tbuckley/cabot-search huggingface dataset:
Anesthesia Not Related to Fludarabine Toxicity
Authors: Kenneth E. Shepherd
Journal: Annals of Internal Medicine (1993)

Letters1 September 1993Anesthesia Not Related to Fludarabine ToxicityKenneth E. Shepherd, MDKenneth E. Shepherd, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-5-199309010-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the brief report by Cohen and colleagues [1] about reversible neurologic toxicity associated with fludarabine. What caught my eye was the statement that general anesthesia (Patient 2) may have potentiated fludarabine toxicity. The authors note that the surgery in Patient 2 was brief, limited in scope, and uncomplicated.I generally appreciate the contribution of the medical evaluation in complex perioperative patients, but some internists' recommendations can be irritating and can have medicolegal implications [2]. I pose this question to Dr. Cohen and his coworkers: Are there specific data concerning fludarabine and anesthesia to ...References1. Cohen RB, Abdallah JM, Gray JR, Foss F. Reversible neurologic toxicity in patients treated with standard-dose fludarabine phosphate for mycosis fungoides and chronic lymphocytic leukemia. Ann Intern Med. 1993; 118:114-6. Google Scholar2. Keats AS. The estimate of anesthetic risk in medical evaluations. Am J Cardiol. 1963; 12:330-3. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1993Volume 119, Issue 5Page: 437KeywordsAnesthesiaGeneral anesthesiaSurgeryToxicity Issue Published: 1 September 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
S60 C - Reactive Protein Reflects Mycobacterial Load In Active Tuberculosis But Cannot Be Used As A Rule-out Diagnostic Test
Authors: K. Clark, J. Brown, J. Hopwood, O. Lynard, D. Creer, R. Barker, C. Smith, R. Breen, I. Cropley, M. Lipman
Journal: Thorax (2014)

<h3>Background</h3> Measurement of the C-reactive protein (CRP) is widely available and is often part of the diagnostic evaluation of patients with suspected Tuberculosis (TB) yet there are little published data regarding its use in this context. We sought to determine CRP’s relationship with TB disease and whether normal CRP levels were seen in those without active TB. <h3>Method</h3> We undertook a retrospective review of electronic records from the London TB service between 2004–2013, obtained blood results from hospital computer systems and reviewed case-notes where there was uncertainty regarding sites of disease or availability of culture results. <h3>Results</h3> Using data from 533 subjects with active TB, 23% of all cases and 16.5% of culture-confirmed cases had a CRP of ≤5 mg/L. Individuals with HIV co-infection had significantly higher median CRP (see Table). There was a significantly higher CRP in smear-positive pulmonary disease and those with a positive culture. Sites of disease that could be expected to have a high mycobacterial load (e.g. pulmonary disease and disseminated disease) had a significantly higher CRP than those such as skin, lymph node or CNS disease, where the mycobacterial load is typically low in HIV negative subjects. HIV status, site of disease and culture status remained significantly associated with CRP in a multivariable linear regression analysis. <h3>Conclusions</h3> These data suggest that CRP cannot be used as a rule-out test for active TB but does reflect mycobacterial load. This has clinical implications given that individuals with a high mycobacterial load may be more infectious (and hence require enhanced contact tracing), be at greater risk of developing drug resistance if non-adherent, and may require prolonged duration of treatment.
Fatal myeloproliferation, induced in mice by TEL/PDGFβR expression, depends on PDGFβR tyrosines 579/581
Authors: Michael H. Tomasson, David W. Sternberg, Ifor R. Williams, Martin Carroll, Danielle Cain, Jon C. Aster, Robert L. Ilaria, Richard A. Van Etten, D. Gary Gilliland
Journal: Journal of Clinical Investigation (2000)

