tbuckley/cabot-search huggingface dataset:
Chemotherapy (CT) dose adjustment for obese or elderly patients: How often does it occur, and should it? Results of an Australian survey
Authors: K. M. Field, S. Kosmider, M. Jefford, R. Jennens, M. Michael, M. Green, P. Gibbs
Journal: Journal of Clinical Oncology (2007)

6539 Background: Determining the optimal starting dose of chemotherapy (CT) for an individual patient (pt) presents a considerable challenge and is generally empirical. While body surface area (BSA)-based dosing has major limitations, it is standard practice worldwide. It may perform particularly poorly in certain scenarios, including the obese or elderly pt, representing an increasing area of clinical practice. We sought to determine the range of approaches employed by medical oncologists Australia-wide when administering CT to these pts. Methods: A questionnaire was developed by a panel of oncologists and mailed to all members of the Medical Oncology Group of Australia. The survey was designed to document the methods of calculating CT doses, with an emphasis on the parameters utilised and also factors considered in a variety of settings, including obese and elderly pts. Results: Evaluable responses were obtained from 181 of 315 medical oncologists and fellows (RR 57.5%). BSA-based dosing was reported as standard practice by 176 (97.2%). In the adjuvant disease setting, 23 (12.7%) use ideal rather than actual body weight (BW), or whichever is less, when prescribing CT. 14.5% (n=25) defined ideal BW as a body mass index (BMI) of 27, while 41% chose BMI 20–25 as ideal. When treating the obese pt (BMI&gt;30), only 6.2% of respondents routinely use actual BW. Of the remainder, 69.5% either routinely cap the dose at 2m 2 or use ideal BW, and 16.4% cap at a maximum dose or at a different BSA. In underweight (BMI&lt;18.5) pts conversely, 95% (n=171) routinely use BSA based on actual BW. 41 respondents (22.7%) routinely dose reduce in the fit elderly population. Conclusions: Many current methods of BSA-based CT dosing demonstrated in this survey are not supported by the available literature. There is strong evidence from adjuvant studies in breast and bowel cancer that actual BSA is desirable; we clearly demonstrate that a substantial number of Australian patients, especially the obese, are being under-dosed, potentially leading to inferior outcomes. Until alternative methods to BSA-based CT dosing are available, education regarding the appropriateness of routine dose adjustments in specific circumstances is urgently required. No significant financial relationships to disclose.
Chemokine Expression Precedes Inflammatory Cell Infiltration and Chemokine Receptor and Cytokine Expression during the Initiation of Murine Lupus Nephritis
Authors: GUILLERMO PÉREZ DE LEMA, HOLGER MAIER, ELENA NIETO, VOLKER VIELHAUER, BRUNO LUCKOW, FRANCISCO MAMPASO, DETLEF SCHLO[Combining Diaeresis]NDORFF
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Lupus nephritis is characterized by immune complex deposition and inflammatory cell infiltration. Therefore, the initiation and progression of lupus nephritis in MRL/MpJ Fas lpr/lpr (MRL/lpr) mice were investigated, with a focus on the expression of several chemokines and chemokine receptors. Mice were monitored for proteinuria from 6 to 20 wk of age, and kidneys were examined every 2 wk by light microscopy, electron microscopy, and immunohistologic analyses. Furthermore, the expression of chemokines, chemokine receptors, and proinflammatory cytokines was analyzed in ribonuclease protection assays. MRL/lpr mice demonstrated increased expression of monocyte chemoattractant protein-1, regulated upon activation, normal T cell-expressed and -secreted protein, inducible protein of 10 kD, and macrophage inflammatory protein-1β at week 8. At that time point, levels of circulating and glomerular immune complexes were increased, and no proteinuria or histopathologic signs of renal damage could be observed. As assessed in immunohistochemical and in situ hybridization analyses, monocyte chemoattractant protein-1 and regulated upon activation, normal T cell-expressed and -secreted protein expression was preferentially located in the glomeruli and interstitium. Mononuclear cell infiltration of the kidney was observed by weeks 10 to 12. At week 12, the renal expression of chemokine receptor 1 (CCR1), CCR2, and CCR5 was increased, mice became proteinuric, and renal damage was histologically evident. Finally, the expression of proinflammatory cytokines was detected (weeks 12 to 14). In summary, ( 1 ) chemokines are upregulated before inflammatory cell infiltration, proteinuria, and kidney damage are observed; ( 2 ) chemokine generation is restricted to sites of subsequent inflammatory cell infiltration, i.e. , glomeruli and interstitium; ( 3 ) chemokine receptor expression parallels mononuclear cell infiltration; and ( 4 ) proinflammatory cytokines are upregulated later, in parallel with inflammatory cell infiltration and the onset of proteinuria. These results support the hypothesis that chemokines initiate leukocyte infiltration and precede proteinuria and renal damage in MRL/lpr mice.
Effect of screening on ovarian cancer mortality in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer randomized screening trial.
Authors: S. S. Buys, E. Partridge, A. Black, C. Johnson, L. Lamerato, C. Isaacs, D. Reding, R. Greenlee, B. Kessel, M. Fouad, D. Chia, L. Ragard, J. Rathmell, P. Hartge, P. Pinsky, G. Izmirlian, J. Xu, P. Prorok, C. D. Berg
Journal: Journal of Clinical Oncology (2011)

5001 Background: Ovarian cancer is among the five leading causes of cancer death in women in the United States. Women diagnosed with early stage disease have significantly improved survival compared to women diagnosed with advanced ovarian cancer. However, the effect on mortality of screening for the early detection of ovarian cancer with CA-125 and transvaginal ultrasound (TVU) is unknown. We evaluated the effect on mortality of screening for ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: PLCO is a randomized controlled trial involving 10 screening centers across the U.S. that recruited 78,216 women aged 55-74 years. Women were randomized to receive either annual screening(intervention arm; 39,105 participants) or usual care (39,111 participants) between November 1993 and July 2001. Women in the intervention arm were offered annual CA-125 testing for6 years and TVU for 4 years. Participants and their health care providers received the screening test results and managed evaluation of abnormal results. All participants were followed for up to 13 years for cancer diagnoses and death. The primary outcome was ovarian cancer mortality. Secondary outcomes included ovarian cancer incidence and complications associated with screening exams and diagnostic procedures. Results: Ovarian cancer was diagnosed in 212 women in the intervention arm and 176 in the usual care arm, for a rate ratio of 1.21 (95% Confidence Interval (CI) 0.99 – 1.48). There were 118 deaths from ovarian cancer in the intervention arm and 100 in the usual care arm, for a mortality rate ratio of 1.18 (95% CI 0.91-1.54). Of 3,285 women undergoing surgery following a false positive exam, 166 encountered at least one serious complication. Deaths from all other causes (excluding ovarian, colorectal and lung cancer) were 2,924 and 2,914 in the intervention and usual care arms, respectively. Conclusions: Screening simultaneously with CA-125 and TVU did not reduce ovarian cancer mortality in women from the general population, and there was evidence of harm from diagnostic evaluation following a false positive screening test.
Establishment and functional characterization of human peritoneal fibroblasts in culture
Authors: A Jörres, K Ludat, J Lang, K Sander, G M Gahl, U Frei, K DeJonge, J D Williams, N Topley
Journal: Journal of the American Society of Nephrology (1996)

The functional and morphologic integrity of the peritoneal membrane is of major importance for the successful treatment of patients with chronic peritoneal dialysis. This study aimed at the establishment and functional characterization of human peritoneal fibroblasts (HPFB) in cell culture. HPFB were isolated from human omentum by enzymatic digestion and cultured. Confluent HPFB could be identified as spindle-shaped cells, growing in parallel arrays and whorls which stained positive for vimentin and negative for factor VIII, cytokeratin 18, and desmin. Maximum cell growth was observed after 24 h in medium supplemented with 10% fetal calf serum. HPFB could be growth arrested and maintained in fetal calf serum-depleted medium (0.1%) for > 48 h without loss of cell viability as evaluated by intracellular ATP determination. Stimulation of resting HPFB for 0.5 to 48 h with increasing doses of interleukin (IL)-1 beta and/or tumor necrosis factor-alpha (1 to 10,000 pg/mL) resulted in a dose- and time-dependent induction of IL-6 messenger RNA and an increase in immunoreactive IL-6 protein secreted into HPFB supernatants, which was significant with IL-1 beta or tumor necrosis factor-alpha doses as low as 1 pg/mL. HPFB IL-6 production could be inhibited by both actinomycin D or cycloheximide, which suggests that the induction of IL-6 occurs both on a transcriptional and a post-transcriptional level. In summary, this cell culture model is expected to facilitate further investigation of the potential role of the HPFB in the peritoneal cytokine network of patients treated with chronic peritoneal dialysis.
Smoking status affects VRI assissted prediction of postoperative FEV1 and DL,CO in patients with lung cancer
Authors: Blagoi Marinov, Anastas Chapkanov, Miroslava Todorova, Georgi Paskalev, Stefan Kostianev
Journal: European Respiratory Journal (2014)

It is unclear whether smoking cessation following surgery influences calculation of predicted postoperative (ppo) values of lung function indices.   Aim : To investigate the influence of smoking status on the accuracy of ppoFEV1 and ppoD L,CO  prediction by means of vibration response imaging (VRI) in patients with lung cancer.   Patients and methods : Thirty seven patients with non small cell lung cancer aged 60.6±8.0 years, 40.5±11.3 pack/years(mean±SD) referred for anatomical lung resection were studied. They underwent comprehensive spirometry and diffusion measurements (MasterScreen Diffusion, E. Jaeger, Germany) and vibration response imaging (VRIxp, DeepBreeze, Or-Akiva, Israel) before and approx. 30 days after the resection. The calculation of the  ppo  values was carried out with proprietary software - O-Plan.   Results : Twenty eight lobectomies and 9 pneumonectomies were performed in the studied population (26 males/11 females). For the whole grouppredicted postoperative values and the actually measured FEV1 and D L,CO  had very good agreement (r=0.846; p L,CO  (52.2±18.5 vs 59.1±16.8; p   Conclusion : In current smokers VRI tends to underestimate the values of both FEV1 and D L,CO  compared with non-smokers. Developing a correction coeficient would be beneficial in patients with borderline lung function.
Assessment of the BODE index, arterial stiffness and endothelial dysfunction in patients with chronic obstructive pulmonary disease
Authors: Gokhan Tireli, A. Fusun Kalpaklioglu
Journal: European Respiratory Journal (2012)

Aim: COPD is a respiratory disorder, but also having systemic effects. Cardiovascular diseases are leading cause of mortality in patients with COPD and have an important prognostic role. In this study, we investigated the mechanisms of COPD associated increased cardiovascular risk, measured by arterial stiffness, endothelial dysfunction and the BODE index.

Method: Fifty men with stable COPD were compared with fifty healthy male control subjects who had approximately same age and normal lung functions. Cardiovascular assessments, which include evaluation of endothelial function, arterial stiffness and echocardiographic measurements, as well as BODE index, were carried out in all subjects.

Results: Arterial stiffness parameters evaluated by photoplethismographic measurement were similar in both groups. However, direct arterial stiffness were detected only in nine subjects with COPD. Nitrate mediated dilation (NMD) measurements were found to be worsened in patients with stable COPD than in control subjects. In the same model, flow mediated dilation (FMD) was associated with NMD positively. In patient group, the BODE index values were found to be statistically higher than the control group. Moreover, BODE index was negatively correlated with FEV1, body mass index and 6-minute walking test, but positively correlated with the MMRC dyspnea scale.

Conclusion: The presence of arterial stiffness, endothelial function abnormalities and endothelium independent smooth muscle dysfunction may indicate the relationship between COPD and the increased risk of cardiovascular disease.
Abstract 14796: Validity of Smartphone Pedometer Apps as a Tool to Monitor Physical Activity Remotely
Authors: Gustavo G Fontana, Alfonso J Tafur, Andrew W Gardner, Ana I Casanegra
Journal: Circulation (2014)

Introduction:  Over 65% of cellphones in the US are smartphones and the market share is rapidly growing. These devices allow many applications through mobile apps. The objective of this study was to evaluate the readiness of free smartphone pedometer apps as a tool to monitor activity.   Hypothesis:  Free pedometer Apps are a valid tool for activity monitoring.   Methods:  We reviewed all the pedometer apps from the app stores, Apple (iOS A) and Android (AA)(combined 93% of market share), and selected them for further review if they were free of charge and capable of storing and sharing data (step count and time). Two independent raters downloaded and evaluated all the selected apps to confirm compliance with requisites, background running and user friendliness. We recruited 12 volunteers to test the Apps without adjusted sensitivity settings. We randomized testing to phone location (waist vs shirt pocket) and walking speed on a treadmill (1, 2, and 3 mph for 6 minutes at each speed) and during a 6-minute walk test. All tests were performed at least twice by each volunteer, and the criterion measure of steps was obtained by manual counting using a hand tally counter. For statistical analysis we used Wilcoxon’s signed rank test, in addition to Pearson correlation coefficients and Bland-Altman plots.   Results:  219 iOS A and 181 AA were reviewed. Of those, 13 iOS A and 9 AA were selected, downloaded and rated by two independent reviewers. Three apps from each system fulfilled the criteria and were analyzed. Accupedo and Pedometer SP (iOS A) and Accupedo (AA) step counts were not statistically different (p>0.05) than the counted steps, Pearson correlation coefficients were significant (p   Conclusion:  Despite the number of free pedometer apps, only a small subset is suitable for remote physical activity monitoring. Apps perform better at walking speeds higher than 1 mph without sensitivity adjustment. The technology and ubiquitous nature of smartphones appears that they are ready to use for activity monitoring in a clinical setting, which may aid in monitoring home walking programs.
Phase II trial of vinorelbine (V) days 1+8 every 3 weeks and trastuzumab (T) weekly as first-line chemotherapy for HER2+ metastatic breast cancer (MBC)
Authors: M. Andersson, D. Nielsen, P. G. Sørensen, M. Ewertz
Journal: Journal of Clinical Oncology (2007)

1091 Background: Weekly V and T as 1. line therapy in patients (pts) with HER2+ MBC is highly effective with reported response rates (RR) from 61–86% and median time to progression (TTP) 8.5–16 months. This study examined V given twice every 3 weeks. Methods: Eligible pts had HER2+ (IHC 3+ or FISH) MBC with measurable disease by RECIST criteria, no prior chemotherapy or T for MBC, and LVEF &gt; 50%. They received V 35 mg/m 2 i.v. days 1+8 every 3 weeks (= 1 cycle) and T weekly (4 mg/kg loading dose, 2 mg/kg thereafter i.v.) until progression or unacceptable toxicity. Planned sample size was 50, but the study was replaced by a randomised trial at 46 pts, all of them eligible. Primary endpoint was RR, secondary endpoints included TTP, overall survival (OS) and toxicity. Results: From December 2001-July 2004 46 pts were recruited at 4 centers. They received 11 (1–54) cycles (median, range). V dose was reduced due to neutropenia in 7.5% of cycles and for other reasons in 14.5%. V treatment was delayed due to neutropenia in 7.8% of cycles and for other reasons in 4.7% of cycles. Median received V dose intensity was 0,78. Cardiotoxicity: asymptomatic reduction of LVEF &gt; 20% or &gt;10% to below 50%: 8 pts (3 to below 50%). Toxicity grade III-IV (pts): Neutropenia: 11. Infections: 5 (one septic death). Constipation 2. 43 pts have progressed and 32 have died. RR: CR: 9 (20%) PR: 13 (28%) SD 11 (24%) (SD&gt; 6 months 9 (20%)) PD: 10 (22%) NE: 3 (7%). Median duration of response: 18.0 months. Median TTP: 11.0 months (95% confidence interval (95%CI) 7.6–14.4). Median OS: 25.4 months (95%CI 22.7–28.0). After progression 24 received docetaxel, 14 capecitabine, 6 epirubicine, and 11 endocrine therapy. Conclusions: V given twice every 3 weeks and T weekly is a highly active and well-tolerated 1. Line treatment for HER2+MBC. Recruitment into the trial was stopped at 46 pts in favor of a phase III-trial which is ongoing in the Nordic countries comparing V (days 1+8) + T with docetaxel+T every 3 weeks. No significant financial relationships to disclose.
Frequency of radiologically confirmed brain metastasis from time of diagnosis of stage IV disease in patients with melanoma.
Authors: R. Noor, C. Wei, N. E. Papadopoulos, K. B. Kim, W. Hwu, M. A. Davies, P. Hwu, J. Homsi, S. E. McIntyre, A. Y. Bedikian
Journal: Journal of Clinical Oncology (2010)

