tbuckley/cabot-search huggingface dataset:
A role for the pregnane X receptor in flucloxacillin-induced liver injury
Authors: Elise Andrews, Martin Armstrong, Jonathan Tugwood, Dan Swan, Philip Glaves, Munir Pirmohamed, Guruprasad P. Aithal, Matthew C. Wright, Christopher P. Day, Ann K. Daly
Journal: Hepatology (2010)

Drug-induced liver injury (DILI) due to flucloxacillin is a rare but serious complication of treatment. There is some evidence that flucloxacillin is a human pregnane X receptor (PXR) agonist. This study was designed to investigate the relevance of PXR to flucloxacillin toxicity and to identify genes changing in expression in response to flucloxacillin. Changes in gene expression in human hepatocytes after treatment with 500 μM flucloxacillin for 72 hours were examined by expression microarray analysis. The ability of flucloxacillin to act as a PXR agonist was investigated with reporter gene experiments. Flucloxacillin DILI cases (n = 51), drug-exposed controls without toxicity (n = 64), and community controls (n = 90) were genotyped for three common PXR polymorphisms. Luciferase reporter assays were used to assess the significance of a promoter region PXR polymorphism. Seventy-two probe sets representing 50 different genes showed significant changes in expression of 1.2-fold or higher. Most genes showing changes greater than 3-fold were known to be rifampicin-responsive, and this suggested a PXR-dependent mode of regulation. Using a luciferase-everted repeat separated by 6 base pairs element construct, we confirmed that flucloxacillin was a PXR agonist. We found a difference in the distribution of a PXR polymorphism (rs3814055; C-25385T) between flucloxacillin DILI cases and controls with the CC genotype associated with an increased risk of disease (odds ratio = 3.37, 95% confidence interval = 1.55-7.30, P = 0.0023). Reporter gene experiments showed lower promoter activity for the C allele than the T allele. Conclusion: Flucloxacillin is a PXR agonist at pharmacologically relevant concentrations, and a functionally significant upstream PXR polymorphism is a risk factor for flucloxacillin-induced DILI. Hepatology 2010
Carcinoma of the Ampulla of Vater: The Endoscopic Approach
Authors: K. Huibregtse, G. N. J. Tytgat
Journal: Endoscopy (1988)

Carcinoma of the ampulla of Vater is a rare tumor. Early and accurate diagnosis of carcinoma of the ampulla of Vater will lead to early treatment and subsequent better prognosis. Endoscopy and endoscopic retrograde cholangiopancreaticography (ERCP) has been shown to be one of the best diagnostic modalities. Furthermore an endoscopic biliary drainage procedure can be performed immediately following the diagnostic procedure. The tumors may be seen as large, fleshy, friable exophytic growths, as ulcerated tumors into the duodenal wall or as a mass behind the orifice of the papilla, covered with normal duodenal mucosa. Forceps biopsies do not always suffice to show malignancy. Large snare biopsies often are necessary. Occasionally the final diagnosis of malignancy can only be made by examination of the surgical resection specimen. Tumors arising inside the ampulla form a bulge, covered by normal duodenal mucosa. An impacted stone may mimic this picture. Endoscopic papillotomy is then mandatory to make the final diagnosis. Histologic examination of forceps biopsies reveals malignancy in only 60 % of cases. When snare biopsy is used, the diagnostic yield increases to 83 %. The optimal treatment of carcinomas of the ampulla of Vater is surgical resection. Preoperative biliary drainage should theoretically be of benefit to the patient. The results of preoperative percutaneous drainage studies are, however, conflicting. Carcinoma of the ampulla of Vater is not resectable in 25-50 % of the patients because of metastatic disease, deep extension of the tumor or general contraindications for major surgery. Endoscopic papillotomy or stent placement as a definitive treatment modality should be reserved for poor surgical candidates and for those patients with limited life expectancy due to meta-static disease.
Birth weight and blood pressure: cross sectional and longitudinal relations in childhood
Authors: P. Whincup, D. Cook, O. Papacosta, M Walker
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To examine cross sectional and longitudinal relations between birth weight and blood pressure in childhood. <b>Design</b>: Cross sectional study of primary school children aged 9-11 years, with analysis in relation to previous measurements at 5-7 years in a subgroup. <b>Setting</b>: 20 primary schools in Guildford and Carlisle. <b>Subjects</b>: 1511 children measured at 9-11 years (response rate 79%), including 549 who had been measured at 5-7 years. <b>Main outcome measures</b>: Blood pressure at 9-11 years, change in blood pressure between 5-7 and 9-11 years, birth weight (based on maternal recall), and placental weight (based on birth records). <b>Results</b>: At 9-11 years birth weight was inversely related both to systolic blood pressure (regression coefficient −2.80 mm Hg/kg; 95% confidence interval −3.84 to −1.76) and to diastolic blood pressure (regression coefficient −1.42 mm Hg/kg; −2.14 to −0.70) once current height and body mass index were taken into account. Placental weight was inversely related to blood pressure after adjustment for current height and body mass index but placental ratio (placental weight to birth weight) was unrelated to blood pressure. Between 5–7 and 9–11 years systolic blood pressure rose more rapidly in children of lower birth weight (regression coefficient −1.71 mm Hg/kg; −3.35 to −0.07). This effect seemed to be stronger in girls. <b>Conclusions</b>: Birth weight rather than placental ratio is the early life factor most importantly related to blood pressure in childhood. The results support the possibility of "amplification" of the relation between birth weight and blood pressure, particularly in girls.
310 MARKED SPIROMETRY DECLINE IN PATIENTS WITH CHRONIC HEPATITIS C DURING TREATMENT WITH ALBINTERFERON ALFA-2B IS SIMILAR TO PEGINTERFERON ALFA-2A
Authors: S. Zeuzem, M. Sulkowski, D. Nelson, Y. Benhamou, Y. Yin, G. Feutren, P. Noble, J. McHutchison
Journal: Journal of Hepatology (2010)
Combined blood and urine testing is more sensitive for HIV
Authors: K. Abbasi
Journal: BMJ (1997)

