tbuckley/cabot-search huggingface dataset:
Magnetic resonance imaging in the diagnosis and follow up of Takayasu's arteritis in children
Authors: Vinz P.R. Aluquin, S. A. Albano, F. Chan, C. Sandborg, P. T. Pitlick
Journal: Annals of the Rheumatic Diseases (2002)

Background: Takayasu9s arteritis (TA) has a mortality rate of up to 40% in children. Because the clinical presentation of TA is often non-specific, accurate and prompt diagnosis depends on a high degree of awareness and appropriate laboratory and imaging studies. Objective: To examine the use of advanced magnetic resonance imaging (MRI) in evaluating, gauging activity, and following the complications of TA. Methods and results: T<sub>1</sub> weighted, T<sub>2</sub> weighted, contrast enhanced MR images, and MR angiograms of the chest and abdomen were obtained in three children (age range 11–14 years). The MRI studies confirmed the diagnosis of active TA and were repeated to evaluate response to treatment. Two patients showed complete resolution of lesions found on MRI at six and 12 months9 follow up, while the third patient showed no significant improvement. Conclusion: MRI can be used to help establish the initial diagnosis of TA in children, and it can also be used to monitor disease activity and to guide treatment.
Gold nephropathy due to auranofin obscured by tolmetin pseudoproteinuria.
Authors: A P Wilson, P J Prouse, J M Gumpel
Journal: Annals of the Rheumatic Diseases (1984)

A 63-year-old woman with seropositive rheumatoid arthritis was successfully treated with auranofin for 12 months. Heavy proteinuria then developed and the drug was stopped. However, the proteinuria apparently became worse. This was later recognised to be a spurious effect due to the introduction of tolmetin. Renal biopsy showed a type I membranous glomerulonephropathy.
The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by <i>LKB1</i> Loss
Authors: Yan Feng, Ye Wang, Zuoyun Wang, Zhaoyuan Fang, Fei Li, Yijun Gao, Hongyan Liu, Tian Xiao, Fuming Li, Yang Zhou, Qiwei Zhai, Xiaolong Liu, Yihua Sun, Nabeel Bardeesy, Kwok-kin Wong, Haiquan Chen, Zhi-qi Xiong, Hongbin Ji
Journal: Cancer Research (2012)

Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here, we show that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes.
<i>KRAS</i> and <i>BRAF</i> Mutation Analysis in Metastatic Colorectal Cancer: A Cost-effectiveness Analysis from a Swiss Perspective
Authors: Patricia R. Blank, Holger Moch, Thomas D. Szucs, Matthias Schwenkglenks
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Monoclonal antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, have led to significant clinical benefits for metastatic colorectal cancer (mCRC) patients but have also increased treatment costs considerably. Recent evidence associates KRAS and BRAF mutations with resistance to EGFR antibodies. We assessed the cost-effectiveness of predictive testing for KRAS and BRAF mutations, prior to cetuximab treatment of chemorefractory mCRC patients. Experimental Design: A life-long Markov simulation model was used to estimate direct medical costs (€) and clinical effectiveness [quality-adjusted life-years (QALY)] of the following strategies: KRAS testing, KRAS testing with subsequent BRAF testing of KRAS wild-types (KRAS/BRAF), cetuximab treatment without testing. Comparison was against no cetuximab treatment (reference strategy). In the testing strategies, cetuximab treatment was initiated if no mutations were detected. Best supportive care was given to all patients. Survival times/utilities were derived from published randomized clinical trials. Costs were assessed from the perspective of the Swiss health system. Results: Average remaining lifetime costs ranged from €3,983 (no cetuximab) to €38,662 (no testing). Cetuximab treatment guided by KRAS/BRAF achieved gains of 0.491 QALYs compared with the reference strategy. The KRAS testing strategy achieved an additional gain of 0.002 QALYs compared with KRAS/BRAF. KRAS/BRAF testing was the most cost-effective approach when compared with the reference strategy (incremental cost-effectiveness ratio: €62,653/QALY). Conclusion: New predictive tests for KRAS and BRAF status are currently being introduced in pathology. Despite substantial costs of predictive testing, it is economically favorable to identify patients with KRAS and BRAF wild-type status. Clin Cancer Res; 17(19); 6338–46. ©2011 AACR.
MRSA bacteraemia in patients on arrival in hospital: a cohort study in Oxfordshire 1997-2003
Authors: David H Wyllie, Tim E A Peto, Derrick Crook
Journal: BMJ (2005)

