tbuckley/cabot-search huggingface dataset:
Abstract P5-02-09: Ki67-labelling index of luminal breast cancers: Agreement of core biopsy and surgical specimen results
Authors: Cornelia M Focke, Thomas Decker
Journal: Cancer Research (2015)

Abstract Objective: To highlight the agreement between Ki67-Labelling indices (LIs) of core biopsies (CB) and related surgical specimens (SSP) in luminal breast cancers (BCs) adopting the recommendations of the St Gallen Consensus Conference 2013 and the International Ki67 In Breast Cancer Working Group. Methods: We investigated CBs and the related SSPs of 220 luminal Her2 negative BCs. To assess the Ki67-LI a total of 510 tumour cells including hot spot, cold spot and an area of intermediate proliferation was counted by one observer. Every positive nucleus was counted, independent of the staining intensity. A Ki67-LI cut-off &amp;lt;20% as recommended by the St Gallen Consensus was used to define luminal A BCs. Agreement between CB and SSP, rates of under- and overestimation, and positive predictive values (PPV) of CB based subtyping (luminal A vs. B) were calculated. Results: In SSP 140/220 BCs (64%) were luminal A, 80 (36%) were luminal B. The agreement between CB and OP was 77% (169/220). Overestimation of proliferation in CB occurred in 10 (4%) and underestimation in 41 (19%) cases. The PPVs of CB based Ki67-LI for luminal A and luminal B were 0.76 (130/171) and 0.79 (39/49), respectively. Conclusion: The agreement of CB and SSP based subtyping of luminal BCs is generally high. However, underestimation of proliferation in CB may result in subtype misclassification in almost one fifth of luminal Her2 negative luminal tumours. Citation Format: Cornelia M Focke, Thomas Decker. Ki67-labelling index of luminal breast cancers: Agreement of core biopsy and surgical specimen results [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-09.
A "common sense revolution" for UK health care?
Authors: J. Dixon
Journal: BMJ (2000)

For the NHS, just like English football, it's been a salutary month. At home some of us might just convince ourselves that the NHS is the envy of the world. But playing away, where we are compared directly with other nations, our performance is found wanting. Ranked 18th overall in the World Health Organization's worldwide league of healthcare systems, we can argue with the referee about the rules.1 But the sneaking suspicion must be that the result is about right; indeed it could have been much worse. Other countries may spend more, be less fair and less efficient, have more trouble containing costs, and have messier organisations than the NHS, but somehow they provide a better overall standard of health care. How do they do it?

At a macro level, the difference between the United Kingdom and other European countries is obvious: the United Kingdom spends less on health care and there is far less private financing and private provision. The benefits of more expenditure are comparatively clear: more and better paid staff, more and newer equipment, and …
Abstract 92: Efficacy of Continuous Venovenous Hemodiafiltration on Survival of Cardiac Arrest in Humans
Authors: Koichiro Shinozaki, Yasunori Sato, Lance B Becker, Shigeto Oda, Hiroyuki Hirasawa
Journal: Circulation (2014)

Introduction: The efficacy of continuous venovenous hemodiafiltration (CVVHDF) on patients suffering cardiac arrest (CA) is unclear. Objective: To identify any efficacy of CVVHDF on post cardiac arrest syndrome (PCAS) in humans. Methods: This was a multicenter study conducted between 2006-09 in Chiba, Japan, involving non-trauma CA adult patients. Patients admitted to acute care units were included. The primary outcome was mortality through the end of the study. Cerebral Performance Category (CPC) score was recorded at 6 months and the blood levels of IL-6 on admission, at 6hr, and 24hr after CA were measured as the secondary outcomes. The application of CVVHDF was left to each physician. The dialysate flow and filtration rate were set at 10-20mL/kg/h and 6-10mL/kg/h, respectively. We evaluated the effect of CVVHDF on survival using the Kaplan-Meier method. A Cox proportional hazard model with a step-wise selection procedure was used to identify independent variables associated with survival time. A matching process based on propensity-score was done to compare neurological outcome and blood IL-6 levels between groups. Results: A total of 227 patients were included. The survival time in the CVVHDF group (n=33) was significantly longer than non-CVVHDF group (long rank, p&lt;0.001). Three factors were identified as indicators of earlier death; Initial ECG of non-VF, whether or not CA occurred before EMS arrival, and if therapeutic hypothermia was used. When being adjusted for those 3 factors, there was no significant difference in association of CVVHDF with mortality (hazard ratio, 1.33; 95% confidential interval, 0.81-2.18; p=0.26). Between the matched groups, there were no differences in the number of patients with good neurological outcome (p=0.24) and in IL-6 levels at 24hr (p=0.08). IL-6 levels on admission (median and interquartile, 69pg/mL [25-193]) and at 6hr (116pg/mL [33-499]) of non-CVVHDF group were significantly lower than those (350pg/mL [142-1493] and 247pg/mL [89-1104]) of CVVHDF group (p=0.002 and p=0.035, respectively). Conclusions: We found no association with the use of CVVHDF and mortality of PCAS patients. The use of CVVHDF was not seen to lower the circulating levels of IL-6 levels in this cohort of patients.
Abstract ES6-3: Tumor infiltrating lymphocytes in breast cancer
Authors: Sherene Loi
Journal: Cancer Research (2015)

Abstract Interest in evaluating the presence of tumor infiltrating lymphocytes (TILs) in breast cancer is growing due to robust data supporting significant prognostic associations as well as the success of the new T cell checkpoint inhibitors in other solid organ cancer types. The positive prognostic associations between TILs present at diagnosis in triple negative (TN) and HER2-overexpressing breast cancer and better outcomes after standard adjuvant therapy strongly suggests that these breast cancer subtypes will be amendable to immunotherapeutic approaches. Current research suggests that TILs represent pre-existing host anti-tumor immunity, with the data reporting that the more TILs that are present in the tumor at diagnosis, the stronger the pre-existing immune response and better clinical outomes. However, only a minority of patients present with high levels of TILs at diagnosis. Current data also reports that biopsies from metastatic disease still can contain significant amounts of TILs. This suggests that these patients can generate an immune response even in advanced disease, albeit weak, as the median values of TILs present seem to be less. This presentation will discuss the data on the prognostic associations of TILs, our current understanding about the content of TILs in breast cancer and how they could be potentially triggered and/or suppressed. I will also discuss our recently published guidelines on how to evaluate TILs in breast cancer (Salgado R et al, 2014). Furthermore I will speculate on how we could potentially augment or re-kick start a more effective anti-tumor immune response in patients with breast cancer. I will also talk about the potential future clinical utility of TILs in breast cancer- it is currently not recommended that TILs are used in treatment decision-making concerning chemotherapy or no chemotherapy in TN breast cancer or trastuzuamb vs no trastuzumab in HER2-positive disease. Phase II efficacy data evaluating T cell checkpoint inhibitors is not yet available in advanced TN and HER2-positive breast cancer, however, phase I data using monotherapy T cell checkpoint inhibition in heavily pre-treated disease seems promising with objective responses meeting RECIST criteria seen. It is unclear what the best biomarker will be in breast cancer patients for immunotherapeutic approaches, but targeting patients with some degree of already pre-existing anti-tumor immunity seems logical. Citation Format: Sherene Loi. Tumor infiltrating lymphocytes in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES6-3.
C-Reactive Protein and Cerebral Small-Vessel Disease
Authors: E. J. van Dijk, N. D. Prins, S. E. Vermeer, H. A. Vrooman, A. Hofman, P. J. Koudstaal, M. M.B. Breteler
Journal: Circulation (2005)

Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts.We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts.Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.
PERITONITIS COMPLICATING A CASE OF NEPHROSIS: TREATMENT WITH PENICILLIN INTRAPERITONEALLY
Authors: L LEVY
Journal: Annals of Internal Medicine (1947)

Case Reports1 September 1947PERITONITIS COMPLICATING A CASE OF NEPHROSIS: TREATMENT WITH PENICILLIN INTRAPERITONEALLYLOUIS LEVY II, M.D.LOUIS LEVY II, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-27-3-467 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCASE REPORTJ. G., white male, aged 12 years, was admitted on December 10, 1944 with a chief complaint of generalized swelling. Nine days previously the patient had developed a "cold" which continued for one week and was accompanied by a low grade fever and general malaise. The patient then noticed a progressive swelling beginning first in the eyelids, and later involving the ankles, legs, hands, and abdomen. The rest of his history was noncontributory.Physical examination on admission revealed temperature of 99° F., respirations 30, pulse 120, and blood pressure 120 mm. of mercury systolic and 70 mm. diastolic.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New Orleans, Louisiana*Received for publication March 16, 1946.From the Department of Medicine, Louisiana State University School of Medicine, and the Charity Hospital of Louisiana at New Orleans, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1947Volume 27, Issue 3Page: 467-469KeywordsAnklesBlood pressureFeversHeart rateHospital medicineInflammationPenicillinPeritonitisRespirationTemperature ePublished: 1 December 2008 Issue Published: 1 September 1947 PDF downloadLoading ...
Monocytic and promyelocytic myeloid‐derived suppressor cells may contribute to <scp>G</scp>‐<scp>CSF</scp>‐induced immune tolerance in haplo‐identical allogeneic hematopoietic stem cell transplantation
Authors: Meng Lv, Xiao‐Su Zhao, Yue Hu, Ying‐Jun Chang, Xiang‐Yu Zhao, Yuan Kong, Xiao‐Hui Zhang, Lan‐Ping Xu, Kai‐Yan Liu, Xiao‐Jun Huang
Journal: American Journal of Hematology (2014)

We investigated the effects of granulocyte colony‐stimulating factor (G‐CSF) on monocytic (M), promyelocytic (P), and granulocytic (G) myeloid‐derived suppressor cells (MDSCs) both in bone marrow and peripheral blood of 20 healthy donors and the association of MDSCs subgroups with acute and chronic graft‐versus‐host disease (aGvHD/cGvHD) in 62 patients who underwent haplo‐identical allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Patients who received a higher absolute counts of M‐MDSCs or P‐MDSCs exhibited lower incidence of grade II–IV aGvHD ( P = 0.001; P = 0.031) and extensive cGvHD ( P = 0.011; P = 0.021). In the multivariate analysis, absolute counts of MDSCs in allografts emerged as independent factors that reduced the occurrence of grade II–IV aGvHD (M‐MDSCs: HR = 0.087, 95% CI = 0.020–0.381, P = 0.001; P‐MDSCs: HR = 0.357, 95% CI = 0.139–0.922, P = 0.033) and extensive cGvHD (M‐MDSCs: HR = 0.196, 95% CI = 0.043–0.894, P = 0.035; P‐MDSCs: HR = 0.257, 95% CI = 0.070–0.942, P = 0.04). Delayed M‐MDSC reconstitution was associated with aGvHD onset. The 3‐year cumulative incidence of transplant related mortality and relapse, 3‐year probability of disease‐free survival, and overall survival did not differ significantly between these subgroups. Our results suggested that G‐CSF‐induced immune tolerance may be mediated by M/P‐MDSCs in allo‐HSCT. Am. J. Hematol. 90:E9–E16, 2015. © 2014 Wiley Periodicals, Inc.
Models versus descriptions: Real differences and language differences
Authors: Jeroen G. W. Raaijmakers, Richard M. Shiffrin
Journal: Behavioral and Brain Sciences (2003)

We argue that an approach that treats short-term memory as activated long-term memory is not inherently in conflict with information recycling in a limited-capacity or working-memory store, or with long-term storage based on the processing in such a store. Language differences aside, real model differences can only be assessed when the contrasting models are formulated precisely.
Brief Report: Lumbar Spinal Stenosis Is a Highly Genetic Condition Partly Mediated by Disc Degeneration
Authors: Michele C. Battié, Alfredo Ortega‐Alonso, Riikka Niemelainen, Kevin Gill, Esko Levalahti, Tapio Videman, Jaakko Kaprio
Journal: Arthritis & Rheumatology (2014)

Objective. Lumbar spinal stenosis is one of the most commonly diagnosed spinal disorders in older adults. Although the pathophysiology of the clinical syndrome is not well understood, a narrow central canal or intervertebral foramen is an essential or defining feature. The aim of the present study was to estimate the magnitude of genetic versus environmental influences on central lumbar spinal stenosis and to investigate disc degeneration and stature or bone development as possible genetic pathways.Methods. A classic twin study with multivariate analyses considering lumbar level and other covariates was conducted. The study sample comprised 598 male twins (147 monozygotic and 152 dizygotic pairs), 35-70 years of age, from the population-based Finnish Twin Cohort. The primary phenotypes were central lumbar stenosis as assessed qualitatively on magnetic resonance imaging (MRI) and quantitatively measured dural sac cross-sectional area. Additional phenotypes (to examine possible genetic pathways) included disc bulging and standing height, as an indicator of overall skeletal size or development.Results. The heritability estimate (h²) for qualitatively assessed central lumbar spinal stenosis on MRI was 66.9% (95% confidence interval [95% CI] 56.8,74.5). The broad-sense heritability estimate for dural sac cross-sectional area was 81.2% (95% CI 74.5, 86.1),with a similar magnitude of genetic influences across lumbar levels (h²=72.4–75.6). The additive genetic correlation of quantitatively assessed stenosis and disc bulging was extremely high. There was no indication of shared genetic influences between stenosis and stature.Conclusion. Central lumbar spinal stenosis and associated dural sac dimensions are highly genetic, and disc degeneration (bulging) appears to be one pathway through which genes influence spinal stenosis.
The role of activated orphan nuclear receptor, PXR, in cancer cell growth and drug metabolism
Authors: Divya Gupta, Hongwei Wang, Hao Li, Michael Sinz, Sean Kim, Michelle Rudek, Jeffery Staudinger, Gary Goldberg, Sridhar Mani
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4495 

Objective: The orphan nuclear receptor, PXR, regulates cancer drug metabolism by affecting the transcription and translation of CYP3A4 and MDR1 genes and may affect cancer cell growth. Controlling the activation of PXR may regulate these processes.

