tbuckley/cabot-search huggingface dataset:
Capecitabine Versus Classical Cyclophosphamide, Methotrexate, and Fluorouracil As First-Line Chemotherapy for Advanced Breast Cancer
Authors: Martin R. Stockler, Vernon J. Harvey, Prudence A. Francis, Michael J. Byrne, Stephen P. Ackland, Bernie Fitzharris, Guy Van Hazel, Nicholas R.C. Wilcken, Peter S. Grimison, Anna K. Nowak, M. Corona Gainford, Akiko Fong, Lisa Paksec, Tatiana Sourjina, Diana Zannino, Val Gebski, R. John Simes, John F. Forbes, Alan S. Coates
Journal: Journal of Clinical Oncology (2011)

We compared oral capecitabine, administered intermittently or continuously, versus classical cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for women with advanced breast cancer unsuited to more intensive regimens.Three hundred twenty-three eligible women were randomly assigned to capecitabine administered intermittently (1,000 mg/m(2) twice daily for 14 of every 21 days; n = 107) or continuously (650 mg/m(2) twice daily for 21 of every 21 days; n = 107), or to classical CMF (oral cyclophosphamide 100 mg/m(2) days 1 to 14 with intravenous methotrexate 40 mg/m(2) and fluorouracil 600 mg/m(2) on days 1 and 8 every 28 days; n = 109). The primary end point was quality-adjusted progression-free survival (PFS); secondary end points included PFS, overall survival (OS), objective tumor response, and adverse events. Intermittent and continuous capecitabine were to be compared first and, if similar (P > .05), combined for definitive comparisons versus CMF.Quality-adjusted PFS (P = .2), objective tumor response rate (20%; P = .8), and PFS (median, 6 months; hazard ratio [HR], 0.86; 95% CI, 0.67 to 1.10; P = .2) were similar in women assigned capecitabine versus CMF. OS was longer in women assigned capecitabine rather than CMF (median, 22 v 18 months; HR, 0.72; 95% CI, 0.55 to 0.94; P = .02). Febrile neutropenia, infection, stomatitis, and serious adverse events were more common with CMF; hand-foot syndrome was more common with capecitabine.Capecitabine improved OS by being similarly active, less toxic, and more tolerable than CMF. Capecitabine is a good first-line chemotherapy option for women with advanced breast cancer who are unsuited to more intensive regimens.
Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment
Authors: C. Marcais
Journal: Journal of Clinical Investigation (2005)

While type 1 hyperlipidemia is associated with lipoprotein lipase or apoCII deficiencies, the etiology of type 5 hyperlipidemia remains largely unknown. We explored a new candidate gene, APOA5, for possible causative mutations in a pedigree of late-onset, vertically transmitted hyperchylomicronemia. A heterozygous Q139X mutation in APOA5 was present in both the proband and his affected son but was absent in 200 controls. It was subsequently found in 2 of 140 cases of hyperchylomicronemia. Haplotype analysis suggested the new Q139X as a founder mutation. Family studies showed that 5 of 9 total Q139X carriers had hyperchylomicronemia, 1 patient being homozygote. Severe hypertriglyceridemia in 8 heterozygotes was strictly associated with the presence on the second allele of 1 of 2 previously described triglyceride-raising minor APOA5 haplotypes. Furthermore, ultracentrifugation fraction analysis indicated in carriers an altered association of Apoa5 truncated and WT proteins to lipoproteins, whereas in normal plasma, Apoa5 associated with VLDL and HDL/LDL fractions. APOB100 kinetic studies in 3 severely dyslipidemic patients with Q139X revealed a major impairment of VLDL catabolism. Lipoprotein lipase activity and mass were dramatically reduced in dyslipidemic carriers, leading to severe lipolysis defect. Our observations strongly support in humans a role for APOA5 in lipolysis regulation and in familial hyperchylomicronemia.
Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients
Authors: L. Machet, F. Nemeth-Normand, B. Giraudeau, A. Perrinaud, J. Tiguemounine, J. Ayoub, D. Alison, L. Vaillant, G. Lorette
Journal: British Journal of Dermatology (2005)