Objective To describe the incidence and determinants of methicillin resistant and methicillin sensitive Staphylococcus aureus (MRSA and MSSA) bacteraemia in patients presenting to acute hospitals. Design Anonymised record linkage study with information from hospital information systems and microbiology databases. Setting One teaching hospital and one district general hospital in Oxfordshire. Participants All patients admitted to a teaching hospital 1 April 1997 to 31 March 2003 and to a district general hospital 1 April 1999 to 31 March 2003. Main outcome measures Detection of MRSA and MSSA from blood cultures taken during the first two days of admission to hospital. Results In the teaching hospital, there were 479 patients with MSSA and 116 with MRSA bacteraemia admitted from the community. Among this group, which comprised 24% of all hospital MRSA cases, 31% (36 cases) of patients had been admitted to renal, oncology, or haematology services for intensive day case therapy. The 69% remaining were most commonly patients admitted as medical or surgical emergencies. At least 91% had been in hospital previously; the median time since discharge was 46 days. About half of cases were in patients in whom MRSA had not been isolated before. Similar epidemiology was observed in the district general hospital. Conclusion Diagnostic algorithms and policies on use of antibiotics need to reflect the fact that a quarter of hospital MRSA cases occur in patients who have previously been in hospital and are subsequently readmitted.
Mapping-by-sequencing accelerates forward genetics in barley
Authors: Martin Mascher, Matthias Jost, Joel-Elias Kuon, Axel Himmelbach, Axel Aßfalg, Sebastian Beier, Uwe Scholz, Andreas Graner, Nils Stein
Journal: Genome biology (2014)

Abstract Mapping-by-sequencing has emerged as a powerful technique for genetic mapping in several plant and animal species. As this resequencing-based method requires a reference genome, its application to complex plant genomes with incomplete and fragmented sequence resources remains challenging. We perform exome sequencing of phenotypic bulks of a mapping population of barley segregating for a mutant phenotype that increases the rate of leaf initiation. Read depth analysis identifies a candidate gene, which is confirmed by the analysis of independent mutant alleles. Our method illustrates how the genomic resources of barley together with exome resequencing can underpin mapping-by-sequencing.
Enhanced Activity of the Myocardial Na <sup>+</sup> /H <sup>+</sup> Exchanger NHE-1 Contributes to Cardiac Remodeling in Atrial Natriuretic Peptide Receptor–Deficient Mice
Authors: Ana Kilic, Ana Velic, León J. De Windt, Larissa Fabritz, Melanie Voss, Danuta Mitko, Melanie Zwiener, Hideo A. Baba, Martin van Eickels, Eberhard Schlatter, Michaela Kuhn
Journal: Circulation (2005)

Background— Atrial natriuretic peptide (ANP), through its guanylyl cyclase-A (GC-A) receptor, not only is critically involved in the endocrine regulation of arterial blood pressure but also locally moderates cardiomyocyte growth. The mechanisms underlying the antihypertrophic effects of ANP remain largely uncharacterized. We examined the contribution of the Na + /H + exchanger NHE-1 to cardiac remodeling in GC-A–deficient (GC-A −/− ) mice. Methods and Results— Fluorometric measurements in isolated adult cardiomyocytes demonstrated that cardiac hypertrophy in GC-A −/− mice was associated with enhanced NHE-1 activity, alkalinization of intracellular pH, and increased Ca 2+ levels. Chronic treatment of GC-A −/− mice with the NHE-1 inhibitor cariporide normalized cardiomyocyte pH and Ca 2+ levels and regressed cardiac hypertrophy and fibrosis, despite persistent arterial hypertension. To characterize the molecular pathways driving cardiac hypertrophy in GC-A −/− mice, we evaluated the activity of 4 prohypertrophic signaling pathways: the mitogen-activated protein kinases (MAPK), the serine-threonine kinase Akt, calcineurin, and Ca 2+ /calmodulin-dependent kinase II (CaMKII). The results demonstrate that all 4 pathways were activated in GC-A −/− mice, but only CaMKII and Akt activity regressed during reversal of the hypertrophic phenotype by cariporide treatment. In contrast, the MAPK and calcineurin/NFAT signaling pathways remained activated during regression of hypertrophy. Conclusions— On the basis of these results, we conclude that the ANP/GC-A system moderates the cardiac growth response to pressure overload by preventing excessive activation of NHE-1 and subsequent increases in cardiomyocyte intracellular pH, Ca 2+ , and CaMKII as well as Akt activity.
Points: Infective endocarditis: a preventable disease?
Authors: P. Lyn
Journal: BMJ (1985)

