tbuckley/cabot-search huggingface dataset:
Abstract 2770: UGT2B17 copy number variation and the association with serum glucuonides and prostate cancer risk
Authors: Delores J. Grant, Cathrine Hoyo, Shannon Oliver, Leah Gerber, Loretta Taylor, Kathryn Newman, Katie Shuler, Elizabeth Calloway, Jonathan N. Livingston, Ricardo M. Richardson, Joellen Schildkraut, Stephen J. Freedland
Journal: Cancer Research (2011)

Abstract Prostate cancer development and treatment has been associated with steroid hormones and/or steroid metabolites. While consensus seems to be building that serum testosterone levels are not related to disease risk, the role of genes involved in steroid metabolism have not been extensively studied. The UDP-glucuronosyltransferase (UGT) enzymes are part of a superfamily of genes involved in phase II detoxification of a wide variety of endogeneous and exogenous substances including bile, odorants, steroids, and drugs. The UGT2B17 gene is expressed in the prostate where it catalyzes the conjugation of a glucuronic acid moiety to steroids such as androstane-3α, 17βdiol. Several studies have examined whether a copy number variant (CNV) of UGT2B17 is associated with prostate cancer risk in case control studies, however, results have been inconclusive, and only one of the studies included African Americans. We examined the relationship of UGT2B17 CNV with prostate cancer risk aggressiveness in a hospital-based, case-control study conducted at the Durham Veterans Administration Hospital, and the relationship between serum levels of the glucuronide of androstane-3α, 17βdiol, AAG, in healthy Caucasians and African Americans. Levels of AAG were measured using ELISA. UGT2B17 genotype was determined by gene-specific copy number assays using Taqman Realtime PCR which showed 0, 1, or 2 alleles of the gene. Whereas CNV was not related to race (p=0.85), a higher CNV was significantly associated with higher androstane-3α, 17βdiol levels in healthy white men (p=0.018) but not non-white men (p=0.94). We found no association between CNV and cancer risk among all men (p=0.59) nor when stratified by white (p=0.70) vs. non-white (p=0.72). Among men with cancer, CNV was not related to Gleason score (p=0.32). These findings suggest that CNV may be associated with serum hormones levels, and these associations may differ between white and non-white men. Serum levels may be altered by other genetic or epigenetic factors in non-white populations. The role of CNV as a risk factor for prostate cancer requires further study in larger samples and with genetic and epigenetic variants. Funded by Department of Defense, NIH NCMHD P20 MD000175, S06-GM008049-33 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 2770. doi:10.1158/1538-7445.AM2011-2770
Dietary prevention of ischaemic heart disease
Authors: C J W Brooks
Journal: BMJ (1980)

provided temptation for use in promotional activities.It is premature to assume that all beta- blocking drugs are equally effective in prevent- ing sudden death and at present it is not known which subgroups of patients might benefit or for how long, and what doses are optimal.Every effort should be made to minimise speculation and over-simplification because of the danger of causing delays in the discovery of relevant mechanisms-or even worse of increasing scepticism and so depriving patients of effective treatment.
BACTERIURIA.REPORT OF A UNIQUE CASE.
Authors: G. PAUL LA ROQUE
Journal: JAMA (1906)

I believe the importance of this affection to be generally underestimated and am positive that the condition is vastly more common than is generally supposed. The term bacteriuria implies the presence of bacteria in the urinary tract above the compressor urethræ muscle. Micro-organisms are always present in the normal male urethra, certainly its anterior portion, and may be found in the urine of most people provided it is voided through this structure. Aside, however, from the trivial urethral discharge occasionally provoked by certain of these organisms, their presence in the anterior urethra causes no symptoms. Apart from the bacteriuria, which always exists as a part of pyuria, there is a simple bacteriuria, without pus, or at least such small quantities of this as to be of minor clinical significance. There is this difference regarding the etiology of the two affections: Pyuria always indicates suppuration in some part of the urogenital
The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single-dose studies.
Authors: Jun Kanno, Lesley Onyon, Shyamal Peddada, John Ashby, Elard Jacob, William Owens
Journal: Environmental Health Perspectives (2003)

