to E2-catechols, thus making E2-quinones unavailable for oxidant damage. Female ACI rats were treated with E2 (3 mg); vitamin C (1% in drinking water); E2 + vitamin C; BHA (0.7% in diet); and E2 + BHA for up to 8 months. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. No tumors were detected in the sham control, vitamin C and BHA treatment groups whereas in the E2 + vitamin C, E2 + BHA, and E2 treatment groups, the breast tumor incidences were 29, 24 and 82% respectively. mRNA and protein expression of NQO1 was analyzed in breast and breast tumor tissues of rats treated with E2 and antioxidants vitamin C or BHA. NQO1 was suppressed in E2-exposed mammary tissue after treatment of rats with E2 for 8 months and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. NQO1 enzyme activity was unchanged in mammary tissue of rats from all the treatment groups. However, NQO1 enzyme activity was decreased in E2-induced mammary tumors. Catechol-O-methyltransferase (COMT) activity was unchanged in the mammary tissue of all the groups except in the E2-treated group. Vitamin C or BHA co-treatment significantly decreased E2-mediated increase in 8-hydroxydeoxyguanosine (8-OHdG, an oxidative DNA damage marker) levels in mammary tissue. To investigate the relationship between NQO1 and 8-OHdG damage, human breast epithelial cell line MCF10A was treated with E2, vitamin C, BHA, dicumarol (NQO1 inhibitor), E2 + vitamin C, and E2 + BHA. E2 and dicumarol significantly increased 8-OHdG levels in MCF-10A cells whereas co-treatment with E2 and antioxidants reverted them back to the normal levels. Our studies suggest a protective role of NQO1 in E2-induced DNA damage and breast carcinogenesis. NQO1 may thus have a unique potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia. 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 4212. doi:10.1158/1538-7445.AM2011-4212
Autoregulation of cerebral blood flow in hypertensive patients. The modifying influence of prolonged antihypertensive treatment on the tolerance to acute, drug-induced hypotension.
Authors: S Strandgaard
Journal: Circulation (1976)

Autoregulation of cerebral blood flow (CBF) was studied by the arteriovenous oxygen difference method in 13 patients with untreated or ineffectively treated severe hypertension, nine patients with effectively treated, formerly severe hypertension, and ten normotensive controls. Resting mean blood pressure in these three groups was 145 +/- 17 (1 SD) mm Hg, 116 +/- 18 mm Hg, and 98 +/- 10 mm Hg, respectively. Blood pressure was decreased by trimethaphan infusion combined with head-up tilt. The lower limit of CBF autoregulation in the three groups was 113 +/- 17 mm Hg, 96 +/- 17 mm Hg, and 73 +/- 9 mm Hg, and the lowest tolerated blood pressure where mild symptoms of brain hypoperfusion were encountered was 65 +/- 10 mm Hg, 53 +/- 18 mm Hg, and 43 +/- 8 mm Hg. These pressures were all significantly higher (P less than 0.01) in the group of untreated or ineffectively treated hypertensive patients than in the normotensive group demonstrating a shift of CBF autoregulation in the former. The observations in effectively treated hypertensive patients strongly suggested a readaptation of CBF autoregulation toward normal in some cases. In four hypertensive patients studied twice it was found that 8-12 months of antihypertensive treatment on average did not influence the lower limit of CBF autoregulation.
Interspinous process device versus standard conventional surgical decompression for lumbar spinal stenosis: randomised controlled trial
Authors: Wouter A Moojen, Mark P Arts, Wilco C H Jacobs, Erik W van Zwet, M Elske van den Akker-van Marle, Bart W Koes, Carmen L A M Vleggeert-Lankamp, Wilco C Peul
Journal: British Journal of Sports Medicine (2014)

Is interspinous process device implantation more effective in the short term (eight weeks) than conventional surgical decompression for patients with intermittent neurogenic claudication due to lumbar spinal stenosis?The use of interspinous implants did not result in a better outcome than conventional decompression, but the reoperation rate was significantly higher.Bony decompression and treatment with interspinous process devices are superior to conservative and non-surgical treatment for intermittent neurogenic claudication due to lumbar spinal stenosis. Interspinous implants surgery is not superior to bony decompression, and the reoperation rate is significantly higher.
Transient Ventricular Fibrillation
Authors: SIDNEY P. SCHWARTZ, LEONARD HALLINGER, ANTHONY IMPERIALLI
Journal: Circulation (1952)

Procaine amide was given intravenously to three patients with transient ventricular fibrillation during established auriculoventricular dissociation at a time when they were free from symptoms as well as during the attacks. It was determined that this drug has a transitory slowing effect upon the auricles. It depresses rhythmicity in the auriculoventricular node, prolongs the refractory period of the ventricles, results in intraventricular conduction disturbance and the development of premature beats of the ventricles followed by the various forms of ventricular acceleration leading to ventricular fibrillation. Because of these alterations in heart rhythms, procaine amide is contraindicated in the treatment of such patients.
Surma and lead poisoning.
Authors: A R Ali, O R Smales, M Aslam
Journal: BMJ (1978)