Experimental procedures: In vitro RNA, protein and transcription based assays in hepatocellular and colon cancer cell lines and PXR wild-type and null mouse studies were performed to demonstrate the effects of ketoconazole on ligand-activated PXR-mediated gene transcription and translation. We also performed the MTT assay to study cell proliferation in ovarian and colon cancer cells with activation of PXR by specific ligands.

Results: Human PXR (hPXR) agonists, paclitaxel and rifampicin, significantly increased the expression of CYP3A4 mRNA when compared to DMSO-treated cells in cell lines derived from hepatocellular carcinoma (HepG2) and colon cancer (LS174T). When these same cells were treated with ketoconazole alone, a modest increase in CYP3A4 mRNA was observed when compared to DMSO controls. However, when ketoconazole was combined with either paclitaxel or rifampicin, the CYP3A4 expression decreased by >90% compared to cells treated with paclitaxel or rifampicin alone. This finding was further confirmed by co-transfecting HepG2 and Cos-1 cells with a plasmid expressing hPXR protein and a reporter plasmid containing CYP3A4 promoter tagged with luciferase gene. There was a dose-dependent decrease in hPXR activation by ketoconazole. We also investigated whether paclitaxel drug levels are affected by PXR in mice. C57BL/6 PXR (+/+) and PXR (-/-) mice were given 20mg/kg paclitaxel intravenously for 5 days. In PXR (+/+) mice, the mean day 1 and day 5 paclitaxel AUC were 28116 and 13582 as compared to day 1 and day 5 paclitaxel AUC of 20205 and 35186 in PXR (-/-) mice. These results suggest that PXR activation by xenobiotic ligands reduces the blood paclitaxel levels in mice by inducing its metabolism and efflux. We further studied the effect of PXR activation on ovarian (SKOV-3) and colon (LS174T) cancer cell lines. Activating PXR by rifampicin and hyperforin (the active metabolite of St. John’s Wort), resulted in cancer cell proliferation. An investigational drug, T1317, which has been shown to activate PXR, confirmed these results.

Conclusion: These in vitro and mouse studies demonstrate that ligand-mediated activation of PXR is associated with variable drug metabolism, reduced blood levels of chemotherapeutic drugs, and cancer cell proliferation. Developing target-specific analogs of ketoconazole may result in more consistent drug levels and decreased cell proliferation in solid tumors.
Localization and Significance of γ-Glutamyltranspeptidase in Normal and Neoplastic Mouse Skin
Authors: Lawrence M. De Young, W. L. Richards, W. Bonzelet, L. L. Tsai, R. K. Boutwell
Journal: Cancer Research (1978)

The suggestion that elevated γ-glutamyltranspeptidase (GGT) activity could be a marker for hepatic neoplasia has prompted us to investigate the role of this enzyme in normal and neoplastic mouse skin. In normal skin, as determined histochemically with N -(γ-l-glutamyl)-4-methoxy-2-naphthylamide as substrate, GGT was found only in the lower epithelium of growing hair follicles. GGT activity was never detected in the interfollicular epidermis of 1-day-old prenatal, newborn, or adult skin. Whole-skin enzyme activity measured biochemically, with l-γ-glutamyl- p -nitroanilide as substrate, was elevated about 9-fold during periods of hair growth. GGT activity rose and then fell abruptly as the mice progressed through the growing phase and then the resting phase of the hair growth cycle.

Skin tumors were induced by initiation with 7,12-dimethylbenz[ a ]anthracene followed by promotion with 12- O -tetradecanoylphorbol-13-acetate. Histochemically, GGT was not present in eight benign papillomas examined. However, single epithelial cells, islands of epithelial cells, and/or follicle-like structures were intensely GGT positive in seven of eight malignant squamous carcinomas examined. The association of GGT activity with normal hair growth and its presence in squamous carcinomas raises the following interesting possibilities: ( a ) aberrant gene activation in malignant interfollicular epidermis; ( b ) a recruitment of follicular cells by invasive malignant interfollicular epidermis; ( c ) a follicular origin for the GGT-positive carcinoma.
Cancer Drug and Progeria
Authors: Tracy Hampton
Journal: JAMA (2005)

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
Lariat—Small Step or Giant Leap?
Authors: Paul D. Varosy
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal