tbuckley/cabot-search huggingface dataset:
OC-102 Coeliac disease, anti-inflammatory drugs or<i>Helicobacter pylori</i>are the most common identifiable causes of lymphocytic duodenosis
Authors: I Aziz, K E Evans, A D Hopper, D M Smillie, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> Lymphocytic duodenosis (LD) is found in 2% of duodenal biopsies. LD is defined by normal villous architecture and intraepithelial lymphocytes (IELs) &gt;25 per 100 enterocytes. This is more commonly recognised as modified Marsh grade 1 on histopathology reports. Such patients should not be diagnosed with coeliac disease, solely by histology, as previous retrospective studies have suggested other associations with LD. <h3>Aims</h3> To prospectively study the aetiology of LD. <h3>Methods</h3> One hundred and sixty five patients with LD were rigorously investigated for coeliac disease and other known associations of LD, by means of revisiting the patient9s history and recent investigations, followed by a combination of gluten challenge, HLA typing, repeat coeliac serology &amp; duodenal biopsies, and exclusion of infection/inflammatory bowel disease. <h3>Results</h3> 127 female: 38 male, age range 17–83 years, median age 46 years. Coeliac disease was present in 21% of patients with LD. In the absence of a positive coeliac diagnosis, LD was most commonly associated with anti-inflammatory drugs (17%), <i>H pylori</i> (16%), gastrointestinal infections (7%), immune dysregulation (6%), inflammatory bowel disease (3%), and IgA deficiency (1%). Overall, there were 49 (30%) cases where no cause was found and the IEL count normalised in 35/49 (71%). Irritable bowel syndrome (IBS) was a clinical diagnosis in 30 of these 49 patients. All patients with coeliac disease were HLA DQ2 or DQ8 positive, compared to 55% of non-coeliacs (p value &lt;0.0001). Patients with coeliac disease were significantly associated with positive endomysial and/or raised tissue transglutaminase antibodies (p&lt;0.0001). There was no statistical difference in age, gender or baseline bloods (haematology/biochemistry/inflammatory markers) between the coeliac and non-coeliac group (p&gt;0.05). <h3>Conclusion</h3> This is the largest cohort of patients systematically investigated for a cause of their LD. A cause can be identified in up to 70% of cases, with coeliac disease, anti-inflammatory drugs and <i>H pylori</i> representing the majority of cases. In those with no apparent cause, there may be an association with IBS and the IEL count becomes normal on repeat biopsy in 71%. <h3>Competing interests</h3> None declared.
Adjuvant trastuzumab for breast cancer: The other side of the coin
Authors: Somasundari Gopalakrishnan, John Linnane
Journal: BMJ (2005)

Adjuvant trastuzumab for breast cancer Assessing HER2/neu status incurs more costs for treatmentEditor-The results of recent trials are likely to continue to fuel the demand for trastuzumab in the adjuvant setting of early breast cancer, 1 as well as a possible neoadjuvant treatment in the near future.However, Dent and Clemons did not discuss the difficulty in obtaining accurate and reproducible assessment of HER2/neu gene overexpression.Immunohistochemical testing measures HER2/neu protein expression whereas in situ hybridisation measures gene amplification.Patients with equivocal immunohistochemical results require in situ hybridisation to determine definitive status because interobserver variability using immunohistochemical testing is appreciable.At least 20% of patients with positive immunohistochemical results will be truly negative for HER2/neu gene amplification; these patients would not benefit from trastuzumab. 2 These difficulties in assessing HER2/ neu status have been encountered in studies testing trastuzumab, and in situ hybridisation testing has been used as the gold standard. 3 As the clinical utility of trastuzumab widens guidelines on HER2/neu testing must be clear to ensure appropriate use of trastuzumab.Clearly this testing will incur additional costs to trastuzumab treatment.
Aesthetics and the Individual in the Practice of Medical Research: Discussion Paper
Authors: D Aldridge
Journal: Journal of the Royal Society of Medicine (1991)

