tbuckley/cabot-search huggingface dataset:
Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke
Authors: Carmen A. Peralta, Leslie A. McClure, Rebecca Scherzer, Michelle C. Odden, Carole L. White, Michael Shlipak, Oscar Benavente, Pablo Pergola
Journal: Circulation (2016)

The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established.Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06).In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering.URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.
Phase II study of pegylated arginine deiminase (ADI-PEG20), a novel targeted therapy for melanoma
Authors: L. G. Feun, N. Savaraj, A. Marini, C. Wu, C. Robles, C. Herrera, S. Spector, K. Luedemann, F. Moffat, J. Bomalaski
Journal: Journal of Clinical Oncology (2006)

8045 Background: Melanoma cells may be sensitive to arginine (Arg) deprivation due to lack of expression of argininosuccinate synthetase (ASS) which is needed to synthesize Arg, a nonessential amino acid in humans, from citrulline (Ctr). ADI-PEG20 lowers plasma Arg levels by catalyzing the conversion of Arg into Ctr. A phase I-II trial of ADI-PEG20 in metastatic melanoma (MM) showed intramuscular (i.m.) weekly doses of 160 IU/m² was well tolerated and resulted in responses in European patients (pts) (JCO 23:7660, 2005). Based on these encouraging results, we performed a phase 2 clinical and pharmacological study of ADI-PEG20 in USA pts with MM. Methods: Pts had weekly i.m. injection of ADI-PEG20 at a starting dose of 160 IU/m². Serum Arg levels were determined q 2 weeks. The dose of ADI-PEG20 was escalated up to 320 IU/m² weekly if Arg levels were still detectable. Tumor evaluation was done q 8 weeks. Tumor samples were assayed for ASS expression using immunohistochemical staining and/or PCR prior to start of therapy and at time of relapse. Results: 17 pts were treated and evaluable. Median age was 69 (range 29- 80). Median performance status was 90 (range 70- 100). Median number of metastatic sites was 2 (range 1- 8). 11 pts had stage M1c and 11 had prior chemotherapy and/or immunotherapy for advanced disease. Responses include partial response (PR) 4 pts (24 %), minor response 2(12 %), mixed response 2 (12%). Duration of PR from start of therapy was 4(+), 6(+), 12, and 16 months. Sites of response include soft tissue/nodal (3 pts) and lung (1 pt). Tumor tissue was available for ASS determination in 12 pts. ASS expression was associated with treatment failure and relapse. Conclusions: This work confirms that ADI-PEG20 appears to be active in MM. Side effects include minor discomfort at the injection site, slight fatigue, and mild elevation of serum uric acid consistent with tumor destruction. ASS expression may correlate with response. This study is continuing to accrue pts. ADI-PEG20 may be beneficial in MM. No significant financial relationships to disclose.
PWE-095 Cost effectiveness of rifaximin-α 550 mg (xifaxan®/targaxan®) in the reduction of recurrence of overt hepatic encephalopathy in united kingdom
Authors: E Berni, CD Poole, P Conway, A Radwan, CJ Currie
Journal: Gut (2015)