The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. This portion of phase 2 assessed the reproducibility of the assay with a battery of positive and negative test substances. Positive agonists of the estrogen receptor included the potent reference estrogen 17-ethinyl estradiol (EE), and the weak estrogen agonists bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. The negative test substance or nonagonist was n-dibutylphthalate. The test substances were coded, and prescribed doses of each test substance were administered in 16 laboratories. Two versions of the uterotrophic assay, the intact immature and the adult ovariectomized female rat, were tested and compared using four standardized protocols covering both sc and po administration. Assay reproducibility was compared using a) EE doses identical to those used in phase 1 and in parallel dose-response studies, b) single doses of the weak agonists identical to one of five doses from the dose-response studies, and c) a single dose of the negative test substance. The results were reproducible and in agreement both within individual laboratories and across the participating laboratories for the same test substance and protocol. The few exceptions are examined in detail. The reproducibility was achieved despite a variety of different experimental conditions (e.g., variations in animal strain, diet, housing protocol, bedding, vehicle, animal age). In conclusion, both versions of the uterotrophic bioassay and all protocols appear robust, reproducible, and transferable across laboratories and able to detect weak estrogen agonists. These results will be submitted along with other data for independent peer review to provide support for the validation of the uterotrophic bioassay.
Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.
Authors: J Fan, Z S Ji, Y Huang, H de Silva, D Sanan, R W Mahley, T L Innerarity, J M Taylor
Journal: Journal of Clinical Investigation (1998)

Transgenic rabbits expressing human apo E3 were generated to investigate mechanisms by which apo E modulates plasma lipoprotein metabolism. Compared with nontransgenic littermates expressing approximately 3 mg/dl of endogenous rabbit apo E, male transgenic rabbits expressing approximately 13 mg/dl of human apo E had a 35% decrease in total plasma triglycerides that was due to a reduction in VLDL levels and an absence of large VLDL. With its greater content of apo E, transgenic VLDL had an increased binding affinity for the LDL receptor in vitro, and injected chylomicrons were cleared more rapidly by the liver in transgenic rabbits. In contrast to triglyceride changes, transgenic rabbits had a 70% increase in plasma cholesterol levels due to an accumulation of LDL and apo E-rich HDL. Transgenic and control LDL had the same binding affinity for the LDL receptor. Both transgenic and control rabbits had similar LDL receptor levels, but intravenously injected human LDL were cleared more slowly in transgenic rabbits than in controls. Changes in lipoprotein lipolysis did not contribute to the accumulation of LDL or the reduction in VLDL levels. These observations suggest that the increased content of apo E3 on triglyceride-rich remnant lipoproteins in transgenic rabbits confers a greater affinity for cell surface receptors, thereby increasing remnant clearance from plasma. The apo E-rich large remnants appear to compete more effectively than LDL for receptor-mediated binding and clearance, resulting in delayed clearance and the accumulation of LDL in plasma.
Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets
Authors: Uwe Rix, Oliver Hantschel, Gerhard Dürnberger, Lily L. Remsing Rix, Melanie Planyavsky, Nora V. Fernbach, Ines Kaupe, Keiryn L. Bennett, Peter Valent, Jacques Colinge, Thomas Köcher, Giulio Superti-Furga
Journal: Blood (2007)
Impact of the Trade Union Act 1984 on the BMA.
Authors: N Ellis
Journal: BMJ (1984)

When the Conservative administration entered office in June 1979 it was widely believed that the tide of industrial relations legislation would recede. Such an assumption could not have been more mistaken: since 1979 the government has enacted three important and extensive pieces of legislation in this area? the Employment Acts of 1980 and 1982 and the Trade Union Act 1984.13 All these are intended to alter radically the be? haviour of trade unions and their members. For the most part professional bodies such as the BMA have been able to observe these changes in employment law from a safe distance; the new legislation on the legality of strikes and picketing was not seen to have any direct bearing on an organisa? tion whose members were unlikely to take part in (or even contemplate) such activities. The main thrust of the legislation was seen to be aimed at the industrial unions, not professional bodies. This pattern was broken by the Trade Union Act 1984, in particular by that part of it that establishes new rules for the election of executive bodies of trade unions. When the govern? ment published its green paper Democracy in Trade Unions in January 1983 the BMA initially assumed that its highly demo? cratic procedures more than satisfied the principles of trade union  enunciated in the discussion paper: voting invariably takes place in conditions of secrecy;  members eligible to vote have the opportunity to do so under a system which provides the best opportunity of a reasonable turn out;  votes are counted fairly; and those who take decisions at the highest levels are properly representative of, and accountable to, the membership as a whole.4 Indeed, was not the BMA, in the words of the celebrated historians Beatrice and Sidney Webb, one of the most highly developed and efficient of  British professional organisations with a complicated constitution, which included all the devices of advanced democracy ? Thus we could continue to believe that the government's proposed legislation was not directed at the medical profession's representative organisation. When the Trade Union Bill was published, however, it was based on more specific and rigorous principles than those first enunciated. The Bill laid down three main provisions for  that every trade union would have to satisfy: that members of a trade union should be able to elect their  executive committee by secret ballot; that there should be consultation with members in a secret ballot before industrial action is taken; and that members should vote at least once every 10 years on whether their union should maintain a political fund. Only the first of these proposals was likely to affect the BMA to any extent. In this area the government's proposals were more specific in that the new legislation would require elections to the governing bodies of trade unions?that is, their principal executive committees?to be conducted in accordance with the following basic principles :
Zinc Supplementation in Young Children with Acute Diarrhea in India
Authors: Sunil Sazawal, Robert E. Black, Maharaj K. Bhan, Nita Bhandari, Anju Sinha, Sanju Jalla
Journal: New England Journal of Medicine (1995)

In developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation.To evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements.Among the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth.For infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.
Copeptin, IGFBP-1, and Cardiovascular Prognosis in Patients With Type 2 Diabetes and Acute Myocardial Infarction
Authors: Linda G. Mellbin, Lars Rydén, Kerstin Brismar, Nils G. Morgenthaler, John Öhrvik, Sergiu B. Catrina
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether C-terminal provasopressin (copeptin) explains the prognostic importance of insulin growth factor binding protein-1 (IGFBP-1) in patients with myocardial infarction and type 2 diabetes. RESEARCH DESIGN AND METHODS Copeptin and IGFBP-1 were analyzed in 393 patients participating in the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial. RESULTS Copeptin was associated with IGFBP-1 (Spearman rank correlation test, r = 0.53; P &amp;lt; 0.001). During follow-up there were 138 cardiovascular events (cardiovascular death, myocardial infarction, and stroke). In univariate Cox proportional hazard regression analyses both biomarkers were predictors of events: the hazard ratio for log copeptin was 1.59 (95% CI 1.41–1.81; P &amp;lt; 0.001) and for log IGFBP-1 was 1.49 (1.26–1.77; P &amp;lt; 0.001). In the final model, adjusting for age and renal function, copeptin was the only independent predictor (1.35 [1.16–1.57]; P &amp;lt; 0.001). CONCLUSIONS Copeptin is an independent predictor of cardiovascular events and appears to at least partly explain the prognostic impact of IGFBP-1 in patients with type 2 diabetes and myocardial infarction. Copeptin may be a pathogenic factor to address to improve outcome in these patients.
Treatment of Status Asthmaticus-Reply
Authors: Susan H. Schwartz
Journal: JAMA (1985)

<h3>In Reply.—</h3> I need to begin my reply with a short statement about subject 2. He arrived in our intensive care unit in the state described, and I am unable to comment about his management at the other hospital. Dr Goldberg has made several valuable comments in his letter. I certainly agree that a patient with status asthmaticus needs to be well and rapidly sedated and paralyzed if necessary to achieve intubation without excessive trauma or prolonged anoxia. The choice of agents used should take into consideration their potential effects on airway tone and mucous production and viscosity. As I noted in my BRIEF REPORT, halothane is by no means an ideal panacea for status asthmaticus. Other agents share the potential bronchodilating effects of halothane, and, perhaps, less arrhythmogenic agents will be available in the future. The use of IV-administered β-adrenergic agents, such as isuprel by drip or terbutaline by
Discharge from the Ear
Authors: R. Youngs
Journal: BMJ (2014)

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### Overview

Discharge from the ear is an unpleasant symptom that reflects infection, inflammation, trauma or rarely neoplasm of the external or middle ear (Box 1). Persistent ear discharge and its associated odour can result in stigmatisation and social isolation in some communities (Figure 1).

#### Causes of Discharging Ears

Otitis externa (acute and chronic)

Otitis media (acute and chronic)

Trauma to the temporal bone

Neoplasms of the ear (very rare)RETURN TO TEXT



Figure 1  
Profuse ear discharge.



The discharge itself arises either from the skin of the external ear canal, the surface of the tympanic membrane (eardrum), or the lining of the middle ear cleft (Figure 2). Discharge from the middle ear cleft often is profuse and mucoid in nature, because of the mucosal lining of the middle ear. In the clinical management of a discharging ear, accurate diagnosis is important and is facilitated by thorough history taking and examination. ENT specialists have the advantage of the use of the operating microscope available in the outpatient setting (Figure 3). Using the microscope in combination with suction equipment allows the specialist to aspirate discharge and closely inspect the ear canal and tympanic membrane. In the …

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Prospective evaluation of risk factors of cutaneous drug reactions to sulfonamides in patients with AIDS
Authors: Muriel Eliaszewicz, Antoine Flahault, Jean-Claude Roujeau, Anne Marie Fillet, Dominique Challine, Samira Mansouri, Pierre Wolkenstein, Sélim Aractingi, Dominique Penso-Assathiany, Caroline Maslo, Isabelle Bourgault-Villada, Olivier Chosidow, Eric Caumes
Journal: Journal of the American Academy of Dermatology (2002)
THE COMPARATIVE BEHAVIOR OF MAMMALIAN EGGS IN VIVO AND IN VITRO
Authors: Gregory Pincus, E. V. Enzmann
Journal: The Journal of Experimental Medicine (1935)

1. A definite chronological sequence of events occurs in the eggs and follicles of rabbits after mating or after the injection of ovulation-inducing substances. The follicle secretes secondary liquor folliculi, and there occurs a separation of the corona radiata from strands connecting it to the follicle cells. The ovum goes through nuclear maturation with as climax the production of the first polar body by the 8th hour after copulation. 2. Thyroxin injections cause indirectly the same effects as mating or pituitary injections but no ovulation occurs. The thyroxin effect occurs later than the pituitary effect and is due to an initiation of atresia in the follicles. 3. Explantation of ova results in typical maturation phenomena which are apparently unaffected by the presence of pituitary hormones or of thyroxin in the culture medium. 4. It is concluded that maturation of the ovum can be obtained simply by isolating it from the normal follicular environment. 5. Normal fertilization can be secured with eggs removed from the follicles.
Darzi review: Annual "quality accounts" will help improve services and increase choice for patients, says Lord Darzi
Authors: Z. Kmietowicz
Journal: BMJ (2008)

A complex and wide ranging network of information gathering systems is being developed to support the drive to improve quality across the NHS—the backbone of Ara Darzi’s next stage review.

From April 2010 all healthcare providers working for the NHS will be legally obliged to publish “quality accounts” on safety, patients’ experience, and clinical outcomes, in the same way that they publish financial accounts. 

The accounts will augment the government’s agenda on choice by giving patients information—accessible through NHS websites—on all health services in England, to help them decide where to be treated.

“By measuring this quality across …
The Incidence of Chronic Peptic Ulcer Found at Necropsy: A Study of 20,000 Examinations Performed in Leeds in 1930-49 and in England and Scotland in 1956
Authors: G. Watkinson
Journal: Gut (1960)

In this study the frequency of gastric, duodenal, and stomal ulcer has been determined in a survey at necropsy. This survey is likely to be much more accurate than those previously reported, as it has been a "forward planned" one and conducted by a group of men interested in this subject. In retrospective studies it is always impossible to know how carefully a particular point has been checked. It has been concluded from this study that the best estimate of the incidence of ulcer in the population as a whole can be made from the frequency of ulcers found in patients dying from causes other than peptic ulcer. The incidence of such active ulcers accords closely with clinical experience in life.
TNF, IFNG and FOXP3 expression in colorectal cancer: potential targets for immunotherapy
Authors: S. Ganapathi, A. Beggs, S. Hodgson, D. Kumar
Journal: Gut (2011)

<h3>Introduction</h3> Colorectal cancer (CRC) progression is associated with suppression of host cell mediated immunity (CMI) and local immune escape mechanisms. A systemic suppression of CMI-associated cytokines, Tumour Necrosis Factor (TNF) and Interferon-γ (IFN-γ) has been demonstrated in patients with CRC.1 FOXP3, a crucial regulatory protein for the development and function of regulatory T-cells could be an important cause of local immune escape mechanism in tumors.2 The aim of the study was to assess immune function in terms of the expression of TNF, IFN- γ and FOXP3 and to identify potential targets for immunotherapy in CRC. <h3>Methods</h3> A total of 60 colorectal cancer (CRC) patients and 15 matched controls were recruited. Total RNA was isolated from the peripheral blood mononuclear cells (PBMC, separated from a venous blood sample), fresh frozen tumour tissue and normal mucosa. TaqMan quantitative PCR (qRT-PCR) was used to determine the relative fold change in the expression of TNF, IFNG, FOXP3 in the PBMC (compared to controls) and tumour (compared to normal mucosa), with GAPDH as internal control. <h3>Results</h3> TNF expression was suppressed in the tumour tissue (median fold change 0.48) compared to normal mucosa. IFN- γ was found to be suppressed in the PBMC (median 0.34) compared to healthy controls. There was a significantly reduced expression of TNF (p = 0.048) and IFNG (p = 0.011) in Stage 4 CRC. There was a significant suppression of IFNG in the recurrent CRC (p = 0.007), left CRC sided CRC (p = 0.027) and after neoadjuvant therapy (p = 0.021). The tumour tissue showed a higher expression of FOXP3 gene compared to normal mucosa (median 2.2). The expression of FOXP3 in tumour was significantly higher when the size of the tumour was more than 50 mm (p = 0.005). Late stage CRC (Stages 3 and 4) showed a significantly high expression of FOXP3 compared to early stages of CRC (Stages 1 and 2) (p = 0.035). <h3>Conclusion</h3> The expression of TNF is suppressed and FOXP3 is enhanced in colorectal tumours and becomes more significant with tumour progression. Suppression of IFN- γ appears to be systemic and is significantly suppressed in left sided CRC and recurrent CRC. Our study has identified potential targets which may increase the chances of response to immunotherapy based on cytokines and T regulatory cell manipulation.