The t(5;12)(q33;p13) translocation associated with chronic myelomonocytic leukemia (CMML) generates a TEL/PDGFβR fusion gene. Here, we used a murine bone marrow transplant (BMT) assay to test the transforming properties of TEL/PDGFβR in vivo. TEL/PDGFβR, introduced into whole bone marrow by retroviral transduction, caused a rapidly fatal myeloproliferative disease that closely recapitulated human CMML. TEL/PDGFβR transplanted mice developed leukocytosis with Gr-1+ granulocytes, splenomegaly, evidence of extramedullary hematopoiesis, and bone marrow fibrosis, but no lymphoproliferative disease. We assayed mutant forms of the TEL/PDGFβR fusion protein — including 8 tyrosine to phenylalanine substitutions at phosphorylated PDGFβR sites to which various SH2 domain–containing signaling intermediates bind — for ability to transform hematopoietic cells. All of the phenylalanine (F-) mutants tested conferred IL-3-independence to a cultured murine hematopoietic cell line, but, in the BMT assay, different F-mutants displayed distinct transforming properties. In transplanted animals, tyrosines 579/581 proved critical for the development of myeloproliferative phenotype. F-mutants with these residues mutated showed no sign of myeloproliferation but instead developed T-cell lymphomas. In summary, TEL/PDGFβR is necessary and sufficient to induce a myeloproliferative disease in a murine BMT model, and PDGFβR residues Y579/581 are required for this phenotype.
Thy-1 triggers mouse thymocyte apoptosis through a bcl-2-resistant mechanism.
Authors: A O Hueber, G Raposo, M Pierres, H T He
Journal: The Journal of Experimental Medicine (1994)

Programmed cell death plays an important role during thymocyte development, since a vast majority (97%) of mouse cortical thymocytes die in thymus, whereas only 3% of these cells are rescued from cell death and positively selected. Although it seems well established that thymocyte fate depends upon appropriate surface-expressed T cell receptor, little is known about the molecular mechanism(s) responsible for the massive thymocyte elimination that occurs in the thymus. We report here that Thy-1 is capable of triggering mouse thymocyte death in vitro through a bcl-2-resistant mechanism. We have previously shown that Thy-1 is involved in mouse thymocyte adhesion to thymic stroma through interaction with an epithelial cell ligand. To examine the Thy-1 signaling function in thymocytes, we have mimicked its interaction with stromal cells by culturing mouse thymocytes onto tissue culture plates coated with monoclonal antibodies (mAb) directed at distinct Thy-1 epitope regions. mAb recognizing determinants in a defined Thy-1 structural domain, but not others, were found to induce marked thymocyte apoptosis as evidenced by morphological and biochemical data. Use of a quantitative DNA dot blot assay indicated that Thy-1-mediated thymocyte apoptosis was not blocked by RNA or protein synthesis inhibitors, EGTA, or by cyclosporin A, and differed, therefore, from "activation-driven cell death". Moreover, Thy-1(+)-transfected, but not wild-type AKR1 (Thy-1-d) thymoma cells underwent apoptosis after ligation with apoptosis-inducing, Thy-1-specific mAb. In contrast to thymocytes, the latter event was inhibitable by RNA and protein synthesis inhibitors, an indication that thymocytes, but not thymoma cells, contain the molecular components necessary for Thy-1-driven apoptosis. We further showed that Thy-1-triggered thymocyte death is a developmentally regulated process operative in fetal thymocytes from day 17 of gestation, but not in peripheral T cells. Indeed, the target of apoptosis by anti-Thy-1 was found to reside mainly within the CD4+8+3- and CD4+8+3lo double positive immature thymocyte subsets. Finally, it is of major interest that Thy-1-mediated apoptosis, which was found to be readily detectable in thymocytes from bcl-2-transgenic mice, represents a thus far unique experimental system for studying bcl-2-resistant thymocyte death mechanism(s).
Economic arguments for the immediate management of moderate-to-severe obstructive sleep apnoea syndrome
Authors: N. Pelletier-Fleury, N. Meslier, F. Gagnadoux, C. Person, D. Rakotonanahary, H. Ouksel, B. Fleury, J-L. Racineux
Journal: European Respiratory Journal (2003)

The objective of this study was to measure the impact of a 6‐month delay in the diagnosis and treatment of patients with moderate obstructive sleep apnoea syndrome (OSAS) (apnoea/hypopnoea index (AHI) &lt;30) or severe OSAS (AHI ≥30) on daytime sleepiness, cognitive functions, quality of life and healthcare expenditure (hospitalisations, medical visits, complementary tests, biological tests and drug prescriptions). In addition, this study aimed to analyse the incremental cost effectiveness ratios related to daytime sleepiness or quality of life following immediate introduction of treatment in these two populations. This study was conducted as a multicentre randomised controlled trial and carried out at two teaching hospitals in France. A total of 171 patients were followed for 6 months, with 82 patients randomised to group 1 “immediate polysomnography” and 89 in group 2 “polysomnography within 6 months”. Patients with severe OSAS were deprived of a significant improvement of their daytime sleepiness (5.1±5.0 at the Epworth Sleepiness Scale score in group 1 versus 0.2±3.4 in group 2) and quality of life (12.4±13.3 at the Nottingham Health Profile score in group 1 versus 0.7±10.1 in group 2) during the waiting time. The impact of delayed management in subjects with less severe OSAS only concerned daytime sleepiness (1.9±3.3 in group 1 versus 0.3±4.3 in group 2). Delayed treatment did not affect cognitive functions or healthcare expenditure regardless of the severity of the disease. Incremental cost effectiveness ratios related to rapid introduction of treatment were significantly lower in the patients with more severe OSAS. These results provide fairly clear medical and economic arguments in favour of early management of patients with more severe forms of obstructive sleep apnoea syndrome.
Opportunities for and challenges of computerisation
Authors: Seth M Powsner, Jeremy C Wyatt, Patricia Wright
Journal: The Lancet (1998)

Information technology offers many potential advantages over paper for the storage and retrieval of patients' data. Enthusiasts predict that soon all records will be stored and viewed on computer, but others are more sceptical. The failure of some computer-based records may be due to poor information design. This paper explores how computers broaden the range of design options but points out that more attention to design is required for computer-based than for paper-based records.
Assisted ventilation. 3. General care of the ventilated patient in the intensive care unit.
Authors: M R Hamilton-Farrell, G C Hanson
Journal: Thorax (1990)

Care of the airway Patients whose conscious level is impaired often require an artificial aid to maintain a clear airway.An oral (Guedel) airway may be sufficient temporarily, ana It allows tne pas- sage of a suction catheter alongside.A naso- pharyngeal airway _ore c,omfbrthJ, and may permit-passage of a fine catheter through the larynx, though this may be traumatic if repeated too often.An endotracheal tube or tracheostomy is necessary to secure the airway against laryn- geal obstruction, to provide a route for artificial ventilation, to allow suction of bron- chial secretions, and to protect the lungs against aspiration of pharyngeal and gastric contents.Early problems with endotracheal tubes include misplacement into the oeso- phagus or a mainstem oroncnus;' and nexion, extension, or turning of the neck may displace the tube tip.Other complications include aspiration past an incompletely inflated balloon cuff,' injuries of oropharyngeal mucus membranes, paralysis and granulomas of vocal cords, and laryngotracheal stenosis.2Acciden- tal and self extubation is a risk, especially with young children,3 and the intlated cuff may damage the larynx as it passes through.Although the oral route is often easier for intubation, nasal endotracheal tubes have the advantages of avoiding trauma tot and of being more comfortable for the awake patient.They are also longer and narrower than oral tubes, and occasionally present problems with suctioning.They may be
The Clinical Case Conference Reconsidered
Authors: J. REGIS MCNAMARA
Journal: American Journal of Psychiatry (1973)

The author questions the effectiveness of the case conference, a procedure that is widely used in mental hospitals. He suggests modifications in the conduct of the conference that involve telling the group about the amount of time, effort, and money expended on cases each session. He also proposes an alternative to the case conference that is based on the "critical paths" approach to time and resource management.
Prediction of outcome in fulminant hepatic failure by serum human hepatocyte growth factor
Authors: Hirohito Tsubouchi, Shuichi Kawakami, Shuichi Hirono, Hiroomi Miyazaki, Masayoshi Kimoto, Terukatsu Arima, Kazuhiko Sekiyama, Makoto Yoshiba, Naokatu Arakaki, Yasushi Daikuhara
Journal: The Lancet (1992)
Farming and Prostate Cancer Among African-Americans in the Southeastern United States
Authors: M. Dosemeci, R. N. Hoover, A. Blair, L. W. Figgs, S. Devesa, D. Grauman, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Farming and Prostate Cancer Among African-Americans in the Southeastern United States Get access Mustafa Dosemeci, Mustafa Dosemeci Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Correspondence to: Mustafa Dosemeci, Ph.D., National Institutes of Health, EPN, Rm. 418, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert N. Hoover, Robert N. Hoover Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Aaron Blair, Aaron Blair Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Larry W. Figgs, Larry W. Figgs Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan Devesa, Susan Devesa Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan Grauman, Dan Grauman Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F. Fraumeni, Jr Joseph F. Fraumeni, Jr Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 22, 16 November 1994, Pages 1718–1719, https://doi.org/10.1093/jnci/86.22.1718 Published: 16 November 1994 Article history Received: 13 June 1994 Revision received: 06 September 1994 Accepted: 13 September 1994 Published: 16 November 1994
Increased Immunogenicity of TA3-Ha Cells Treated With the Antitumor Antibiotic Macromomycin (B)
Authors: Emanuela Coronetti, Muriel M. Lippman
Journal: JNCI Journal of the National Cancer Institute (1976)