<h3>Introduction</h3> Hepatic encephalopathy (HE) is associated with high morbidity and mortality. Rifaximin-α 550 mg (XIFAXAN®/TARGAXAN®) is effective in reducing the recurrence of episodes of overt HE. Our aim was to determine the cost effectiveness of rifaximin-α 550 mg versus standard care (lactulose) in patients with cirrhosis in the UK. <h3>Method</h3> This economic evaluation used a Markov state transition model. The outcome metric was the incremental cost effectiveness ratio (ICER), derived from estimates of the cost/quality adjusted life years (QALYs). The payer perspective was that of UK National Health Service. Outcome data were from two trials of rifaximin-α 550 mg. Population outcome data were from a complementary study of patients with liver cirrhosis treated within the NHS. UK Costs data (2012) were derived from published sources. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. The time horizon was five years. Costs and benefits were discounted at 3.5%. Extensive sensitivity analyses were carried out. Real world data describing the use of rifaximin-α 550 mg in the UK NHS were also applied into the model for length of stay in hospital and the number of admissions. <h3>Results</h3> The average cost for the included elements of care was £22,971 in the rifaximin-α 550 mg arm and £23,545 in the lactulose arm, a difference of -£573. The corresponding values for benefit were 2.56 QALYs and 1.75 QALYs per person, respectively, a difference of 0.81 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included length of stay in hospital and the number of admissions to hospital. Evaluation to 10 years and lifetime resulted in ICERs of £3,024/QALY and £5,068/QALY, respectively. <h3>Conclusion</h3> Rifaximin-α 550 mg in patients with recurrent HE in the context of liver cirrhosis represented good value for money compared to standard care, by reducing episodes of overt HE, the likelihood of hospital admission and hospital length of stay. This analysis was funded by Norgine. <h3>Disclosure of interest</h3> E. Berni Consultant for: Norgine, C. Poole Consultant for: Norgine, P. Conway Employee of: Norgine, A. Radwan Employee of: Norgine, C. Currie Consultant for: Norgine.
Parent perceptions of offspring responses to parental communication of <i>BRCA1/2</i> test results
Authors: A. R. Bradbury, L. Patrick-Miller, B. Egleston, C. Sands, M. Feigon, K. Pawlowski, C. Ibe, M. Daly, O. Olopade, C. Daugherty
Journal: Journal of Clinical Oncology (2009)

1511 Background: Many BRCA1/2 mutation carriers report sharing their genetic test results with their minor children. The impact of this communication on offspring remains unknown. Methods: 163 parents who had BRCA1/2 testing completed qualitative interviews regarding their experiences with communication of their genetic test results to offspring. Descriptive responses were coded and response proportions utilized to summarize results. We used multiple regressions fit by GEE to test associations with disclosure. We controlled for parent mutation status in each regression. Results: 163 parents (52 BRCA1/2 mutation carriers) reported on 323 offspring 5 to 25 years old at the time of parent genetic testing. 107 (66%) parents reported disclosing to at least one offspring. Child age (p &lt; 0.001) and parent cancer history (p = 0.004) were positively associated with disclosure. Parents without a BRCA1/2 mutation were more likely to communicate test results than parents with a mutation (p = 0.007). Among parents who disclosed, few (14%) reported they perceived their offspring to have had an initial negative affective or behavioral response. Others (13%) reported offspring concern for self and family. Reports of initial negative responses and concern were more frequent among parents with a mutation or a variant of uncertain significance. Many parents reported that the communication had no significant impact (39%) or a positive impact (36%) on their offspring. Conclusions: Many parents report sharing BRCA1/2 test results with their offspring. Parent self-reports suggest that they do not perceive most offspring to experience adverse reactions to this communication. Self-reports suggest that offspring learning of a BRCA1/2 mutation or a variant of uncertain significance may be more susceptible to initial negative reactions. Further research is necessary to explore psychosocial and behavioral responses to learning of hereditary risk during childhood and adolescence, and to inform the development of interventions to optimize adaptive response. No significant financial relationships to disclose.
Expression of Breast Epithelial Differentiation Antigens in Human Primary Breast Cancer
Authors: C S Foster, A M Neville
Journal: JNCI Journal of the National Cancer Institute (1987)

Monoclonal antibody LICR-LON-M18 is a marker of normal human breast epithelial cell differentiation. The epitope recognized by LICR-LON-M18 is a prominent component of luminal plasma membranes of nonneoplastic resting and lactating human breast epithelial cells but is rarely expressed by human breast carcinomas. With the use of competitive binding-inhibition studies, the immunodominant portion of the LICR-LON-M18 epitope was shown to be the following oligosaccharide sequence [with galactose (Gal) and N-acetylglucosamine (GlcNAc)]: Gal beta 1----4GlcNAc beta 1----. This structure was distinct from Gal beta 1----3GalNac, which was bound by peanut agglutinin (PNA) and was not recognized by LICR-LON-M18 [corrected]. With the use of biochemical techniques, the present data not only confirmed sialylation and consequent "masking" of the LICR-LON-M18 epitope and PNA determinants in human breast carcinomas but also identified the particular groups of glycoproteins involved in this process. These studies provided additional support for the thesis that sialylation of human breast carcinoma glycoproteins represented an enhancement of specific differentiation events normally regulated in the morphogenesis of nonneoplastic human breast epithelium and that specific glycoproteins became masked during the genesis of primary human breast cancer.
Pulmonary embolism (PE) in patients with pulmonary sarcoidosis (PS)
Authors: Olga Baranova, Vitalii Perlei, Aleksei Gichkin, Valentina Zolotnitskaya, Alexandra Speranskaya
Journal: European Respiratory Journal (2014)

Aim: to analyze causes of PE and to describe of clinical, radiological and hemodynamic characteristics of PE in PS pts.

Matherial and methods. We studied 27 cases PE in pts PS Patients were subjected to clinical and radiological (CT, perfusion scinthiography, HRCT, CT-angiography, and SPECT with 99m) researches, echodopplercardiography (EDC) . 

Results. The main PE cause was deep venous thrombosis in 17 pts (0.63). All pts had predisposing factors for venous thromboembolism, including trombophilia. PE was found in 2 pts with morphologically confirmed cardiac sarcoidosis with right heart failure. Clinical symptoms were: dispnoea (0.88), haemoptysis (0.70), chest pain (0.62), cough (0.37), tachypnoea (0.70), tachycardia (0.48). Comparison EDC data of pts and healthy volunteers revealed: increasing of systolic pulmonary artery pressure (29.74±2.06 mm Hg, p<0.01 vs 23.7 ± 1.0 mm Hg in control group). , right ventricular wall diastolic thickness (0.39±0.06 cm, p<0.05 vs 0.26±0.02 cm), right ventricular diastolic dimension (2.78±0.13 cm, p<0.05 vs 2.51± 0.08 cm) and decreasing of fraction right ventricular wall systolic thickness (0.44±0.07 vs 0.59±0.04), E/A right ventricular diastolic filling ratio (1.28±0.05 vs 1.64±0.05), E/A left ventricular diastolic filling ratio (1.17±0.21 vs 1.69±0.04). The combination of CT-angiography and SPECT revealed additionally in 10 cases signs of PE, including thrombosis «in situ» in 3 PS pts of 4 stage.

Conclusions: 1. The modern methods investigations (EDC, CT-angiography, SPECT) allow detection PE in PS patients, including thrombosis «in situ». 2. The main cause of PE is DVT with the presence of predisposing factors for venous thromboembolism, including markers of trombophilia.
Combination chemotherapy of irinotecan with fluoropyrimidine in taxane, anthracycline, and fluoropyrimidine-pretreated metastatic breast cancer
Authors: H. Chang, S. Han, D. Oh, S. Im, T. Kim, Y. Bang
Journal: Journal of Clinical Oncology (2009)

