tbuckley/cabot-search huggingface dataset:
Effective audit: reporting to the National Confidential Enquiry into Perioperative Deaths.
Authors: L. Clark, P. Doyle, E. Duran, P. Kishore
Journal: BMJ (1992)

OBJECTIVE--To investigate the effectiveness of computer based and manual district and unit information systems for identifying hospital deaths eligible for reporting to the National Confidential Enquiry into Perioperative Deaths (NCEPOD). DESIGN--Prospective six to 10 week study of hospital (death register, immediate coding of medical records) and district information systems followed by six month assessment after modification to entry of data. SETTING--Acute units within Lewisham and North Southwark Health District. PATIENTS--All 290 patients dying in hospital during the six weeks, for whom the medical records were obtainable in 231. MAIN OUTCOME MEASURES--Sensitivity and specificity of the information systems in ascertaining eligible surgical deaths (patients dying in hospital who had during 30 days previously had a surgical procedure while under the care of a consultant in a surgical specialty) tested against validated list of screened medical records. RESULTS--Of 231 medical records, 30 (12 from Lewisham, 18 from North Southwark) met the national inquiry9s criteria. The computer based systems of both units detected less than 60% of eligible deaths (sensitivity 53%, specificity 83%); the death register detected about 60% (sensitivity 61%, specificity 89%); manual systems detected all eligible deaths. Subsequent modification to ensure immediate coding of records into the computerised systems during follow up failed to show any improvement. IMPLICATIONS--Routine hospital information systems may miss up to half the deaths eligible for NCEPOD.
Liver structure and function in cholelithiasis: Effect of chenodeoxycholic acid
Authors: G. D. Bell, H. Y. I. Mok, M. Thwe, G. M. Murphy, K. Henry, R. H. Dowling
Journal: Gut (1974)

Although, in suitable patients, oral chenodeoxycholic acid (CDCA) dissolves gallstones, the results of recent animal studies suggest that it might be hepatotoxic. Liver function was therefore studied in patients with gallstones before and during treatment with CDCA and liver biopsies were carried out both in patients with cholelithiasis given bile acid therapy and in those who had been given no medical treatment. In 25 patients treated with 0·5-1·5 g CDCA/day (7-20 mg kg body weight<sup>−1</sup> day<sup>−1</sup>) there was no significant change in serum bilirubin, albumin, globulin, transaminase, isocitric dehydrogenase, alkaline phosphatase, and gamma glutamyl transpeptidase levels before and at monthly intervals during six months9 treatment. The kinetics of bromsulphthalein (BSP) clearance and its apparent transport maximum were not significantly changed during CDCA therapy. The mean fasting serum bile acid concentrations of 18·0 ± SEM 1·2 μmoles/litre before and 20·0 ± 3·5 μmoles/litre during treatment were both significantly greater than control values. Liver histology was not appreciably different in 11 patients treated with CDCA from that in eight patients with untreated cholelithiasis and in three patients who had received CDCA three to four months before biopsy. These results suggest that in doses of 0·5 to 1·5 g/day CDCA is not hepatotoxic in man.
1091-207 Primary and secondary prevention implantable cardioverter defibrillator patients have similar proportions of ventricular tachyarrhythmia detections and equivalent risk for spurious therapies: Results from painFREE Rx II
Authors: Michael O Sweeney, Mark S Wathen, Ismaile Abdalla, Paul J DeGroot, Mary F Otterness, Alice J Stark
Journal: Journal of the American College of Cardiology (2004)
Fibroblasts mediate T cell survival: a proposed mechanism for retention of primed T cells.
Authors: S Scott, F Pandolfi, J T Kurnick
Journal: The Journal of Experimental Medicine (1990)

This report describes a salvage pathway whereby activated T lymphocytes revert to nonproliferating cells in the absence of antigen or mitogenic signals. After the removal of mitogenic cytokines, cultured T lymphocytes cease dividing and rapidly begin to undergo cell death. However, the addition of fibroblasts to interleukin 2 (IL-2)-propagated T cells results in prolonged survival of the previously activated T lymphocytes in the absence of proliferation. The prevention of cell death is also achieved by conditioned medium from the fibroblasts. T lymphocytes cultured with fibroblasts or the conditioned medium retain the ability to be restimulated if mitogenic stimuli are added to the culture. The activity is not accounted for by IL-1-7. The studies suggest a stromal cell-mediated, nonspecific mechanism for survival of primed T lymphocytes in a nonproliferating state.
Involving bosses is crucial to keep up momentum on safety
Authors: L. Hitchen
Journal: BMJ (2008)

Getting chief executives involved in increasing the safety of hospital patients is important to keep staff motivated and to deliver improvements, say experts.

