tbuckley/cabot-search huggingface dataset:
Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.
Authors: E Estey, P Thall, M Andreeff, M Beran, H Kantarjian, S O'Brien, S Escudier, L E Robertson, C Koller, S Kornblau
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). PATIENTS AND METHODS A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count &lt; 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved. Results were compared with those in 85 newly diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF. RESULTS Patients in both groups were relatively old (median age of all patients, 63 years), and were likely to have prognostically unfavorable cytogenetic abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF accelerated recovery to &gt; or = 1,000 neutrophils (P &lt; .0001; median, 34 days for FA, 21 days for FLAG), but logistic regression provided no evidence that the CR rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63% and 53%, respectively. This may reflect relatively high rates of death before neutrophil recovery in both groups. Rates of infection were similar in both groups. The follow-up duration in remission is short, and much of these data remain censored. To date, survival is similar with FA and FLAG. CONCLUSION On average, G-CSF before, during, and after FA had no effect on CR or infection rates in this population, in which elderly patients and poor prognostic factors were prevalent. The use of FA and laminar airflow rooms rather than more usual therapy needs to be considered when analyzing the results.
Inverse Relationship of Interferon Production and Virus Content in Cell Lines From Burkitt's Lymphoma and Acute Leukemias
Authors: Barbara E. Swart, Bobby G. Young
Journal: JNCI Journal of the National Cancer Institute (1969)

Significant quantities of interferon were detected in 6 of 7 uninoculated cell culture sublines tested: 4 Burkitt's lymphoma cell lines (EB1, EB2, AL1, and AL3) and 2 acute leukemia cell lines (SK-L2 and SK-L3). The EB3 Burkitt's cell line produced barely detectable quantities of interferon. The interferon titer produced varied with the cell subline and ranged from 1–64. The interferon titers obtained varied inversely with the herpes-like Epstein-Barr (EB) virus content of the cell lines.
Prospective Analysis of the Relation Between DSM-III Anxiety Disorders and Alcohol Use Disorders
Authors: Matt G. Kushner, Kenneth J. Sher, Darin J. Erickson
Journal: American Journal of Psychiatry (1999)

Cross-sectional studies show a robust association between anxiety disorders and alcohol use disorders (comorbidity); however, this methodology does not allow for the testing of causal models. The authors attempted to overcome this limitation by examining comorbid relationships prospectively.Male and female college students were assessed as freshmen (year 1), and then again at years 4 and 7, for selected 12-month anxiety disorders (generalized anxiety disorder, agoraphobia, and social phobia or panic) diagnosed according to the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and DSM-III and for 12-month DIS/DSM-III alcohol use disorders (alcohol dependence alone and alcohol abuse or dependence).Cross-sectionally, the odds of having either an anxiety disorder or an alcohol use disorder were two- to fivefold greater when the other condition was present. Prospectively, the odds of developing a new alcohol dependence diagnosis at year 7 increased from 3.5 to five times for those diagnosed with an anxiety disorder at years 1 or 4. Conversely, the odds of developing a new anxiety disorder at year 7 increased by about four times for those diagnosed with alcohol dependence at years 1 or 4. When alcohol abuse and dependence were combined, the pattern of findings was similar, albeit weaker. Multivariate path models provide similar results and highlight the reciprocal influence of alcohol use disorders and anxiety disorders.Alcohol use disorders (especially alcohol dependence) and anxiety disorders demonstrate a reciprocal causal relationship over time, with anxiety disorders leading to alcohol dependence and vice versa.
Aerosolized liposomal cyclosporine A for treatment of progressive allograft dysfunction following lung transplantation
Authors: Franziska Ihle, Matthias Griese, Werner von Wulffen, Rudolf Hatz, Jürgen Behr, Claus Neurohr
Journal: European Respiratory Journal (2013)