Blood lead concentrations were measured in 62 Asian children, of whom 37 had definitely had surma applied to their eyes and 25 were thought not to have done. The mean concentration in those who had not used surma was 0.98 +/- SD 0.42 mumol/1 (20.3 +/- 8.7 microgram/100 ml) compared with 1.65 +/- 0.68 mumol/4 (34.2 +/- 14.1 microgram/100 ml) in those who had. Analysis of 29 different samples of surma showed 23 of them to be composed largely of lead sulphide. We conclude that the use of surma is associated with high blood lead concentrations. In our cases most of it had been obtained abroad, and hence government restrictions might be ineffective in limiting its use: a better method of prevention might be to inform the leaders of Asian communities of the risks.
Medical Privacy and Medical Research — Judging the New Federal Regulations
Authors: George J. Annas
Journal: New England Journal of Medicine (2002)

Americans support both protecting the privacy of medical records and encouraging medical research. Thus, it is not surprising that a move to change practices in these two areas has generated attention and comment. The new federal regulations, promulgated under the authority of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), were adopted to protect the privacy of medical records. They were not specifically designed to facilitate or limit medical research.1 Nonetheless, the regulations have prompted strong objections from the biotechnology industry and from academic medicine. The Association of American Medical Colleges and the Biotechnology Industry Organization have argued . . .
Angina and indomethacin.
Authors: D. Golding
Journal: BMJ (1970)

BmnDICJOL their sera of agglutinins against brucella antigen, it is easy to see that overdiagnosis is something that must constantly be guarded against.At present, the serological tests for brucellosis in any patient must not only be interpreted in the light of his symptonatology, but also with cognizance of the serological values obtained in the community in which he lives, and of his epidemiological history.'2Previous authors have been too ready to accept a history of symptoms obtained by questionnaire as evidence of clinical brucellosis when allied to positive serological tests, resulting in very high reported incidences of the disease in veterinary surgeons.87Critical evaluation of each individual is necessary to give an indication of the true incidence of brucellosis in any occupationally exposed group.5-Iam, etc.,
System of accelerating methods of evaluating toxicity and hazardous properties of substances.
Authors: S A Shigan
Journal: Environmental Health Perspectives (1979)

By studying a group of organophosphorus compounds (PhOC), system of methods for developing models of chronic intoxication was approved, the purpose of which was to establish safe levels of chemical pollutants in the water. The magnitudes of threshold doses (TD) and ineffective doses (MID) were obtained by using MACrv (maximum admissible concentrations of substances in the air of industrial plants) and TLV [indices of admissible levels of substances in the air of industrial plants (USA standards)]. In compiling estimated and experimentally established MAC for 21 substances, variations were recorded within the range of 2-10 times. Forecasting on the basis of ED50, Elim and other measures during 5-20 day experiments made it possible to estimate threshold and inactive doses of PhOC during chronic intoxication, as well as to determine a cumulative coefficient and distribute these compounds into two series, according to the degree of their hazard. This project made it possible to determine cumulative properties simultaneously and forecast the chronic toxicity of the PhOC group under investigation.
Prognostic PET 18F-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non–Small Cell Lung Cancer
Authors: Viswam S. Nair, Olivier Gevaert, Guido Davidzon, Sandy Napel, Edward E. Graves, Chuong D. Hoang, Joseph B. Shrager, Andrew Quon, Daniel L. Rubin, Sylvia K. Plevritis
Journal: Cancer Research (2012)

Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.
Aspirin Sensitivity
Authors: Raghava R. Gollapudi, Paul S. Teirstein, Donald D. Stevenson, Ronald A. Simon
Journal: JAMA (2004)