Mark Patten, a consultant anaesthetist and clinical director at Luton and Dunstable Hospital NHS Trust, told a London conference that success in reducing the number of central line infections at the trust is partly due to the involvement of Stephen Ramsden, the trust’s chief executive.

Just one central line infection has been reported in the hospital’s critical care department in the past 12 months. Beforehand the department saw one or two infections every month. 

“Because the chief executive came and challenged us, and because he demonstrated his commitment by turning up, that is how we did it,” said …
Abstract LB-365: Regulation of VEGFR-2 by leptin-Notch signaling crosstalk in mammary cancer cells
Authors: Shanchun Guo, Miles Fuller, Ruben R. Gonzalez-Perez
Journal: Cancer Research (2010)

Abstract VEGFR-2 (Flk-1 or KDR) is generally recognized as the major form that mediates VEGF-induced response and the earliest marker for endothelial cell development. More importantly, VEGFR-2 directly regulates tumor angiogenesis and cancer cell survival through autocrine/paracrine mechanisms. We have previously reported that leptin signaling induced the growth of breast cancer mainly through the up-regulation of pro-angiogenic and pro-proliferative molecules, i.e., VEGF/VEGFR-2. Disruption of leptin signaling markedly reduced the growth of tumors and the expression of VEGFR-2 in mouse models of syngeneic and human breast cancer xenografts (ER+ and ER-). On the other hand, Notch signaling is essential for tumor angiogenesis. We hypothesized that a crosstalk between Notch and leptin signaling could impact the expression of VEGFR-2 in breast cancer. To test this hypothesis, the 5′-end transcription region of mouse VEGFR-2 gene was cloned and used to establish VEGFR2-Luc assays in mouse mammary tumor (MT) cells. Leptin induced VEGFR-2-Luc activity through JAK2, JNK, p38 MAP kinase, as well as PKC signaling pathways and up-regulated several members of Notch family (Notch 1∼4) in MT. Interestingly, leptin-induced VEGFR-2 transcriptional activity was significantly inhibited by a gamma-secretase inhibitor which blocks Notch pathway activation. These results suggest that leptin and Notch signaling crosstalk could impact on angiogenesis and growth of MT. Furthermore, VEGFR-2 transcription and expression was heavily depending on VEGFR-2 gene methylation and histone acetylation that could be linked to leptin's effects. Our results provide novel evidence on how VEGFR-2 could be regulated in breast cancer. Present data reinforce the idea that disruption of leptin signaling could reduce tumor angiogenesis/growth by inhibiting leptin-mediated up-regulation of VEGFR-2 and/or by negatively impacting on signals from some key members of Notch family. This might help to design new pharmacological strategies aimed at controlling breast cancer growth and angiogenesis. [This work was supported in part by NIH/NCI 1SC1CA138658-02; NIH/ARRA/3SC1CA138658-02S1; NIH/UAB Breast SPORE Career Development Award and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP)]. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-365.
Cancer Chemotherapy: Teaching Old Drugs New Tricks
Authors: Brigid Kane
Journal: Annals of Internal Medicine (2001)

Current Clinical Issues18 December 2001Cancer Chemotherapy: Teaching Old Drugs New TricksBrigid KaneBrigid KaneSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-12-200112180-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For most of the millions of patients with cancer (Table), the toxicity associated with cancer chemotherapy is frequently the rate-limiting factor in the use of potentially effective drugs. The indiscriminate cytotoxicity of cancer drugs—the killing of healthy and cancerous cells alike—means that it is often not possible to use what should be the best available single or combination chemotherapeutic agents. Other consequences of the toxicity of cancer chemotherapy include using a suboptimal dose or intermittent dosing schedules (alternating chemotherapy with rest periods) or forgoing chemotherapy altogether. The elderly and patients with comorbid illnesses are most likely to forgo or ask ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology for cancer drug design, delivery, and theranostics applicationsEnhancing therapeutic efficacy of anticancer drugs through targeting of functionalized niosomesAntineoplastic Agents and the Associated Myelosuppressive EffectsManagement of Hematology/Oncology Patients in the EDAntibody production: Polyclonal-derived biotherapeutics 18 December 2001Volume 135, Issue 12Page: 1107-1110KeywordsAdverse reactionsCancer chemotherapyCancer treatmentCellsChemotherapyDrugsErythropoietinFood and Drug AdministrationHalf lifeToxicity ePublished: 18 December 2001 Issue Published: 18 December 2001 CopyrightCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 34: Investigating PIN1 as a genetic modifier in Li-Fraumeni syndrome
Authors: Anita Villani, Ana Novokmet, David Malkin
Journal: Cancer Research (2014)

Abstract Background: Li-Fraumeni syndrome (LFS) is characterized by marked clinical heterogeneity in site and age of cancer onset. The prolyl-isomerase, Pin1 (peptidylprolyl cis/trans isomerase, NIMA-interacting 1), has been shown to serve a fundamental role in mutant TP53 oncogenic gain of function and the promotion of aggressive cancer phenotypes. We sought to determine whether alterations in PIN1 modify the phenotype of patients with germline mutations in TP53. Methods: The PIN1 promoter and coding regions were sequenced from peripheral blood lymphocyte samples of 107 individuals with Li-Fraumeni syndrome and documented TP53 mutations. The expression and activity levels of PIN1 were determined in paired patient-derived lymphoblastoid cell lines. Results: Multivariate analysis of PIN1 variants with TP53 mutation status and selected clinical parameters is in progress. A comprehensive summary of observed associations will be presented. Conclusions: Demonstration of a modifying effect of PIN1 on the cancer phenotype conferred by a germline TP53 mutation may aid in the management of patients with Li-Fraumeni syndrome, including the implementation of patient-specific modifications of surveillance strategies for pre-symptomatic tumor detection. Citation Format: Anita Villani, Ana Novokmet, David Malkin. Investigating PIN1 as a genetic modifier in Li-Fraumeni syndrome. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 34. doi:10.1158/1538-7445.CANSUSC14-34
Unusual Reactions to Tetanus Toxoid
Authors: David F. Fardon
Journal: JAMA (1967)

FLUID TETANUS TOXOID is so widely used that, hopefully, almost everyone will receive injections of it. Allergic responses beyond mild, transient injection-site erythema and induration are fortunately rare. A rather severe systemic reaction and a unique local reaction are reported here. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 30-year-old woman dropped a heavy object on her left great toe a few minutes before treatment. She was found to have a shallow laceration at the base of the nail which required no sutures. The area was cleansed with hexachlorophene soap and a splint was applied. The skin over the left deltoid muscle was cleansed with alcohol and 0.5 ml of purified fluid tetanus toxoid from a single-dose needle-cartridge unit was injected into the muscle. She complained of mild itching and pain in the area of the injection site but returned to work in no apparent distress. No other medications were applied or
Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells.
Authors: G Zeng, M J Quon
Journal: Journal of Clinical Investigation (1996)

Hypertension is associated with insulin-resistant states such as diabetes and obesity. Nitric oxide (NO) contributes to regulation of blood pressure. To gain insight into potential mechanisms linking hypertension with insulin resistance we directly measured and characterized NO production from human umbilical vein endothelial cells (HUVEC) in response to insulin using an amperometric NO-selective electrode. Insulin stimulation of HUVEC resulted in rapid, dose-dependent production of NO with a maximal response of approximately 100 nM NO (200,000 cells in 2 ml media; ED50 approximately 500 nM insulin). Although HUVEC have many more IGF-1 receptors than insulin receptors (approximately 400,000, and approximately 40,000 per cell respectively), a maximally stimulating dose of IGF-1 generated a smaller response than insulin (40 nM NO; ED50 approximately 100 nM IGF-1). Stimulation of HUVEC with PDGF did not result in measurable NO production. The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME). Wortmannin (an inhibitor of phosphatidylinositol 3-kinase [PI 3-kinase]) inhibited insulin-stimulated production of NO by approximately 50%. Since PI 3-kinase activity is required for insulin-stimulated glucose transport, our data suggest that NO is a novel effector of insulin signaling pathways that are also involved with glucose metabolism.
Health Care and the Road to the Presidency in 2012
Authors: Joan Stephenson, Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
413 Functional features of HCV-specific CD8 mediated responses associated with different outcomes of HCV infection
Authors: M MALPELI, A PENNA, M PILLI, A ZERBINI, S CERIONI, A CAVALLI, A ORLANDINI, A CIVIDINI, M MASSARI, C FERRARI
Journal: Hepatology (2003)

The hepatitis C virus (HCV) production system consists of transfecting the human hepatoma cell line Huh7 with genomic HCV RNA (JFH1). To monitor HCV replication by fluorescence microscopy, we constructed a recombinant HCV clone expressing Azami-Green (mAG), a bright green fluorescent protein, by inserting the mAG gene into the nonstructural protein 5A (NS5A) gene; the resultant clone was designated JFH1-hmAG. The Huh-7.5.1 (a subclone of Huh7) cells transfected with JFH1-hmAG RNA were found to produce cytoplasmic NS5A-mAG, as readily visualized by fluorescence microscopy, and infectious virus, as assayed with the culture supernatant, indicating that JFH1-hmAG is infectious and replication-competent. Furthermore, the replication of this virus was inhibited by interferon alpha in a dose-dependent manner. These results suggest that JFH1-hmAG is useful for studying HCV life cycle and the mechanism of interferon’s anti-HCV action and for screening and testing new anti-HCV drugs.
The distribution of melanin in skin determined in vivo
Authors: P.J. Matts, P.J. Dykes, R. Marks
Journal: British Journal of Dermatology (2007)