Suspension cultures of TA3-Ha mouse mammary tumor cells were treated in vitro with a single dose of macromomycin(B) (MCR) at 1 mug/ml for 24 hours. This dose, which is cytostatic but not lethal, increased the immunogenicity of the cells. Adoptive transfer of spleen cells sensitized to MCR/TA3-Ha cells evoked an immune response against MCR-treated TA3-Ha cells but not against normal TA3-Ha cells. The therapeutic effect of MCR treatment (in this case) was, to a very small extent, due to the cytostatic action and more profoundly to the increased immunogenicity of the cells so treated.
Role of the Akt/FoxO3a Pathway in TGF-β1–Mediated Mesangial Cell Dysfunction
Authors: Mitsuo Kato, Hang Yuan, Zhong-Gao Xu, Linda Lanting, Shu-Lian Li, Mei Wang, Mickey C.-T. Hu, Marpadga A. Reddy, Rama Natarajan
Journal: Journal of the American Society of Nephrology (2006)

Diabetic nephropathy (DN) is characterized by mesangial cell (MC) expansion and accumulation of extracellular matrix proteins. TGF-beta is increased in MC under diabetic conditions and in DN and activates key signaling pathways, including the phosphoinositide-3-kinase/Akt (PI3K/Akt) pathway. FoxO transcription factors play roles in cell survival and oxidative stress and are negatively regulated by Akt-mediated phosphorylation. We tested whether phosphorylation-mediated inactivation of FoxO3a by TGF-beta can mediate MC survival and oxidative stress. TGF-beta treatment significantly increased levels of p-Akt (activation) and p-FoxO3a (inactivation) in cultured MC. This FoxO3a inactivation was accompanied by significant decreases in the expression of two key FoxO3a target genes, the proapoptotic Bim and antioxidant manganese superoxide dismutase in MC. TGF-beta treatment triggered the nuclear exclusion of FoxO3a, significantly inhibited FoxO3a transcriptional activity, and markedly protected MC from apoptosis. A PI3K inhibitor blocked these TGF-beta effects. It is interesting that p-Akt and p-FoxO3A levels also were increased in renal cortical tissues from rats and mice at 2 wk after the induction of diabetes by streptozotocin, thus demonstrating in vivo significance. In summary, TGF-beta and diabetes can increase FoxO3a phosphorylation and transcriptional inactivation via PI3K/Akt. These new results suggest that Akt/FoxO pathway regulation may be a novel mechanism by which TGF-beta can induce unopposed MC survival and oxidant stress in early DN, thereby accelerating renal disease.
Haptoglobin Genotype Is Predictive of Major Adverse Cardiac Events in the 1-Year Period After Percutaneous Transluminal Coronary Angioplasty in Individuals With Diabetes
Authors: Ariel Roguin, Werner Koch, Adnan Kastrati, Doron Aronson, Albert Schomig, Andrew P. Levy
Journal: Diabetes Care (2003)

OBJECTIVE—The goal of this study was to determine whether the haptoglobin (Hp) genotype was predictive of restenosis and major adverse cardiac events (MACEs) after percutaneous transluminal coronary angioplasty (PTCA) in individuals with diabetes. RESEARCH DESIGN AND METHODS—A consecutive series of 935 diabetic patients treated with oral agents and/or insulin were followed for 1 year after PTCA. The primary study end point was angiographic restenosis, MACEs and secondary study end points were defined as target vessel revascularization, myocardial infarction, and death. Two alleles exist at the Hp gene locus, denoted 1 and 2. The Hp genotype (Hp 1–1, Hp 2–1, or Hp 2–2) was determined by PCR. RESULTS—In multivariate analysis controlling for all known determinants of outcome after PTCA, we found that the Hp genotype was a highly significant independent predictor of MACEs in the 1-year period after PTCA in individuals with diabetes. This was predominantly due to differences in the risk of myocardial infarction during that period: Hp 1–1, 0 of 129 (0%); Hp 2–1, 20 of 424 (4.7%); and Hp 2–2, 32 of 382 (8.4%); P &amp;lt; 0.0001. CONCLUSIONS—The Hp genotype seems to be highly predictive of adverse cardiac events, particularly myocardial infarction, in the 1-year period after PTCA. Determination of the Hp genotype may be useful in the evaluation of new therapies to reduce cardiovascular risk after PTCA.
Gefitinib Modulates the Function of Multiple ATP-Binding Cassette Transporters <i>In vivo</i>
Authors: Markos Leggas, John C. Panetta, Yanli Zhuang, John D. Schuetz, Brad Johnston, Feng Bai, Brian Sorrentino, Sheng Zhou, Peter J. Houghton, Clinton F. Stewart
Journal: Cancer Research (2006)

Abstract The 4-anilinoquinazoline (4-AQ) derivative gefitinib (Iressa) is an oral epidermal growth factor receptor tyrosine kinase inhibitor. Oral administration of 4-AQ molecules, such as gefitinib, inhibits ATP-binding cassette (ABC) transporter–mediated drug efflux and strongly increases the apparent bioavailability of coadministered drug molecules that are transporter substrates. Based on in vitro studies investigating 4-AQ interactions with several transporters, these effects have primarily been attributed to the inhibition of breast cancer resistance protein (BCRP; ABCG2). Although 4-AQ shows in vitro inhibition of P-glycoprotein [multidrug resistance protein (MDR1); ABCB1], the in vivo effect on this and other transporters is not known. In our studies, pretreatment of Abcg2−/− and Mdr1(a/b)−/− mice with gefitinib increased oral absorption and decreased systemic clearance of topotecan, a model substrate, indicating that additional transporters were inhibited. These results were extended to human orthologues using engineered cell lines to show that gefitinib inhibited the efflux of BCRP and MDR1 substrates and restored vincristine sensitivity in MDR1-expressing cells. Although gefitinib inhibited BCRP more potently than MDR1 (10-fold), the inhibition of both transporters occurred at clinically relevant concentrations (e.g., 1-5 μmol/L). These studies illustrate the broad implications for the therapeutic combination of gefitinib or other 4-AQ molecules with agents that are BCRP and MDR1 substrates. 4-AQ molecules may offer a means to increase the low and variable oral drug absorption of transporter substrates while decreasing interpatient variability and reversing tumor drug resistance. (Cancer Res 2006; 66(9): 4802-7)
A patient tumor-derived orthotopic xenograft mouse model replicating the group 3 supratentorial primitive neuroectodermal tumor in children
Authors: Zhigang Liu, Xiumei Zhao, Yue Wang, Hua Mao, Yulun Huang, Mari Kogiso, Lin Qi, Patricia A. Baxter, Tsz-Kwong Man, Adekunle Adesina, Jack M. Su, Daniel Picard, King Ching Ho, Annie Huang, Laszlo Perlaky, Ching C. Lau, Murali Chintagumpala, Xiao-Nan Li
Journal: Neuro-Oncology (2014)

Supratentorial primitive neuroectodermal tumor (sPNET) is a malignant brain tumor with poor prognosis. New model systems that replicate sPNET's molecular subtype(s) and maintain cancer stem cell (CSC) pool are needed.A fresh surgical specimen of a pediatric sPNET was directly injected into the right cerebrum of Rag2/SCID mice. The xenograft tumors were serially sub-transplanted in mouse brains, characterized histopathologically, and subclassified into molecular subtype through qRT-PCR and immunohistochemical analysis. CSCs were identified through flow cytometric profiling of putative CSC markers (CD133, CD15, CD24, CD44, and CD117), functional examination of neurosphere forming efficiency in vitro, and tumor formation capacity in vivo. To establish a neurosphere line, neurospheres were propagated in serum-free medium.Formation of intracerebral xenograft tumors was confirmed in 4 of the 5 mice injected with the patient tumor. These xenograft tumors were sub-transplanted in vivo 5 times. They replicated the histopathological features of the original patient tumor and expressed the molecular markers (TWIST1 and FOXJ1) of group 3 sPNET. CD133(+) and CD15(+) cells were found to have strong neurosphere-forming efficiency in vitro and potent tumor-forming capacity (with as few as 100 cells) in vivo. A neurosphere line BXD-2664PNET-NS was established that preserved stem cell features and expressed group 3 markers.We have established a group 3 sPNET xenograft mouse model (IC-2664PNET) with matching neurosphere line (BXD-2664PNET-NS) and identified CD133(+) and CD15(+) cells as the major CSC subpopulations. This novel model system should facilitate biological studies and preclinical drug screenings for childhood sPNET.