Background There is still lack of consensus regarding the most effective follow-up for stage I and II melanoma patients although some consensus conferences have provided guidelines stating that clinical examination should be the standard. Objectives Our aim was to study the value of adding ultrasound lymph node examination (7·5 MHz) to the routine clinical examination recommended by French guidelines in melanoma follow-up. Methods A cohort of melanoma patients was enrolled between 1 July 1995 and 1 July 2000 in a follow-up protocol including clinical examination performed four times a year for thick melanomas (Breslow index ≥ 1·5 mm) and twice a year for thin melanomas (Breslow index < 1·5 mm) according to French guidelines, and ultrasound lymph node examination performed every 6 months for thick melanomas and every year for thin melanomas. Follow-up was continued up to 1 July 2003. When clinical or ultrasound examination indicated signs of node recurrence, surgical biopsy of the involved node was performed. When ultrasound examination was only suspicious, another ultrasound examination was performed within the following 3 months. The results of both clinical and ultrasound examinations were compared with histopathology examination when node biopsy was performed. Results Ultrasound follow-up was performed for 373 patients (213 females and 160 males). Mean age at diagnosis of melanoma was 59 years (range 14–90, SD 15). In total, 1909 ultrasound examinations combined with clinical examination were analysed. Node biopsy was performed in 65 patients and demonstrated melanoma metastases in 54. Sensitivity of clinical examination and ultrasound examination was 71·4%[95% confidence interval (CI) 55·4–84·3] and 92·9 (95% CI 80·5–98·5), respectively, P = 0·02. Specificity of clinical examination and ultrasound examination was 99·6% (95% CI 99·2–99·8) and 97·8% (95% CI 97·0–98·4), respectively. Despite this apparent superiority of ultrasound examination over palpation, only 7·2% of the patients really benefited from ultrasound examination (earlier lymph node metastasis detection or avoidance of unnecessary surgery), while 5·9% had some deleterious effect from ultrasound examination (unnecessary stress caused by repetition of ultrasound examination for benign lymph nodes, useless removal of benign lymph node). Conclusions This study confirms the greater sensitivity of ultrasound examination to clinical examination in the diagnosis of node metastases from cutaneous melanoma. However, the place of ultrasound in routine follow-up is at least questionable as only a very small proportion of patients (1·3%) really benefited from adding ultrasound examination to clinical examination.
Early Versus Late Functional Outcome After Successful Percutaneous Pulmonary Valve Implantation
Authors: Philipp Lurz, Johannes Nordmeyer, Alessandro Giardini, Sachin Khambadkone, Vivek Muthurangu, Silvia Schievano, Jean-Benoit Thambo, Fiona Walker, Seamus Cullen, Graham Derrick, Andrew M. Taylor, Philipp Bonhoeffer
Journal: Journal of the American College of Cardiology (2011)
Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis; correlation with clinical features.
Authors: F C Hay, L J Nineham, R Perumal, I M Roitt
Journal: Annals of the Rheumatic Diseases (1979)

Solid phase radioimmunometric methods have been used to assay immune complexes and IgG and IgM antiglobulins in paired samples of synovial fluid and serum from patients with rheumatoid arthritis (RA) or osteoarthrosis. Over 60% of RA patients had some increase in complexes in their sera, while nearly 90% had synovial fluid complexes. Moreover, the levels of complexes within the joint were much higher than in the serum. Both IgG and IgM antiglobulins were raised in most RA patients. The levels of IgG antiglobulins--and to a less extent IgM antiglobulins--were nearly always higher in synovial fluid than in the corresponding serum sample.A strong correlation was found between the levels of immune complex and IgG antiglobulin. A marked association was seen between the presence of subcutaneous nodules and increased IgG antiglobulins.
Alcohol Consumption Before and After Breast Cancer Diagnosis: Associations With Survival From Breast Cancer, Cardiovascular Disease, and Other Causes
Authors: Polly A. Newcomb, Ellen Kampman, Amy Trentham-Dietz, Kathleen M. Egan, Linda J. Titus, John A. Baron, John M. Hampton, Michael N. Passarelli, Walter C. Willett
Journal: Journal of Clinical Oncology (2013)

Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear.We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast cancer who were residents of Wisconsin, Massachusetts, or New Hampshire and diagnosed from 198 to 200 at ages 20 to 79 years. All women reported on prediagnostic intake; a subsample of 4,881 reported on postdiagnostic intake.During a median follow-up of 11.3 years from diagnosis, 7,780 deaths occurred, including 3,484 resulting from breast cancer. Hazard ratios (HR) and 95% CIs were estimated. Based on a quadratic analysis, moderate alcohol consumption before diagnosis was modestly associated with disease-specific survival (compared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and ≥ 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers.Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.
Homocysteine Upregulates Soluble Epoxide Hydrolase in Vascular Endothelium In Vitro and In Vivo
Authors: Donghong Zhang, Xina Xie, Yequn Chen, Bruce D. Hammock, Wei Kong, Yi Zhu
Journal: Circulation Research (2012)

