tbuckley/cabot-search huggingface dataset:
Experimentation in Children
Authors: A. Herbert Schwartz
Journal: JAMA (1970)

To the Editor:—  It is ironic that Experimentation in Children ( 210: 77, 1969) by William J. Curran, JD, and Henry K. Beecher, MD, is published concomitant with the planned closure of most Children's General Clinical Research Centers.  It would be  mistake to believe as Curran and Beecher might have us do that  clear distinction between therapeutic or nontherapeutic research is commonly the case rather than a little of this and  little of that. However, as  child psychiatrist with four years of experience as the Assistant Director of the Yale Children's General Clinical Research Center, the most significant criticism remains  question—who discerns the discernible risks? Just as psychological risks are not mentioned in this article, they are rarely overtly considered by otherwise sensitive researchers. This does not generally reflect  lack of concern but  lack of knowledge concerning psychological risks and the short-term and long-term
Jaundice, Choledocholithiasis, and a Nondilated Common Duct
Authors: Richard A. Greenwald
Journal: JAMA (1978)

In two cases of jaundice due to choledocholithiasis, the biliary tree was not dilated on skinny-needle transhepatic cholangiography. Visualization of the biliary tree before arriving at a diagnosis in certain cases of jaundice is needed.
The Spontaneous and Induced Production of Fas-ligand by Eosinophils from Subjects with Aspirin Hypersensitivity, Allergic Rhinitis and Healthy Volunteers
Authors: I. Kuprys-Lipinska, M. Kupczyk, M. Bochenska-Marciniak, P. Gorski, P. Kuna
Journal: Journal of Allergy and Clinical Immunology (2006)
Dose Dependent Effects of G-CSF on Ca27.29 in Early Stage Breast Cancer Patients.
Authors: P. Hepp, B. Rack, A. Schneeweiss, I. Schrader, R. Lorenz, H. Tesch, U. Soeling, M. Rezai, B. Gerber, W. Lichtenegger, M. Beckmann, W. Janni
Journal: Cancer Research (2009)

Abstract Background:13% of 2556 patients (pts) examined in the SUCCESS trial showed elevated levels of Ca27.29 only after chemotherapy (SABCS2008). Early data indicate a possible relationship between the administration of G-CSF and a rise in the tumor marker. This analysis focuses on the dose dependency of this effect.Methods:The SUCCESS Trial is a phase III trial comparing FEC-Docetaxel vs. FEC-Doc-Gemcitabine regime and 2 vs. 5 years of treatment with zoledronate in patients with primary breast cancer in 3754 pts (BC) (N+ or high risk). Blood samples for this analysis are drawn before and after chemotherapy (CHT). Ca27.29 has been measured with ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). The cutoff for Ca27.29 is &amp;gt;=32 U/ml. For chi² analysis patients were grouped to increasing or not increasing values of Ca27.29 and 1 to 6 cycles with G-CSF or no G-CSF at all. The absolute difference of Ca27.29 values before and after CHT was correlated with the number of G-CSF cycles administered.Results:The analysis of Ca27.29 is based on the data of 2556 pts. 1252 pts (49%) received at least one course of G-CSF. 338 pts (13%) exceeded the threshold for CA27.29 only after CHT. In this group 209 pts (62%) received G-CSF and 129 (38%) did not. 1043 pts with stable or decreased CA27.29 received G-CSF (47%) and 1175 did not (53%). This difference was highly significant (p&amp;lt;0.0001). Correlating the number of G-CSF cycles received during CHT with the absolute difference in Ca27.29 levels showed a highly significant positive correlation of 0.13 (Spearman-Rho; p&amp;lt;0.0001[two-sided]).Discussion and Conclusion:This analysis gives strong evidence that there is a dose dependent correlation between elevated levels of CA27.29 post CHT and the application of G-CSF. This might be attributed to an illegitimate expression of MUC-1 in leucocytes during leucopoiesis. Whether this effect is also related to the destruction of remaining disseminated tumor cells needs to be further evaluated. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6030.
Single flexible sigmoidoscopy screening could help prevent colorectal cancer
Authors: S. Mayor
Journal: BMJ (2002)

Single flexible sigmoidoscopy screening at the age of 60 years offers an acceptable, feasible, and safe method to detect early colorectal cancer, a major UK study has shown.

