tbuckley/cabot-search huggingface dataset:
The relation between treatment benefit and underlying risk in meta-analysis
Authors: S. J Sharp, S. G Thompson, D. G Altman
Journal: BMJ (1996)

In meta-analyses of clinical trials comparing a treated group with a control group it has been common to ask whether the treatment benefit varies according to the underlying risk of the patients in the different trials, with the hope of defining which patients would benefit most and which least from medical interventions.The usual analysis used to investigate this issue, however, which uses the observed proportions of events in the control groups of the trials as a measure of the underlying risk, is flawed and produces seriously misleading results.This arises through a bias due to regression to the mean and will be particularly acute in meta-analyses which include some small trials or in which the variability in the true under- lying risks across trials is small.Approaches which previously have been thought to be more appropriate are to substitute the average proportion of events in the control and treated groups as the measure ofunderlying risk or to plot the proportion of events in the treated group against that in the control group (L'Abbe plot).However, these are still subject to bias in most cir- cumstances.Because of the potentially seriously flawed conclusions that can result from such analyses, they should be replaced either by statis- tically appropriate (but more complex) approaches or, preferably, by analyses which investigate the dependence of the treatment effect on measured baseline characteristics of the patients in each trial.
Renal Tubular Dysfunction
Authors: Roger W. Sevy
Journal: JAMA (1966)

This monograph presents the genetic and biochemical mechanisms, clinical characteristics, and the therapeutic management of renal tubular disorders. Genetically caused disorders are emphasized, and the author hopes the book will be particularly valuable for pediatricians.  The first chapter very briefly reviews the essential principles of renal structure and function, and emphasizes the accepted basic concepts rather than detailed factual information. It presents the concepts in relatively simplified fashion. The second chapter briefly summarizes modern methods for investigating renal-tubule functions, and stresses the essential value or applicability of a given method (eg, paper chromatography) rather than the methodology per se.  Chapters 3 through 7 discuss, in order, cystinuria and Hartnup disease; phosphogluco-aminoaciduria; renal glucosuria, phosphaturia, renal acidosis, and glycinuria; galactosemia and Wilson's disease; and cystinosis. Chapter 8 considers genetically determined diseases of the renal tubules involving other organs, and chapter 9, abnormal renal-tubule responses to hormones. These areas are covered in
TREATMENT FOR ACUTE TRAUMATIC HEMATOMA OF EXTERNAL EAR
Authors: Harry A. Britton
Journal: JAMA (1927)

This condition, which is common among boxers and wrestlers and is less frequently found among men engaged in other sports, responds as a rule to a very simple treatment. During the last five years I have had the opportunity to treat about 100 cases, and in all of these I have obtained good results. I feel that I can promise a perfect ear if instructions are followed. The treatment consists first in aspirating the blood or serum which is present and then applying pressure to the anterior and posterior surfaces so as to place and keep the surfaces once separated by the fluid in apposition. Aspiration can be done immediately or at any time within five days after the date of injury. This pressure should be applied for six or seven days, and can then be safely removed. To get the best results the ear should be carefully protected, and not be injured even
Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1
Authors: Mingjian Lu, Min Wan, Karla F Leavens, Qingwei Chu, Bobby R Monks, Sully Fernandez, Rexford S Ahima, Kohjiro Ueki, C Ronald Kahn, Morris J Birnbaum
Journal: Nature Medicine (2012)
Improved metabolic profiles in insulin-treated diabetic patients given an alpha-glucosidehydrolase inhibitor.
Authors: R J Walton, I T Sherif, G A Noy, K G Alberti
Journal: BMJ (1979)

An alpha-glucosidehydrolase inhibitor (acarbose; BAY g 5421) taken with food was compared with dummy tablets in seven insulin-treated diabetic patients over eight-hour periods that included breakfast, lunch, and two snacks. Acarbose diminished the postprandial increases in blood glucose, lactate, and pyruvate concentrations and may therefore be of value in the management of insulin-dependent diabetes.
Idiopathic progressive pulmonary fibrosis.
Authors: D Davies, J S Crowther, A MacFarlane
Journal: Thorax (1975)