Testing samples of both blood and urine can increase the sensitivity of detection of HIV-1 antibodies compared with serum or urine testing alone.

Howard Urnovitz, chief science officer, and his team of researchers from the Calypte Biomedical Corporation, say that this finding may open new avenues in the development of an AIDS vaccine ( Nature Medicine 1997;3:1258).

The team tested blood and urine samples from 11344 patients and found that in 1181 individuals 1156 samples were positive for HIV-1 antibodies …
Workshop on Medical Device Clinical Trial Development and Design
Authors: Stuart L. Nightingale
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites
Authors: Andreas Festa, Ralph D’Agostino, Steven S. Rich, Nancy S. Jenny, Russell P. Tracy, Steven M. Haffner
Journal: Circulation (2003)

Background— The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease. Methods and Results— Insulin resistance was measured with a frequently sampled intravenous glucose tolerance test in the Insulin Resistance Atherosclerosis Study (IRAS), and PAI-1 4G/5G promoter genotype was established by allele-specific polymerase chain reaction amplification of genomic DNA. There were 287 subjects with the 4G/4G genotype (18.4%), 691 heterozygote subjects (44.2%), and 586 carriers of the 5G/5G genotype (37.5%). The genotype distribution was different across the 3 ethnic groups ( P =0.001). PAI-1 levels were lower in blacks than in non-Hispanic whites and Hispanics and lower in non-Hispanic whites than in Hispanics (all P =0.0001). Subjects homozygous for the 4G allele had the highest plasma PAI-1, heterozygote subjects were intermediate, and 5G homozygotes had the lowest levels of PAI-1. These patterns remained unaffected by adjustments for age, gender, clinical center, glucose tolerance status, body mass index, waist, triglycerides, and insulin resistance. Multiple linear regression analyses showed that the 4G/5G genotype explained very little of the variation in PAI-1 levels (0.63% in non-Hispanic whites, 0.99% in Hispanics, and 2.37% in blacks), and interaction analyses revealed no significant differences in the relation of circulating PAI-1 levels to the 4G/5G genotype by ethnicity ( P =0.4). Conclusions— We have shown ethnic differences in the PAI-1 4G/5G polymorphism along with corresponding differences in circulating PAI-1 levels. The association of the genotype with PAI-1 levels was seen consistently among all 3 ethnic groups and was unaffected by metabolic covariates, including insulin resistance.
Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: A double-blind placebo-controlled crossover study
Authors: Jacques F. Caron, Christian C. Libersa, André R. Kher, Salem Kacet, Hervé Wanszelbaum, Bernard A. Dupuis, Jean-Marie Poirier, Jean P. Lekieffre
Journal: Journal of the American College of Cardiology (1985)
Are we promoting stress and anxiety?
Authors: P. Whelan
Journal: BMJ (1997)

In 1989 carcinoma of the prostate was a decidedly provincial, indeed, almost homely type of disease. It had been known for more than 30 years to have a high latent prevalence, varying between 1:3 and 1:2 of all men, depending on their age, but it seemed to have a relatively small, clinical incidence. The diagnosis was made in most patients during their eighth decade, usually by the pathologists, following a prostatectomy for relief of obstructive urinary symptoms. In at least half the patients metastases were present at diagnosis. As this tumour, since the Nobel prize winning work of Huggins and Hodges in 1940, was known to be androgen dependent, all these patients were placed on either female hormones or underwent bilateral orchidectomy. Their median survival was a couple of years.