The study contacted a total of 354 262 people aged 55-64 years in 14 UK centres to ask if they would attend for flexible sigmoidoscopy screening if invited. Just over half (194 726; 55%) of the people said yes. This group was then randomly allocated to screening or to a control group; the controls were not contacted further.

Nearly three quarters (40 674 of …
Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study
Authors: Geoffrey Dusheiko, Janice Main, Howard Thomas, Olle Reichard, Christine Lee, Amar Dhillon, Suhra Rassam, Aril Fryden, Henk Reesink, Margaret Bassendine, Gunnar Norkrans, Theo Cuypers, Nico Lelie, Paul Telfer, Jon Watson, Christine Weegink, Peter Sillikens, Ola Weiland
Journal: Journal of Hepatology (1996)
In vitro correlates of low dose Ara‐C efficacy: Clinical, cytogenetic, and bone marrow culture analysis
Authors: Daniel J. Weisdorf, Robert T. Perri, Martin M. Oken, Wesley J. Miller, Diane C. Arthur, Joy L. Machnicki
Journal: American Journal of Hematology (1987)

Abstract Low‐dose Ara‐C (10 mg/m 2 subcutaneously bid) has been used as an alternative therapy for acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes. We sought to define its therapeutic mechanism by assessing clinical and cytogenetic responses to treatment in conjunction with careful in vitro study of both morphologic and functional characteristics of bone marrow cells cultured with Ara‐C. Sixteen patients (12 ANLL, four myelodysplastic syndrome) were treated. All developed pancytopenia and 11 of 12 had bone marrow hypoplasia during treatment. Four had a meaningful clinical response while five more showed in vivo leukemic cell sensitivity to low‐dose Ara‐C. Seven showed no reponse. Cells with cytogenetic abnormalities were either decreased in number or eradicated during clinical improvement. Liquid culture of marrow mononuclear cells with Ara‐C (.033‐.333 μg/ml × 7 days) produced little evidence of morphologic or functional differentiation (ten of 11 studied). No functional maturation was observed in cells from clinically responding patients. We conclude that low‐dose Ara‐C is modestly effective for some patients with ANLL or myelodysplasia. However, no evidence for in vivo leukemic differentiation is suggested by either in vitro culture studies or cytogenetic correlates of clinical response. In vitro marrow culture studies failed to predict clinical response to Ara‐C.
Abstract 5619: Preclinical development of anti-SLC34A2 antibody drug conjugate as a therapeutic for non-small cell lung and ovarian cancers.
Authors: Kedan Lin, Crystal Zhang, Eric Harstad, Hajime Hiraragi, Willy Solis, Siao Ping Tsai, Keyang Xu, Maria Hristopoulos, Rayna Venook, Bonnee Rubinfeld, Paul Polakis
Journal: Cancer Research (2013)

Abstract SLC34A2, also known as type II Na/Pi co-transporters NaPi2b or NaPi3b, is a member of solute carrier protein family SLC34. SLC34A2 is highly expressed on cancers of the lung, ovary and thyroid as well as on normal lung pneumocytes, and is a promising target for antigen-directed therapy. Antibody drug conjugates (ADCs) specify the delivery of a cytotoxic drug to cells expressing an accessible antigenic target. Here we have appended monomethyl auristatin E (MMAE) to an antibody recognizing SLC34A2. Anti-SLC34A2-vc-MMAE inhibits tumor growth in multiple ovarian and non-small cell lung cancer xenograft models that express SLC34A2. Anti-SLC34A2 antibody and its conjugate cross-react with both human and monkey, and toxicity studies in monkeys are conducted to identify both target- and MMAE-related effects. Anti-SLC34A2-vc-MMAE was well tolerated in monkeys at efficacious doses and produced dose-related bone marrow suppression and increased apoptosis and mitotic figures consistent with MMAE-related pharmacology. Despite high levels of expression in normal lung of non-human primate, the cross-reactive ADC exhibited an acceptable safety profile with a dose-limiting toxicity unrelated to normal tissue expression. Overall, our preclinical results suggest that the antibody drug conjugate targeting the SLC34A2 may provide an effective new therapy for the treatment of NSCLC and ovarian cancer. Citation Format: Kedan Lin, Crystal Zhang, Eric Harstad, Hajime Hiraragi, Willy Solis, Siao Ping Tsai, Keyang Xu, Maria Hristopoulos, Rayna Venook, Bonnee Rubinfeld, Paul Polakis. Preclinical development of anti-SLC34A2 antibody drug conjugate as a therapeutic for non-small cell lung and ovarian cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5619. doi:10.1158/1538-7445.AM2013-5619
Short-Term Insight Psychotherapy for Hysterical Personalities
Authors: Miguel A. Leibovich
Journal: Psychotherapy and Psychosomatics (1974)