Aim:  The aim of this study was to evaluate aerosolized liposomal cyclosporine a (LCsA) in lung transplant recipients (LTR) with progressive chronic lung allograft dysfunction (CLAD) after failure of conventional therapy (pulsed steroids, azithromycine, montelucast, extracorporeal photophoresis).   Methods:  Descriptive data analysis was performed prospectively based on lung function testing.   Results:  6 LTR (age 38±11.8 years; 3 male; 4 DLTx; 2 HLTx; 5.7±5.1 years after Tx, BOS 1 n=1; BOS 2 n=1; BOS 3 n=4) received LCsA 10mg twice daily p.i. for 50 days (4-365d) as add-on therapy to tacolimus, mycophenolate mofetil and steroids. Two patients inhaled    Conclusion:  This case series of selected, treatment-resistant CLAD patients suggest that the use of LCsA in LTR is safe. The therapeutic potential of LCsA in LTR with CLAD should be investigated in future controlled trials.   eFlow® device and LCsA was provided by PARI Pharma GmbH.
Long-Term Survival in Metastatic Transitional-Cell Carcinoma and Prognostic Factors Predicting Outcome of Therapy
Authors: Dean F. Bajorin, Paul M. Dodd, Madhu Mazumdar, Melissa Fazzari, John A. McCaffrey, Howard I. Scher, Harry Herr, Geralyn Higgins, Mary G. Boyle
Journal: Journal of Clinical Oncology (1999)

The variation in reported survival of patients with metastatic transitional-cell carcinoma (TCC) treated with systemic chemotherapy may be a consequence of pretreatment patient characteristics. We hypothesized that a prognostic factor-based model of survival among patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy could account for such differences and help guide clinical trial design and interpretation.A database of 203 patients with unresectable or metastatic TCC was retrospectively subjected to a multivariate regression analysis to determine which patient characteristics had independent prognostic significance for survival. Patients were assigned to three risk categories depending on the number of unfavorable characteristics. Patient selection in phase II studies was addressed by developing a table of expected median survival for patient cohorts that had varying proportions of patients from the three risk categories.Two factors had independent prognosis: Karnofsky performance status (KPS) less than 80% and visceral (lung, liver, or bone) metastasis. Median survival times for patients who had zero, one, or two risk factors were 33, 13.4, and 9.3 months, respectively (P =.0001). The median survival time of patient cohorts could vary from 9 to 26 months simply by altering the proportion of patients from different risk categories.The presence of baseline KPS less than 80% or visceral metastasis has an impact on survival. Reporting the proportion of patients with zero, one, and two risk factors will facilitate understanding of the relevance of the median survival in phase II trials. Phase III trials should stratify patients according to the number of risk factors to avoid imbalance in treatment arms.
Detailed Molecular Delineation of 13q14.3 Loss in B-Cell Chronic Lymphocytic Leukemia
Authors: Martin M. Corcoran, Omid Rasool, Yie Liu, Arati Iyengar, Dan Grander, Rachel E. Ibbotson, Mats Merup, Xiushan Wu, Vadim Brodyansky, Anne C. Gardiner, Gunnar Juliusson, Robert M. Chapman, Ganka Ivanova, Mary Tiller, Gosta Gahrton, Nick Yankovsky, Eugene Zabarovsky, David G. Oscier, Stefan Einhorn
Journal: Blood (1998)
Microsphere‐Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells
Authors: Madhumita Patel, Hyo Jung Moon, Bo Kyung Jung, Byeongmoon Jeong
Journal: Advanced Healthcare Materials (2015)

Neuronal differentiation of tonsil‐derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)‐poly( l ‐alanine) aqueous solution to 37 °C through the heat‐induced sol‐to‐gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12–18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr‐1), neuron specific enolase, microtubule associated protein‐2, neurofilament‐M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool.
Cytotoxic therapy-induced D-xylose malabsorption and invasive infection during remission-induction therapy for acute myeloid leukemia in adults.
Authors: E J Bow, R Loewen, M S Cheang, T B Shore, M Rubinger, B Schacter
Journal: Journal of Clinical Oncology (1997)

PURPOSE To study the sequential changes in the intestinal absorption of an oral pentose probe, D-xylose, in patients receiving therapy for untreated acute myeloid leukemia (AML), and to correlate these changes to infectious morbidity. PATIENTS AND METHODS Serial D-xylose absorption studies were conducted in 110 consecutive adult patients admitted to a university-affiliated tertiary care hospital for remission-induction therapy for untreated newly diagnosed AML. Serial serum D-xylose levels were obtained 1 hour after a 5-g oral dose of D-xylose at baseline and weekly for 4 weeks until marrow recovery. These results were correlated with invasive infection using multivariate techniques. RESULTS The mean (+/- SEM) serum D-xylose levels were 0.88 +/- 0.03, 0.69 +/- 0.03, 0.58 +/- 0.02, 0.53 +/- 0.02, and 0.73 +/- 0.02 mmol/L at baseline and weeks 1 to 4, respectively (P &lt; .0001, analysis of variance [AN-OVA]). Time to malabsorption varied with induction regimen (P = .007, log-rank test). Bloodstream infections during week 2 correlated with malabsorption (P = .007). Neutropenic enterocolitis correlated independently with induction regimen (P = .009), malabsorption at week 2 (P = .02), and the development of candidemia (P = .005). Hepatosplenic fungal infection correlated with induction regimen (P = .03), malabsorption at week 2 (P = .02), and fever at diagnosis (P = .003). Malabsorption was unrelated to the duration of severe neutropenia and the administration of parenteral nutrition. CONCLUSION Serial D-xylose absorption studies in subjects with AML produced a characteristic profile of cytotoxic therapy-related damage to the functional integrity of the intestinal epithelium that was regimen dependent, myelosuppression independent, and predictive for invasive infectious complications. Further study to validate these observations appears warranted.
Abstract 353: Characterization Of Human Plasma Proteome Dynamics Using Deuterium Oxide
Authors: Ding Wang, David A Liem, Edward Lau, Dominic C Ng, Brian J Bleakley, Martin Cadeiras, Mario C Deng, Maggie P Lam, Peipei Ping
Journal: Circulation Research (2014)

Protein turnover half-life is a critical determinant of cardiac homeostasis and can reveal previously unknown disease mechanisms. We recently developed a theoretical method to quantify protein half-life in human using stable isotopes in deuterium oxide (D 2 O). Our goal in the present study is to demonstrate the immediate clinical translation potential of the method by evaluating its safety, feasibility, efficacy, and reproducibility in 10 healthy human subjects. The enrolled human subjects (4 females/6 males; age 22 - 51 y/o; body weight 51 - 108 kg) were labeled with a tailored protocol (UCLA IRB#12-000899), wherein each subject orally consumed weight-adjusted doses of (~45 mL each) 70% D 2 O daily for 14 days to enrich body water and proteins with deuterium. Throughout labeling, the subjects maintained regular food and fluid intake, and normal daily activities. Vital signs and medical health questionnaires were taken daily till 14 days post-labeling. We followed long-term physical conditions and the physiological clearance of D 2 O from body water for up to 240 days post-labeling, finding no physiological effects or signs of discomfort. To monitor label enrichment and post-labeling clearance in the subjects, we measured the D 2 O level of plasma and saliva samples with GC-MS. Both body fluids were reliable sources for monitoring label enrichment kinetics, giving consistent values of individual enrichment levels (0.9-2.2%) and rates (0.15-0.40 d −1 ) in all subjects. Post-labeling D 2 O level naturally subsided with a characteristic half-life of ~7 days (0.1 d −1 ). With LC-MS and the in-house informatics platform Proturn, we successfully characterized the turnover dynamics of &gt;600 human plasma proteins, the largest such human dataset to-date. We detected diverse protein half-life in plasma, e.g., from albumin (18.3 d) to IGF2 (8 h). Importantly, the method can quantify protein half-life with only a single time point, suggesting it can be used to study the dynamics of one single cardiac biopsy (e.g., during heart transplant). In summary, D 2 O labeling is a safe, accessible, and effective technique for widespread clinical investigations of protein turnover dynamics. We further discuss its implications in understanding cardiac disease mechanisms.
Using the tolerable-dose diagram in the design of phase I combination chemotherapy trials.
Authors: E L Korn, R Simon
Journal: Journal of Clinical Oncology (1993)

