tbuckley/cabot-search huggingface dataset:
Authors' reply to Makowska-Webb, Byatt, D'Costa, and Hart
Authors: G. Stansby, R. Agarwal, B. Hunt, S. Ballard
Journal: BMJ (2012)

Background: Recent evidence suggests a role for the insulin-like growth factor-1Ec (IGF-IEc) transcript variant in cancer biology. The aim of the present study was to investigate whether IGF-IEc expression is associated with prostate cancer stage. Materials and Methods: Formalin-fixed and paraffin-embedded prostate cancer surgical specimens from 83 patients were assessed by immunohistochemistry for IGF-IEc expression. Results: Normal prostate epithelium was negative or demonstrated mild IGF-IEc cytoplasmic expression whereas prostate cancer exhibited mild to strong cytoplasmic immunoexpression. The mean IGF-1Ec expression, was significantly lower (p=0.004) in localized (stage ≤IIb) prostate cancer, compared to locally advanced tumors (stage ≥III). Only one out of 83 (1.2%) prostate cancer samples was completely negative for IGF-IEc. A weak-positive correlation was also observed between IGF-IEc expression levels and Gleason score (r=0.247; p=0.024). Conclusion: The present data demonstrate that the expression of IGF-IEc is positively-associated with more advanced stage and higher Gleason score of prostate carcinomas.
Completeness of Safety Reporting in Randomized Trials
Authors: John P. A. Ioannidis, Joseph Lau
Journal: JAMA (2001)

ContextRandomized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting; however, generalizable data on drug safety reporting are sparse.ObjectiveTo scrutinize the completeness of safety reporting in randomized trials.Design, Setting, and PatientsSurvey of safety reporting in 192 randomized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm (N = 130074 patients). Trial reports were identified from comprehensive meta-analyses in 7 medical areas.Main Outcome MeasuresAdequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects; article space allocated to safety reporting and predictors of such reporting.ResultsSeverity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39% and 29% of trial reports, respectively. Only 46% of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity. For these 3 parameters, there was significant heterogeneity in rates of adequate reporting across topics (P = .003, P<.001, and P = .02, respectively). Overall, the median space allocated to safety results was 0.3 page. A similar amount of space was devoted to contributor names and affiliations (P = .16). On average, the percentage of space devoted to safety in the results section was 9.3% larger in trials involving dose comparisons than in those that did not (P<.001) and 3.8% smaller in trials reporting statistically significant results for efficacy outcomes (P = .047).ConclusionsThe quality and quantity of safety reporting vary across medical areas, study designs, and settings but they are largely inadequate. Current standards for safety reporting in randomized trials should be revised to address this inadequacy.
Abstract 412: Role of Interferon Regulatory Factor (IRF)-3 in lung tumor microenvironment
Authors: Hidekazu Shirota, Dennis M. Klinman
Journal: Cancer Research (2011)

Abstract Cytokines present in the tumor microenvironment influence whether a cancer progresses or is rejected. For example, IFNs promote anti-tumor immunity and thus contribute to tumor rejection whereas IL-10 and TGFb can inhibit anti-tumor immunity and thereby contribute to tumor survival. We find that IFNbeta levels are significantly up-regulated in the microenvironment surrounding lung tumors. In the B16 F10 mouse melanoma lung metastasis model, CD11c+ alveolar cells respond to tumor challenge by rapidly up-regulating their expression of IFNbeta. This induction of IFNbeta was totally absent in IRF3 KO mice but intact in MyD88 and TRIF KO mice. Challenge studies indicate that IRF3 KO mice develop more lung metastasis and have shorter survival than controls. These findings suggest that CD11c+ cells play an important role in tumor recognition, and that they mount an IRF3/IFNbeta pathway specific response that slows tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 412. doi:10.1158/1538-7445.AM2011-412
Pilot study of recombinant human granulocyte-macrophage colony–stimulating factor in the treatment of chronic hepatitis B
Authors: Julio Martin, Orencio Bosch, Gloria Moraleda, Javier Bartolome, Juan Antonio Quiroga, Vicente Carreño
Journal: Hepatology (1993)

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 μg/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-α2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2′,5′-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 μg (and was reduced to 1.5 μg); this effect was reversible after cessation of recombinant human granulocyte-macrophage colonystimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colonystimulating factor administration is safe and tolerable at doses of 0.5 to 1 μg/kg body wt and may exert an antiviral effect in chronic hepatitis B. The efficacy of granulocyte-macrophage colony-stimulating factor should be considered in the prevention of hematological disorders and in the increased susceptibility to bacterial infections, during interferon therapy in chronic hepatitis B virus infection. (HEPATOLOGY 1993;18:775-780).
Perinatal HIV Infection
Authors: Susan Ellen Cohn
Journal: JAMA (1996)