The different stages of the therapeutic process of short-term insight psychotherapy for hysterical personality disorders is described. This method is found useful to help in the emotional maturation of these patients who, despite the fact that they do not appear to have major psychological problems, suffer a great deal and deprive themselves from achieving gratifying relationships. It is felt that the planning of the overall strategy of therapy before it begins is important, as well as the structuring of the therapeutic process in well delineated stages. A strict criteria for patient selection and the therapist's technique are emphasized. A clinical case serves as illustration.
[546] THE VALUE OF PEGINTERFERON o-2a THERAPY FOR CHRONIC C HEPATITIS IN HEMODIALYSED PATIENTS
Authors: F. lonita-Radu, P. Nuta, F. Fanea, L. Petrescu, C. Klein, D. Popescu, I. Nicolescu, T. Nicolaie, A. Rotaru, R. Ionescu
Journal: Journal of Hepatology (2007)
Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice
Authors: C Cooke
Journal: Cardiovascular Research (2003)

Objective: Oxidative stress has increasingly been implicated in the development and progression of many vascular diseases. Previous work from our laboratory indicated that peroxynitrite alters vasoactive pathways in endothelial cells, which could potentially reduce vascular relaxation. To test this hypothesis in vivo, we utilized an animal model of endogenous oxidative stress, the CuZn superoxide dismutase (SOD) knockout mouse, to assess vascular function. Methods: Vascular reactivity of mouse mesenteric arteries was assessed in the presence or absence of inhibitors to nitric oxide synthase (NOS) and/or prostaglandin H synthase (PGHS). Endothelial-dependent function was also measured after the addition of exogenous SOD. Peroxynitrite formation was detected by nitrotyrosine immunofluorescence in mesenteric arteries. Results: Our data indicate that endothelial-dependent relaxation responses to methacholine are highly reduced in SOD−/− mice (P<0.01, ANOVA). In only the wild-type mice, NOS or PGHS inhibition significantly blunted relaxation, suggesting that vasodilators from these pathways are present only in the controls and not in SOD−/− mice. A combination of NOS and PGHS inhibitors reduced methacholine relaxation in both wild type and SOD−/− mice. This residual EDHF-like relaxation was not different between groups. After incubation with exogenous SOD, endothelial-dependent relaxation could be partially restored in SOD−/− mice, due to increased NOS-mediated vasodilation. In addition, peroxynitrite formation was significantly elevated in mesenteric arteries from SOD−/− mice. Conclusion: Our data suggest that in a novel animal model of oxidative stress, vessel function is compromised due to alterations in NOS and PGHS-dependent relaxation responses.
Psychological problems associated with lymphomas
Authors: R. I Harris
Journal: BMJ (1987)

<h3>Objectives</h3> Determine the safety, feasibility and initial efficacy of a multicomponent telerehabilitation programme for COVID-19 survivors. <h3>Design</h3> Pilot randomised feasibility study. <h3>Setting</h3> In-home telerehabilitation. <h3>Participants</h3> 44 participants (21 female, mean age 52 years) discharged home following hospitalisation with COVID-19 (with and without intensive care unit (ICU) stay). <h3>Interventions</h3> Participants were block randomised 2:1 to receive 12 individual biobehaviourally informed, app-facilitated, multicomponent telerehabilitation sessions with a licenced physical therapist (n=29) or to a control group (n=15) consisting of education on exercise and COVID-19 recovery trajectory, physical activity and vitals monitoring, and weekly check-ins with study staff. Interventions were 100% remote and occurred over 12 weeks. <h3>Primary and secondary outcome measures</h3> The primary outcome was feasibility, including safety and session adherence. Secondary outcomes included preliminary efficacy outcomes including tests of function and balance; patient-reported outcome measures; a cognitive assessment; and average daily step count. The 30 s chair stand test was the main secondary (efficacy) outcome. <h3>Results</h3> No adverse events (AEs) occurred during testing or in telerehabilitation sessions; 38% (11/29) of the intervention group compared with 60% (9/15) of the control group experienced an AE (p=0.21), most of which were minor, over the course of the 12-week study. 27 of 29 participants (93%; 95% CI 77% to 99%) receiving the intervention attended ≥75% of sessions. Both groups demonstrated clinically meaningful improvement in secondary outcomes with no statistically significant differences between groups. <h3>Conclusion</h3> Fully remote telerehabilitation was safe, feasible, had high adherence for COVID-19 recovery, and may apply to other medically complex patients including those with barriers to access care. This pilot study was designed to evaluate feasibility; further efficacy evaluation is needed. <h3>Trial registration number</h3> NCT04663945.
[281] ADIPONECTIN ATTENUATES CD95/FAS EXPRESSION AND APOPTOSIS IN HUMAN HepG2 HEPATOMA CELLS: IMPLICATIONS FOR TREATING FATTY LIVER DISEASES
Authors: G. Marquitan, L. Bechmann, A. Katsounas, M. Schlattjan, M. Odenthal, G. Gerken, A. Canbay
Journal: Journal of Hepatology (2007)
Community-Based Medical Education in the Philippines
Authors: Frank J. Lepreau
Journal: JAMA (1990)

The Institute of Health Sciences at Palo on Leyte Gulf represents a bold initiative to counteract the perennial exodus of nurses and physicians, an exodus that leaves the Philippines with dangerously inadequate medical services. Organized within the University of the Philippines, the institute is separate from the university's traditional medical school, operating under its own dean. The institute's program clearly holds promise for the Philippines and may provide an example for other developing nations. Statistics illustrate the problem. The ratio of nurses to the population is 1:5245. In 1986, 129 schools graduated 6270 nurses; at this writing there were 96 000 registered nurses abroad and 64 000 in the Philippines. Mothers often raise daughters to be nurses who will go abroad to work and send money home. The ratio of physicians to the population is 1:6423. Twenty-seven medical schools graduate 3500 physicians annually, and at least 65% of them emigrate
PHENOLTETRACHLORPHTHALEIN LIVER FUNCTION TEST
Authors: GEORGE HOWARD HOXIE
Journal: JAMA (1924)

The work of Lyons on duodenal drainage, and the work of Piersol and Bockus1in testing out the phenoltetrachlorphthalein function test of the liver, have brought to the attention of the practical medical men of the country an alluring promise of possible attainment in the field of diagnosis of diseases of the right upper quadrant of the abdomen. It is generally admitted that disturbances in this region are the most puzzling that we have to deal with. We are tempted, therefore, to try out every new suggestion made along this line. The purpose of this report is, therefore, to present the results of some of these attempts to utilize in actual practice the suggestions thus obtained.  Because Piersol and Bockus, as well as others, have demonstrated that the appearance time of the dye in the duodenal tube is proportional to the total amount of dyestuff excreted in two hours,
Steroid Aerosols for Asthma
Authors: M. HENRY WILLIAMS
Journal: Annals of Internal Medicine (1977)