Five patients with progressive fibrotic lung disease are described. The dominant symptom was slowly increasing dyspnoea, and cough and sputum were not prominent. Marked weight loss was also a feature. There was severe restrictive impairment of ventilation with normal arterial gas tensions. The changes were confined to the upper parts of the lung in some but others had more generalized disease. The duration has varied so far from two to 17 years. The lung changes are considered to be due to dense progressive fibrosis. Necropsy in two confirmed this. Histologically there was monotonous fibrosis with lymphoid collections and secondary bronchiectasis, a picture similar to that found in association with ankylosing spondylitis. None of these patients had joint disease. Tuberculosis was excluded as a cause by exhaustive bacteriological tests and the failure of chemotherapy to stop deterioration. All other recognized types of infective and non-infective progressive lung fibrosis were also excluded, and this is not considered to be a variant of cryptogenic fibrosing alveolitis. Though these patients have many features in common they do not necessarily have the same pathogenesis. They are presented as an encouragement to further study.
Purinergic regulation of acid/base transport in human and rat biliary epithelial cell lines
Authors: Ákos Zsembery, Carlo Spirlì, Anna Granato, Nicholas F. LaRusso, Lajos Okolicsanyi, Gaetano Crepaldi, Mario Strazzabosco
Journal: Hepatology (1998)

Biliary epithelial cells (cholangiocytes) are responsible for rapid regulation of bile volume and alkalinity. Secretin and other hormones raising intracellular cyclic adenosine monophosphate (cAMP) concentrations promote biliary HCO3 secretion by stimulating apical Cl- channels and Cl-/HCO3- exchange (AE2). Cholangiocyte ion transport may also be stimulated by locally acting mediators; for example, adenosine 5'-triphosphate (ATP), a secretagogue that can be released into the bile by hepatocytes and cholangiocytes, activates Cl- conductances and Na+/H+ exchange (NHE) in cholangiocyte cell lines. To further explore the role of extracellular ATP in the paracrine regulation of carrier mechanisms regulating cholangiocyte H+/HCO3- secretion, we investigated the effects of nucleotides on intracellular pH regulation (measured by microfluorimetry with 2'7'-bis(2-carboxyethyl)-5,6,carboxyfluorescein [BCECF]) in human (MZ-ChA-1) and rat (NRC-1) cholangiocyte cell lines. In MZ-ChA-1 cells, 10 mol/L ATP, uridine 5'-triphosphate (UTP), and ATPgammas significantly increased NHE activity. The pharmacological profile of agonists was consistent with that anticipated for receptors of the P2Y2 class. ATP did not increase AE2 activity, but, when given to cells pretreated with agents raising intracellular cAMP, had a synergistic stimulatory effect that was inhibited by amiloride. To assess the polarity of purinergic receptors, monolayers of NRC-1 cells were exposed to apical or basolateral nucleotides. Apical administration of purinergic agonists, but not adenosine, increased basolateral NHE activity (ATPgammaS > UTP > ATP). Basolateral administration of purinergic agonists induced a weaker activation of NHE, which was instead strongly stimulated by adenosine and by adenosine receptor agonists (NECA = R-PIA = S-PIA). In conclusion, this study demonstrates that, consistent with the proposed role for biliary ATP in paracrine and autocrine control of cholangiocyte ion secretion, extracellular ATP stimulates cholangiocyte basolateral NHE activity through P2Y2 receptors that are predominantly expressed at the apical cell membrane.
Improving Improvement for Childhood Asthma
Authors: Charles J. Homer
Journal: JAMA (2011)

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
Human Macrophages Promote the Motility and Invasiveness of Osteopontin-Knockdown Tumor Cells
Authors: Jiasen Cheng, De-Hua Huo, Dong-Ming Kuang, Jine Yang, Limin Zheng, Shi-Mei Zhuang
Journal: Cancer Research (2007)

Abstract Increasing evidence indicates that macrophages in tumor stroma can significantly modify the malignant phenotypes of tumors. Osteopontin (OPN) is frequently overexpressed in cancers with high metastatic capacity and, thus, has been considered as a potential therapeutic target. To find out whether macrophages can affect the outcome of OPN-knockdown tumor cells, we used RNA interference (RNAi) to stably silence the OPN expression in the highly invasive human hepatoma cell line SK-Hep-1. Silencing of OPN markedly decreased the motility and invasiveness of the SK-Hep-1 cells. Further studies using this cell model revealed that coculture with human macrophages or macrophage-conditioned medium largely restored the migration and invasion potential of OPN-knockdown tumor cells. Moreover, such macrophage-promoted motility can be effectively blocked either by the addition of OPN-neutralizing antibody to the cocultured medium or by silencing OPN expression in macrophages. These results indicate that macrophage-derived OPN can compensate for the decrease of OPN and thereby restore the metastatic potential of OPN-knockdown tumor cells. Further characterization of the underlying mechanisms disclosed that macrophage-derived OPN exerted its function independently of the actin cytoskeleton rearrangement or the activation of matrix metalloproteinase and Rho families. Our results suggest that there are fine-tuned complex interactions between cancer cells and stroma cells, which may modify the outcome of cancer therapy, and therefore should be considered for the rational design of anticancer strategy. [Cancer Res 2007;67(11):5141–7]
Engager T Cells: A New Class of Antigen-specific T Cells That Redirect Bystander T Cells
Authors: Kota Iwahori, Sunitha Kakarla, Mireya P Velasquez, Feng Yu, Zongzhen Yi, Claudia Gerken, Xiao-Tong Song, Stephen Gottschalk
Journal: Molecular Therapy (2014)

Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer. Adoptive immunotherapy with antigen-specific T cells has shown promise for the treatment of malignancies. However, infused T cells are unable to redirect resident T cells, limiting potential benefit. While the infusion of bispecific T-cell engagers can redirect resident T cells to tumors, these molecules have a short half-life, and do not self amplify. To overcome these limitations, we generated T cells expressing a secretable T-cell engager specific for CD3 and EphA2, an antigen expressed on a broad range of human tumors (EphA2-ENG T cells). EphA2-ENG T cells were activated and recognized tumor cells in an antigen-dependent manner, redirected bystander T cells to tumor cells, and had potent antitumor activity in glioma and lung cancer severe combined immunodeficiency (SCID) xenograft models associated with a significant survival benefit. This new class of tumor-specific T cells, with the unique ability to redirect bystander T cells, may be a promising alternative to current immunotherapies for cancer.
The relationship between physical game demands and injury rehabilitation in international rugby union: a global positioning system analysis
Authors: G Coughlan, B Green, P Pook, E Toolan, S O'Connor
Journal: British Journal of Sports Medicine (2011)

Background Over the past 10 years the methodologies and technology of recording professional rugby union game data has greatly improved with global positioning system (GPS) now the gold standard. Objective The aims of the present study were to evaluate the physical demands of the game at an international rugby union level using a GPS and establish the potential of the system in providing feedback to the management (sports medicine and coaching) team in relation to the mechanism/prevention of injury, as well as rehabilitation and exercise load prior to return to play. Setting International rugby union team. Patients Two international rugby union players were recruited to participate in this investigation. Interventions GPS data generated by the two players (one forward and one back) in an international test match were analysed, Main outcome measurements Specifically speed zones and bodyload sustained in tackles and scrum activities. Results The back covered a greater overall distance compared to the forward. The forward had a higher number of entries into the low speed zones of standing/non-purposeful movements and walking with fewer entries into the high-intensity running and maximal speed running. Work-to-rest ratios were identical for both players over the course of the game. The forward player sustained a significantly higher number of impacts and total bodyload. Total and average bodyload in tackles made were larger for the back, with this trend reversed for tackles against. Conclusion GPS data provides important performance indicators, assists in the development of conditioning and training protocols, as well as injury management and return to play criteria for players. This information should be utilised to identify injury prevention strategies and game characteristics, as well as improving player welfare.
South Africa: Two-Language Medicine
Authors: STANLEY S. GILDER
Journal: Annals of Internal Medicine (1974)

Abroad1 August 1974South Africa: Two-Language MedicineSTANLEY S. GILDERSTANLEY S. GILDERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-2-264 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMedical education in the Republic of South Africa has in the last thirty years taken on a quality unique in the world. It has quite rapidly become bilingual to the extent that over 40% of present undergraduates are learning medicine in Afrikaans and not in English, the other official language of the Republic. If one extrapolates from the present curve, in the near future over half of all those graduating will have been taught almost exclusively in Afrikaans.The bilingual teaching of medicine within a country is not new. Canada has used both French and English for years; Belgium, both... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 110 Nuffield St., Rietondale, Pretoria Republic of South Africa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1974Volume 81, Issue 2Page: 264-264KeywordsForecastingMedical educationUndergraduates Issue Published: 1 August 1974 PDF DownloadLoading ...
An eye for form
Authors: L Farrell
Journal: BMJ (1994)

The flags are up, the money's down, The frightened bookies quake. Come on, me boys, and give a cheer, Begod, ‘tis Cottage Rake!’