To the Editor.  —The article by Dr Fiscus and colleagues 1 on perinatal zidovudine treatment in North Carolina provides encouraging data regarding effective strategies for prevention of perinatal human immunodeficiency virus (HIV) infection. Unfortunately, their geographic comparisons did not use standard definitions, leaving some question regarding the validity and interpretation of the  and rural differences they report. Two geographic classification systems most often used in health-related research are those of the US Bureau of the Census (Census) and the US Office of Management and Budget (OMB). 2,3 The Census characterizes all cities and places with 2500 or more people as urban and the remainder as rural. In contrast, OMB classifies US counties as metro politan or nonmetropolitan, based on whether they are located within a metropolitan statistical area (MSA). Metropolitan statistical areas are counties, groups of counties, or, in New England, towns, representing economic areas with a central city
Variability of corticosteroid responses during exercise stress in active and sedentary middle-aged males.
Authors: J. A. White, A. H. Ismail, G. D. Bottoms
Journal: British Journal of Sports Medicine (1975)

Two groups of middle-aged male subjects (both N=11), one active (mean age 44.6 years) and one sedentary (mean age 43.7 years), undertook a graded exercise stress test on a bicycle ergometer in the post-absorptive state. Blood serum corticosteroid levels were measured at the following stages of metabolism; at rest, under conditions of submaximal and "maximal' exercise and during recovery. The active group showed no significant change in mean serum corticosteroid levels from resting values, during exercise and recovery. However the sedentary group displayed a significant increase in mean serum corticosteroid levels from a resting value of 5.81 plus or minus 0.41 mub-g/100 ml. (mean plus or minus S.E.) to 7.83 plus or minus 0.71 mug/100 ml. during "maximal' exercise (p smaller than 0.05), which was maintained throughout recovery 7.82 plus or minus 0.70 ug/100 ml (p smaller than 0.05). Futhermore the active group demonstrated significantly lower mean serum corticosteroid levels compared with the sedentary group under conditions of submaximal (p smaller than 0.05) and "maximal' (p smaller than 0.01) exercise and during recovery (p smaller than 0.01). It was concluded that the variability in the response patterns of serum corticosteroids during exercise stress in active and sedentary middle-aged males, reflected the physiological differences observed between the two groups of subjects.
Science of Cancer and Aging
Authors: Irmgard Irminger-Finger
Journal: Journal of Clinical Oncology (2007)

This review provides an overview of a selection of the most pertinent molecular pathways that link cancer and aging and focuses on those where recent advances were most important. When organizing the bulk of information on this subject, I became aware of the fact that the most evident partition, namely, mechanisms that influence aging and mechanisms that influence cancer occurrence, is difficult to apply. Most mechanisms explaining the aging process are also those that influence carcinogenesis. Mechanisms that are described in tumor suppressor pathways are also contributors to the aging process. From an intuitive point of view, there are phenomena that have traditionally been contributed to aging others to cancer-inducing factors and they are presented herein.
SUSTAINED CLINICAL IMPROVEMENTS AFTER INTRAMYOCARDIAL INJECTION OF MESENCHYMAL STROMAL CELLS IN PATIENTS WITH SEVERE STABLE CORONARY ARTERY DISEASE &amp;ndash; 24 MONTHS FOLLOW-UP
Authors: Anders Bruun Mathiasen, Mandana Haack-S&oslash;rensen, Erik Jorgensen, Jens Kastrup
Journal: Journal of the American College of Cardiology (2012)
Doctors as lapdogs to drug firms
Authors: Augusto Pimazoni
Journal: BMJ (2006)

How doctors' anonymity in family courts is under threat Gornall is way out of dateEditor-Gornall is embarrassingly out of date in his detailed analysis of the B case (which was dealt with by the family courts nearly three years ago), and its relevance to proposed changes in the law to make the English family court system more transparent. 1 Since then, notwithstanding the ever increasingly exaggerated claims from some quarters that opening the family courts would harm children and deter court experts, the courts themselves are acknowledging the need for English family courts to do their business in the more transparent way that courts in Canada, Australia, and of course Scotland have done without apparent difficulty for years.Several High Court judgments have recorded judicial support for more openness to increase public confidence, and Gornall fails to mention that the president and many of his senior judges are in favour of change in this direction.In a landmark case which was decided on 3 November, Munby J agreed that an ongoing case where parents dispute expert evidence that they injured their child should be open to the media.The local authority concerned issued a "position statement" to the press and the reporting in the Times, Guardian, and the Mail on Sunday set out both sides' cases, as did the broadcasting media.A BBC "Real Story" programme on the case allowed a senior official from the local authority ample time to put their case.No vilification of any experts involved was reported.It is likely that more judges will follow Munby J's example and more public interest cases will be opened to the media pending any change in the law.Will the skies fall in?I doubt it, but your readers can judge for themselves.Hopefully they will understand that in complex childcare cases where expert evidence may be tenuous and the stakes for children are very high, public debate can stimulate awareness of the problems faced by all professionals involved in child protection.It's difficult getting the balance right, but doing it in secret doesn't help.
THE DOSAGE OF ULTRAVIOLET RADIATION IN INFANTS WITH TETANY
Authors: HARRY BAKWIN
Journal: JAMA (1930)