Rationale: Hyperhomocysteinemia is a risk factor of atherogenesis. Soluble epoxide hydrolase (sEH) is a major enzyme that hydrolyzes epoxyeicosatrienoic acids and attenuates their cardiovascular protective effects. Whether homocysteine (Hcy) regulates sEH and the underlying mechanism remains elusive. Objective: To elucidate the mechanism by which Hcy regulates sEH expression and endothelial activation in vitro and in vivo. Methods and Results: Hcy treatment in cultured human endothelial cells dose-dependently and time-dependently upregulated sEH mRNA and protein. Hcy increased the expression of adhesion molecules, which was markedly reversed by inhibiting sEH activity. Hcy-induced sEH upregulation is associated with activation of activating transcription factor-6 (ATF6). Bioinformatics analysis revealed a putative ATF6-binding motif in the promoter region of the sEH gene, which was found at a methylation site. Site-directed mutagenesis and chromatin immunoprecipitation assays demonstrated that Hcy treatment or ATF6 overexpression promoted ATF6 binding to the promoter of sEH and increased its activity. Results of methylation-specific polymerase chain reaction revealed that the ATF6 binding site on the sEH promoter was partially methylated and was demethylated with Hcy. SiRNA knockdown of ATF6α or SP1 blocked and ATF6 overexpression and DNA methyltransferase inhibitor mimicked the effect of homocysteine on sEH upregulation. In vivo, immunofluorescence assay revealed elevated expression of sEH and adhesion molecules in the aortic intima of mice with mild hyperhomocysteinemia, which was attenuated by sEH deletion or inhibition. Conclusion: ATF6 activation and DNA demethylation may coordinately contribute to Hcy-induced sEH expression and endothelial activation. Inhibition of sEH may be a therapeutic approach for treating Hcy-induced cardiovascular diseases.
Domain Stealing by Receptors in a Protein Transport Complex
Authors: Joanne M. Hulett, Peter Walsh, Trevor Lithgow
Journal: Molecular Biology and Evolution (2007)

The mitochondrion is an essential cellular compartment in eukaryotes. The mitochondrial proteins Tom20 and Tom22 are receptors that ensure recognition and binding of proteins imported for mitochondrial biogenesis. Comparison of the sequence for the Tom20 and Tom22 subunits in the yeasts Saccharomyces cerevisiae and Saccharomyces castellii, show a rare case of domain stealing, where in Saccharomyces castellii Tom22 has lost an acidic domain, and Tom20 has gained one. This example of domain stealing is a snapshot of evolution in action and provides excellent evidence that Tom20 and Tom22 are subunits of a single, composite receptor that binds precursor proteins for import into mitochondria.
Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and south Asians in Leicestershire.
Authors: C S Probert, V Jayanthi, A O Hughes, J R Thompson, A C Wicks, J F Mayberry
Journal: Gut (1993)