ContextAlthough acetylsalicylic acid (aspirin) is commonly used for patients with chronic cardiovascular disease, a minority of patients have a sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.ObjectiveTo provide a diagnostic strategy for evaluating and treating patients with aspirin sensitivity, with additional consideration for issues specific to patients with coronary artery disease (CAD).Evidence AcquisitionPublished articles were identified through a search of MEDLINE and the Cochrane databases using the dates 1966 to June 2004 and the search terms aspirin allergy, coronary artery disease, aspirin desensitization, and aspirin sensitivity. References of retrieved articles were also reviewed for pertinent studies. Articles were included in this review if they were controlled studies, published in the English language, and appeared in a peer-reviewed journal.Evidence SynthesisThe prevalence of aspirin-exacerbated respiratory tract disease is approximately 10% and for aspirin-induced urticaria the prevalence varies from 0.07% to 0.2% of the general population. Aspirin sensitivity is most often manifested as rhinitis and asthma or urticaria/angioedema induced by cross-reacting nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase 1. The primary mechanism of sensitivity is less often related to drug-specific IgE antibody production leading to urticaria/angioedema and rarely to anaphylaxis. Most patients with acetylsalicylic acid sensitivity are able to undergo desensitization therapy safely and successfully except in cases of chronic idiopathic urticaria. However, there have not been any randomized trials that specifically focus on the efficacy of aspirin desensitization. Furthermore, experience with acetylsalicylic acid desensitization in patients with CAD is very limited. After successful desensitization, acetylsalicylic acid therapy must be indefinitely continued to prevent resensitization.ConclusionsAcetylsalicylic acid sensitivity is common and desensitization can be performed safely in many patients. Large-scale trials are warranted to determine the safety and efficacy of acetylsalicylic acid desensitization therapy in patients with concomitant CAD because data are currently limited to small case series.
Occupational Risks for Child-Care Providers and Teachers
Authors: Larry K. Pickering
Journal: JAMA (1990)

Exposure to large numbers of preschool children in out-ofhome child-care settings is associated with an increased frequency of acquiring a variety of communicable diseases.<sup>1,2</sup>This increase in frequency exists not only for the children but also for their parents and for their adult care givers.<sup>3</sup>Although one might assume such exposure merely accelerates the process of acquiring natural immunity to a variety of unavoidable communicable diseases, an increased risk for significant morbidity due to several infectious agents has been identified among both preschool children and adults in the day-care setting. Infants and toddlers attending day care are at greater risk for chronic or recurrent otitis media, for bacterial meningitis, for dehydration due to diarrheal disease, and for serious lower respiratory tract infection.<sup>4-6</sup>Parents and care givers exposed to children attending day care are at increased risk for illness due to shigellosis and hepatitis A, which is usually
The Evaluation of Clinical Predictions
Authors: Alan R. Shapiro
Journal: New England Journal of Medicine (1977)

Abstract Clinical predictions are never certain but are inherently probabilistic. The accuracy coefficient, a measure of probabilistic accuracy based on probability assigned to outcomes that occur, was used to assess the skill of clinical rheumatologists in predicting patient outcomes. Physicians' scores correlated well with degree of clinical experience. An approach to evaluation based on the measure provides a sensitive assessment of marginal benefit of technologies such as laboratory tests, diagnostic procedures or computer consultations. Most currently used methods of computer prediction were not as accurate as the best physicians tested. By allowing measurement of ability to individualize predictions to each patient's unique characteristics, the accuracy-coefficient approach has potential use in physician assessment. (N Engl J Med 296:1509–1514, 1977)
Activated endothelium binds lymphocytes through a novel binding site in the alternately spliced domain of vascular cell adhesion molecule-1.
Authors: L Osborn, C Vassallo, C D Benjamin
Journal: The Journal of Experimental Medicine (1992)

Vascular cell adhesion molecule-1 (VCAM-1) is induced on endothelial cells by inflammatory cytokines, and binds mononuclear leukocytes through the integrin very late antigen-4 (VLA-4) (alpha 4 beta 1). This adhesion pathway has been implicated in a diverse group of physiological and pathological processes, including B cell development, leukocyte activation and recruitment to sites of inflammation, atherosclerosis, and tumor cell metastasis. The major form of VCAM-1 (VCAM-7D) has seven extracellular immunoglobulin (Ig)-like domains, of which the three NH2-terminal domains (domains 1-3) are similar in amino acid sequence to domains 4-6. By functional analysis of VCAM-7D relative to VCAM-6D (a minor 6-domain form of VCAM-1 in which domain 4 is deleted because of alternative splicing), and chimeric constructs between VCAM-1 and its structural relative intercellular adhesion molecule-1 (ICAM-1), we show that either the first or the homologous fourth domain of VCAM-1 is required for VLA-4-dependent adhesion. Either of these binding sites can function in the absence of the other. When both are present, cell binding activity is increased relative to monovalent forms of the molecule. The homologous binding regions appear to have originated by internal duplication of a portion of a monovalent ancestral gene, before the mammalian radiation. Thus VCAM-1 exemplifies evolution of a functionally bivalent cell-cell adhesion molecule by intergenic duplication. We have also produced a new class of anti-VCAM-1 monoclonal antibodies that block domain 4-dependent adhesion, and demonstrate that both binding sites participate in the adhesion function of VCAM-1 on endothelial cells in vitro. Therefore both sites must be blocked in clinical, animal, or in vitro studies depending on the use of anti-VCAM-1 antibodies to inactivate the VCAM-1/VLA-4 adhesion pathway.
Psychiatrists, lawyers, and service users unite against proposed bill
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Concern that the government's new mental health bill for England and Wales will lead to the wrong people being detained and treated has united an unprecedented number of organisations in a campaign to demand its complete rewrite.

Dr Mike Shooter, president of the Royal College of Psychiatrists, who met with lawyers, nurses,social workers, psychologists, carers, service providers, and charities last week, called …
Quantification of Volumetric Coronary Blood Flow With Dual-Energy Digital Subtraction Angiography
Authors: Sabee Molloi, Atila Ersahin, Jerry Tang, James Hicks, Cyril Y. Leung
Journal: Circulation (1996)

As a solution to the well-documented problems associated with visual interpretation of coronary arteriograms, more physiological methods of assessing coronary artery stenosis are being investigated. Volumetric coronary blood flow (BF) can be a valuable aid in the analysis of functional significance of arterial obstruction.The left anterior descending coronary artery (LAD) of 15 anesthetized pigs (40 to 50 kg) was dissected free from the epicardium in its proximal portion, and a transmit-time ultrasound flow probe of the appropriate size was applied. A vascular occluder was positioned distal to the flow probe for flow adjustments. Contrast injections (2 to 4 mL/s for 3 seconds) were made into the left main coronary artery during image acquisition with a motion-immune dual-energy digital subtraction angiography (DE DSA) system. Tissue-suppressed energy-subtracted images were used to generate time-density curves. BF measurements were made in the LAD vascular bed with use of the time-density curve, with consideration that blood was momentarily replaced with contrast during the injection. In 19 comparisons, the mean BF, measured with the use of DE DSA, correlated extremely well with the mean ultrasound flow (DE DSA=0.90 ultrasound+3.10 mL/min, r=.96). Also, contrast injection increased the BF by an average of only 15% during the image-acquisition time interval.Accurate BF measurements can be made with motion-immune DE DSA. The BF measurements can be completed before the onset of significant changes in BF due to contrast injection. Furthermore, it is possible to make the BF measurements during routine coronary arteriography.
Sarcoplasmic Reticulum Calcium Overloading in Junctin Deficiency Enhances Cardiac Contractility but Increases Ventricular Automaticity
Authors: Qunying Yuan, Guo-Chang Fan, Min Dong, Beth Altschafl, Abhinav Diwan, Xiaoping Ren, Harvey H. Hahn, Wen Zhao, Jason R. Waggoner, Larry R. Jones, W. Keith Jones, Donald M. Bers, Gerald W. Dorn, Hong-Sheng Wang, Héctor H. Valdivia, Guoxiang Chu, Evangelia G. Kranias
Journal: Circulation (2007)

Abnormal sarcoplasmic reticulum calcium (Ca) cycling is increasingly recognized as an important mechanism for increased ventricular automaticity that leads to lethal ventricular arrhythmias. Previous studies have linked lethal familial arrhythmogenic disorders to mutations in the ryanodine receptor and calsequestrin genes, which interact with junctin and triadin to form a macromolecular Ca-signaling complex. The essential physiological effects of junctin and its potential regulatory roles in sarcoplasmic reticulum Ca cycling and Ca-dependent cardiac functions, such as myocyte contractility and automaticity, are unknown.The junctin gene was targeted in embryonic stem cells, and a junctin-deficient mouse was generated. Ablation of junctin was associated with enhanced cardiac function in vivo, and junctin-deficient cardiomyocytes exhibited increased contractile and Ca-cycling parameters. Short-term isoproterenol stimulation elicited arrhythmias, including premature ventricular contractions, atrioventricular heart block, and ventricular tachycardia. Long-term isoproterenol infusion also induced premature ventricular contractions and atrioventricular heart block in junctin-null mice. Further examination of the electrical activity revealed a significant increase in the occurrence of delayed afterdepolarizations. Consistently, 25% of the junctin-null mice died by 3 months of age with structurally normal hearts.Junctin is an essential regulator of sarcoplasmic reticulum Ca release and contractility in normal hearts. Ablation of junctin is associated with aberrant Ca homeostasis, which leads to fatal arrhythmias. Thus, normal intracellular Ca cycling relies on maintenance of junctin levels and an intricate balance among the components in the sarcoplasmic reticulum quaternary Ca-signaling complex.
Failing to Thrive
Authors: Lisa Rosenbaum
Journal: New England Journal of Medicine (2010)

My mother and I were on vacation in New York when we got a call from my aunt and uncle, both psychiatrists, in Portland, Oregon. My 90-year-old, demented paternal grandmother seemed to be having a stroke. They wanted to know whether they should take her to the emergency room.“She's stuporous,” my mother, a cardiologist, relayed to me, an internal medicine resident at the time. “Acting funny.”“Stuporous?” I asked. “Are we talking near-coma stuporous?” Maybe there was a less foreboding, psychiatric type of “stuporous.”A Do Not Resuscitate–Do Not Intubate order had been signed, and there was some murmuring . . .