tbuckley/cabot-search huggingface dataset:
A flow cytometry detection at a protein level of human papillomavirus
Authors: Vasiliki E. Kalodimou, Marina Kontogiorgi, Apostolos Papalois, Stefanos Chandakas
Journal: Clinical Cancer Research (2010)

Abstract Introduction: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and a necessary cause of cervical cancer. Fortunately about 90% of HPV infections clear within two years without treatment. Only in a small amount of the women infected with oncogenic types of HPV the infection will progress to high-grade lesions or even cervical cancer in the absence of treatment. During persistent infections the viral genomes often integrate into the host chromosome, which results as an over expression of the viral proteins E6 and E7. These oncoproteins induce immortalization and malignant transformation of cells conferring a certain growth advantage to the infected cells. Method: A total of 100 women undergoing routine cervical cytology samples joined this cohort study. A Thin Prep Pap Test sample was taken following consent for study participation and was tested for HPV. Cytological screening of the samples was done by trained cytologists. After sample collection, a 1 ml aliquot was removed and prepared for flow cytometric analysis and the rest of the sample was sent for PCR analysis. The samples were run on a Beckman Coulter FC500 with a 488 nm argon laser, with forward (FS) and side (SS) scatter. The gating was fixed for all samples. The instrument was set to measure counts collected from the whole volume of the samples under investigation Results: In the total of 100 cases, 4 specimens were characterized as unsatisfactory. For the rest 96 specimens, 82 specimens were found to be positive for the HPV virus and 14 negative. In the total of 100 cases the analysis of flow cytometry and PCR detection gives the same results in most cases. The cervical cells found in the liquid specimen are resolved in distinct populations using forward and side scatter of a flow cytometer. All samples in the study were analyzed using previously established gates for the presence of endocervical, ectocervical and polymorphonuclear cells. Each population was determined and the percentage of cells included was counted. The total time of analysis depended on the density of each specimen. Conclusion: HPV analysis by flow cytometry takes advantage of the fact that those oncogenic genotypes over express E6 and E7 mRNA following integration of HPV into genomic DNA. If the percentage is over 2% the result is positive, and if is lower is a negative result. With a negative result the risk of having a cervical cancer in the future is almost null. It can identify persistent HPV infections that can progress to high-grade lesions, detects the oncogenic activity, analyzing cervical cells that over express oncoproteins E6 and E7, and can be used at any time of woman life because there is no low age limit. The specificity and positive predictive value was higher than PCR analysis. This might be very useful in screening young women, a cohort in which the prevalence of HPV DNA positivity may be as high as 20%.
Predictors of delayed smear conversion after 2 months of tuberculosis treatment
Authors: Hajer ben Abdelghaffar, Eya Tangour, Leila Fekih, Soraya Fenniche, Ines Akrout, Hela Hassene, Dorra Greb, Hela Kammoun, Wided Ben hamad, Dalinda Belhabib, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2012)

Late smear conversion after 2 months of tuberculosis (TB) treatment represents a major problem. Objectives: Isolate the environmental, clinical, radiological, bacteriological and biological factors associated with a delayed smear conversion. Methods: We analyzed records from 60 tuberculosis patients, from which 20 had a delayed smear conversion. Those patients were compared in terms of clinical presentation, radiological, bacteriological and biological results, environmental data and evolution under treatment. Results: Smoking was significantly associated with delayed smear conversion (85% of patients with a late conversion were smokers versus 47.5%,p 0.05), as well as history of diabetes type II (25% with late smear conversion versus 4% of controls p=0035). This correlation was established for a delayed consultation (2 months) p 0.01. Radiological data showed that bilateral lesions and extended unilateral lesions were significantly associated with delayed smear conversion (p 0.03, p 0003). Biologically, a frank increase in CRP was statistically predictive of late conversion. (p 0.02). A positive association between the occurrence of adverse events that did not require discontinuation of treatment and delayed smear conversion was also found (p 0.02). A positive correlation has not been established for the geographical distance, the low economic level, for a body mass index below 18.5 kg/m2. In terms of bacteriology, the load of bacilli was not significantly associated with delayed smear conversion. Conclusion: Identifying predictors of late smear conversion may allow us to set up effective preventive measures to fight against the spread of the disease and limit its complications.
Bevacizumab for Recurrent Glioblastoma Multiforme: A Meta-Analysis
Authors: Eric T. Wong, Shiva Gautam, Christopher Malchow, Melody Lun, Edward Pan, Steven Brem
Journal: Journal of the National Comprehensive Cancer Network (2011)

The FDA's approval of bevacizumab for recurrent glioblastoma on May 9, 2009, was based on the significant response rate and clinical benefits seen from randomized phase II studies. Large-scale phase III data are unavailable. In an effort to determine benchmark efficacy parameters for bevacizumab and analyze its dose–response effect, the authors performed a meta-analysis of 15 studies published from 2005 to 2009, involving 548 patients with a median age of 53 years (range, 5–74 years), that used bevacizumab to treat recurrent glioblastoma. Median overall survival was 9.3 months (95% CI, 7.9–10.6 months). The respective 6-month progression-free and 6-month overall survival rates were 45% (95% CI, 34%–57%) and 76% (95% CI, 69%–84%), respectively. Median time to tumor progression was 6.1 months (95% CI, 4.2–8.1 months). The response analysis yielded a 6% complete response (95% CI, 2%–9%), 49% partial response (95% CI, 37%–61%), and 29% stable disease (95% CI, 20%–38%). No difference was seen in bevacizumab dose–response benefit between 5 mg/kg and 10 to 15 mg/kg. The efficacy benchmarks from this meta-analysis did not differ from those of the recently published randomized phase II studies. The lack of a dose–response effect would require confirmation in a prospectively conducted clinical trial.
Genetic markers of multi-drug and extensive drug resistant M. tuberculosis in Kyrgyz Republic
Authors: Jainagul Isakova, Nurmira Sovhozova, Almaz Aldashev
Journal: European Respiratory Journal (2012)

Tuberculosis (TB) is still a major cause of morbidity and mortality worldwide and also in Kyrgyz Republic. Decades of tuberculosis treatment failures in Kyrgyz Republic led to acquired resistance to the first-line antituberculous drugs, isoniazid (INH) and rifampicin (RIF), resulting in multidrug resistant tuberculosis (MDR-TB) (300-400 cases per year). Switch to second line drugs lead to acquisition of resistance to them and spread of XDR-TB. XDR tuberculosis cases represent about 3 to 10% of MDR cases in the countries like Kyrgyz Republic.

The aim of this study is the identification of mutation in rpoB, katG, inhA, ahpC and gyrA genes in MDR-Tb cases in Kyrgyz Republic.

Materials and methods. DNA samples of M. tuberculosis (M.Tb) were collected from 99 sputum samples from adult patients with primary MDR-TB. Mutations associated with resistance to rifampicin, isoniazid and fluoroquinolone were analyzed by biochip assay.

Results. We have demonstrated that in the rpoB gene of MDR M.tb strains the prevalent point mutation was Ser531Leu (59%). Among strains resistant to isoniasid the mutations of katG gene were found in 91% (inhA gene – 7% and ahpC gene -2%, respectively). The most frequent mutations in katG was Ser315Thr (91% of cases). The frequent mutations of gyrA gene were Asp94Gly and Ala90Val.

Conclusion: In Kyrgyz Republic the main cases of M.Tb resistance to rifampicin is Ser531Leu mutation in rpoB gene, to isoniazid – Ser315Thr mutation of katG gene. The cause of resistance to fluoroquinolone are gyrA gene – Asp94Gly and Ala90Val.
Post-transplantation Lymphoproliferative Disease
Authors: Stephen A. Wheless, Margaret L. Gulley, Nancy Raab-Traub, Patrick McNeillie, Isabel P. Neuringer, Hubert J. Ford, Robert M. Aris
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Elevation in Epstein-Barr virus (EBV) circulating DNA has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but few published data exist in the study of lung-transplant recipients.To determine if elevated EBV DNA levels, in combination with other risk factors, were predictive of PTLD.We conducted a retrospective, single-center study examining all lung transplant recipients (n = 296) and EBV DNA levels (n = 612) using real-time TaqMan polymerase chain reaction. There were 13 cases of PTLD overall, of which 5 occurred in the era of EBV DNA monitoring.EBV DNA levels were distributed differently among seropositive and seronegative patients, with the latter having higher values (P < 0.0001). Among the cohort of pretransplantation seropositive patients, there was one diagnosed with PTLD. The EBV DNA level in this patient was elevated at the time of PTLD diagnosis (sensitivity = 100%, specificity = 100% for PTLD). Among the cohort of pretransplantation seronegative patients, there were four with a diagnosis of PTLD. In all four patients, the EBV DNA level was detectable (sensitivity = 100%, specificity = 24%), but in only two was it elevated (sensitivity = 50%, specificity = 22%). HLA-A3 expression in the recipient and/or donor conferred additional risk for PTLD among the seronegative patients (P = 0.026 to 0.003). No other PTLD risk factor was found.EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.
Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors
Authors: Nicolas Thiault, Julie Darrigues, Véronique Adoue, Marine Gros, Bénédicte Binet, Corine Perals, Bertrand Leobon, Nicolas Fazilleau, Olivier P Joffre, Ellen A Robey, Joost P M van Meerwijk, Paola Romagnoli
Journal: Nature Immunology (2015)
Carers of patients receiving palliative care
Authors: G. Luff, M. Blanch, D. Oliver, D. Gallagher
Journal: BMJ (1998)

Editor—In one of the articles in the ABC of Palliative Care, Ramirez et al focus on carers.1 The Association of Hospice and Specialist Palliative Care Social Workers is alarmed to see the marginal role that the authors give to social workers in the column indicating sources of support for carers. Social workers in palliative care perform many tasks and are often responsible for setting up and running bereavement services. We use counselling skills to support both the patients and their carers, contributing appreciably to their psychosocial support. We have particular skills gained, for instance, in fostering and adoption, which help children come to terms with loss and change, and this is an area of work that is developing rapidly. 

We would like to draw the authors’ attention to an excellent article on social work in palliative care as it would give them an understanding of the skills that we have and the work we undertake.2 In this article, Monroe discusses the social worker’s role in the multiprofessional team and details some of the specialist skills that social workers bring to palliative care. She points out that social workers are well placed to look holistically at the needs of the patients and their families. Social workers’ training encourages an understanding of social and cultural backgrounds and a knowledge of the law and other social institutions. Monroe uses a case study format to illustrate how this knowledge combined with particular communication skills can help in assessing the family’s needs and enabling both the professional team and the family to mobilise resources on their behalf. The Association of Hospice and Specialist Palliative Care Social Workers would be happy to help any readers who would like to broaden their understanding of the role of social workers.
Double-ended Pigtail Polyethylene Stents in Management of Benign and Malignant Ureteric Obstruction
Authors: Peter A Jones, R A Moxon, M R Pittam, L Edwards
Journal: Journal of the Royal Society of Medicine (1983)

Surgical urinary diversion for incurable pelvic malignancy has a high morbidity and mortality, and external drainage provides less than ideal palliation. Six patients with ureteric obstruction caused by cancer have been managed by operative or endoscopic insertion of self-retaining polyethylene tubes. These techniques also have applications in non-malignant disease, and the treatment of two patients with benign ureteric stricture is described.
Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.
Authors: A P Venook, M J Egorin, G L Rosner, T D Brown, T M Jahan, G Batist, R Hohl, D Budman, M J Ratain, C M Kearns, R L Schilsky
Journal: Journal of Clinical Oncology (1998)

PURPOSE To characterize the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics of paclitaxel in patients with abnormal liver function. PATIENTS AND METHODS Adults with tumors appropriate for paclitaxel therapy who had abnormal liver function tests were eligible. Patients were assigned to one of three treatment cohorts: I, AST level twofold normal and bilirubin level less than 1.5 mg/dL; II, bilirubin level 1.6 to 3.0 mg/dL; and III, bilirubin level greater than 3.0 mg/dL. Doses were explored in at least three patients within each cohort. Although designed to assess a 24-hour infusion schedule, the trial was extended to also assess a 3-hour regimen. Pharmacokinetics were to be studied in all patients. RESULTS Eighty-one patients were assessable for toxicity. Patients with bilirubin levels greater than 1.5 mg/dL had substantial toxicity at all doses explored, whereas the toxicity for patients with elevated AST levels occurred at doses that ranged from 50 to 175 mg/m2 administered over 24 hours. In most patients, the DLT was myelosuppression. The pharmacokinetic data were insufficient to adequately evaluate the relationship between pharmacokinetics and toxicity in patients who received 24-hour infusions but provided evidence of a longer exposure to paclitaxel than anticipated for the doses used in this study in the 3-hour infusion group. CONCLUSION If paclitaxel is used for patients with elevated levels of AST or bilirubin, dose reductions are necessary, and an increase in toxicity can be anticipated. The increased myelosuppression observed is at least partially because of altered paclitaxel pharmacokinetics in such patients.
SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming
Authors: Andrea Burgalossi, Sangyong Jung, Guido Meyer, Wolf J. Jockusch, Olaf Jahn, Holger Taschenberger, Vincent M. O'Connor, Tei-ichi Nishiki, Masami Takahashi, Nils Brose, Jeong-Seop Rhee
Journal: Neuron (2012)
Historical Prediction Modeling Approach for Estimating Long-Term Concentrations of PM<sub>2.5</sub>in Cohort Studies before the 1999 Implementation of Widespread Monitoring
Authors: Sun-Young Kim, Casey Olives, Lianne Sheppard, Paul D. Sampson, Timothy V. Larson, Joshua P. Keller, Joel D. Kaufman
Journal: Environmental Health Perspectives (2016)

Introduction:Recent cohort studies have used exposure prediction models to estimate the association between long-term residential concentrations of fine particulate matter (PM2.5) and health. Because these prediction models rely on PM2.5 monitoring data, predictions for times before extensive spatial monitoring present a challenge to understanding long-term exposure effects. The U.S. Environmental Protection Agency (EPA) Federal Reference Method (FRM) network for PM2.5 was established in 1999.Objectives:We evaluated a novel statistical approach to produce high-quality exposure predictions from 1980 through 2010 in the continental United States for epidemiological applications.Methods:We developed spatio-temporal prediction models using geographic predictors and annual average PM2.5 data from 1999 through 2010 from the FRM and the Interagency Monitoring of Protected Visual Environments (IMPROVE) networks. Temporal trends before 1999 were estimated by using a) extrapolation based on PM2.5 data in FRM/IMPROVE, b) PM2.5 sulfate data in the Clean Air Status and Trends Network, and c) visibility data across the Weather Bureau Army Navy network. We validated the models using PM2.5 data collected before 1999 from IMPROVE, California Air Resources Board dichotomous sampler monitoring (CARB dichot), the Children's Health Study (CHS), and the Inhalable Particulate Network (IPN).Results:In our validation using pre-1999 data, the prediction model performed well across three trend estimation approaches when validated using IMPROVE and CHS data (R2 = 0.84–0.91) with lower R2 values in early years. Model performance using CARB dichot and IPN data was worse (R2 = 0.00–0.85) most likely because of fewer monitoring sites and inconsistent sampling methods.Conclusions:Our prediction modeling approach will allow health effects estimation associated with long-term exposures to PM2.5 over extended time periods ≤ 30 years.Citation:Kim SY, Olives C, Sheppard L, Sampson PD, Larson TV, Keller JP, Kaufman JD. 2017. Historical prediction modeling approach for estimating long-term concentrations of PM2.5 in cohort studies before the 1999 implementation of widespread monitoring. Environ Health Perspect 125:38–46; http://dx.doi.org/10.1289/EHP131
Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy.
Authors: M Hirsh, A Lipton, H Harvey, E Givant, K Hopper, G Jones, J Zeffren, D Levitt
Journal: Journal of Clinical Oncology (1990)

Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer.
Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review.
Authors: D E Weissman
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.3.543 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3280744 Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review. D E WeissmanxD E WeissmanSearch for articles by this author Show More Department of Medicine, Medical College of Wisconsin, Milwaukee 53226. https://doi.org/10.1200/JCO.1988.6.3.543 First Page PDF © 1988 by American Society of Clinical Oncology
The Selection of Hormonal Therapy in Prostate Cancer: Who, When, and for How Long?
Authors: Charles J. Ryan, Eric J. Small
Journal: Journal of the National Comprehensive Cancer Network (2004)

Androgen deprivation is the foundation for the systemic therapy of advanced prostate cancer. Multiple trials have tested combined androgen blockade versus androgen deprivation alone in patients with advanced disease. These studies suggest a slight advantage to the combined approaches that contain flutamide and bicalutamide, but the lack of dramatic differences in outcome makes monotherapy reasonable, especially in patients with more indolent disease. Intermittent androgen deprivation is an alternative that may allow patients to reduce the total time on androgen suppression as well as possibly delay the onset of androgen independence. A number of secondary hormonal therapies, including deferred and secondary antiandrogens, ketoconazole, and estrogens have shown modest response proportions. Patients with less advanced disease such as a rising prostate-specific antigen have varied outcomes, and no standard approach exists. In this group, noncastrating forms of hormonal therapy are being evaluated. Patients undergoing definitive local therapy who have high-risk features may benefit from early, as opposed to deferred, androgen deprivation. This review examines the evidence for the current state of the art in hormonal therapy in patients with prostate cancer and focuses, in particular, on treatment composition and timing as well as the rationale for the use of hormonal therapy in early stage disease.