The family history of patients identified during incidence studies in Leicestershire were investigated and the prevalence and comparative risks calculated; 1254 patients aged 15 to 80 years were sent a questionnaire about their family history. All cases with a positive family history were reviewed and confirmed cases included in the study. In Europeans the standardised prevalence of Crohn9s disease was 75.8/10(5) and that of ulcerative colitis 90.8/10(5). The prevalence of Crohn9s disease among South Asians was 33.2/10(5) and that of ulcerative colitis 135/10(5). The prevalence of Crohn9s disease in Europeans was significantly greater than that in Hindus (chi 2 = 16, p &lt; 0.001), while the prevalence of ulcerative colitis was significantly lower in Europeans than Hindus (chi 2 = 27, p &lt; 0.001) and Sikhs (chi 2 = 4.4, p &lt; 0.05). The comparative risk of developing ulcerative colitis in first degree relatives of Europeans patients with ulcerative colitis was increased by approximately 15, but the risk of Crohn9s disease was not increased. The comparative risk of developing Crohn9s disease among first degree relatives of patients with Crohn9s disease was increased by up to 35, the comparative risk of ulcerative colitis was approximately 3. The risk among relatives of South Asian patients with Crohn9s disease was not increased, but the risk of ulcerative colitis to relatives of patients with ulcerative colitis was. This study supports the view that Crohn9s disease and ulcerative colitis arise in people with a genetic predisposition and exposed to some, as yet unknown, environmental factor.
P843 ALTERATION IN GLUCOSE METABOLISM AFTER AN ORAL GLUCOSE LOAD AND RELATIONSHIP WITH LIVER DAMAGE IN PATIENTS WITH NAFLD
Authors: E. Vanni, L. Mezzabotta, C. Rosso, M. Gaggini, R. Gambino, F. Salomone, E. Buzzigoli, C. Saponaro, F. Saba, D. Ciociaro, G.P. Caviglia, M.L. Abate, S. Carenzi, A. Smedile, M. Rizzetto, M. Cassader, A. Gastaldelli, E. Bugianesi
Journal: Journal of Hepatology (2014)
Diabetes: Models, Signals, and Control
Authors: C. Cobelli, C. Dalla Man, G. Sparacino, L. Magni, G. De Nicolao, B.P. Kovatchev
Journal: IEEE Reviews in Biomedical Engineering (2009)

The control of diabetes is an interdisciplinary endeavor, which includes a significant biomedical engineering component, with traditions of success beginning in the early 1960s. It began with modeling of the insulin-glucose system, and progressed to large-scale in silico experiments, and automated closed-loop control (artificial pancreas). Here, we follow these engineering efforts through the last, almost 50 years. We begin with the now classic minimal modeling approach and discuss a number of subsequent models, which have recently resulted in the first in silico simulation model accepted as substitute to animal trials in the quest for optimal diabetes control. We then review metabolic monitoring, with a particular emphasis on the new continuous glucose sensors, on the analyses of their time-series signals, and on the opportunities that they present for automation of diabetes control. Finally, we review control strategies that have been successfully employed in vivo or in silico, presenting a promise for the development of a future artificial pancreas and, in particular, discuss a modular architecture for building closed-loop control systems, including insulin delivery and patient safety supervision layers. We conclude with a brief discussion of the unique interactions between human physiology, behavioral events, engineering modeling and control relevant to diabetes.
QT Dispersion in Patients with End-Stage Renal Failure and during Hemodialysis
Authors: ISTVÁN LŐORINCZ, JÁNOS MÁTYUS, ZSOLT ZILAHI, CSABA KUN, ZSOLT KARÁNYI, GYÖRGY KAKUK
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Interlead variability of the QT interval in surface electrocardiogram (ECG), i.e. , QT dispersion, reflects regional differences in ventricular recovery time, and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT and corrected QT (QTc) interval and dispersion in chronic hemodialyzed patients. Data of 34 nondiabetic patients (male/female = 21/13; mean age, 54 ± 15 yr) on chronic hemodialysis were studied. Polysulfone capillaries and bicarbonate dialysate containing (in mEq/L) 135 Na + , 2.0 K + , 1.5 Ca 2+ , and 1.0 Mg 2+ were used. Simultaneous 12-lead ECG were recorded before and after hemodialysis in a standard setting. The QT intervals for each lead were measured manually on enlarged (×3) ECG by one observer using calipers. Each QT interval was corrected for patient heart rate: JOURNAL/jasn/04.03/00001751-199906000-00016/math_16MM1/v/2023-03-15T155848Z/r/image-jpeg (in milliseconds [ms]). The average cycle intervals were 853 ± 152 ms predialysis and 830 ± 173 ms postdialysis; the difference was not significant. The maximal QT interval changed significantly from 449 ± 43 to 469 ± 41 ms ( P &lt; 0.01). The corrected maximal QT interval increased significantly from 482 ± 42 to 519 ± 33 ms ( P &lt; 0.01). The QT dispersion changed from 56 ± 15 to 85 ± 12 ms ( P &lt; 0.001) and the corrected QT interval dispersion from 62 ± 18 to 95 ± 17 ms ( P &lt; 0.001). During hemodialysis, the serum potassium and phosphate levels decreased from 5.5 ± 0.8 to 3.9 ± 0.5 (mM) and from 2.3 ± 0.5 to 1.6 ± 0.4 (mM), respectively, whereas calcium increased from 2.2 ± 0.23 to 2.5 ± 0.22 (mM). It is concluded that hemodialysis increases the QT and QTc interval and QT and QTc dispersion in patients with end-stage renal failure. Thus, it may be stated that the nonhomogeneity of regional ventricular repolarization increases during hemodialysis. Measurement of QT and QTc dispersion is a simple bedside method that can be used for analyzing ventricular repolarization during hemodialysis.
Hypertension Does Not Account for the Accelerated Atherosclerosis and Development of Aneurysms in Male Apolipoprotein E/Endothelial Nitric Oxide Synthase Double Knockout Mice
Authors: Jiqiu Chen, Peter J. Kuhlencordt, Joshua Astern, Robert Gyurko, Paul L. Huang
Journal: Circulation (2001)

