tbuckley/cabot-search huggingface dataset:
Gastrin is a target of the β-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis
Authors: Theodore J. Koh, Clemens J. Bulitta, John V. Fleming, Graham J. Dockray, Andrea Varro, Timothy C. Wang
Journal: Journal of Clinical Investigation (2000)

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene occur in most colorectal cancers and lead to activation of β-catenin. Whereas several downstream targets of β-catenin have been identified (c-myc, cyclin D1, PPARδ), the precise functional significance of many of these targets has not been examined directly using genetic approaches. Previous studies have shown that the gene encoding the hormone gastrin is activated during colon cancer progression and the less-processed forms of gastrin are important colonic trophic factors. We show here that the gastrin gene is a downstream target of the β-catenin/TCF-4 signaling pathway and that cotransfection of a constitutively active β-catenin expression construct causes a threefold increase in gastrin promoter activity. APCmin–/+ mice overexpressing one of the alternatively processed forms of gastrin, glycine-extended gastrin, show a significant increase in polyp number. Gastrin-deficient APCmin–/+ mice, conversely, showed a marked decrease in polyp number and a significantly decreased polyp proliferation rate. Activation of gastrin by β-catenin may therefore represent an early event in colorectal tumorigenesis and may contribute significantly toward neoplastic progression. The identification of gastrin as a functionally relevant downstream target of the β-catenin signaling pathway provides a new target for therapeutic modalities in the treatment of colorectal cancer.
Scientists say they are 95% certain that humanity is responsible for climate change
Authors: N. Hawkes
Journal: BMJ (2013)

The role of humans in climate change is more certain than ever, concludes a new scientific assessment from the Intergovernmental Panel on Climate Change.

Despite a pause since 1998 in rises in global temperature, the panel’s report for policy makers summarising the current state of scientific knowledge is 95% certain that the rise detected over the longer term is the result of human activity—up from 90% certain in 2007.1 Warming of the climate system is “unequivocal,” the report says, with changes since the 1950s “unprecedented over decades to millennia” and each of the past three decades successively warmer than any decade since the 1850s.

The report concedes that the climate models on which its projections were based cannot explain why temperatures have not risen since 1998 but argues that people …
Facing the Wild West of Health Care Reform — Donald Berwick, Pioneer
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2010)

Dr. Donald M. Berwick, who has tirelessly pioneered efforts to improve the quality of medical care and the safety of patients, faces new challenges as he assumes the reins of the Centers for Medicare and Medicaid Services (CMS). Democrats and Republicans alike were surprised when President Barack Obama announced his recess appointment of Berwick to the key CMS post, which had not been filled by a confirmed administrator since October 2006. A White House spokesperson said Obama acted because “many Republicans in Congress have made it clear . . . that they were going to stall the nomination as long as they . . .
Nocturnal Oxygen Desaturation in Sickle Cell Anemia
Authors: James K. Walsh
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We read with interest the recent article by Scharf et al entitled "Nocturnal Oxygen Desaturation in Patients With Sickle Cell Anemia" (1983;249:1753). Certainly, patients with sickle cell disease experiencing significant nocturnal hypoxemia may be more likely to suffer from vaso-occlusive crises during sleep. However, the author's speculation that reductions in nocturnal oxygen saturation "may occur regularly in patients with sickle cell disease" implies that the hypoxemia documented in their patients was secondary to sickle cell anemia. We believe that this suggestion is unwarranted based on the case material provided. Scharf et al assert that hypoxemia occurred "without concomitant obstructive or central apnea" or significant degree of hypopnea. However, use of thermistors to monitor airflow does not allow reliable quantification of airflow. This is of particular importance for patient 1, since even mildly hypertrophic tonsils have been shown to obstruct the airway during sleep<sup>1</sup>(although not always
Controlled trials of a sulphonamide given weekly to prevent exacerbations of chronic bronchitis.
Authors: A. Pines
Journal: BMJ (1967)

Chronic Intestinal Ischaemia-Watt et al.series of 19.cases of Heard et al. (1963) the mean duration of symptoms was four to five months.This suggests that prolonged investigation and indecision are undesirable in the management of these cases. SummaryFive cases of visceral ischaemia are presented.Successful operative and clinical results were obtained in three of the four cases of chronic intestinal ischaemia and in one case of coeliac axis stenosis.Malabsorption was a feature of four cases.Abnormalities of faecal fat, jejunal histology, disaccharidase activity, and bromsulphalein excretion were present, and improvement or reversion to normal followed successful operation.Chronic intestinal ischaemia should be strongly suspected in middle-aged patients with atypical abdominal pain and loss of weight, especially when alimentary carcinoma is suspected and barium studies are negative.Successful revascularization of the abdominal viscera can be achieved when the diagnosis has been proved by lateral aortography.We wish to thank Mr. C. J. Longland for permission to include Case 2 in this report and Dr. D. Murray for the histological examination of the intestinal biopsies.
Biomedically relevant chemical and physical properties of coal combustion products.
Authors: G L Fisher
Journal: Environmental Health Perspectives (1983)

The evaluation of the potential public and occupational health hazards of developing and existing combustion processes requires a detailed understanding of the physical and chemical properties of effluents available for human and environmental exposures. These processes produce complex mixtures of gases and aerosols which may interact synergistically or antagonistically with biological systems. Because of the physicochemical complexity of the effluents, the biomedically relevant properties of these materials must be carefully assessed. Subsequent to release from combustion sources, environmental interactions further complicate assessment of the toxicity of combustion products. This report provides an overview of the biomedically relevant physical and chemical properties of coal fly ash. Coal fly ash is presented as a model complex mixture for health and safety evaluation of combustion processes.
Comments on the Fourteenth Rheumatism Review
Authors: JOSEPH LEE HOLLANDER
Journal: Annals of Internal Medicine (1962)

Editorial1 May 1962Comments on the Fourteenth Rheumatism ReviewJOSEPH LEE HOLLANDER, M.D., F.A.C.P.JOSEPH LEE HOLLANDER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-5-807 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptContinuing in the custom of more than a quarter of a century, the ANNALS OF INTERNAL MEDICINE publishes another of the reviews of American and English literature pertaining to the field of rheumatology. These Reviews have all been prepared by successive committees of the American Rheumatism Association, working on the task as a "labor of love" to bring to the attention of physicians in internal medicine the importance of, and progress in, this relatively little-known aspect of medicine. The Review appears as a supplement to this issue.The originalReview, organized and prepared under the editorial direction of Dr. Philip... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe Differential Diagnosis of Arthralgia 1 May 1962Volume 56, Issue 5_Part_1Page: 807-810KeywordsRheumatology Issue Published: 1 May 1962 PDF DownloadLoading ...
Update in Allergy and Immunology
Authors: Anthony Montanaro, Stephen A. Tilles
Journal: Annals of Internal Medicine (2001)

Updates from the Annual Session20 February 2001Update in Allergy and ImmunologyAnthony Montanaro, MD and Stephen A. Tilles, MDAnthony Montanaro, MDFrom Oregon Health Sciences University, Portland, Oregon.Search for more papers by this author and Stephen A. Tilles, MDFrom Oregon Health Sciences University, Portland, Oregon.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-4-200102200-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The medical literature addressed many different topics in the field of allergy and immunology in the past year. For this Update, we focus on topics that are particularly relevant to internal medicine: latex allergy, trimethoprim–sulfamethoxazole (TMP-SMX) allergy, environmental controls for persons with allergies, food allergy, use of inhaled corticosteroids, use of monoclonal anti-IgE antibody, asthma, and allergic rhinitis.Latex AllergyAlthough latex allergy has become an increasingly important allergic disorder in U.S. society, it presents a difficult diagnostic problem in both primary and specialty care. One of the major difficulties in diagnosing latex allergy has been the lack of a ...References1. Guidelines for the Diagnosis and Management of Asthma. Expert Panel Report 2. National Asthma Education and Prevention Program. Bethesda, MD: National Institutes of Health; 1997. NIH publication no. 97-4051. Google Scholar2. Yunginger JW, Sweeney KG, Sturner WQ, Giannandrea LA, Teigland JD, Bray M, et al . Fatal food-induced anaphylaxis. JAMA. 1988;260:1450-2. [PMID: 0003404604] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Anthony Montanaro, MD; Stephen A. Tilles, MDAffiliations: From Oregon Health Sciences University, Portland, Oregon.Corresponding Author:Anthony Montanaro, MD, Division of Allergy and Immunology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201; e-mail, amontanaro@ohsu.edu.Current Author Addresses:Drs. Montanaro and Tilles: Division of Allergy and Immunology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byUrticaria 20 February 2001Volume 134, Issue 4Page: 291-297KeywordsAllergy and immunologyAsthmaCorticosteroid therapyDustHumidityLatexMitesRhinitisSkin testsVaccines ePublished: 20 February 2001 Issue Published: 20 February 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Financial strains must not jeopardise work of volunteers in NHS and social care
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Commissioners and service providers need to better plan the role of volunteers in both the health and social care sectors if they are to avoid alienating the swathes of people who provide their time for free and ease growing tensions with those in paid jobs, a report from a leading think tank has said.1

An estimated three million people in England volunteer in the NHS, health charities, and social care organisations—the same number in paid employment in the NHS and social care systems, says the report from the King’s Fund. …
AI-04 * MECHANISMS OF GLIOMA FORMATION: PERIVASCULAR GLIOMA INVASION IS A VEGF-INDEPENDENT MECHANISM OF TUMOR VASCULARIZATION
Authors: G. Baker, V. Yadav, S. Motsch, C. Koschmann, A. Calinescu, Y. Mineharu, S. Camelo-Piragua, D. Orringer, S. Bannykh, W. Nichols, A. deCarvalho, T. Mikkelsen, M. Castro, P. Lowenstein
Journal: Neuro-Oncology (2014)

Malignant glioma cells associate with various microanatomical brain structures such as blood vessels, white matter tracts, and brain parenchyma as they spread throughout the brain. However, how these distinct brain tumor invasion patterns coordinate tumor growth and influence clinical outcomes remains unknown. We have investigated how perivascular growth affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. We show that orthotopically implanted rodent and human malignant glioma cells, as well as de-novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma, and peripheral cancer metastasis to the human brain each use brain perivascular space as a means for tissue invasion. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual gliomas cells use perivascular space as a conduit for tumor invasion. We generated an agent-based computational model, which recapitulated biologically observed perivascular glioma growth without the need for neoangiogenesis. This in-silico result prompted us to test whether neoangiogenesis is indeed required for tumor progression in perivascularly invading glioma by treating tumor-bearing animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel-normalization, yet failed to reduce tumor growth or improve survival of mice implanted orthotopically with gliomas from mouse or human origin, or mice subjected to sleeping-beauty generated endogenous gliomas; in all models tested anti-angiogenics exacerbated brain tumor invasion. Our results provide compelling experimental evidence for the recently described failure of clinically used anti-angiogenics to extend the survival of human glioma patients. Given that anti-angiogenics may be beneficial in some patients suffering from certain genetically identifiable glioma subtypes, whether there are mouse or human glioma cells whose growth in-vitro can be reduced by anti-angiogenic approaches remains to be determined.
Prices and Profits in the Pharmaceutical Industry
Authors: M. H. Cooper
Journal: BMJ (1967)

Background/Aim: We aimed to elucidate the prognostic impact of tumor doubling time (DT) and radical surgery when classified by DT in patients with metachronous liver, lung, or peritoneal metastases of colorectal cancer (CRC). Patients and Methods: We reviewed the data of 1941 patients who underwent curative surgery for CRC and calculated DT for recurrences using computed tomography. Results: Short DT was an independent prognostic risk factor in liver (p&lt;0.001) and peritoneal (p=0.03) metastases. Survival was significantly better in patients who underwent surgery than in those who did not, both in short and long DT groups in any metastatic organ (p&lt;0.01). Patients with long DT gained significantly better prognostic benefit from surgery than those with short DT in liver (p=0.01) and peritoneal (p=0.04) metastases. Conclusion: Surgery is recommended for resectable metastases, especially in patients with liver and peritoneal metastases with long DT.
Case of Mal-Assimilation of the Phosphates and Carbonates.-Reply
Authors: G. Betton Massey
Journal: JAMA (1892)

<h3>To the Editor of the Journal of the American Medical Association</h3><h3>Sir:</h3> In sending you the stenographic report of the Transactions of the American Electro-Therapeutic Association at its meeting in September, I presumed its value to you as news would be impaired by undue delay, hence the several speakers were not given an opportunity to correct the notes of their remarks. The discussions are therefore verbatim, and allowing for the possible existence of slight errors in notes that fill more than four hundred pages of manuscript, are an exact reproduction of what the speakers actually said. I well know that few physicians speak in public with the same directness and brevity with which they write, but if the reports of the discussions that occur at these great annual meetings are to be published immediately, as they should be, it becomes impossible to submit the separate notes of five different sessions
Postal survey of management of cervical Chlamydia trachomatis infection in English and Welsh general practices
Authors: D. Mason, S. Kerry, P. Oakeshott
Journal: BMJ (1996)

Chlamydia trachomatis infection in women is common, often asymptomatic, and may cause pelvic inflammatory disease, tubal infertility, or ectopic pregnancy. Screening for chlamydia in Britain is haphazard, and the management of infected people is sometimes inadequate.1 However, despite recommendations for expansion of chlamydia testing in primary care,2 little is known about the diagnosis and management of cervical chlamydia infection in general practice. We did a cross sectional survey of general practices to find out how many offer chlamydia testing and how they would manage a woman found to have chlamydia infection.

In June 1994 we sent a confidential postal questionnaire to a random stratified sample of 500 general practices drawn from all 98 family health services authorities in England and Wales. The introductory letter was addressed to the practice managers, who were asked to give …
Evaluation of Human Papillomavirus Testing in Primary Screening for Cervical Abnormalities
Authors: Shalini L. Kulasingam, James P. Hughes, Nancy B. Kiviat, Constance Mao, Noel S. Weiss, Jane M. Kuypers, Laura A. Koutsky
Journal: JAMA (2002)

ContextHuman papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined.ObjectiveTo determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard).Design, Setting, and ParticipantsBetween December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)–based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated.Main Outcome MeasureSensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies.ResultsThe estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of ≥ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of ≥ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%-75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (≥30 years) vs younger women.ConclusionsTesting for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.
The Physician and the Nurse — Their Interprofessional Work in Office and Hospital Ambulatory Settings
Authors: John P. Connelly, John D. Stoeckle, Edna S. Lepper, Ruth M. Farrisey
Journal: New England Journal of Medicine (1966)

THERE are not enough doctors now nor will there be enough in the future, according to present standards, to care for the health needs of the country. One obvious way to make the most of the physician's unique skills is to transfer some of his less demanding functions to other professionally trained people.1 This delegation of clinical work or "Task Allocation" is already widespread in the hospital, but only recently has purposeful consideration been given to the ways in which nurses can promote better care of the ambulatory patient by assuming a new role. The effectiveness of a planned program . . .
Marital and Family Issues in Patients with Chronic Pain
Authors: Ranjan Roy
Journal: Psychotherapy and Psychosomatics (1982)

This paper attempts to review the relevant literature pertaining to the family issues in chronic pain. To begin with, a rationale is developed for adopting a family approach to the understanding of physical and psychosomatic disorders. Pain literature is examined to demonstrate the significance of family factors in the etiology, perpetuation and treatment of chronic pain. Overall research in this entire field remains somewhat weak and thus the findings are of a tentative nature. On the other hand, the clinical significance of family factors in chronic pain are critical and cannot be ignored. The need for better designed research in this field is of utmost importance.
Transcatheter Harvest of a Dislocated Sapien Valve With an Inoue Balloon Through the Left Subclavian Artery
Authors: Sophie Tkebuchava, Wolfgang Bothe, Hans-Reiner Figulla, Marcus Ferrari, Hristo M. Kirov, Khosro Hekmat, Oliver Gastmann, Torsten Doenst
Journal: Journal of the American College of Cardiology (2012)