‘Art does not reproduce the visible, rather it makes visible. Formerly we used to represent things visible on earth, things we either liked to look at or would have liked to see. Today we reveal that reality that is behind all living things, thus expressing the belief that the visible world is merely an isolated case in relation to the universal, and there are many more latent realities’ Paul Klee 1
Treatment of Cockroach Allergen Asthma Model with Imatinib Attenuates Airway Responses
Authors: Aaron A. Berlin, Nicholas W. Lukacs
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

In the present study it was determined whether a pharmacologic approach to blocking receptor tyrosine kinase-mediated activation during allergic airway responses could be beneficial. To examine these responses, allergic mice were given a single oral dose of imatinib at clinically relevant concentrations, ranging from 0.05 to 50 mg/kg, by oral gavages just before allergen challenge. The reduction in the allergen-induced responses was significant and centered on reducing overall inflammation as well as pulmonary cytokine levels. In particular, the treatment of the mice with imatinib significantly attenuated airway hyperreactivity and peribronchial eosinophil accumulation, and significantly reduced Th2 cytokines, interleukin-4 and interleukin-13. In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals. Together these data demonstrate that the pharmacologic inhibitor imatinib may provide a clinically attractive therapy for allergic, asthmatic responses.
Filaggrin mutations, atopic eczema, hay fever, and asthma in children
Authors: Stephan Weidinger, Maureen O'Sullivan, Thomas Illig, Hansjörg Baurecht, Martin Depner, Elke Rodriguez, Andreas Ruether, Norman Klopp, Christian Vogelberg, Stephan K. Weiland, W.H. Irwin McLean, Erika von Mutius, Alan D. Irvine, Michael Kabesch
Journal: Journal of Allergy and Clinical Immunology (2008)
THE ANTICOMPLEMENTARY EFFECT OF KIDNEY TISSUE
Authors: Paul B. Beeson, D. Rowley
Journal: The Journal of Experimental Medicine (1959)

In studying the problem of the peculiar susceptibility of the kidney to coliform bacterial infection it was found that kidney tissue, unlike that of other organs, interferes with the ability of normal serum to destroy these organisms. The effect was attributable to strong anticomplementary activity, 5 to 15 times greater than that of other organs. Inactivation of complement by kidney tissue was found to have characteristics of a chemical reaction, the active principle being heat-labile, non-dialysable, and difficult to separate from tissue particles. Attempts to purify it or to obtain it in a soluble form usually resulted in great loss in activity. The component of complement affected was the fourth; i.e., that which is characterized by susceptibility to injury by ammonia. Similarities were found to exist between the conditions of ammonia formation and complement inactivation by kidney homogenates, the most notable being enhancement by phosphate and glutamine. The possibility is suggested that these findings may help to explain the vulnerability of the kidney to certain infections, especially those due to bacteria which are destroyed by the combined action of complement and antibody.
Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape
Authors: Joseph G. Crompton, Manikandan Narayanan, Suresh Cuddapah, Rahul Roychoudhuri, Yun Ji, Wenjing Yang, Shashank J. Patel, Madhusudhanan Sukumar, Douglas C. Palmer, Weiqun Peng, Ena Wang, Francesco M. Marincola, Christopher A. Klebanoff, Keji Zhao, John S. Tsang, Luca Gattinoni, Nicholas P. Restifo
Journal: Cellular and Molecular Immunology (2015)

To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8+ T cells. Using a ChIP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 (H3K4me3) and H3 lysine 27 (H3K27me3) trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8+ T-cell subsets. Taken together, our results suggest that CD8+ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory.
Inguinal Hernia: Infancy and Childhood
Authors: Thomas V. Santulli
Journal: JAMA (1961)

A study was undertaken to determine the advisability of bilateral operation in all children with unilateral inguinal hernias. In a group of patients who had repair of a unilateral hernia, the incidence of a subsequent contralateral hernia was 12 per cent. In another group who presented clinically unilateral hernias and were subjected to exploration of the opposite side, the incidence of positive exploration was 56 per cent. The discrepancy between the two groups is discussed. From this study and the philosophy based on the concept of expected incidence of eventual bilaterality, the authors do not recommend routine exploration of the contralateral side.
Treatment of anti-HCV positive chronic liver disease with recombinant alpha-2b interferon for nine months
Authors: R. Pérez, R. Pravia, A. Linares, M. Rodríguez, J.L.S. Lombraña, S. Riestra, A. Suárez, C.A. Navascuéz, N.G. Sotorrío, L. Rodrigo
Journal: Journal of Hepatology (1991)
Erythema nodosum and coeliac disease
Authors: J.M. Durand, P. Lefevre, C. Weiller
Journal: British Journal of Dermatology (1991)

Journal Article Erythema nodosum and coeliac disease Get access J.M. Durand, J.M. Durand Department of Internal Medicine, CHU Timone, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar P. Lefèvre, P. Lefèvre Department of Internal Medicine, CHU Timone, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar C. Weiller C. Weiller Department of Internal Medicine, CHU Timone, 13385 Marseille Cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 3, 1 September 1991, Pages 291–292, https://doi.org/10.1111/j.1365-2133.1991.tb14758.x Published: 01 September 1991
Website of patients' experiences launches new module on depression
Authors: Zosia Kmietowicz
Journal: BMJ (2004)

An internet health resource that draws on the experiences of patients to inform others has launched a new module on depression, its first mental health condition.

The Database of Individual Patient Experiences (DIPEx) already provides information on 13 conditions, including breast cancer, heart disease, and epilepsy, and distinguishes itself from other sites by relating people's personal experiences of an illness (www.dipex.org).

For the depression module researchers interviewed 38 men and women between the ages of 16 and 57 from all …
From soft to hard drugs.
Authors: M M Glatt
Journal: BMJ (1970)

KWIJOULfrequent intervals, partly to assess our attempts to modify the fatal course of the illness, and partly to bring what comfort and support we can to the patients and their relatives in the face of the inevitable.Some years ago, a suggestion that this degenerative disease might be metabolic in origin and correlatable with aminoacid therapy led one of us to try the effect of high dosage of aminoacids, glycocyamine and betaine,l but that idea, like all others, proved totally ineffectual.Later we ventured into a similarly fruitless (and unreported) essay using raw liver.
THE PATHOLOGY OF EXOPHTHALMIC GOITER.
Authors: W. G. MacCALLUM
Journal: JAMA (1907)

The symptom-complex which we know under various names as exophthalmic goiter, Graves' disease, Basedow's disease, etc., has been very extensively studied, but even yet there is not perfect unanimity of opinion as to the anatomic changes which underlie these symptoms. Nearly all writers, except certain clinicians who have not made anatomic investigations, agree that there are always changes in the thyroid, although there has been much debate as to whether these changes are constant in character or not. There are others who think that the lesions must be sought in the sympathetic system or in the central nervous system, while still others regard the disease as the result of a functional disturbance of the nervous system and do not expect to find gross anatomic changes. Other attendant lesions in the eyes, in the skin, the muscles, the digestive tract and in the lymphoid tissue and thymus have been frequently described,
The Role of Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cancer
Authors: Daniel Cho, Sabina Signoretti, Meredith Regan, James W. Mier, Michael B. Atkins
Journal: Clinical Cancer Research (2007)

Abstract Inhibitors of the mammalian target of rapamycin (mTOR) have shown promising efficacy in early-stage trials in patients with advanced renal cell carcinoma (RCC). Most RCCs have been shown to possess biallelic alterations in the von Hippel-Lindau (VHL) gene, resulting in accumulation of hypoxia-inducible factors 1α and 2α, as well as their downstream targets including vascular endothelial growth factor (VEGF). The observed clinical efficacy of mTOR inhibitors in patients with RCC may be mediated in part by the dependence of efficient hypoxia-inducible factor translation on the mTOR pathway. mTOR inhibitors have entered more advanced phase clinical trials either as single agents or in combination with other targeted agents or IFN, which might ultimately result in regulatory approval of one or more agents. Given the likely nonoverlapping mechanism of action of mTOR inhibitors and VEGF pathway–targeted agents, mTOR inhibitors may prove useful if administered in combination or after resistance to VEGF inhibitors. With an increasing number of active agents for treatment of patients with RCC, efforts must continue to develop patient selection models based on predictive biomarkers to direct therapy to appropriate patients.
Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor β signaling, promoting cirrhosis and hepatocellular carcinoma
Authors: Koichi Matsuzaki, Miki Murata, Katsunori Yoshida, Go Sekimoto, Yoshiko Uemura, Noriko Sakaida, Masaki Kaibori, Yasuo Kamiyama, Mikio Nishizawa, Junichi Fujisawa, Kazuichi Okazaki, Toshihito Seki
Journal: Hepatology (2007)

Abstract Many patients with chronic hepatitis caused by hepatitis C virus (HCV) infection develop liver fibrosis with high risk for hepatocellular carcinoma (HCC), but the mechanism underling this process is unclear. Conversely, transforming growth factor beta (TGF-β) activates not only TGF-β type I receptor (TβRI) but also c-Jun N-terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Whereas the TβRI/pSmad3C pathway suppresses epithelial cell growth by upregulating p21WAF1 transcription, JNK/pSmad3L-mediated signaling promotes extracellular matrix deposition, partly, by upregulating plasminogen activator inhibitor 1 (PAI-1). We studied the domain-specific Smad3 phosphorylation in biopsy specimens representing chronic hepatitis, cirrhosis, or HCC from 100 patients chronically infected with HCV, and correlated Smad3 phosphorylation with clinical course. As HCV-infected livers progressed from chronic hepatitis through cirrhosis to HCC, hepatocytic pSmad3L/PAI-1 increased with fibrotic stage and necroinflammatory grade, and pSmad3C/p21WAF1 decreased. Of 14 patients with chronic hepatitis C with strong hepatocytic pSmad3L positivity, 8 developed HCC within 12 years; only 1 of 12 showing little pSmad3L positivity developed HCC. We further sought molecular mechanisms in vitro . JNK activation by the pro-inflammatory cytokine interleukin-1β stimulated the pSmad3L/PAI-1 pathway in facilitating hepatocytic invasion, in the meantime reducing TGF-β-dependent tumor-suppressive activity by the pSmad3C/p21WAF1 pathway. Conclusion: These results indicate that chronic inflammation associated with HCV infection shifts hepatocytic TGF-β signaling from tumor-suppression to fibrogenesis, accelerating liver fibrosis and increasing risk for HCC. (HEPATOLOGY 2007;46:48–57.)
Dermatological surgery: a comparison of activity and outcomes in primary and secondary care
Authors: J.M.R. Goulding, S. Levine, R.A. Blizard, F. Deroide, V.J. Swale
Journal: British Journal of Dermatology (2009)

Dermatological surgery is carried out by a variety of practitioners in primary and secondary care.To explore the activity and histopathological outcomes among different groups of dermatological surgeons dealing with skin cancers.Reports for all new skin tumour specimens processed by our histopathology department over a continuous 3-month period were reviewed retrospectively.One thousand, one hundred and eleven new skin tumour specimens were identified. General practitioners (GPs) were least accurate in clinical diagnosis, with 42.8% (59/138) of their request forms including the eventual histological diagnosis, compared with 69.5% (328/472) for dermatologists (odds ratio, OR 0.33, 95% confidence interval, CI 0.22-0.48). Inappropriate procedures were most often performed by plastic surgeons, usually involving large excision biopsies for benign lesions in elderly patients [6.6% (20/305) of their specimens vs. 0% for dermatologists, exact P < 0.001]. Excision biopsies performed by GPs had the highest rate of margin involvement by tumour of any specialty [68% (15/22) of such specimens vs. 8% (9/116) for dermatologists; OR 25.47, 95% CI 8.26-78.53]. As per National Institute for Health and Clinical Excellence guidance, 13.8% (19/138) of tumours operated on by GPs should instead have been referred to secondary care for initial surgical management.This study presents a strong case for dermatologists to continue to provide the lead in diagnosis of skin lesions, and in selection and execution of dermatological surgical procedures.
Clindamycin and Diarrhea
Authors: Gary D. Friedman
Journal: JAMA (1976)

Of 298 outpatients receiving clindamycin for a variety of indications, diarrhea developed in ten (3.4%); none were diagnosed as having pseudomembranous colitis. This is well within the range of relative frequencies of diarrhea development (0% to 22.2%) reported in 45 previous studies. Reliance solely on computer-recorded instances of diarrhea yielded a substantial underestimate of diarrhea occurrence, but the rate was still significantly higher (<i>P</i>&lt;.05) in clindamycin users than in nonusers. (<i>JAMA</i>236:2498-2500, 1976)
An Era of Stress for Health Institutions
Authors: Robert J. Blendon
Journal: JAMA (1981)

The United States enters the 1980s beset with serious economic problems. The picture currently projected from long-term economic forecasts supplemented by national opinion polls for the early to mid-1980s suggests a downturn in our nation's economy and a sharp decrease in monies available for further growth or improvements in America's medical care system. These prospects have serious implications for many of America's most important health care institutions, their health professionals, and how plan for the future.
Midline versus mediolateral episiotomy
Authors: S. B Thacker
Journal: BMJ (2000)

First described by a Scottish midwife in the 1740s, episiotomy was not used widely until the middle of the 20th century.1 Prominent obstetricians in the United States argued that childbirth was a “decidedly pathological process” and that a small incision would speed labour, decrease trauma, and allow the perineum to be restored to nearly virginal condition after proper suturing.2 3 This became standard practice in the United States and to a lesser degree in Europe throughout most of the century. The type of incision varied: in the United States, for example, midline episiotomy was preferred, in the United Kingdom the mediolateral procedure was standard. What is the evidence that routine episiotomy is beneficial or that one incision is better than another?

The first systematic review of this procedure was published in 1983.4 The evidence at that time—three studies with control groups and no randomised controlled trials—concluded that “little research has been done to test the benefit of the procedure, and no published study could be considered adequate in its design and execution to determine whether hypothesized benefits do in fact …
Evidence for Associated Cutaneous Microangiopathy in Diabetic Patients With Neuropathic Foot Ulceration
Authors: Nathalie Chabbert-Buffet, Claude LeDevehat, Taraneh Khodabandhelou, Eric Allaire, Jean Pierre Gaitz, Laurent Tribout, Nathalie Abdoucheli-Baudot, Michel Vayssairat
Journal: Diabetes Care (2003)

Prospective Diabetes Study Group: Intensive blood-glucose control with sulphonylurea
One in 10 acute heart failure patients is given IV fluids despite evidence, study shows
Authors: S. Mayor
Journal: BMJ (2015)

One in 10 patients with acute decompensated heart failure is given intravenous (IV) fluids during the first two days of hospital admission even though this is known to be associated with worse outcomes, a US study has found.1

“Many signs and symptoms of heart failure are the result of volume overload,” said the researchers, writing in the Journal of the American College of Cardiology: Heart Failure . Diuretic therapy, which …
Algorithmic method for assessing urinary incontinence in elderly women.
Authors: P Hilton, S L Stanton
Journal: BMJ (1981)

In young patients the assessment of urinary incontinence is based increasingly on the results of complex urodynamic investigations. The value of such techniques in the elderly, however, is as yet unproved. Based on the clinical and urodynamic findings in 100 incontinent elderly women an algorithmic method for managing such patients was devised. A retrospective study comparing the algorithmic outcome with the results of standard urodynamic assessment showed that 60% of invasive investigations could be avoided by this method with minimal loss of diagnostic accuracy.