In patients with localised disease many were treated by observation only, some had radiotherapy, some radical surgery, and some were started on hormone treatment immediately. Given the apparently slow nature of disease progression and competing mortalities in this age group, it was a perception, supported by the scientific literature, that all treatments had broadly similar survival curves. The concept in this group was that more men died with their prostate cancer rather than of it. At least half the men who died from prostate cancer were …
Health-Related Quality of Life in Patients Treated for Anaplastic Oligodendroglioma With Adjuvant Chemotherapy: Results of a European Organisation for Research and Treatment of Cancer Randomized Clinical Trial
Authors: Martin J.B. Taphoorn, Martin J. van den Bent, Murielle E.L. Mauer, Corneel Coens, Jean-Yves Delattre, Alba A. Brandes, Peter A.E. Sillevis Smitt, Hans J.J.A. Bernsen, Marc Frénay, Cees C. Tijssen, Denis Lacombe, Anouk Allgeier, Andrew Bottomley
Journal: Journal of Clinical Oncology (2007)

Little is known about the health-related quality of life (HRQOL) of patients treated for anaplastic oligodendrogliomas. The impact of combined procarbazine, CCNU (lomustine), and vincristine (PCV) chemotherapy after radiotherapy (RT) compared with RT alone on HRQOL in the randomized European Organisation for Research and Treatment of Cancer (EORTC) 26951 trial was studied.Adult patients with anaplastic oligodendrogliomas received RT alone or RT plus PCV chemotherapy. HRQOL was assessed with the EORTC Quality of Life Questionnaire C30 and Brain Cancer Module. Seven prespecified HRQOL end points were selected. We hypothesized that chemotherapy would impair HRQOL during treatment but that there would be a similar HRQOL between treatment arms once off treatment. Assessments were performed at randomization, at the end of RT, and then every 3 to 6 months until progression.A total of 368 patients were randomly assigned to one of the two arms; overall, 58% were male, and the median age was 49 years. Compliance with HRQOL was 78% at baseline and dropped to 55% to 72% up to 2.5 years post-RT. Baseline scores demonstrated considerable impairments in HRQOL for both treatment groups. The longitudinal analysis showed a significant increase in nausea/vomiting in the RT plus PCV chemotherapy arm during and shortly after chemotherapy. Because of a difference in baseline scores for fatigue and physical functioning, the differences between treatment arms during PCV did not reach significance. The nonselected scales of appetite loss and drowsiness demonstrated significant differences between treatment arms during chemotherapy in favor of the RT arm. The long-term results showed no difference between arms.The major impact of PCV on HRQOL is on nausea/vomiting, loss of appetite, and drowsiness during and shortly after treatment. There are no long-term effects of PCV chemotherapy.
Questioning academic integrity
Authors: R. Smith
Journal: BMJ (1994)

Academic conflict of interest has suddenly been given a high profile in Britain. The media have discovered that the Portman Group, which lobbies for the drink trade, offered £2000 each to five academics to produce anonymous criticisms of a book on alcohol policy.1 The media, which have been awash with stories of “sleaze” in public life, are also concerned about the funding by the drink trade of the Alcohol Research Group in Edinburgh.2 3 These stories are forcing academics to reconsider the rules of academic life.

Alcohol Policy and the Public Good upset the Portman Group because it argues that increasing the taxation of alcohol reduces alcohol problems and that the current safe limits on alcohol consumption have a scientific basis.4 Published in association with the World Health Organisation, the book is the result of a two year review by an international group of 16 well known researchers chaired by Griffith Edwards, professor of addiction behaviour, University of London.

The Portman Group managed to obtain a prepublication copy from the WHO regional office in Copenhagen, and George Winstanley, director of strategy for the group, wrote to the academics, giving them a clear idea of what he wanted in the review:

“I do not think that this book can be allowed to go unchallenged. Apart from its excessive length, it is in my opinion, unsatisfactory in the way it selects the evidence and draws conclusions from it. Results are reported and research cited selectively. Evidence which does …
Treatment of aggressive keratoacanthomas by radiotherapy
Authors: Bernadine Donahue, Jay S. Cooper, Stephen Rush
Journal: Journal of the American Academy of Dermatology (1990)

Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas.
Gloomy prognoses keep lawyers happy but are bad for patients
Authors: Richard Lawson
Journal: BMJ (2006)

L ast year my sister had a massive subarachnoid haemorrhage, resulting in her being in a coma for four months. She has made a miraculous recovery and is now living in her own home with some support. Throughout the course of her illness her surgical treatment could not be faulted, apart from the inevitable time spent waiting.