Editorial Notes1 May 1977Steroid Aerosols for AsthmaM. HENRY WILLIAMS JR., M.D.M. HENRY WILLIAMS JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-5-650_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCorticosteroids are widely and effectively used for treatment of asthma. Although necessary for control of symptoms in many patients, prolonged treatment is associated with unpleasant and dangerous side effects: hypercorticism, adrenal suppression, and steroid dependence. Many attempts have been made to develop aerosols that can be inhaled so as to exert a topical effect on the lung without producing systemic toxicity (1). Until recently, it has not been possible to have effective local action without systemic absorption, but during the past few years a number of new aerosols have been developed that do possess topical activity (2-5). Of these, beclomethasone...References1. WILLIAMS M: Steroid and antibiotic aerosols. Am Rev Respir Dis 110:122-127, 1974 MedlineGoogle Scholar2. BROWNSTOREYGEORGE HGW: A new steroid aerosol for the treatment of allergic asthma. Br Med J 1:585, 1972 CrossrefMedlineGoogle Scholar3. CLARK T: Effect of beclomethasone dipropionate delivered by aerosol in patients with asthma. Lancet 1:1361, 1972 CrossrefMedlineGoogle Scholar4. CAMERONCOOPERCROMPTON SEG: Substitution of beclomethasone aerosol for oral prednisolone in treatment of chronic asthma. Br Med J 4:205, 1973 CrossrefMedlineGoogle Scholar5. WILLIAMSKANESHIM MCC: Treatment of asthma with triamcinolone acetonide delivered by aerosol. Am Rev Respir Dis 109:538-543, 1974 MedlineGoogle Scholar6. BALLIN J: Evaluation of a new aerosolized steroid for asthma therapy. Beclomethasone dipropionate (Vanceril Inhaler). JAMA 236:2891-2893, 1976 CrossrefMedlineGoogle Scholar7. WILLIAMS M: Corticosteroid aerosols for the treatment of asthma. JAMA 231:406-407, 1975 CrossrefMedlineGoogle Scholar8. BONDAREVSKYSHAPIROSCHEY EMG: Beclomethasone dipropionate use in chronic asthmatic patients. JAMA 236:1969-1971, 1976 CrossrefMedlineGoogle Scholar9. BYYNY R: Withdrawal from glucocorticoid therapy. N Engl J Med 295:30-32, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: M. HENRY WILLIAMSJR., M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1977Volume 86, Issue 5Page: 650-650KeywordsAsthmaLungsPatientsToxicity ePublished: 1 December 2008 Issue Published: 1 May 1977 PDF downloadLoading ...
Th17 Cells Are Long Lived and Retain a Stem Cell-like Molecular Signature
Authors: Pawel Muranski, Zachary A. Borman, Sid P. Kerkar, Christopher A. Klebanoff, Yun Ji, Luis Sanchez-Perez, Madhusudhanan Sukumar, Robert N. Reger, Zhiya Yu, Steven J. Kern, Rahul Roychoudhuri, Gabriela A. Ferreyra, Wei Shen, Scott K. Durum, Lionel Feigenbaum, Douglas C. Palmer, Paul A. Antony, Chi-Chao Chan, Arian Laurence, Robert L. Danner, Luca Gattinoni, Nicholas P. Restifo
Journal: Immunity (2011)
Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance
Authors: Laura Bonapace, Beat C. Bornhauser, Maike Schmitz, Gunnar Cario, Urs Ziegler, Felix K. Niggli, Beat W. Schäfer, Martin Schrappe, Martin Stanulla, Jean-Pierre Bourquin
Journal: Journal of Clinical Investigation (2010)

In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL.
Deadly Medicine: Doctors and True Crime
Authors: Donald W. Goodwin
Journal: JAMA (1975)

The author of this book about murderer doctors believes doctors commit murder more often than most people do. Real murder, not the inadvertent kind. What silicosis is to mining, he says, murder is to medicine. His evidence is 16 physicians and one medical student who, over a century and a half, were accused of murder and thus rated a chapter in his book. "I would be hard put to it," he writes, "to find a comparable number of lawyers, soldiers, clergymen, butchers, bakers and candlestick makers who had killed wives, relatives, and neighbors." Perhaps. If he had looked hard enough for candlestick makers, he might have found 16 plus one apprentice, and who can say what a search for lawyers might have produced. It seems more of the latter are in the pokey these days than doctors. The fact is, the MDs he writes about received a high amount of
SUCTION DRAINAGE OF SUPRAPUBIC BLADDER WOUNDS: DESCRIPTION OF A NEW PUMP
Authors: Charles W. Bethune
Journal: JAMA (1918)

One of the most unpleasant features of suprapubic bladder drainage is the constant saturation of the dressings with urine, together with the all-pervading odor, not to mention the present high cost of dressings. The patient's skin becomes excoriated, and he also suffers the discomfort of frequently lying in a puddle if the attendants do not promptly change the saturated pads. Numerous attempts have been made to remedy this with various ingenious suction devices, the first of which I believe was Dawbarn's. Davis<sup>1</sup>uses a vacuum bottle arrangement; Hume, Logan and Kells<sup>2</sup>an electric pump with an alarm clock switch; Wallace<sup>3</sup>an apparatus invented by Edmund White, resembling the Dawbarn. All of these appliances have faults which I have tried to obviate. Dawbarn's and White's require the bringing of several gallons of water to the pump daily and the removal of an equal amount. Davis' requires an air
Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance
Authors: Jie An, Deborah M Muoio, Masakazu Shiota, Yuka Fujimoto, Gary W Cline, Gerald I Shulman, Timothy R Koves, Robert Stevens, David Millington, Christopher B Newgard
Journal: Nature Medicine (2004)