ABSTRACT It is curious how little attention is paid to the subject of dosage in treatment with ultraviolet radiant energy. There is a widespread impression that, if excessive skin irritation is avoided, the greater the amount of ultraviolet radiation given, the better; yet numerous observations indicate that the effect is not proportional to the dosage and that an effect produced by a smaller dose may be reversed when a larger dose is given. Thus, Koenigsfeld1 has found that small doses of ultraviolet radiation lead to protein deposition while large doses lead to protein destruction. According to Gottschalk and Nonnenbruch,2 small amounts of ultraviolet radiation reduce the oxygen consumption of frog muscle, while large amounts increase it. Koopman3 has reported an increase in the complement activity of the serum calcium of guinea-pigs after short periods of irradiation, while after prolonged irradiation complement activity disappears and death invariably results. Pena
New P2Y12Inhibitors Versus Clopidogrel in Percutaneous Coronary Intervention
Authors: Anne Bellemain-Appaix, David Brieger, Farzin Beygui, Johanne Silvain, Ana Pena, Guillaume Cayla, Olivier Barthélémy, Jean-Philippe Collet, Gilles Montalescot
Journal: Journal of the American College of Cardiology (2010)
Abstract 1964: Masitinib antagonizes ATP-binding cassette subfamily c member 10-mediated paclitaxel resistance: a preclinical study
Authors: Rishil Kathawala, Kamlesh Sodani, Kang Chen, Atish Patel, Alaa Abuznait, Nagaraju Anreddy, Yue-Li Sun, Amal Kaddoumi, Charles R. Ashby, Zhe-Sheng Chen
Journal: Cancer Research (2014)

Abstract Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multi-drug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at non-toxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 μM) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors and lungs compared to paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10. Citation Format: Rishil Kathawala, Kamlesh Sodani, Kang Chen, Atish Patel, Alaa Abuznait, Nagaraju Anreddy, Yue-Li Sun, Amal Kaddoumi, Charles R. Ashby, Zhe-Sheng Chen. Masitinib antagonizes ATP-binding cassette subfamily c member 10-mediated paclitaxel resistance: a preclinical study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1964. doi:10.1158/1538-7445.AM2014-1964
Blunted Cardiac Responses to Receptor Activation in Subjects With Thr164Ile β <sub>2</sub> -Adrenoceptors
Authors: Otto-Erich Brodde, Rainer Büscher, Ralph Tellkamp, Joachim Radke, Stefan Dhein, Paul A. Insel
Journal: Circulation (2001)

Background —Recent evidence indicates that certain genotypes of β 2 -adrenoceptors (AR) may indicate an increased risk of cardiovascular disease or an increased rate of disease progression. Of particular importance, the Thr164Ile polymorphism, which is found in ≈4% of humans, shows decreased receptor signaling, blunted cardiac response when expressed in transgenic mice, and is associated with a decreased survival rate in patients with congestive heart failure. Methods and Results —In this study, we compared functional activity, ie, chronotropic (heart rate increases) and inotropic (duration of the electromechanical systole) responses to intravenously administered terbutaline, in 6 subjects (4 women and 2 men) who were heterozygous for Thr164Ile with the responses in 12 volunteers (6 women and 6 men) who were homozygous for wild-type (WT) β 2 -AR (ie, Arg16, Gln27, and Thr164). The β 2 AR polymorphism significantly affected the dose-response curves for terbutaline-induced inotropic and chronotropic responses: compared with WT individuals, subjects with the Thr164Ile receptor had substantial blunting in maximal increases in heart rate (WT, 29.7±3.9 beats/min; Ile164, 20.7±1.9 beats/min; P =0.016) and a shortening of the duration of electromechanical systole (WT, 51.9±4.5 ms; Ile164, 37.9±4.6 ms; P =0.02). Conclusions —These data show that humans with the Ile164 genotype show blunted cardiac β 2 -AR responsiveness, which may help explain the decreased survival of patients with this genotype in the setting of congestive heart failure.
Metabolism of properdin in normal subjects and patients with renal disease.
Authors: J B Ziegler, F S Rosen, C A Alper, W Grupe, I H Lepow
Journal: Journal of Clinical Investigation (1975)

