tbuckley/cabot-search huggingface dataset:
Myocardial beta-adrenergic receptor expression and signal transduction after chronic volume-overload hypertrophy and circulatory congestion.
Authors: H K Hammond, D A Roth, P A Insel, C E Ford, F C White, A S Maisel, M G Ziegler, C M Bloor
Journal: Circulation (1992)

BACKGROUND The volume-overload, high-output state induced by aortocaval fistula is unique because it is not generally associated with marked abnormalities of contractile function. Thus, changes in beta-adrenergic receptor (beta AR) expression should reflect more directly the influence of neurohumoral adrenergic tone, clarifying the manner in which peripheral (neurohumoral) versus primary myocardial factors are operative in decreased beta AR-dependent signal transduction. METHODS AND RESULTS We examined the beta-adrenergic receptor-responsive adenylyl cyclase pathway in hearts from pigs subjected to volume-overload hypertrophy with circulatory congestion. Nine pigs underwent initial pharmacological and hemodynamic studies, and, 5 weeks after aortocaval fistula placement, when signs of circulatory congestion were evident, these measurements were repeated. Biochemical analyses of plasma and myocardium from these animals and seven normal animals were compared. Experimental animals showed signs of circulatory congestion (tachypnea, weight gain, pulmonary rales) within 3-4 weeks of fistula placement. Necropsy showed ascites and biventricular cardiac hypertrophy, but no fibrosis or inflammation was present on histological inspection. Heart rate responsiveness to beta AR stimulation was blunted, with ED50, for isoproterenol increased 133% (p less than 0.001) after development of circulatory congestion. Biochemical analyses of the beta AR-responsive adenylyl cyclase pathway showed uniform decreases in beta AR number in right atrium, right ventricle, and left ventricle (36-41% decreases, p less than 0.005). Downregulation was selective for beta 1-receptors, and remaining receptors in the right and left ventricles showed low-affinity agonist binding, suggesting an uncoupling from Gs. All measures of adenylyl cyclase activity were diminished significantly in membrane homogenates from the right atrium (mean reduction, 50 +/- 10%) and left ventricle (mean reduction, 44 +/- 8%) after volume overload. Finally, we found that amounts of cardiac Gs, as measured in reconstitution assays, were decreased in both the right atrium (p less than 0.02) and the left ventricle (p less than 0.01) of volume-overloaded animals but that levels of pertussis toxin substrate were unchanged. CONCLUSIONS Biochemical findings occurred in the absence of myocardial inflammation or fibrosis and without pharmacological interventions, suggesting that circulatory congestion, with attendant elevation in plasma norepinephrine, may be a sufficient stimulus to induce such changes. The data are compatible with a catecholamine-driven beta AR pathway desensitization. Thus, a primary defect in intrinsic contractile function is not a necessary component for abnormalities of the myocardial beta AR-responsive adenylyl cyclase pathway.
Effect of N-Butylscopolamine on Sphincter of Oddi Motility in Patients during Routine ERCP - a Manometric Study
Authors: H.-D. Allescher, H. Neuhaus, F. Hagenmüller, M. Classen
Journal: Endoscopy (1990)

N-butylscopolamine is a generally accepted drug for the suppression of gut motility. Although it is used during routine ERCP, only few systematic studies have been carried out in patients to investigate its action on sphincter of Oddi motility. In the present study the effect of N-butylscopolamine on the motilily of the sphincter of Oddi region has been evaluated in 17 patients undergoing routine diagnostic ERCP. The pressure parameters of these patients were compared with "normal values" obtained in 23 volunteers. A dose of 40 mg of N-butylscopolamine bromide (Buscopan®) i.v. significantly reduced the contraction frequency of the sphincter of Oddi from 5.4 ± 1.2/min to 1.0 ± 1.4/min (p < 0.001), the contraction amplitude from 106.3 ± 27.8 mmHg to 55.2 ± 23.5 (p < 0.01) mmHg, and the basal sphincter of Oddi pressure from 13.9 ± 3.0 mmHg to 11.0 ± 3.5 mmHg (p < 0.05), but had no effect on the pressure gradient between the common bile duct and the duodenum. These results clearly demonstrate that N-butylscopolamine inhibits contractions of the sphincter of Oddi, and may thus facilitate the intubation of the papilla.
Changing the threshold of body mass index that indicates obesity affects health targets
Authors: T. Hill, J. Roberts
Journal: BMJ (1996)