> We are giving gloomy prognoses to keep ourselves out of court 

The aneurysm was embolised, the tracheotomy and gastrostomy tubes were duly inserted, and a shunt was fitted when she began to develop hydrocephaly. Technically the work was faultless, but at every stage a bleak prognosis was given. Initially, there was much sucking of teeth and shaking of heads among the doctors as we viewed the large areas of black on the computed tomography scans; and at the end, before the shunt was inserted to relieve increasing intracranial pressure, we …
BMJ author hits out at attempts to dismiss findings of possible racial bias in RCGP exam
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The author of a paper in the BMJ that found evidence of possible “subjective bias owing to racial discrimination” in the exam for membership of the Royal College of General Practitioners (MRCGP) has hit out at the college and the General Medical Council for trying to play down his findings.

Aneez Esmail, a UK authority on racial discrimination whom the GMC had asked to investigate whether there was any evidence of racial bias in the clinical skills assessment part of the MRCGP exam, told the BMJ that he had been “taken aback by the vehemence of [the GMC’s and RCGP’s] attempt to exonerate themselves” from accusations of possible racial bias in the exam.

He said it was difficult to identify any other explanation for his findings. “The critical point is that the nature of the CSA [clinical skills assessment] is that it is open to subjective bias,” he told the BMJ . 

Clare Gerada, chairwoman of the RCGP, refuted the allegations and claimed that the GMC report that Esmail coauthored made no findings of potential …
How will primary care groups work?
Authors: T. Butler, M. Roland
Journal: BMJ (1998)

Delivery of the 10 year strategy for health set out in the white paper will depend to an important degree on the effectiveness of the new primary care groups in delivering local health improvement programmes, in partnership with health authorities. From April 1999, 500 new primary care groups, typically serving populations of 100 000, will replace nearly 4000 existing commissioning organisations, including general practice fundholders. They will be resourced out of current fundholding allowances.

Primary care groups will involve all local general practitioners, along with community nurses. The white paper outlines four progressive forms of primary care group: giving advice to health authorities on commissioning; managing devolved budgets; independent primary care trusts responsible for some devolved commissioning; and primary care trusts responsible for commissioning all primary and secondary care services with a fully integrated budget. It is not yet clear how primary care groups will relate to optometrists, pharmacists, or dentists. For …
Hazards for elderly people admitted for respite and social care
Authors: J. Oliver
Journal: BMJ (1986)

Hazards for elderly people admitted for respite and social care Judith Oliver; Christine H McAlpine, mrcp, and others; Elaine Murphy, mrcpsych; M Gill, mrcp; G S Rai, md, and others; R J Lenton, mrcp, and others; M J P Power, mrcp, and others; G R Burston, frcp. 481 Retinal changes in malignant/accelerated hypertension O Wrong, frcp. 483 HMOs: America today, Britain tomorrow? D S Grimes, frcp; J A Duncan, ffarcs. 483 The future of BCG vaccination in schools in England and Wales K M Citron, frcp. 483
Alterations in the Microbiota Drive Interleukin-17C Production from Intestinal Epithelial Cells to Promote Tumorigenesis
Authors: Xinyang Song, Hanchao Gao, Yingying Lin, Yikun Yao, Shu Zhu, Jingjing Wang, Yan Liu, Xiaomin Yao, Guangxun Meng, Nan Shen, Yufang Shi, Yoichiro Iwakura, Youcun Qian
Journal: Immunity (2014)
Reviews and Notes: Neurology: Stroke: A Clinical Approach
Authors: Lawrence M. Brass
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 May 1994Reviews and Notes: Neurology: Stroke: A Clinical ApproachLawrence M. BrassLawrence M. BrassYale University School of Medicine, New Haven, CT 06510.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-9-199405010-00031 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Stroke: A Clinical ApproachSecond edition. Louis R. Caplan. 562 pages. Stoneham, Massachusetts: Butterworth-Heinemann; 1993. $90.00.The many syndromes and options for diagnosis and management of patients with stroke is often bewildering, even for experienced neurologists. If you have ever wanted to discuss a case with an internationally recognized stroke authority, Dr. Caplan's text should be in your library. All major areas of clinical cerebrovascular disease are addressed wonderfully through review of recent literature and application of existing knowledge to the practice of vascular neurology.A few dozen texts are available on cerebrovascular disease. Some are more detailed in their ... Author, Article, and Disclosure InformationAffiliations: Yale University School of Medicine, New Haven, CT 06510. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1994Volume 120, Issue 9Page: 815-816KeywordsCerebrovascular diseasesClinical epidemiologyMolecular biologyNeurologyPatientsResearch laboratoriesStrokeStroke rehabilitationSurgeryYoung adults ePublished: 15 August 2000 Issue Published: 1 May 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...