e12003 Background: Irinotecan (I) has some efficacy in taxane (T) and anthracycline (A)-refractory breast cancer, and combination of I and fluoropyrimidine (F) shows synergistic effects in preclinical model. We conducted this study to reveal the clinical outcomes of I and F combination therapy in T, A, and F-pretreated metastatic breast cancer. Methods: We consecutively enrolled metastatic breast cancer patients treated with I and F combination chemotherapy from 2000 to 2008 in Seoul National University Hospital. They all had been previously heavily treated with T, A, and F. We retrospectively analyzed the clinical outcomes. Results: Twenty-five patients were enrolled. The median age was 38 years (range: 30–56years). The performance status was: ECOG 1 (11 patients), 2 (13), and 3 (1). The most commonly involved site was bone (16 patients), liver (13), and lung (12). The biologic subtype was: hormone receptor (+) 17 patients, HER-2 (+) 2, triple-negative (TNBC) 6. The median time from diagnosis of metastatic breast cancer to the initiation of IF therapy was 34 months (range: 12–97 months). The used regimens were: FOLFIRI (18 patients), TS-1/ irinotecan (6), capecitabine/irinotecan (1). Response was evaluable in 24 patients. There was no CR/PR. Stable disease was shown in 29.2% and 70.8% was PD, that is disease control rate was 29.2% (95% CI:10–45%). The median duration of disease control was 3.9 months (95% CI 3.7–4.2, range 2.4–11). The progression-free survival was 1.4 months (95% CI:0.7–21, range: 0.5–11.4), and overall survival was 6 months (95% CI: 4.2–7.8, range: 1–23). According to the biologic subtypes, the median PFS was 2.0 vs. 1.3 months (p=0.895) and OS was 4 vs. 6 months (p=0.807) respectively in TNBC VS Non-TNBC. In multivariate analysis, patients with good PS showed longer OS (p = 0.035). The Gr 3/4 hematologic toxicity was: neutropenia 18.6%, anemia 1.3%, thrombocytopenia 1.3%. And the major Gr 3/4 non-hematologc toxicity was: diarrhea (4%), hand-foot syndrome (0%), fatigue (0%). No treatment-related death was occurred. Conclusions: Treatment of I combined with F might be an option in metastatic breast cancer patients heavily treated with T, A, and F, irrespective of TNBC. Further prospective studies are warranted. No significant financial relationships to disclose.
Deciphering the fundamental mechanisms of atrial fibrillation: a quest for over a century
Authors: Stanley Nattel, Dobromir Dobrev
Journal: Cardiovascular Research (2016)

Atrial fibrillation (AF), the most frequent clinical arrhythmia, is associated with increased cardiovascular morbidity and mortality, with stroke, myocardial infarction, and heart failure being the most critical complications.1 Presently available drugs for AF therapy have moderate efficacy and important limitations, particularly increasing the risk of life-threatening proarrhythmic events and bleeding complications.1,2 Ablation procedures are moderately effective and relatively safe, but the increasing size of the patient population limits applicability to only a small proportion of patients.1 Therefore, drug therapy is still the mainstay of AF treatment. Although maintenance of sinus rhythm (rhythm control) appears preferable, clinical studies failed to demonstrate clear advantages to rate over rhythm control, likely because current pharmacological approaches do not target the critical determinants of the fundamental mechanisms of AF.3,4 A better mechanistic understanding of the molecular basis of AF is expected to foster the development of safer and more effective treatment approaches.

Although the basic mechanisms of AF have been described in the medical literature for over a century, the underlying cellular and molecular mechanisms are incompletely understood.5 It is assumed that independent of the underlying cause, which may be very diverse, ectopic impulse formation (ectopic activity) and re-entry are the two major determinants of AF pathophysiology.2 Re-entry requires a vulnerable substrate and an initiating trigger. The likelihood of re-entry formation is determined by the tissue properties of conduction and refractoriness, with conduction disturbances and short refractoriness making formation …
Spontaneous Adverse Drug Reaction Reporting Vs Event Monitoring: A Comparison
Authors: A P Fletcher
Journal: Journal of the Royal Society of Medicine (1991)

Spontaneous adverse drug reaction (ADR) reporting is the mainstay of national and international drug safety evaluation in the post-approval phase. A major criticism of the method has been a high, but essentially unquantifiable, level of under-reporting by doctors. A direct comparison has been made between spontaneous ADR reporting and an observational event monitoring system for a group of more than 44 000 patients receiving one or other of a group of seven new drugs. The data suggests that under-reporting by the spontaneous system may be as high as 98% for several clinical events believed to be associated with drug treatment.
포스터전시 : 단일 기관의 건강검진 수검자 중 정상 ALT의 범위
Authors: 빈홍건, 김용훈, 선한경, 강민경, 권창일, 고광현, 박필원, 홍성표, 황성규, 임규성
Journal: Clinical and Molecular Hepatology (2009)
Technetium 99m compounds for visualization of body organs
Authors: M. K. Loken
Journal: JAMA (1965)