Morris mentions several precipitating causes of infective endocarditis culled from the studies by Bayliss et al' 2 (25 May, p 1532).I would like to draw attention to an important and often forgotten route of introduction of sepsis in patients at risk in hospitals- from intravenous drip or venepuncture sites. 3Recently, we saw two children aged 11 and 12 who presented with relapse of their rheumatic fever with flitting arthralgia, pericardial rubs, and fever.These symptoms subsided on aspirin and bed rest but a week later a high swinging fever was noted, with changing heart murmurs and evidence of heart failure in one case.One of the blood cultures subsequently grew a penicillin resistant Staphylococcus aureus.The child died despite high dose intravenous penicillin, cefuroxime, and cloxacillin.In the second case no pathogens were grown despite repeated blood cultures, but the fever was later controlled with cefuroxime, cloxacillin, and gentamycin.The most likely site of entry of the organism was through the drip site, where both children had developed mild cellulitis, and neither had received any antibiotics.Poorly cleaned venepuncture sites for routine blood investigations were another possible site of entry.Routine setting up of drips in casualty is a common practice and is often far from being an aseptic procedure.Those who practise this must realise that it is not without risk, especially to patients with valvular heart disease.We believe that care with cleaning the drip site with iodine, introduction of the intravenous cannula by an aseptic technique, and regular change of drip sites before cellulitis sets in are the best ways of preventing infective endocarditis in patients at risk.
System of Scientific Advisory Boards at the National Cancer Institute
Authors: P. C. Rambaut, B. S. Bynum, V. T. DeVita
Journal: JNCI Journal of the National Cancer Institute (1989)

This article describes the Boards of Scientific Counselors of the National Cancer Institute (NCI) and focuses on their role and their relationship to the other advisory boards used by NCI in the governance of the National Cancer Program. The advisory boards consist of the President's Cancer Panel, the National Cancer Advisory Board, the Boards of Scientific Counselors of the four programmatic divisions, and the Frederick Cancer Research Facility Advisory Committee. Each of these boards is an element of the organized system by which NCI obtains its scientific advice. The system provides a forum in which scientific directions and priorities are debated, ideas for research initiatives compete, and advice is given on the allocation of research and training funds. This article is a sequel to a number of earlier papers reviewing the corporate management structure that has been developed over the past decade at NCI.
Modern surgical approaches to female reproductive tract
Authors: T Tulandi
Journal: Human Reproduction Update (1996)

Laparoscopic and hysteroscopic surgery have changed the management of many gynaecological disorders. Procedures that previously required a long duration of hospitalization can now be done on an outpatient basis or with a short hospital stay. Surgical treatment remains the definitive and universal treatment of ectopic pregnancy and it can be safely done by laparoscopy. Most reproductive operations are done by laparoscopy and the results appear to be similar to those obtained with laparotomy. Those needing a laparotomy will be better treated by in-vitro fertilization. Laparoscopic ovarian drilling is a viable alternative for infertile women with polycystic ovarian syndrome. Most ovarian cysts and endometriosis should be treated by laparoscopy. Although uterine myomas can be removed by laparoscopy, the uterine integrity after the procedure is questionable. Surgery should be reserved for women who have completed their family or those with pedunculated or shallow intramural myomas. Alternatively, a laparoscopically assisted myomectomy can be done. For laparoscopic hysterectomies for benign lesions, supracervical hysterectomy appears to be a good option. Hysteroscopy has changed our management, particularly for abnormal uterine bleeding. A submucous myoma and polyp can be removed by hysteroscopy and, as an alternative to hysterectomy, endometrial ablation can be done. In the future, most procedures will be done by endoscopy and laparotomy will be reserved only for selected cases.
Tachyphylaxis to angiotensin in man
Authors: E. R. Lumbers, R. F. Whelan
Journal: Cardiovascular Research (1970)

Neither angiotensin acid nor angiotensin amide infused repeatedly or continuously into the brachial artery at the elbow induced tachyphylaxis of the forearm and hand vessels. Similar results were obtained with noradrenaline and acetylcholine, whereas tachyphylaxis was readily induced to intra-arterial infusions of vasopressin. It is concluded that tachyphylaxis plays no role in the vascular response to angiotensin in normal subjects and that the reduced vascular response to angiotensin seen in patients with reno-vascular hypertension is not solely due to high concentrations of circulating angiotensin.
Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure
Authors: P. Christian Schulze, Juergen Kratzsch, Axel Linke, Nina Schoene, Volker Adams, Stephan Gielen, Sandra Erbs, Sven Moebius‐Winkler, Gerhard Schuler
Journal: European Journal of Heart Failure (2003)
Inhibition of HER-2/neu Kinase Impairs Androgen Receptor Recruitment to the Androgen Responsive Enhancer
Authors: Yuanbo Liu, Samarpan Majumder, Wesley McCall, Carolyn I. Sartor, James L. Mohler, Christopher W. Gregory, H. Shelton Earp, Young E. Whang
Journal: Cancer Research (2005)