e19012 Background: Melanoma has a high rate of brain metastasis (BM) with grave prognosis. Up to 75% of patients (pts) with MM are found to have BMs in autopsy series. Early diagnosis (Dx) of BM allows effective intervention with surgical resection or stereotactic radiosurgery possible. The objective of this study is to assess the cumulative incidence (CI) of new BMs over the course of stage IV melanoma free of BMs. Methods: Chemotherapy (CRx) naïve stage IV MM pts treated on 12 clinical trials conducted over 15 years were reviewed. Information about pt demographics, tumor stage, and Rx outcomes were collected. Eight factors including age, gender, site of primary, tumor M stage, number of organ met sites, serum albumin, and LDH at time of Dx of stage IV disease were chosen to determine their predictive value of the risk to BMs. The CI of confirmed BM was calculated at 12 weeks intervals using the method of Gray (1988). Results: The characteristics of the 230 pts with BMs were similar to those of 370 BM-free pts in terms of median age, gender, and site of primary melanoma. See Table for the % of patients who developed BM at 12-week intervals. Over 75% of the 233 pts who eventually developed BM are confirmed within 60 weeks from the onset of stage IV MM. Conclusions: MRI of the brain in asymptomatic MM pts beyond 60 weeks has very low yield. Supported in part by Chiron Corporation and Carol Courtney Memorial Fund. Characteristics Cumulative % pts developed brain mets Week 12 24 36 48 60 % by last follow-up Of all pts with brain mets, % diagnosed by 60 weeks All patients 7.3 16.3 24.3 28.7 32.0 38.6 83.5 No. of met organ sites 0 2.9 6.6 10.3 14.7 16.9 25.4 67.6 1 7.0 15.8 25.0 31.2 37.1 44.9 86.0 2 8.3 22.0 30.3 32.6 33.3 37.9 87.9 >=3 16.7 28.3 40.0 40.0 40.0 41.7 95.9 M stage M1a 2.8 6.4 10.6 14.9 17.0 25.2 68.6 M1b 5.8 17.5 29.2 37.0 44.2 54.3 81.9 M1c 10.2 20.3 28.2 30.8 32.8 36.9 89.3 Serum albumin Normal 6.7 16.6 25.2 29.8 33.4 39.8 84.5 Low 14.3 17.9 19.6 19.6 21.4 25.0 85.7 Serum LDH Normal 5.7 13.4 21.3 26.4 30.8 39.0 79.6 Elevated 9.7 21.8 30.1 32.0 34.0 36.4 93.3 Site of primary Head/neck 5.1 14.1 22.2 27.3 30.3 39.0 78.9 Trunk/abdomen 10.2 21.7 28.7 33.1 36.6 40.6 90.3 Limbs 3.4 8.1 18.1 23.5 27.5 32.3 85.4 Unknown 8.2 17.3 24.5 26.5 28.6 41.8 68.3 No significant financial relationships to disclose.
Chronology and Pattern of Human Chromosome Replication. I. Blood Leukocytes of Normal Subjects&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y. Kikuchi, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1964)

The timetable of replication of the 46 chromosomes in normal blood cells has been delineated following their short-term culture (72 hrs). The incorporation of tritiated thymidine, added at 1 to 28 hours before fixation of the cells, was used to determine the chronology of chromosome replication. Over 2,000 metaphases (and their autoradiographs) of normal subjects (3 males and 3 females) were examined. There was a definite sequence to the order in which the chromosomes began and completed deoxyribonucleic acid (DNA) replication. Thus, one of the autosomes of group B (B4) is the first to begin replication, followed by groups A, B3, and C and the X chromosomes—the latest to begin replication being groups F and G. The completion of chromosomal replication was characterized by several salient features: 1) One X chromosome in the female cells and the Y chromosome in the male cells were the last to replicate; 2) among the autosomes, members of group B (B4) and D (D13) replicated last; 3) groups F and G were the earliest to finish replication. The order in which the chromosomal DNA began and finished replication was consistent from subject to subject. As previously reported by others, one X chromosome in female cells and the Y chromosome in male cells were more heavily labeled than any other chromosome when thymidine-H3 was added late in the synthesis period ( S-period); in contrast, the homologous X chromosome in female and the X chromosome in male cells were not heavily labeled. Asynchrony and variation in replication characterized each pair of homologous chromosomes and various regions of individual chromatids. The data indicate that the S-period begins approximately 16 to 20 hours and the G2-period (the time lapse between completion of the S-period and beginning of mitosis) 3 hours before metaphase in leukocytes. The delineation of the chronology and pattern of human chromosome replication in normal blood cells can serve as a reference for comparison with results obtained in normal cells of different origin and in abnormal cells (leukemia, cancer, congenital disorders).