tbuckley/cabot-search huggingface dataset:
Bringing science to the art of diagnosis
Authors: P Moayyedi
Journal: Gut (2004)

Which gastrointestinal symptoms are useful in distinguishing organic from functional disease?

Patients and clinicians are becoming increasingly intolerant of diagnostic uncertainty. This is reflected in the rising demand for endoscopic procedures1 implicitly suggesting that gastrointestinal symptoms are an unreliable indicator of serious pathology. Unfortunately, the growing array of tests that are being demanded for patients are placing further pressures on already stretched health care budgets. The natural reaction to this is to evaluate whether we can improve on the value of the history to diagnose gastrointestinal disease. This process was started over 30 years ago when researchers such as Card and colleagues2,3 and de Dombal and colleagues4,5 evaluated the use of computers to aid the clinician in making diagnoses in patients with upper gastrointestinal symptoms. The enthusiasm for this approach faded when data suggested that computer improved diagnostic accuracy of computers was not sufficient to prevent investigations.6 The paucity of subsequent research in this field is disappointing as it would be useful to know what information computers were using that enhanced diagnostic acumen. The article by Hammer and colleagues7 in this issue of Gut [see page 666] is therefore refreshing as it prospectively evaluates a wide range of gastrointestinal symptoms to establish which are useful in distinguishing organic from functional disease. The strength of this study is that it evaluates a large relatively unselected group of patients, reducing spectrum and selection bias.8 It also divided patients into those with and without organic disease rather than subdividing the data into different diagnoses. This improves the power of the study and gives the clinician overall information on whether the …
A theme issue “by, for, and about” Africa
Authors: Jimmy Volmink, Lola Dare, Jocalyn Clark
Journal: BMJ (2005)

outcomes may be observed to change over time in the absence of any intervention. 9Observed changes therefore may not be due to the intervention itself but to an independent secular trend.Additionally, the effects of other ongoing local, regional, or national initiatives may confound the results of evaluations.Without a matched community control, attributing any independent effect of the intervention itself is difficult.Study designs with community comparisons must adequately control for potential confounding factors.Overall, retail interventions may have either a small but important effect or no effect on diet and health.Although these studies had similar aims and results, uncertainty over the efficacy of retail led interventions stems from problems of interpretation owing to differences in study design.However, the implications for the future development of dietary interventions are similar.Changes in fruit and vegetable consumption, although small, are consistent with other evidence.Two recent reviews of dietary interventions for cancer risk found an average increase of 0.6 portions of fruit and vegetables per day, 10 11 and relatively small increases in fruit and vegetable consumption may have encouraging prospects for the prevention of disease. 12 The potential negative impacts of large scale retail interventions need to be understood and accounted for-improved retail provision may also increase the availability of foods associated with poor diet.Activities such as advertising and price promotion that surround store opening may be important mediators of impact and effect.If new retail provision is to have an impact on diet and health, we need a multidimensional approach that also tackles food awareness, affordability, and acceptability in addition to retail change.Changing access through improving retail provision alone may not have a substantial impact on diet and health.Changing knowledge without ensuring access seems problematic intuitively.An approach that changes knowledge and access simultaneously may have a better chance of securing improvements in diet and health and a reduction in health inequalities.
Defining T helper (CD4) cell-specific disease signatures in active, inactive and autologous stem cell transplanted lupus patients by global gene expression profiling
Authors: Chieko Kyogoku, Joachim Grün, Robert Biesen, Tobias Alexander, Falk Hiepe, Andreas Radbruch, Andreas Grützkau
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects multiple organs, whose pathology is mainly caused by the augmented interferon (IFN) signaling pathway. The objective of this study was to analyse the particular role of peripheral CD4+T cells in the pathogenesis of SLE by global gene expression profiling. The major focus was set on the comparison of disease-active and -inactive patients either by standard drug treatment or by autologous stem cell transplantation (ASCT) that is assumed to completely reset the autoreactive immunologic memory. <h3>Materials and methods</h3> Affymetrix HG U133 Plus 2.0 gene expression arrays were made from purified peripheral CD4+T cells from six active SLE, two inactive SLE by standard drug treatment and three inactive SLE who underwent ASCT as well as three healthy donors. The list of IFN pathway-related genes was obtained from Ramos PS <i>et al</i>1 (Arthritis Rheum 2011). In total, 2220 genes were chosen as targeted IFN signatures in this analysis. The data were analysed using BioRetis database and GENESIS clustering software. <h3>Results</h3> Comparing IFN-imprints in active, inactive and ASCT-treated inactive SLE patients, it was obvious that inactive patients treated by low-dose cortisone showed only a marginal IFN-signature (233 probe sets) as compared to active patients (573). Unexpectedly, 562 differentially expressed probe sets were identified in ASCT-treated patients who are under long-term remission for 8–13 years. Considering the expression magnitude of IFN-regulated transcripts, it was quite obvious that a clear quantitative difference was observed in the strength of the IFN imprints detected in CD4+T cells from active patients and ASCT-treated patients. Although 322 IFN pathway-related probe sets were detected in common for active patients and ASCT-treated patients, about two-third of them (202) had much higher expression levels in active patients. <h3>Conclusion</h3> The authors could show for the first time leucocyte-specific IFN signatures for peripheral monocytes and CD4+T cells. Comparing IFN responses in active, inactive and ASCT-treated inactive SLE patients, the striking IFN signature of active SLE patients was dramatically attenuated in the successfully treated patients, although an IFN-imprint was still detectable in all SLE patients including ASCT-treated and inactive SLE. Further analyses using monocytes data from ASCT-treated patients are under way in order to clarify the role of IFN signatures on the disease phenotype of SLE. This knowledge may help to improve and to expand diagnostic applications regarding disease activity and therapy stratification of SLE patients.
Aspirin before a clot busting drug is more effective than after
Authors: S. Gottlieb
Journal: BMJ (2002)

Patients who have had a heart attack and take aspirin before taking clot busting drugs are more likely to survive than those who take the drugs in reverse order, researchers have found.

It is not clear why the order makes a difference, but the reduction in mortality may indicate that aspirin improves the restoration of blood flow to the heart, according to Dr Dov Freimark of Sheba Medical Center in Tel-Hashomer, Israel, lead author of the study ( American Journal of Cardiology 2002;89:381-5).

The …
Neutrophil chemokines in cultured nasal fibroblasts
Authors: C. Rudack, W. Hermann, J. Eble, J.‐M. Schroeder
Journal: Allergy (2002)

Background: To gain insight into the mechanisms responsible for tissue neutrophil immigration in sinusitis, primary nasal fibroblasts are analyzed for synthesizing and delivering neutrophil chemokines. Methods: Primary nasal fibroblast cell culture was treated with tumor necrosis factor (TNF)‐α concentrations of 20 and 200 ng/ml for 2, 8, 24 and 72 h. Chemokine concentrations in supernatants were determined by enzyme‐linked immunoassay (ELISA) and chemokine mRNA expression in fibroblasts was measured by reverse transcriptase polymerase chain reaction (RT‐PCR). Biological chemotactic activity was identified by three‐step high‐performance liquid chromatography (HPLC) and by bioassay measuring neutrophil chemotaxis in a single Boyden chamber system. Results: Interleukin (IL)‐8 and growth‐related oncogene (GRO)‐α were induced in nasal fibroblast culture by proinflammatory stimulus. After 24 h of stimulation neutrophil chemotactic activity only was detected for IL‐8. Granulocyte chemotactic protein (GCP)‐2 mRNA was already significantly up‐regulated after 2 h of stimulation. Conclusion: Induction of IL‐8 protein dominates chemokine synthesis 24 and 72 h after stimulation, whereas induction of GCP‐2 mRNA seems to have a role in the early phase after 2 h of exposition with TNF‐α.
Community mental health services: a vision for the future.
Authors: E Murphy
Journal: BMJ (1991)

The nineteenth century asylum movement was the outcome of 50 years of campaigning by humane men of conscience who thought that they had found a solution both to providing care for people with mental disorders and also to curing them.Their efforts culminated in the 1845 Lunacy Act, which obliged all county councils to establish pauper lunatic asylums for the local population.There was almost universal agreement at the time about what needed to be done-a shared vision that fuelled the enthusiasm of politicians, social reformers, doctors, clergymen, and other influential people.
Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy
Authors: M V Stankov, M El Khatib, B Kumar Thakur, K Heitmann, D Panayotova-Dimitrova, J Schoening, J P Bourquin, N Schweitzer, M Leverkus, K Welte, D Reinhardt, Z Li, S H Orkin, G M N Behrens, J H Klusmann
Journal: Leukemia (2013)
The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins
Authors: Patrick J. O'Hara, Paul O. Sheppard, Henning Thógersen, Domenick Venezia, Betty A. Haldeman, Vicki McGrane, Khaled M. Houamed, Christian Thomsen, Teresa L. Gilbert, Eileen R. Mulvihill
Journal: Neuron (1993)
Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: A systematic review
Authors: Kirsten Boonstra, Ulrich Beuers, Cyriel Y. Ponsioen
Journal: Journal of Hepatology (2012)

Studies on the epidemiology of primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC) show variable outcome. We aimed at systematically reviewing the incidence and prevalence rates, as well as geographical distribution and temporal trends of PSC and PBC.A systematic search of literature was performed in Medline and EMBASE (search last conducted January 10th, 2011).Population-based epidemiological studies reporting incidence and/or prevalence rates for PSC or PBC in a defined geographical area of at least 100,000 adult inhabitants were considered relevant.Study area, study period, number of patients, number of inhabitants, incidence per 100,000 inhabitants per year, prevalence per 100,000 inhabitants, method of case-finding, method of case-ascertainment, male/female ratio and in case of PSC, occurrence of inflammatory bowel diseases (IBD) were extracted from retrieved articles.The literature search yielded 2286 abstracts of which 31 articles fulfilled all inclusion criteria. Studies varied in size from 10 to 770 patients in catchment areas from 100,312 to 19,230,000 inhabitants. The incidence and prevalence rates for PSC range from 0 to 1.3 per 100,000 inhabitants/year and 0-16.2 per 100,000 inhabitants, respectively. PBC incidence rates range from 0.33 to 5.8 per 100,000 inhabitants/year and prevalence rates range from 1.91 to 40.2 per 100,000 inhabitants; prevalence rates are increasing in time.Incidence and prevalence rates of both PSC and PBC vary widely and seem to be increasing. True population-based studies are scarce and therefore large population-based studies combining meticulous case-finding and case-ascertainment strategies are necessary.
Is interleukin-6 a gender-specific risk factor for liver cancer?
Authors: Leif E. Sander, Christian Trautwein, Christian Liedtke
Journal: Hepatology (2007)

Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
Institutions must also be accountable for research integrity
Authors: M. Cosentino, M. Picozzi
Journal: BMJ (2013)

Scientific misconduct includes serious breaches of integrity (fabrication, falsification, and plagiarism) and questionable research practices (failure to keep records, mismanagement of data, incomplete acknowledgment, and ghost/guest authorship). The need to ensure that the scientific community and the public have an accurate and complete record of research is increasing.1

The Singapore statement on research integrity, the first international guideline on …
Volume regulation and plasma membrane injury in aerobic, anaerobic, and ischemic myocardium in vitro. Effects of osmotic cell swelling on plasma membrane integrity.
Authors: C Steenbergen, M L Hill, R B Jennings
Journal: Circulation Research (1985)

The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the intracellular space of intact cells; therefore, an increase in tissue inulin content is an excellent marker of loss of plasma membrane integrity. Cell volume was increased during exposure of aerobic slices to hypotonic media, but the inulin-diffusible space was not increased and electron micrographs showed no detectable plasma membrane alterations. Likewise, during prolonged anoxic isotonic incubation, no evidence of plasma membrane damage was observed. Incubation in anoxic hypotonic media for 60 minutes resulted in a larger increase in cell volume than under aerobic conditions, but plasma membrane integrity was maintained. Extended anoxic hypotonic incubation (300 minutes) produced no further change in tissue water, but the inulin-diffusible space was increased and electron micrographs revealed breaks in the plasma membranes primarily in association with large subsarcolemmal blebs. Likewise, myocardial slices incubated in isotonic anoxic media for 240 minutes and hypotonic anoxic media for 60 minutes had an increased inulin-diffusible space and the ultrastructural appearance was similar. This ultrastructural appearance is indistinguishable from that observed in myocytes lethally injured by ischemia. Measurements of tissue osmolarity during total ischemia showed that osmotically induced cell swelling could occur in ischemic myocardium prior to the onset of plasma membrane disruption. Our results indicate that cell swelling per se is incapable of rupturing plasma membranes; however, after prolonged periods of energy deficiency, the plasma membrane or its cytoskeletal scaffold become injured, which allows the membrane to rupture if the cell is swollen, as might occur during ischemia or reperfusion.
Special Commentary: Food and Drug Administration and American Academy of Ophthalmology Sponsored
Authors: Flora Lum, Michelle E. Tarver, Malik Y. Kahook, Thomas A. Oetting, Eva Rorer, Gene Hilmantel, Don Calogero, Tina Kiang, John P. Berdahl, Anne L. Coleman, Malvina B. Eydelman
Journal: Ophthalmology (2015)
Risk Factors for Breast Cancer for Women Aged 40 to 49 Years
Authors: Heidi D. Nelson, Bernadette Zakher, Amy Cantor
Journal: Annals of Internal Medicine (2012)

Letters2 October 2012Risk Factors for Breast Cancer for Women Aged 40 to 49 YearsHeidi D. Nelson, MD, MPH, Bernadette Zakher, MBBS, and Amy Cantor, MD, MPHHeidi D. Nelson, MD, MPHFrom Oregon Health & Science University, Portland, OR 97239., Bernadette Zakher, MBBSFrom Oregon Health & Science University, Portland, OR 97239., and Amy Cantor, MD, MPHFrom Oregon Health & Science University, Portland, OR 97239.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-7-201210020-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with the comments from Dr. Autier, that identifying factors associated with increased risk for death from breast cancer, not just incidence, to guide screening for women in their 40s would be useful. However, it is also correct that few studies have reported this association.Our systematic review focused on the many published studies of risk factors for breast cancer incidence specifically for women in their 40s who would be candidates for mammography screening under current U.S. guidelines (1). Our results indicated that extremely dense breasts on mammography and first-degree relatives with breast cancer were each associated ...References1. Nelson HD, Zakher B, Cantor A, Fu R, Griffin J, O'Meara ES, et al. Risk factors for breast cancer for women aged 40 to 49 years: a systematic review and meta-analysis. Ann Intern Med. 2012;156:635-48. [PMID: 22547473] LinkGoogle Scholar2. van Ravesteyn NT, Miglioretti DL, Stout NK, Lee SJ, Schechter CB, Buist DS, et al. Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years: a comparative modeling study of risk. Ann Intern Med. 2012;156:609-17. [PMID: 22547470] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Oregon Health & Science University, Portland, OR 97239.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2350. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRisk Factors for Breast Cancer for Women Aged 40 to 49 Years Heidi D. Nelson , Bernadette Zakher , Amy Cantor , Rongwei Fu , Jessica Griffin , Ellen S. O'Meara , Diana S.M. Buist , Karla Kerlikowske , Nicolien T. van Ravesteyn , Amy Trentham-Dietz , Jeanne S. Mandelblatt , and Diana L. Miglioretti Risk Factors for Breast Cancer for Women Aged 40 to 49 Years Philippe Autier Metrics Cited ByBreast Cancer Risk Related to Combined Oral Contraceptive Use 2 October 2012Volume 157, Issue 7Page: 529KeywordsBreast cancerClinical epidemiologyConflicts of interestDecision makingDisclosureMammographyMedical risk factorsOral contraceptive therapySystematic reviews ePublished: 2 October 2012 Issue Published: 2 October 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Cilia and Cystic Fibrosis
Authors: William W. Waring
Journal: New England Journal of Medicine (1973)

Physicians who treat children with cystic fibrosis or the increasing numbers of adults with the disease will perhaps be bemused by a paper by Sanchis and his co-workers in this week's Journal. These Canadian investigators report their observations of mucociliary clearance of an inhaled radioactive aerosol from the lungs of children with the disease. As all pediatricians know, these children begin life with apparently normal lungs, but subsequently a rather typical picture of progressive obstructive pulmonary disease develops. Cough, originally absent for a variable period, becomes intermittent, then chronic, and finally productive of ever increasing quantities of mucopurulent yellow . . .
Jay McLean, MD
Authors: George J. Hill
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Your unpleasant and unwarranted criticism of the career of Jay McLean (<b>201</b>:770, 1967) begs a rebuttal. Dr. McLean's remarkable career as a medical investigator, clinician, and teacher is amply documented in your editorial. His unique contribution to medicine in the discovery of heparin is, in itself, sufficient reason for us to be grateful that he overcame the vissicitudes of poverty and loneliness which you have described. His professional career encompasses academic surgery, physiology, radiology, oncology, and public health, and he held responsible positions in each of these fields. Few of our most esteemed medical educators have exceeded these activities in scope or depth. There is no factual basis in your editorial to substantiate the charge that "his intellectual impact in developing surgery upon physiological principles was of little moment."
Neonatal Duodenal Obstruction Caused by Annular Pancreas in Two Mongoloid Children
Authors: Herman W. Hyatt
Journal: JAMA (1962)

ANNULAR PANCREAS, apparently due to the ventral primordium's failure to rotate as a whole, is a rare congenital anomaly. In view of this rarity, it is felt that report of 2 mongoloid patients in whom this anatomical defect caused neonatal duodenal obstruction would be of interest. Report of Cases Case1.—-On April 20, 1959, a 34-year-old Rh-positive, group AB, para 4, gravida 5, white housewife with Raynaud's disease gave birth to a 5-lb., 15-oz. (2.69 kg.) female infant. Polyhydramnios complicated the pregnancy. Examination of the infant revealed mongoloid facies, slight cyanosis, a high-pitched cry, a small oval head, a Grade 1 to 2 systolic murmur heard best in the right scapular region, an enlarged liver felt 3 fingerbreadths below the right costal margin, a palpable spleen, absent Moro reflex, and extreme flaccidity of the body. Shortly after birth the infant was placed in an incubator and oxygen was administered. Five