Abstract Advanced prostate cancer invariably recurs despite androgen deprivation therapy. The androgen receptor (AR) likely plays a key role in this progression and in the continued survival and proliferation of prostate cancer cells in the low androgen environment. Cross-talk with growth factor receptors, such as epidermal growth factor receptor (EGFR) family, has been postulated as a potential mechanism to activate AR in recurrent prostate cancer. We have investigated the role of HER-2/neu (ErbB-2) tyrosine kinase in AR function by characterizing the effect of inhibiting endogenous HER-2 activity in LNCaP cells. We used two independent methods, expression of intracellular single-chain antibody against HER-2 and treatment with a novel dual EGFR/HER-2 kinase inhibitor GW572016 (lapatinib). Expression of intracellular HER-2 antibody scFv-5R and treatment with GW572016 inhibited HER-2 signaling. This HER-2 inhibition led to impairment of AR-mediated functions, such as androgen-stimulated growth and the induction of endogenous prostate-specific antigen (PSA) mRNA and protein. Androgen-stimulated recruitment of AR and histone acetylation at the androgen responsive enhancer of the PSA gene, detected by chromatin immunoprecipitation analysis, were impaired by HER-2 inhibition. GW572016 was more potent in its ability to inhibit PSA expression and AR recruitment and histone acetylation than the EGFR-selective kinase inhibitor ZD1839 (gefitinib), consistent with the HER-2 kinase playing the major role in AR regulation. These results show that HER-2 signaling is required for optimal transcriptional activity of AR in prostate cancer cells and suggest that HER-2 inhibition may provide a novel strategy to disrupt AR function in prostate cancer.
Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register
Authors: J. Lyth, J. Hansson, C. Ingvar, E. Månsson-Brahme, P. Naredi, U. Stierner, G. Wagenius, C. Lindholm
Journal: British Journal of Dermatology (2012)

Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark's level of invasion for risk stratification of T1 cutaneous melanoma.From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13,026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11,165 patients with complete data.Ulceration, tumour thickness and Clark's level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2-1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0-7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2-21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark's level of invasion, three distinct prognostic subgroups were identified.
Modulation of Extracellular Superoxide Dismutase Expression by Angiotensin II and Hypertension
Authors: Tohru Fukai, Martin R. Siegfried, Masuko Ushio-Fukai, Kathy K. Griendling, David G. Harrison
Journal: Circulation Research (1999)

Angiotensin II and hypertension increase vascular oxidant stress. We examined how these might affect expression of the extracellular superoxide dismutase (ecSOD), a major form of vascular SOD. In mice, angiotensin II infusion (1.1 mg/kg for 7 days) increased systolic blood pressure from 107+/-3 to 152+/-9 mm Hg and caused a 3-fold increase in ecSOD, but there was no change in the cytosolic Cu/Zn SOD protein, as determined by Western blot analysis. This was associated with a similar increase in ecSOD mRNA as assessed by RNase protection assay and was prevented by losartan. Induction of ecSOD by angiotensin II was not due to hypertension alone, because hypertension caused by norepinephrine (5.6 mg. kg-1. d-1) had no effect on ecSOD. Similarly, exposure of mouse aortas to angiotensin II (100 nmol/L) in organoid culture increased ecSOD by approximately 2-fold. In the organoid culture, angiotensin II-induced upregulation of ecSOD was prevented by losartan (10 micromol/L) and PD985059 (30 micromol/L), a specific inhibitor of p42/44 MAP kinase kinase. Angiotensin II activates the NADH/NADPH oxidase; however, diphenyleneiodonium chloride (10 micromol/L), an inhibitor of this oxidase, did not prevent p42/44 MAP kinase phosphorylation or ecSOD induction by angiotensin II. Finally, in human aortic smooth muscle cells, angiotensin II moderately increased transcriptional rate (as assessed by nuclear run-on analysis) but markedly increased ecSOD mRNA stability. Thus, angiotensin II increases ecSOD expression independent of hypertension, and this increase involves both an increase in ecSOD transcription and stabilization of ecSOD mRNA. This effect of angiotensin II on ecSOD expression may modulate the oxidative state of the vessel wall in pathological processes in which the renin-angiotensin system is activated.
Epirubicin Increases Long-Term Survival in Adjuvant Chemotherapy of Patients With Poor-Prognosis, Node-Positive, Early Breast Cancer: 10-Year Follow-Up Results of the French Adjuvant Study Group 05 Randomized Trial
Authors: Jacques Bonneterre, Henri Roché, Pierre Kerbrat, Alain Brémond, Pierre Fumoleau, Moïse Namer, Marie-Josèphe Goudier, Simon Schraub, Pierre Fargeot, Isabelle Chapelle-Marcillac
Journal: Journal of Clinical Oncology (2005)

The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05.We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy.Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively.Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.