EDITOR,—Body mass index, calculated from a subject's height and weight, is widely used to indicate obesity.1 Although the index is acknowledged as an adequate summary of obesity, the thresholds for categorising underweight, normal weight, overweight, and obesity have varied. In the past, different thresholds were accepted for men and women, with women broadly requiring a lower body mass index for inclusion in each category.2 Underweight was indicated in a man by a body mass index of <20.0 and in a woman by a body mass index of <18.6. Obesity …
Eye Symptoms in Brain Tumors
Authors: Joel G. Sacks
Journal: JAMA (1971)

What a truly marvelous book this is! Equal congratulations are due both the author and the translator. The work is scholarly and beautifully presented; the translation is lucid and nearly conversational in tone. Professor Huber writes with the weight of enormous personal experience; this is what makes the book so valuable. He discusses data derived from 2,500 cases of brain tumors on record at the Neurosurgical Clinic at the University of Zürich and has supplemented this with an appropriate review of the relevant literature. This book "tells it like it is" while giving acknowledgement to all the "standard" material that one would expect to find in a text on the subject. The author points out that some of the generally accepted material has doubtful clinical significance. For example, he speaks of the difficulty in eliciting Wernicke's hemianopic pupillary phenomenon in lesions of the anterior cerebral pathways; anyone who has tried
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy
Authors: Christian S. Hinrichs, Rosanne Spolski, Chrystal M. Paulos, Luca Gattinoni, Keith W. Kerstann, Douglas C. Palmer, Christopher A. Klebanoff, Steven A. Rosenberg, Warren J. Leonard, Nicholas P. Restifo
Journal: Blood (2008)
Management of hyperglycaemia in type 2 diabetes: the end of recurrent failure?
Authors: R J Heine, M Diamant, J-C Mbanya, D M Nathan
Journal: BMJ (2006)

The epidemic of type 2 diabetes imposes an enormous and growing burden on health care worldwide. The number of people with type 2 diabetes around the world is estimated to rise from 151 million in 2000 to 300 million by 2025.1 The recognition that strict glycaemic control can reduce microvascular complications has made the effective treatment of hyperglycaemia a priority.2 3 4 5 6 Recently, the diabetes control and complications trial reported that intensive therapy aimed at normoglycaemia has beneficial effects on cardiovascular disease in type 1 diabetes.7 In type 2 diabetes, epidemiological data from the UK prospective diabetes study suggest that lowering glycaemia will reduce the risk of cardiovascular disease.8 The treatment of hyperglycaemia in type 2 diabetes is complex; combinations of glucose lowering drugs are often needed to achieve and maintain blood glucose at target values. The development of new classes of drugs to lower blood glucose has increased the treatment options for type 2 diabetes and has contributed to the uncertainty surrounding these new therapeutic approaches. Here we present a management guideline that may help healthcare providers treat patients with type 2 diabetes. 

#### Sources and selection criteria

This review is largely based on the recently published American Diabetes Association/European Association for the Study of Diabetes treatment guideline for type 2 diabetes.9 We also searched the Cochrane Library for evidence based guidelines using the keywords “type 2 diabetes”, “blood glucose lowering agents”, “glucose monitoring”, “lifestyle”, and “exercise and diet” 

Studies have shown that the development of microvascular disease is reduced when glycaemic control is improved and have helped establish treatment targets for glycaemia in type 2 diabetes.4 6 Ideally glycated haemoglobin (HbA1C) should be as close to normal as possible without imposing a high risk of severe hypoglycaemia. The upper limit of normal of the …
Second Neoplasms in Survivors of Childhood Cancer: Findings From the Childhood Cancer Survivor Study Cohort
Authors: Anna T. Meadows, Debra L. Friedman, Joseph P. Neglia, Ann C. Mertens, Sarah S. Donaldson, Marilyn Stovall, Sue Hammond, Yutaka Yasui, Peter D. Inskip
Journal: Journal of Clinical Oncology (2009)

To review the reports of subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort that were made through January 1, 2006, and published before July 31, 2008, and to discuss the host-, disease-, and therapy-related risk factors associated with SNs.SNs were ascertained by survivor self-reports and subsequently confirmed by pathology findings or medical record review. Cumulative incidence of SNs and standardized incidence ratios for second malignant neoplasms (SMNs) were calculated. The impact of host-, disease-, and therapy-related risk factors was evaluated by Poisson regression.Among 14,358 cohort members, 730 reported 802 SMNs (excluding nonmelanoma skin cancers). This represents a 2.3-fold increase in the number of SMNs over that reported in the first comprehensive analysis of SMNs in the CCSS cohort, which was done 7 years ago. In addition, 66 cases of meningioma and 1,007 cases of nonmelanoma skin cancer were diagnosed. The 30-year cumulative incidence of SMNs was 9.3% and that of nonmelanoma skin cancer was 6.9%. Risk of SNs remains elevated for more than 20 years of follow-up for all primary childhood cancer diagnoses. In multivariate analyses, risks differ by SN subtype, but include radiotherapy, age at diagnosis, sex, family history of cancer, and primary childhood cancer diagnosis. Female survivors whose primary childhood cancer diagnosis was Hodgkin's lymphoma or sarcoma and who received radiotherapy are at particularly increased risk. Analyses of risk associated with radiotherapy demonstrated different dose-response curves for specific SNs.Childhood cancer survivors are at a substantial and increasing risk for SNs, including nonmelanoma skin cancer and meningiomas. Health care professionals should understand the magnitude of these risks to provide individuals with appropriate counseling and follow-up.
PolyI.polyC12U-mediated inhibition of loss of alloantigen responsiveness viral replication in human CD4+ T cell clones exposed to human immunodeficiency virus in vitro.
Authors: J Laurence, J Kulkosky, S M Friedman, D N Posnett, P O Ts'o
Journal: Journal of Clinical Investigation (1987)

Two alloreactive human CD4+ T cell clones, recognizing HLA-DR2 and HLA-DR1 determinants, lost their specific proliferative capacity after infection with HIV. This system was used to explore the effect of polyI.polyC12U on HIV replication and immune suppression. The mismatched double-stranded RNA blocked HIV-associated particulate reverse transcriptase activity and viral-mediated cytopathic effects. Also, polyI.polyC12U preserved the alloreactivity of T cell clones after exposure to HIV.PolyI.polyC12U appeared to act at a level subsequent to host cell infection and reverse transcription. It had no effect on the enhancement of gene expression by the HIV transcription unit tatIII. These findings indicate that early in the course of infection of CD4+ T lymphocytes, HIV can directly abrogate proliferation to specific allodeterminants, and that this function is preserved in the presence of polyI.polyC12U. They also provide insight into the mechanism of antiviral action of a class of agent with potential clinical utility in AIDS.
Scintigraphic Skeletal ???Doughnut??? Sign Due to Giant Cell Tumor of the Fibula
Authors: PURUSHOTHAM VELUVOLU, B DAVID COLLIER, ALI T. ISITMAN, GUILLERMO F. CARRERA, ROBERT S. HELLMAN, STEPHEN FRY
Journal: Clinical Nuclear Medicine (1984)

Although the “doughnut” sign in brain scintigraphy is a well known phenomenon, similar findings have recently been reported in bone scintigraphy in osseous and nonosseous lesions. A skeletal doughnut sign in bone scintigraphy caused by giant cell tumor of the proximal fibula is presented with a brief review of literature.
Isolation and <i>In vitro</i> Propagation of Tumorigenic Breast Cancer Cells with Stem/Progenitor Cell Properties
Authors: Dario Ponti, Aurora Costa, Nadia Zaffaroni, Graziella Pratesi, Giovanna Petrangolini, Danila Coradini, Silvana Pilotti, Marco A. Pierotti, Maria Grazia Daidone
Journal: Cancer Research (2005)

Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24(-/low) cells, which exclusively retain tumorigenic activity and display stem cell-like properties. However, at present, direct evidence that breast cancer-initiating cells can be propagated in vitro is still lacking. We report here the isolation and in vitro propagation of breast cancer-initiating cells from three breast cancer lesions and from an established breast carcinoma cell line. Our breast carcinoma-derived cultures encompassed undifferentiated cells capable of self-renewal, extensive proliferation as clonal nonadherent spherical clusters, and differentiation along different mammary epithelial lineages (ductal and myoepithelial). Interestingly, cultured cells were CD44+/CD24- and Cx43-, overexpressed neoangiogenic and cytoprotective factors, expressed the putative stem cell marker Oct-4, and gave rise to new tumors when as few as 10(3) cells were injected into the mammary fat pad of SCID mice. Long-term cultures of breast tumorigenic cells with stem/progenitor cell properties represent a suitable in vitro model to study breast cancer-initiating cells and to develop therapeutic strategies aimed at eradicating the tumorigenic subpopulation within breast cancer.
Hospitalization Among Diabetic Children and Adolescents and the General Population in Germany
Authors: Andrea Icks, Joachim Rosenbauer, Reinhard W. Holl, Matthias Grabert, Wolfgang Rathmann, Guido Giani
Journal: Diabetes Care (2001)

OBJECTIVE—To compare hospitalization in a multicenter-based cohort of diabetic children and adolescents (aged 1–19 years) in Germany with that of the general population. RESEARCH DESIGN AND METHODS—Based on standardized documentation, hospital stays after manifestation were ascertained in diabetic subjects 1–19 years of age in 1997. Hospitalization data in the general German population were derived from official statistics. Incidence rates and numbers of hospital days were estimated. Ratios of hospitalization incidences and numbers of hospital days between the diabetic and the general population were calculated. Costs for hospital care in the German diabetic population in 1997 were determined. RESULTS—A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean ± SD] 12.2 ± 4.3 years, diabetes duration 4.6 ± 4.4 years). Hospitalization incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25–0.29) and 1.80 (1.75–1.84) in the diabetic population and 0.0948 (0.0946–0.0949) and 0.6416 (0.6412–0.6420) in the general population. The standardized ratio of hospital incidences was 3.1 (2.9–3.2), and the ratio of numbers of hospital days was 2.8 (2.7–2.9). Costs for hospital care after manifestation were estimated to be $506 (U.S. dollars) per person-year and $12.4 million in the whole German diabetic population aged 1–19 years in 1997; including hospital stays at diabetes onset, total annual costs were $24 million ($970 per person-year). CONCLUSIONS—Diabetic children and adolescents in Germany had an approximately three times higher hospitalization risk and three times more hospital days than the age-matched general population. Including hospitalization at diabetes onset, the annual costs of hospital care for the German diabetic population aged 1–19 years amounted to ∼1% of all costs for hospital care in this age-group. Thus, costs were largely overproportional (diabetes prevalence 0.1%).
The "British System" of Heroin Maintenance
Authors: Lorrin M. Koran
Journal: JAMA (1973)

To the Editor.—  Although much clinical research is needed before we begin large-scale heroin maintenance programs, Dr. Lewis' five objections to heroin maintenance inThe Journal(223:546, 1973) are specious. His first two objections (rendering addiction less costly... [and] freeing additional supplies of heroin) fit all treatments from therapeutic communities to methadone. His third objection (heroin maintenance  make our international  of eliminating opium... unrealistic) whips a horse that deserves mercy killing. This goal is already politically and economically unrealistic 1 and may be medically indefensible; have double-blind studies proved synthetic narcotics equivalent to natural ones for all clinical purposes? If opium were unavailable,  not illicit sources manufacture and supply synthetic narcotics? Dr. Lewis' fourth objection (other treatments would be unable to compete with heroin maintenance)  not apply to controlled, clinical heroin maintenance studies. It also ignores British success in coupling heroin maintenance with other treatments and
3 SAFETY AND EFFICACY OF INTERFERON-FREE REGIMENS OF ABT-450/r, ABT-267, ABT-333 +/− RIBAVIRIN IN PATIENTS WITH CHRONIC HCV GT1 INFECTION: RESULTS FROM THE AVIATOR STUDY
Authors: K.V. Kowdley, E. Lawitz, F. Poordad, D.E. Cohen, D. Nelson, S. Zeuzem, G.T. Everson, P. Kwo, G.R. Foster, M. Sulkowski, W. Xie, L. Larsen, A. Khatri, T. Podsadecki, B. Bernstein
Journal: Journal of Hepatology (2013)
Young people carry a disproportionate burden of sexually transmitted infections in UK
Authors: A. Cole
Journal: BMJ (2008)

The number of diagnoses of sexually transmitted infections rose again last year in the United Kingdom, the latest figures show, and young people aged 16 to 24 years were disproportionately affected.

Overall the number of infections diagnosed in UK genitourinary medicine clinics rose by 6%, from 375 843 in 2006 to 397 990 in 2007, says a report from the Health Protection Agency.

The number of diagnoses of genital herpes rose by 20%, while those of chlamydia and genital warts went up by 7%. Diagnoses of gonorrhoea and syphilis fell marginally.

Despite the fact that young people make up only one in eight of the population, they accounted for around half of all new diagnoses, including …
NHS authority may not fix what isn't really broken
Authors: Stephen Gillam
Journal: BMJ (2006)

An independent NHS?In April this year, Fiona Godlee wrote in her editor's choice that the UK health service needs to be protected from party politics to halt the rapid turnaround in policies that seem to be destabilising the system.She argued that an independent NHS authority could be run by a board of governors responsible for managing health care within a set budget and a broad political framework.We asked four opinion leaders for their views on whether it is time to give the NHS more independence.
Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients
Authors: E. Roupie, E. Lepage, M. Wysocki, J.-Y. Fagon, J. Chastre, D. Dreyfuss, H. Mentec, J. Carlet, C. Brun-Buisson, F. Lemaire, L. Brochard
Journal: Intensive Care Medicine (1999)
Hepatic Injury after Interferon-α Therapy for Chronic Hepatitis C
Authors: Yukihiro Shimizu
Journal: Annals of Internal Medicine (1994)

Letters1 November 1994Hepatic Injury after Interferon-α Therapy for Chronic Hepatitis CYukihiro Shimizu, MD, Shuji Joho, MD, and Akiharu Watanabe, MDYukihiro Shimizu, MDSearch for more papers by this author, Shuji Joho, MDSearch for more papers by this author, and Akiharu Watanabe, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-9-199411010-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We describe a patient with chronic hepatitis C virus (HCV) infection who had severe hepatic injury during interferon-α therapy and who was successfully treated with prostaglandin E1 and prednisone.A 54-year-old man with chronic active HCV infection received intramuscular interferon-α 2a (Canferon A, Takeda Pharmaceutical Company, Japan), 9 × 106/U three times a week, in March 1992. The patient's serum alanine aminotransferase (ALT) level returned to normal in April. In May, he reported an itchy eruption, and his serum ALT level began to increase. On 15 June, his serum ALT level reached 811 kU, and interferon therapy ...References1. Sinclair SB, Greig PD, Blendis LM, Abecassis M, Roberts EA, Phillips MJ, et al. Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report. J Clin Invest. 1989; 84:1063-9. Google Scholar2. Marcellin P, Colin JF, Boyer N, Bernuau J, Degott C, Hirschauer C, et al. Fatal exacerbation of chronic hepatitis B induced by recombinant α-interferon (Letter). Lancet. 1991; 338:828. Google Scholar3. Wandl UB, Kloke O, Niederle N. Liver failure due to recombinant α interferon for chronic myelogenous leukaemia. Lancet. 1992; 339:123-4. Google Scholar Author, Article, and Disclosure InformationAuthors: Yukihiro Shimizu, MD; Shuji Joho, MD; Akiharu Watanabe, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAcute exacerbation of vasculitis during interferon-α therapy for hepatitis C-associated cryoglobulinaemiaAcute hepatitis induced by α-interferon, associated with viral clearance, in chronic hepatitis CDrugs acting on the immune systemInterferon alpha 2A 1 November 1994Volume 121, Issue 9 Page: 723 Keywords Alanine aminotransferase Antibodies Autoantibodies Bilirubin Chronic hepatitis C Interferons Prostaglandin Prothrombin time Serum glutamic oxaloacetic transaminase Superinfections ePublished: 15 August 2000 Issue Published: 1 November 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen
Authors: Laura A. Johnson, Richard A. Morgan, Mark E. Dudley, Lydie Cassard, James C. Yang, Marybeth S. Hughes, Udai S. Kammula, Richard E. Royal, Richard M. Sherry, John R. Wunderlich, Chyi-Chia R. Lee, Nicholas P. Restifo, Susan L. Schwarz, Alexandria P. Cogdill, Rachel J. Bishop, Hung Kim, Carmen C. Brewer, Susan F. Rudy, Carter VanWaes, Jeremy L. Davis, Aarti Mathur, Robert T. Ripley, Debbie A. Nathan, Carolyn M. Laurencot, Steven A. Rosenberg
Journal: Blood (2009)