Properdin deposition has been recognized in glomeruli of patients with acute and chronic nephritis and lupus nephritis, and low serum properdin levels have been found in these disorders. These findings suggest that properdin may be involved in the production of glomerular damage and that low properdin levels may be due to hypercatabolism. The study was designed to examine the metabolism of properdin in normal subjects and to look for an abnormality in five patients with systemic lupus erythematosus with renal involvement and in six patients with membranoproliferative glomerulonephritis or dense deposit disease (MPGN). Highly purified human properdin was prepared by elution from zymosan, followed by DEAE-cellulose and carboxymethyl-Sephadex chromatography, and labeled with 125I by the iodine monochloride method. Parameters of metabolism were determined by monitoring plasma and urinary radioactivity at frequent intervals after the intravenous injection of 1-2 muCi of labeled material. The fractional catabolic rate (FCR) of properdin in normal subjects was found to have a very narrow range of 0.78-1.0,% of the plasma pool per hour (mean 0.95%). In systemic lupus erythematosus, the FCR was regularly elevated with a range of 1.21-2.30% (mean 1.70%). In MPGN, FCR was elevated in three patients (1.22, 1.94, and 2.08%) and within or below the normal range in three (0.78, 1.00, and 1.00%). Properdin levels were reduced in two patients who had the highest FCR's noted in the study. Properdin synthetic rates in normals varied from 4.1 to 14.3 mug/kg per h (mean 9.1) and was not found to be reduced in any patient. Properdin catabolism was found to be normal in a patient deficient in the C3b inactivator. These studies show that properdin is hypercatabolized in patients with renal disease and that decreased properdin levels when they occur in these patients can be entirely explained on the basis of this hypercatabolism.
Cimetidine-Induced Coma in Cirrhosis of the Liver
Authors: Milton L. Levine
Journal: JAMA (1978)

<h3>To the Editor.—</h3> Cimetidine, a potent H<sub>2</sub>-receptor antagonist, has been recently introduced for the suppression of gastric acid secretion.<sup>1,2</sup>This medication has the ability to produce gynecomastia and breast swelling when used for a prolonged period (as in the Zollinger-Ellison syndrome)<sup>3</sup>and apparently has a mild sedative effect when given orally.<sup>4</sup>Although the usual route of administration is oral, the medication can be given intramuscularly and intravenously (IV). I recently observed a patient in whom profound coma developed while receiving cimetidine, which reversed when the therapy was discontinued. I believe this potential side effect of cimetidine should be brought to the attention of treating physicians. <h3>Report of a Case.—</h3> A 53-year-old bartender, who admits to a 25-year history of excessive alcohol use (which he claims he discontinued three months before hospitalization), was admitted to Franklin General Hospital,Valley Stream, NY, for massive upper gastrointestinal (GI) bleeding.
Predicting infections in high‐risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine: Aretrospective multicenter study
Authors: Drorit Merkel, Kalman Filanovsky, Anat Gafter‐Gvili, Liat Vidal, Ariel Aviv, Moshe E. Gatt, Itay Silbershatz, Yair Herishanu, Ariela Arad, Tamar Tadmor, Najib Dally, Anatoly Nemets, Ory Rouvio, Aharon Ronson, Katrin Herzog‐Tzarfati, Luiza Akria, Andrei Braester, Ilana Hellmann, Shay Yeganeh, Arnon Nagler, Ronit Leiba, Moshe Mittelman, Yishai Ofran
Journal: American Journal of Hematology (2012)

Hypomethylating agents have become the standard therapy for patients with high‐risk myelodysplastic syndrome ( MDS ). In Israel, azacitidine ( AZA ) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA ‐treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high‐risk MDS and 27 acute myeloid leukemia ( AML )], with a median age of 71.6 (range 29–92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin ( Hb ) and platelet ( PLT ) counts were found to be associated with infections (24.4% vs. 12.9%, P &lt; 0.0001; 27% vs. 13.5%, P &lt; 0.0001; 20.4% vs. 11%, P &lt; 0.0001 and 29.2% vs. 14.2%, P &lt; 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10 9 /L and neutrophil count below 0.5 × 10 9 /L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered. Am. J. Hematol. 88:130–134, 2013. © 2012 Wiley Periodicals, Inc.