tbuckley/cabot-search huggingface dataset:
Synovial sarcoma - Is adjuvant treatment of value? A retrospective review of adults and children treated at a single centre
Authors: M. S. Braun, M. Leahy, R. E. Taylor, W. Merchant, I. J. Lewis
Journal: Journal of Clinical Oncology (2005)

9023 Background Synovial Sarcomas (SS) are rare tumours where the role of adjuvant therapy remains controversial. Our institution has adopted a philosophy of surgery alone for resectable tumours, reserving chemotherapy and/or radiotherapy for marginal, unresectable or metastatic disease. Methods 33 children and adults over a 14 year period. Median age at diagnosis was 27 years (range 7–71). Staging and treatment: stage 1 <5cms = 11/13 surgery alone, 2 additional RXT; stage 1 > 5cms = 3/7 surgery alone, 4 additional chemotherapy/RXT; stage 2 = 1/6 surgery alone, 5 additional treatment. Stage 3 =1, and stage 4 =6, all had chemotherapy and/or radiotherapy. Radiotherapy doses were50–64 Gy in 25–32 fractions, and chemotherapy was alkylating agent and doxorubicin based. Results Diagnosis increased from 1.55 to 4.75 cases/year after introduction of t(X:18) testing. 92% (12/13) of Stage 1 <5cm remain in first remission (CR1), and 100% (13/13) are currently alive and disease free. In contrast 43% (3/7) with Stage 1 >5cm are in CR1 and 43% alive with disease or have died. Of 6 stage 2 tumours 33% (2/6) are in CR1, 17% (1/6) in second remission, and 50% (3/6) are alive with disease, or have died. Overall 65% (17/26) of stage 1 &2 tumours remain relapse free and 77% are in CR1 or CR2 after 4.6years median follow-up (range: 0.5–15.6 yrs). The 4 patients treated with chemotherapy have all relapsed. Only 1 of 6 patients with metastases responded to chemotherapy (median survival 201 days). Conclusions The introduction of t(X:18) testing increased the diagnostic rate of SS. Small tumours have an excellent prognosis when treated by complete resection alone and are unlikely to benefit significantly from adjuvant treatment. Despite additional treatment, overall results for larger and metastatic tumours are unsatisfactory and large collaborative international studies are required to improve outcomes. No significant financial relationships to disclose.
Chemoprophylaxis of influenza.
Authors: W H Manwaring
Journal: BMJ (1968)

BotRl 137 " coping behaviour," the functions of which are, firstly, to protect the parent from overwhelming environmental and psychological stress and, secondly, to deal effectively with the medical and psychological care of the child.Continuity of care is more difficult to achieve in Britain than in those countries where there are family paediatricians.In Britain the diagnosis is usually made in hospital and it is the paediatrician who first tells the parents.As there are so many others concerned in the subsequent treatment it is better if the paediatrician can assume the responsibility of being the sheet-anchor for the child and the parents until, in favourable cases, the family doctor can resume his care.
Validated LC–MS/MS method for determination of YH-8, a novel PKnB inhibitor, in rat plasma and its application to pharmacokinetic study
Authors: Qianqian Zhai, Jing Pang, Guoqing Li, Congran Li, Xinyi Yang, Liyan Yu, Yucheng Wang, Jian Li, Xuefu You
Journal: Acta Pharmaceutica Sinica B (2015)

(E)-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography–tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1–500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%–6.8%, with accuracy of the method being 100.69%–106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at −70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.
Symposium Overview
Authors: Candece L. Gladson
Journal: Neuro-Oncology (2005)

The following two reviews are part of the symposium on angiogenesis begun in the April 2005 issue of Neuro-Oncology.In the review by Bergers and Song, the authors describe the important role of pericytes in regulating blood vessel maturation and survival, useful markers of pericytes, and the similarity of pericyte function in embryogenesis and tumor angiogenesis.Fig. 1C from this review is the cover photograph for this issue of the journal.It demonstrates the architecture of brain capillaries and highlights the contribution of pericytes, the complex tight junctions of brain capillary endothelial cells, and astrocytic foot processes to the formation of the blood-brain barrier.In the second review by Abounader and Laterra, the authors describe the functional role of scatter factor (SF)/hepatocyte growth factor (HGF) in promoting cell growth, invasion, and angiogenesis in tumors.They discuss published data indicating that SF/HGF levels are signifi cantly elevated in glioblastoma tumors and that SF/HGF can function in both a paracrine and autocrine manner to promote tumorigenicity.SF/HGF synthesized by glioblastoma tumor cells binds to its receptor c-Met on endothelial cells, promoting tubule formation (angiogenesis), and SF/HGF can also bind to c-Met expressed on glioblastoma tumor cells, promoting tumor cell proliferation and invasion.This review suggests that the SF/HGF-c-Met signaling pathway is an important target for new glioblastoma tumor therapies.
Abstract P004: Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lindsay G Smith, Pamela L Lutsey, Laura R Loehr, Anna Kucharska-Newton, Lin Y Chen, Alanna M Chamberlain, Lisa M Wruck, Sue Duval, Sally C Stearns, Alvaro Alonso
Journal: Circulation (2014)

Background: Atrial fibrillation (AF) is associated with increased risk of hospitalization. However, little is known about the impact of AF on non-inpatient healthcare utilization or about sex or race differences in AF-related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results: ARIC cohort participants with incident AF enrolled in fee-for-service Medicare, Parts A and B, for at least 12 continuous months between 1991 and 2009 were matched on age, sex, race and center to up to three participants without AF. Healthcare utilization was ascertained from inpatient and outpatient Medicare claims and classified based on primary ICD-9 code. The analysis included 944 AF and 2,761 non-AF participants. The average number of days hospitalized per year was 13.1 (95% confidence interval [CI]: 11.5-15.0) and 2.8 (95% CI: 2.5-3.1) for those with and without AF, respectively. The corresponding number of outpatient claims per year was 53.2 (95% CI: 50.4-56.1) and 23.0 (95% CI: 22.2-23.8) for those with and without AF, respectively (Table). Most utilization in AF patients was attributable to non-AF conditions, particularly other-cardiovascular disease (CVD)-related reasons; the adjusted rate ratio for days hospitalized per year for other-CVD-related reasons was 4.76 (95% CI: 3.51 - 6.44) for those with compared to those without AF. There was suggestive evidence that sex modified the association between AF and inpatient utilization, with AF related to greater utilization in women than men. The association between AF and healthcare utilization was similar in whites and blacks. Conclusions: This study highlights the considerably greater healthcare utilization (inpatient and outpatient) among those with AF; the differential in utilization due to other-CVD-related reasons was substantial. In addition to recommended heart rate or rhythm treatment, accompanying cardiovascular comorbidities should be evaluated and managed.
Advantages of the Orbis-Sigma Valve in the treatment of triventricular hydrocephalus
Authors: P. M. Rampini, M. Caroli, M. Zavanone, E. Sganzerla, M. Farabola
Journal: Neuro-Oncology (1991)

Cerebrospinal fluid overdrainage due to shunt systems currently used for the treatment of hydrocephalus is the most important cause of failure (8). Overdrainage makes the cerebral ventricles to collapse, inducing their walls to adhere to the ventricular catheter, favouring its obstruction.
Abstract 5070: Progression of Urine Albumin Excretion Despite of Optimized Therapies to Reduce Atherosclerotic Risk Factors has an Adverse Outcome in Patients with Coronary Artery Disease
Authors: Yoshinobu Kitta, Mitsumasa Hirano, Takamitsu Nakamura, Yasushi Kodama, Keita Sano, Ken-ichi Kawabata, Jyun-ei Obata, Kiyotaka Kugiyama
Journal: Circulation (2008)

Although microalbuminuria is considered a strong risk factor of future cardiovascular disease (CVD), it remains unclear whether changes in urine albumin excretion (UAE) in response to a reduction of coronary risk factors may provide prognostic information in patients with coronary artery disease (CAD). Thus, this study assessed the hypothesis that changes in UAE in response to optimized therapy for reduction of CAD risk may predict future CVD events in patients with CAD. This study enrolled of 213 patients with newly diagnosed CAD who had microalbuminuria (30 mg/day ≤ UAE &lt; 300 mg/day) at entry. Patients with late-stage chronic kidney disease (GFR &lt; 60 ml/min/1.73 m 2 ) at entry were excluded. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. All patients had a repeated test of UAE at 6 months (2 nd test) after the 1 st UAE test. Thereafter, all patients were prospectively followed up for 3 years or until the occurrence of 1 of the following events: CVD death, nonfatal myocardial infarction, unstable angina pectoris requiring revascularization, or ischemic stroke. Progression of UAE at the 2 nd test was defined as &gt; 50% increase from the UAE at the 1 st test. UAE at 2 nd test was progressed in 62 (29%) patients, while it was not progressed in the remaining 151 (71%) patients. UAE at entry was comparable between patients with and without progression of UAE (52 ± 6.2 vs.61 ± 4.7 mg/day, respectively, p = ns). During follow-up period, events occurred in 15 (24%) of the 62 patients with progression of UAE and in 16 (10%) of the 151 patients without progression of UAE (p &lt; 0.01 by chi-square test). Using a multivariate Cox hazards analysis, progression of UAE was a predictor of future CVD events that was independent of UAE at 1 st test, use of medications, age, and traditional CAD risk factors (HR 2.5, 95%CI 1.2 – 4.8, p = 0.01). Progression of urine albumin excretion despite individualized and optimized therapies to reduce CAD risk factors represents an adverse outcome in CAD patients. Periodic measurement of urine albumin excretion may be useful for risk stratification in CAD.
Abstract A67: Defining signaling pathways governing metastatic potential in pancreas cancer
Authors: Martin C. Whittle, Markus Carlson, Sunil R. Hingorani
Journal: Cancer Research (2015)

Abstract Pancreas cancer is an aggressively metastatic disease in which circulating tumor cells (CTC) often colonize distant organs long before diagnosis. Approximately 45% of patients present at diagnosis with metastatic disease, and this increases to 90% at the time of death. Even after surgical resection of the primary tumor, local and distant recurrence develops in approximately two thirds of cases. These sobering statistics highlight the need to define mechanisms and vulnerabilities of metastasis that can be targeted to improve patient outcomes. To better understand the process of pancreatic cancer metastasis, we study the KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre (KPC) model of autochthonous pancreas cancer. KPC mice spontaneously develop invasive and metastatic disease to numerous sites, including the liver and lungs, at rates similar to those seen in humans. Lineage tracing, performed by selectively expressing fluorescent reporters in pancreatic cells of KPC mice, has revealed a rare population of CTC that may be precursors to these metastatic foci. Building on this model, we show that alteration of TGFβ pathway components significantly affects the metastatic potential of autochthonous tumors, and that the timing and balance of signaling is critical in the metastatic process. These differences in metastatic potential are reflected in the numbers and functional properties of the respective CTC. Our distinct models with drastically different metastatic potentials provide clues to understanding the signaling mechanisms driving metastasis in pancreas cancer. Citation Format: Martin C. Whittle, Markus Carlson, Sunil R. Hingorani. Defining signaling pathways governing metastatic potential in pancreas cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A67.
Health care rationing
Authors: R. Crawshaw
Journal: BMJ (1996)

Nomogram for number needed to treat will be of limited use EDITOR,-Gilles Chatellier and colleagues suggest that in calculations of the "number needed to treat" a nomogram based on the formula 1 should be used in Pc x relative risk reduction preference to 1The two formulas are, PC...Pi however, equivalent and will both suffer from the same problems when Pc and Pi differ by an amount greater than Pc.The nomogram is consequently useful in only a limited number of circumstances-for example, when published study results have been adjusted for confounding effects and only relative risks or odds ratios are reported.In these cases such estimates could then be combined with an estimate of the baseline risk to yield the number needed to treat.
初级医疗机构的预警症状——该症状明显增加癌症患病风险，但是仍然很少确诊
Authors: 张国庆（译）, 焦顺昌（校）
Journal: BMJ (2007)

在初级医疗机构很少能诊断新发癌症，全科医生（GPs）在诊断恶性肿瘤中的作用受到了挑战。在英国，每年每位全科医生接诊患者1500例，其中平均只有1．39例为肺癌，0．23例为食管癌，0．99例为大肠癌，0．45例为肾癌或膀胱癌。我们寻找一些诊断办法以使我们能够从众多担心自己患有癌症或无任何特异性表现的人群中将那些少数的肿瘤患者挑选出来。
Development and Performance of an Algorithm to Estimate the Child-Turcotte-Pugh Score From a National Electronic Healthcare Database
Authors: David E. Kaplan, Feng Dai, Ayse Aytaman, Michelle Baytarian, Rena Fox, Kristel Hunt, Astrid Knott, Marcos Pedrosa, Christine Pocha, Rajni Mehta, Mona Duggal, Melissa Skanderson, Adriana Valderrama, Tamar H. Taddei
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract 2714: Electrophysiological Characteristics in Idiopathic Ventricular Fibrillation Compared to Brugada Syndrome
Authors: Nobuhiro Nishii, Satoshi Nagase, Hiroshi Morita, Shigeki Hiramatsu, Takeshi Tada, Masato Murakami, Kazufumi Nakamura, Yoshiki Hata, Kengo F Kusano, Hiroshi Ito
Journal: Circulation (2009)

Background: Idiopathic ventricular fibrillation (IVF) is a rare but fatal tachyarrhythmia that occurs in patients without structural and electrophysiological abnormality. A steeply sloped action po...
Abstract 19411: Inter-Atrial Regional Adipose Burden in Relation To Metabolic Abnormalities as a Novel Clinical Marker for Left Atrial Remodeling in Preserved Ejection Fraction Heart Failure
Authors: Chung-Lieh Hung, Chun-Ho Yun, Yau-Huei Lai, Jen-Yuan Kuo, Yih-Jer Wu, Chuan-Chuan Liu, Hung-I Yeh
Journal: Circulation (2012)

Background: Excessive visceral adipose tissue, a marker of abnormal metabolic process, has recently been shown to exert effects on cardiac struture and function. However, data regarding regional fat burden on left atrial (LA) mechanics and contractile function in subjects with heart failure and preserved ejection fraction (HFpEF) remained elusive. Methods: Totally studied 48 heart failure patients with preserved left ventricular ejection fraction (HFpEF) from heart failure (HF) outpatient clinics. Another 58 hypertensives and 26 normal volunteers were recruited from health evaluation center at the same time of patients enrollment. Myocardial deformation imaging from all directions, cardiac twist and left atrial (LA) strain analyzed. Global epicardial (EAT), thoracic peri-aortic (TAT) adipose tissue and regional inter-atrial fat burden (IAF, in thickness) were quantified by multi-detector Computed Tomography (MDCT) (Sensation 16, Siemens Medical Solutions, Forchheim, Germany) off-line analysis (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Metabolic risk scoring (MS) was calculated by NCEP ATP III score. Results: Compared to hypertensives and normal group, patients with HFpEF tended to have higher LV mass index and LA diameter though similar LVEF (all p&lt;0.05) observed. In addition, EAT, TAT and IAF all correlated with MS (trend p&lt;0.05), and were all significantly higher in HFpEF group (ANOVA p&lt;0.05), which were accompanied by significantly reduced LV deformation from all three directions and cardiac twist as well as lower LA strain (all p&lt;0.05). In a multivariate model adjusting for age, gender, body mass index, blood pressure, MS and LV mass, for each increased standard deviation of IAF were independently associated with reduced LA strain (ß coef: -0.35, p=0.018). Conclusions: Fat pad surrounding inter-atrial region in relation to metabolic abnormalities may influence left atrial mechanical function in terms of atrial deformation. Our data suggested that such excessive regional adipose burden may partly play a role in the pathogenesis of early stage heart failure.
Wellbeing of gay, lesbian, and bisexual doctors Commentary: The medical profession should face up to its own homophobia
Authors: B. P Burke
Journal: BMJ (2001)

# Wellbeing of gay, lesbian, and bisexual doctors {#article-title-2}

Gay, lesbian, and bisexual doctors have long had a largely covert presence within the medical profession; their visibility is a relatively recent phenomenon. The American Psychiatric Association's landmark decision in 1973 to remove homosexuality from the nomenclature of psychiatric disorders was a major catalyst for this, allowing homosexual and bisexual doctors to take tentative steps into the culture at large. A search of the medical literature yields information on medical attitudes towards homosexual and bisexual patients, but little about homosexual and bisexual doctors themselves. Their challenges and triumphs are likely to be similar to those of other minority groups within the profession, except that they can choose whether to make their minority status known to patients and colleagues. 1 2

Although societal tolerance towards sexual minorities has greatly improved since 1973, “coming out” as a homosexual or bisexual doctor remains a difficult decision, with both personal and professional consequences. Such doctors have to ask themselves several questions in deciding whether to come out:

Wellbeing implies personal and professional satisfaction and the ability to effectively integrate the two to form satisfying relationships with patients and colleagues and to attain their respect. In this article we review the literature on those factors most likely to affect the wellbeing of gay, lesbian, and bisexual doctors: homophobia, the difficulties encountered by homosexual …
Phase II clinical study of combination therapy with irinotecan and S-1(IRIS) for inoperable recurrent advanced colorectal cancer: Hokkaido Gastrointestinal Cancer Study Group study HGCSG-0302)
Authors: Y. Komatsu, S. Yuki, H. Akita, M. Kudo, M. Tateyama, T. Saga, T. Megro, G. Suzuki, Y. Sakata, M. Asaka
Journal: Journal of Clinical Oncology (2006)

3589 Background: We planned to conduct a phase II clinical study of combination therapy with irinotecan and S-1, a new oral anticancer drug of the fluorinated pyrimidine type. We reported the interium reports of this study in colorectal cancer patients at GI cancer Symposium 2006. Methods: The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20–75 years. Irinotecan was administered at a dose of 100 mg/m 2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m 2 ) was administered after breakfast and dinner and then withdrawn for 2 weeks. Results: Forty patients were enrolled in the present study. There were 23 men and 17 women. The median age was 62 years (range: 34 to 74 years). Two patient showed grade 4 neutropenia, but the next course could be given safely after dose reduction. Three patients had grade 3 diarrhea, but therapy could be continued with addition of an antidiarrheal drug. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. To date, 231 cycles (median 8, range 1–19) have been administered. Median relative dose intensity was 97% for S-1 and 87% for irinotecan. 36 pts are evaluable for efficacy: RR was 47.2% (95% CI, 30.9–63.5%) and Disease Control Rate (PR + SD) was seen in 94.4% of pts. PFS of this regimen is 320 days. MST is not reached. Conclusions: IRIS therapy achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer. It seems that IRIS is a good treatment equal to FOLFIRI. In addition, this regimen could qualify as a candidate for future combination therapy with a molecular-targeting drug. The latest data will be reported at the meeting. No significant financial relationships to disclose.
Rapid emergence and antigenic diversification of the norovirus 2012 Sydney variant in Denmark, October to December, 2012
Authors: J Fonager, L S Hindbæk, T K Fischer
Journal: Eurosurveillance (2013)

The norovirus (NoV) season in Denmark in late 2012 was characterised by an increase in the number of NoV infections caused mainly by the 2012 Sydney variant, but also by the 2009 New Orleans variant. Analysis of approximately 85% of the capsid gene from 10 Sydney 2012 and 9 New Orleans 2009 isolates showed rapid antigenic diversification of the Sydney 2012 variant shortly after its emergence. We also present new primers useful for transmission tracking.
Handbuch der Neurochirurgie. Klinik und Behandlung der Raumbeengenden Intrakraniellen Prozesse. IV H.-H. Löhr, R. Luft, H. Olivecrona, A. Ragnell, G. Simon, H. Vieten, and O. Wilcke (eds.). New York: Springer-Verlag, 1967. 677 pp. $97.50
Authors: Renato Baserga
Journal: Cancer Research (1968)