Choosing maximum-tolerated doses (MTDs) of agents to be administered in combination is more complicated than choosing the MTD for a single agent. This is because there are many combinations of doses that will be tolerated. We offer guidance in targeting specific MTD combinations, and suggest trial designs to achieve these targets.A graphical method based on a simple, previously described mathematical model is used to guide the phase I trial design. The method involves constructing a tolerable-dose diagram, which displays the toxicities that are expected to occur at various dose combinations. The data required for the method are the single-agent toxicity profiles of the agents. Designs for combinations of taxol with fluorouracil, carboplatin, doxorubicin, cyclophosphamide, and cisplatin are used to demonstrate the methods.For all of the drugs considered here, leukopenia is dose-limiting or nearly dose-limiting. Consequently, no major improvement in total dose-intensity is achievable by combining these drugs. If leukopenia can be eliminated or substantially reduced by use of chemoprotective agents, then a cyclophosphamide/taxol combination appears promising from a dose-intensity point of view. For other combinations, the doses must be reduced from single-agent MTD levels. In the absence of biologic information such as concentrations needed for optimal modulation, it is suggested that single-agent MTDs be reduced approximately proportionately for each drug in the combination.Tolerable-dose diagrams are useful for planning phase I trials of combinations of agents. They can suggest which combinations are promising from a dose-intensity perspective, as well as dose-escalation schemes for combinations to be pursued for dose-intensity or other considerations.
Patients with a High Polygenic Risk of Breast Cancer do not have An Increased Risk of Radiotherapy Toxicity
Authors: Leila Dorling, Gillian C. Barnett, Kyriaki Michailidou, Charlotte E. Coles, Neil G. Burnet, John Yarnold, Rebecca M. Elliott, Alison M. Dunning, Paul D.P. Pharoah, Catharine M. West
Journal: Clinical Cancer Research (2015)

Abstract Purpose: It has been hypothesized that increased predisposition to breast cancer may correlate with radiosensitivity, and thus increased risk of toxicity following breast irradiation. This study investigated the relationship between common breast cancer risk variants and radiotherapy toxicity. Experimental Design: SNP genotypes were determined in female breast cancer patients from the RAPPER (Radiogenomics: Assessment of polymorphisms for predicting the effects of radiotherapy) study using the Illumina CytoSNP12 genome-wide array. A further 15,582,449 genotypes were imputed using the 1000 Genomes Project reference panel. Patient (n = 1,160) polygenic risk scores were generated by summing risk-allele dosages, both unweighted and weighted by published effect sizes for breast cancer risk. Regression models were used to test associations of individual variants and polygenic risk scores with acute and late toxicity phenotypes (telangiectasia, breast edema, photographically assessed shrinkage, induration, pigmentation, breast pain, breast sensitivity, and overall toxicity). Results: Genotypes of 90 confirmed breast cancer risk variants were accurately determined and polygenic risk scores were approximately normally distributed. Variant rs6964587 was associated with increased breast edema 5 years following radiotherapy (Beta, 0.22; 95% confidence interval, 0.09–0.34; P = 7 × 10−4). No other associations were found between individual variants or the unweighted (P &amp;gt; 0.17) or weighted (P &amp;gt; 0.13) polygenic risk score and radiotherapy toxicity. This study had &amp;gt;87% power to detect an association between the polygenic risk score (relative risk &amp;gt; 1.1) and toxicity. Conclusions: Cancer patients with a high polygenic predisposition to breast cancer do not have an increased risk of radiotherapy toxicity up to 5 years following radiotherapy but individual variants may increase risk. Clin Cancer Res; 22(6); 1413–20. ©2015 AACR.
Maternal and Perinatal Mortality Associated with Cesarean Section in Alberta (1955-1959)
Authors: D C Ritchie
Journal: JAMA (1963)

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Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe
Authors: R Köck, K Becker, B Cookson, J E van Gemert-Pijnen, S Harbarth, J Kluytmans, M Mielke, G Peters, R L Skov, M J Struelens, E Tacconelli, A Navarro Torné, W Witte, A W Friedrich
Journal: Eurosurveillance (2010)

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare- and community-associated infections worldwide. Within the healthcare setting alone, MRSA infections are estimated to affect more than 150,000 patients annually in the European Union (EU), resulting in attributable extra in-hospital costs of EUR 380 million for EU healthcare systems. Pan-European surveillance data on bloodstream infections show marked variability among EU Member States in the proportion of S. aureus that are methicillin-resistant, ranging from less than 1% to more than 50%. In the past five years, the MRSA bacteraemia rates have decreased significantly in 10 EU countries with higher endemic rates of MRSA infections. In addition to healthcare-associated infections, new MRSA strains have recently emerged as community- and livestock-associated human pathogens in most EU Member States. The prevention and control of MRSA have therefore been identified as public health priorities in the EU. In this review, we describe the current burden of MRSA infections in healthcare and community settings across Europe and outline the main threats caused by recent changes in the epidemiology of MRSA. Thereby, we aim at identifying unmet needs of surveillance, prevention and control of MRSA in Europe.