Background Apolipoprotein E (apoE)/endothelial nitric oxide synthase (eNOS) double knockout (DKO) mice demonstrate accelerated atherosclerosis and develop abdominal aortic aneurysms and aortic dissection, suggesting a role for eNOS in suppressing atherogenesis. To test whether accelerated atherosclerosis and aortic aneurysms were due to hypertension, we administered hydralazine to male apoE/eNOS DKO mice to reduce blood pressure. Methods and Results Male apoE/eNOS DKO mice were treated with hydralazine in their drinking water (250 mg/L) using a dose that lowers the blood pressure to levels seen in apoE KO mice. The mice were fed a Western-type diet for 16 weeks, and lesion formation was assessed by inspection of the vessel and staining with Sudan IV. Hydralazine-treated, normotensive male apoE/eNOS DKO mice developed increased aortic lesion areas (30.0±2.8%, n=11) compared with male apoE KO mice (14.6±0.8%, n=7). The extent of lesion formation was not significantly different from male apoE/eNOS DKO mice that were not given hydralazine (28.3±3.1%, n=9). Four of 11 hydralazine-treated male apoE/eNOS DKO mice developed abdominal aortic aneurysms. Conclusions Hypertension is not required for the accelerated atherosclerosis seen in apoE/eNOS DKO animals, and control of hypertension during a 16-week period does not prevent aortic aneurysm formation.
AGE AS AFFECTING THE OSMOTIC AND MECHANICAL FRAGILITY OF DOG ERYTHROCYTES TAGGED WITH RADIOACTIVE IRON
Authors: W. B. Stewart, J.M. Stewart, M. J. Izzo, L. E. Young
Journal: The Journal of Experimental Medicine (1950)

Radioactive iron was administered to three normal dogs, two of which had previously been bled, in order to tag a group of erythrocytes of approximately known age. The osmotic fragility of the newly formed tagged cells was significantly greater than that of the general cell population during the first few days after injection of the iron, while the mechanical fragility of the young cells was less than that of the general red cell population. As the cells aged and approached the end of their life span, their susceptibility to destruction by trauma inflicted by rolling glass beads exceeded that of the general cell population. The osmotic behavior of the old cells was not distinctive. The increased mechanical fragility of senescent cells suggests that the life span of erythrocytes may be limited at least in part by changes within the cell which render it more susceptible to destruction by mechanical wear and tear in the circulation. It is emphasized, however, that the trauma produced by rolling glass beads may be quite unlike that inflicted upon red cells in vivo. A decrease in circulating radioactive iron was observed in each experiment soon after the mechanical fragility of the tagged cells began to exceed that of the total cell population. The lowest point on the curve representing circulating radioiron was noted at 119, 119, and 122 days respectively after injection of iron in the three experiments. Estimates of the life span of dog erythrocytes obtained in this way agree with those provided by other methods.
Diagnostic fibreoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates.
Authors: R A Matthay, W C Farmer, D Odero
Journal: Thorax (1977)

Nineteen immunocompromised patients with pulmonary infiltrates underwent diagnostic fibreoptic bronchoscopy with transbronchial forceps and brush biopsy. A specific diagnosis was obtained in 21/25 procedures (10/11 focal lesions and 11/14 diffuse legions). The most common diagnosis was infection, and organisms isolated included bacteria, fungi, Pneumocystis carinii, and herpes simplex. A pneumothroax requiring tube drainage occurred in two cases and mild lung parenchymal bleeding was noted in two others. It is concluded that fibreoptic bronchoscopy with forceps and brush biopsy can be performed safely with an excellent diagnostic yield in immunocompromised hosts with lung lesions. Supplemental oxygen should be administered during fibreoptic procedures in these patients and platelet transfusions should be given when thrombocytopenia is present.