The racehorse trainer Vincent O'Brien retired just recently. To those of us who share a passion for the turf, he was the nonpareil, a man with an unrivalled gift for choosing and nurturing champions. Gold Cups, Grand Nationals, Derbys - all were plundered by his unique skills. Legend has it that the great Nijinsky was picked out of a field full of larger and more imposing individuals; only the eye of a genius could see through the veneer of size and beauty and perceive instead the …
Carbohydrate and protein contents of grain dusts in relation to dust morphology.
Authors: W V Dashek, S A Olenchock, J E Mayfield, G H Wirtz, D E Wolz, C A Young
Journal: Environmental Health Perspectives (1986)

Grain dusts contain a variety of materials which are potentially hazardous to the health of workers in the grain industry. Because the characterization of grain dusts is incomplete, we are defining the botanical, chemical, and microbial contents of several grain dusts collected from grain elevators in the Duluth-Superior regions of the U.S. Here, we report certain of the carbohydrate and protein contents of dusts in relation to dust morphology. Examination of the gross morphologies of the dusts revealed that, except for corn, each dust contained either husk or pericarp (seed coat in the case of flax) fragments in addition to respirable particles. When viewed with the light microscope, the fragments appeared as elongated, pointed structures. The possibility that certain of the fragments within corn, settled, and spring wheat were derived from cell walls was suggested by the detection of pentoses following colorimetric assay of neutralized 2 N trifluoroacetic acid hydrolyzates of these dusts. The presence of pentoses together with the occurrence of proteins within water washings of grain dusts suggests that glycoproteins may be present within the dusts. With scanning electron microscopy, each dust was found to consist of a distinct assortment of particles in addition to respirable particles. Small husk fragments and "trichome-like" objects were common to all but corn dust.
White House proposes doubling spending on combating antibiotic resistance to $1.6bn in 2016
Authors: M. McCarthy
Journal: BMJ (2015)

US President Barack Obama will ask Congress to almost double the funding for federal efforts to combat antibiotic resistance in his budget for 2016, White House officials said on 27 January. This will raise US spending on these programmes to more than $1.2bn (£0.8bn; €1bn). 

The US Centers for Disease Control and Prevention has estimated that antibiotic resistant bacteria cause at least two million cases of illness and 23 000 deaths in the US alone each year, incurring at least $20bn in excess direct health costs and up to $35bn in lost productivity caused by admissions to hospital and sick days.

Under the president’s proposal, $650m …
Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice.
Authors: D A Arenberg, S L Kunkel, P J Polverini, M Glass, M D Burdick, R M Strieter
Journal: Journal of Clinical Investigation (1996)

The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.
Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3γ1(Ala-Ala)
Authors: Kevan C. Herold, Joshua B. Burton, Fleur Francois, Ena Poumian-Ruiz, Mariela Glandt, Jeffrey A. Bluestone
Journal: Journal of Clinical Investigation (2003)

Dimeric Fc receptor (FcR) nonbinding anti-CD3 antibodies have been developed to minimize toxicities associated with classical anti-CD3 monoclonal antibodies (e.g., OKT3). Studies with murine analogs of non-FcR–binding antibodies have shown reduced mitogenicity compared to OKT3. In a trial of an FcR nonbinding humanized anti-CD3 mAb hOKT3γ1(Ala-Ala) for treatment of patients with type 1 diabetes, we found significant increases in IL-10 and IL-5 in the serum of 63% and 72% of patients, respectively, and TNF-α and IL-6 levels that were lower than those previously reported following OKT3 therapy. The activation signal delivered by hOKT3γ1(Ala-Ala) was associated with calcium signaling and cytokine production by previously activated human cells in vitro. However, the production of IL-10, compared to IFN-γ on a molar basis, was greater after culture with hOKT3γ1(Ala-Ala) than with OKT3. Flow cytometric studies confirmed that OKT3 induced IFN-γ and IL-10 production, but hOKT3γ1(Ala-Ala) induced only detectable IL-10 production in CD45RO+ cells. Moreover, in vivo, we found IL-10+CD4+ T cells after drug treatment. These cells were heterogeneous but generally CD45RO+, CTLA-4–, and expressed CCR4. A subgroup of these cells expressed TGF-β. Thus, the non-FcR binding anti-CD3 mAb, hOKT3γ1(Ala-Ala) delivers an activation signal to T cells that is quantitatively and qualitatively different from OKT3. It leads to the generation of T cells that might inhibit the autoimmune response and may be involved in the beneficial effect on β cell destruction in Type 1 diabetes.