Technetium 99m is readily available from a<sup>99</sup>Mo-<sup>99m</sup>Tc generator and possesses nearly ideal physical properties for organ visualization when used with either a scanner or scintillation camera. Brain phantom studies indicate that comparable resolution of pseudotumors containing<sup>99m</sup>Tc may be obtained with either unit. Studies of more than 100 patients suspected of having brain lesions indicated that<sup>99m</sup>Tc in the pertechnetate form is satisfactory for cranial scintiphotography. Albumin is tagged radioactively with<sup>99m</sup>Tc in our laboratories and used for placental localization. A colloid of this material is obtained by controlling heating. Small particles (200<sub>μ</sub>) are used for visualization of liver and spleen. Macroaggregates (50<sub>μ</sub>to 100<sub>μ</sub>) obtained by continued heating are used for lung scintiphotograms. Animal and human studies with preparations of albumin labeled with radioactive technetium (<sup>99m</sup>Tc) have yielded good results with no adverse side effects noted.
Beyond proforma consent for childhood cancer research.
Authors: S L Leikin
Journal: Journal of Clinical Oncology (1985)

A critical negotiation is that of obtaining informed consent from those responsible for the child with cancer who is to be involved in clinical research. It requires that the researcher weigh the merits to society of the proposed research trial and the interests of the patient and family. The clinical setting in which agreement to participate is requested and the regulations of the DHHS for such investigations also place special demands on all of those involved. This article is an ethical and psychosocial analysis of informed consent. It is intended to provide pediatric physician-investigators with a better understanding of this complex process to improve their fiduciary relationship with decision makers.
Gene expression analysis of head and neck squamous cell carcinoma using formalin-fixed paraffin embedded tissue
Authors: C. H. Chung, J. Carter, K. Ely, B. A. Murphy, B. B. Burkey, J. L. Netterville, S. Levy, A. J. Cmelak, R. J. Slebos, W. G. Yarbrough
Journal: Journal of Clinical Oncology (2005)

5537 Background: TNM staging is the most reliable prognosticator of survival in Head and Neck Squamous Cell Carcinoma (HNSCC). However, clinical outcome varies widely even between patient groups with comparable stage. Recently, we reported the molecular classification of 60 HNSCC tumors based on gene expression profiles that identified a group of patients with worse recurrence-free survival (Log-rank: p=0.02, Chung, et al., Cancer Cell, 2004). However, the assay has limitations for clinical use because it requires the availability of fresh frozen tumor specimens. Therefore, we performed gene expression analysis from formalin-fixed paraffin embedded (FFPE) tissue for molecular classification. Methods: Eight FFPE tumors from HNSCC patients were cut and macro-dissected for tumor cellularity >70%. RNA was isolated and amplified using the Paradise Reagent System (Arcturus, Mountain View, CA), and labeled with Enzo BioArray High Yield RNA Transcript Labeling Kit (Affymetrix, Santa Clara, CA) according to the Manufacturer’s recommendations. One of the eight tumors also had a matching fresh frozen tumor that was analyzed identically with FFPE tumors. The labeled RNA was fragmented and hybridized onto Affymetrix Human X3P Arrays. The systematic bias in the array data between Agilent Human 1 cDNA arrays (60 fresh frozen tumors) from the previous study and X3P arrays (8 FFPE tumors and 1 fresh frozen tumor) was corrected using Distance Weighted Discrimination (DWD). The 69 tumors were clustered using the previously determined classifier genes. Results: All eight FFPE tumors and one fresh frozen tumor hybridized with satisfactory signals. The matched FFPE and fresh frozen tumors from the identical patient clustered next to each other on the sample dendrogram. Three of 8 FFPE tumors clustered in the poor-RFS group and all three were deceased while the other group had only one death. Conclusions: This preliminary data suggests that gene expression analysis is feasible using FFPE tissue and that patients can be classified into the previously identified HNSCC prognosis groups. This will allow the study of archived specimens and broaden the clinical application of DNA microarray analyses. No significant financial relationships to disclose.