There continues to be a need for objective, noninvasive methods to measure melanin concentration in vivo in human skin, independent of the confounding chromophore, haemoglobin. Existing methods are limited by a lack of specificity and inability to resolve the spatial distribution of these chromophores.To validate and calibrate the measurement of eumelanin in vivo using SIAscopic techniques, relating this with histologically and analytically determined eumelanin concentrations in nonsun-exposed skin from subjects of Fitzpatrick skin types I-VI.Observations were made in five subjects from each of the Fitzpatrick skin types I-VI using chromophore mapping by contact and noncontact SIAscopy and other noninvasive spectrophotometric means. Measurements were performed on the inner aspect of both upper arms. Subsequently two 4 mm punch biopsies were taken from the inner upper arm, one per arm after injection of local anaesthesia. One biopsy was fixed in formalin and processed for histology; specifically, sections were stained for melanin using a silver staining technique and the amount of melanin was graded microscopically. The other biopsy was subjected to an analytical assay to yield precise quantitative measures of melanin. The correlation between the different methods of melanin measurement was determined.Clear, significant correlations were obtained between contact and noncontact SIAscope-derived eumelanin values and actual eumelanin tissue content (determined both histologically and analytically), across the full range of Fitzpatrick skin types. There was no correlation between SIAscope-derived eumelanin and haemoglobin values, indicating efficient separation of the two chromophores.New contact and noncontact chromophore SIAscopic mapping techniques provide robust, rapid noninvasive measures of the concentration and spatial distribution of eumelanin in vivo, independent of haemoglobin, which correspond to true tissue values for this chromophore.
Abstract 4450: Comparison of structural elements in RasGRP3 and RasGRP1 controlling membrane interaction
Authors: Agnes Czikora, Noemi Kedei, Peter M. Blumberg
Journal: Cancer Research (2014)

Abstract RasGRP comprises a family of guanine nucleotide exchange factors that activate small GTPases, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP3 has a region homologous to the phosphoinositide binding region of RasGRP1. The objective of this study was to explore the hypothesis that this region of RasGRP3, like that of RasGRP1, indeed contributes to phosphoinositide binding. For these studies, we prepared full length RasGRP1/3, RasGRP1/3 C1 domain, and truncated (C1-SuPT-PT) RasGRP1 and RasGRP3 green fluorescent protein labeled constructs to transfect human prostate adenocarcinoma (LNCaP) and human cervical carcinoma (HeLa) cells. In HeLa cells, both RasGRP1 and RasGRP3 translocated to the endonuclear membranes, most probably to the Gogli in response to phorbol ester (PMA) and other agents. In the LNCaP cells, which are a PTEN mutant cell line with markedly elevated phosphoinositide levels, RasGRP1 translocates to the plasma membrane. In contrast, the full length RasGRP3 does not translocate to the plasma membrane even though it has a PT (plasma membrane-targeting) domain with a basic/hydrophobic cluster of amino acids (BHC) similar to that of RasGRP1. In parallel, we examined the translocation of the C1 domains of RasGRP1/3 and of the truncated RasGRP1/3 constructs, as well as the corresponding constructs with amino acid substitutions in the predicted phosphoinositide binding domain of RasGRP3. The RasGRP1 translocated to the plasma membrane in response to PMA. The C1 domain of RasGRP3 was insufficient for targeting RasGRP3 to the plasma membrane. However, truncated RasGRP3, which contains the PT domain, showed stronger translocation. Substituting amino acids (Asp647, Lys648 and Ala651) in the PT domain of full length RasGRP3 triggered the plasma membrane translocation in the LNCaP cells. We conclude that the differences in the BHC section of the PT domain of RasGRP3 play an important role in the membrane translocation of RasGRP3 and will reduce its sensitivity to membrane phosphoinositide levels. Citation Format: Agnes Czikora, Noemi Kedei, Peter M. Blumberg. Comparison of structural elements in RasGRP3 and RasGRP1 controlling membrane interaction. [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 4450. doi:10.1158/1538-7445.AM2014-4450
1998 equivalence of sensory responses to single and mixed volatile organic compounds at equimolar concentrations.
Authors: J D Prah
Journal: Environmental Health Perspectives (1998)

Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance.