tbuckley/cabot-search huggingface dataset:
Screening for Chlamydia trachomatis in Asymptomatic Women Attending Family Planning Clinics: A Cost-Effectiveness Analysis of Three Strategies
Authors: M. Rene Howell
Journal: Annals of Internal Medicine (1998)

Background: Screening women for Chlamydia trachomatis in family planning clinics is associated with a reduced incidence of chlamydial sequelae. However, the question of whom to screen to maintain efficient use of resources remains controversial. Objective: To assess the cost-effectiveness of chlamydial screening done according to three sets of criteria in asymptomatic women attending family planning clinics. Design: Cost-effectiveness analysis done by using a decision model with the perspective of a health care system. Model estimates were based on analysis of cohort data, clinic costs, laboratory costs, and published data. Setting: Two family planning clinics in Baltimore, Maryland. Patients: 7699 asymptomatic women who presented between April 1994 and August 1996. Intervention: Three screening strategies-screening according to the criteria of the Centers for Disease Control and Prevention (CDC), screening all women younger than 30 years of age, and universal screening-were retrospectively applied and compared. All women were tested with polymerase chain reaction. Measurements: Medical outcomes included sequelae prevented in women, men, and infants. Total costs included screening program costs and future medical costs of all sequelae. The incremental cost-effectiveness ratios of each strategy were calculated. Results: Without screening, 152 cases of pelvic inflammatory disease would occur at a cost of $676 000. Screening done by using the CDC criteria would prevent 64 cases of pelvic inflammatory disease at a cost savings of $231 000. Screening all women younger than 30 years of age would prevent an additional 21 cases of pelvic inflammatory disease and save $74 000. Universal screening would prevent an additional 6 cases of pelvic inflammatory disease but would cost $19 000 more than age-based screening, or approximately $3000 more per case of pelvic inflammatory disease prevented. If the prevalence of C. trachomatis is more than 10.2% or if less than 88.5% of infections occur in women younger than 30 years of age, universal screening provides the greatest cost savings. Conclusions: These results suggest that age-based screening provides the greatest cost savings of the three strategies examined. However, universal screening is desirable in some situations. In general, screening done by using any criteria and a highly sensitive diagnostic assay should be part of any chlamydial prevention and control program or health plan.
Effect of intravenous corticosteroid on ex vivo leukotriene generation by blood leucocytes of normal and asthmatic patients
Authors: P. P Hood, T. P Cotter, J. F Costello, A. P Sampson
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The cysteinyl-leukotrienes (LTC<sub>4</sub>, LTD<sub>4</sub>, LTE<sub>4</sub>) are critical bronchoconstrictor and eosinophilotactic mediators in asthma while LTB<sub>4</sub> is a potent neutrophil chemoattractant. Glucocorticosteroids are front line anti-inflammatory treatment for asthma but the evidence that they reduce leukotriene (LT) synthesis in vivo is poor. <h3>METHODS</h3> In a randomised, double blind, placebo controlled, crossover trial immunoassays were used to measure ex vivo synthesis of LTC<sub>4</sub>and LTB<sub>4</sub> by calcium ionophore stimulated blood leucocytes and bronchoalveolar lavage (BAL) cells of eight normal subjects and eight patients with mild allergic asthma 4–6 hours after intravenous administration of a single 100 mg dose of methylprednisolone. <h3>RESULTS</h3> Ionophore stimulated synthesis of LTC<sub>4</sub> (but not LTB<sub>4</sub>) in blood granulocytes tended to be higher in asthmatic subjects (mean 9.7 ng/10<sup>6</sup> cells) than in normal subjects (4.2 ng/10<sup>6</sup> cells; p = 0.08) and intravenous methylprednisolone reduced synthesis of LTC<sub>4</sub> (but not LTB<sub>4</sub>) to normal levels (2.9 ng/10<sup>6</sup> cells; 95% CI for the reduction 1.0 to 12.5 ng/10<sup>6</sup> cells; p = 0.03). In blood mononuclear cells methylprednisolone reduced LTC<sub>4</sub>synthesis in asthmatic subjects from 1.26 to 0.79 ng/10<sup>6</sup>cells (95% CI for the reduction 0.26 to 0.79, p = 0.014) and tended to reduce LTC<sub>4</sub> synthesis in normal subjects from 1.51 to 0.86 ng/10<sup>6</sup> cells (p = 0.08). Methylprednisolone also significantly reduced synthesis of LTB<sub>4</sub> in mononuclear cells from both subject groups (p = 0.014). It had no effect on LT synthesis in BAL cells from either group nor on LT levels in BAL fluid. <h3>CONCLUSIONS</h3> Intravenous methylprednisolone can reduce synthesis of leukotrienes in blood granulocytes and mononuclear cells within six hours of a single intravenous dose.
Mitogenic Signaling via Platelet-Derived Growth Factor β in Metanephric Mesenchymal Cells
Authors: Brent Wagner, Jill M. Ricono, Yves Gorin, Karen Block, Mazen Arar, Dan Riley, Goutam Ghosh Choudhury, Hanna E. Abboud
Journal: Journal of the American Society of Nephrology (2007)

Mice deficient in either platelet-derived growth factor (PDGF) B chain or PDGF receptor (PDGFR) β lack mesangial cells. PDGF stimulates proliferation and migration of metanephric mesenchymal cells, from which mesangial cells are derived. Binding of PDGF to PDGFR-β induces autophosphorylation at specific tyrosine residues and activates various effector proteins, including phosphatidylinositol-3-kinase (PI3-K). This study explored the role of PI 3-K and reactive oxygen species (ROS) in PDGF-mediated signaling using cells established from wild-type and PDGFR-β −/− metanephric blastemas at 11.5 days post-conception. PDGF-induced effects that were dependent on PI3-K activation were determined using PDGFR-β −/− cells made to express “add-back” mutant PDGFR-β capable of binding PI3-K. We found that PDGF is mitogenic for mesenchymal cells expressing PDGFR-β, and PI3-K is an important regulator of PDGF-induced DNA synthesis. Activation of ERK1/2 is partially dependent on PI3-K, and both the PI3-K and MEK-ERK1/2 pathways contribute to PI3-K–dependent mitogenesis. In addition, PDGF-induced DNA synthesis in wild-type cells was found to be dependent on ROS that are generated downstream of PI3-K activation. Using antisense oligonucleotides and small interfering RNA, we determined that the NAD(P)H oxidase Nox4 produces these ROS that activate Akt and the MEK-ERK1/2 mitogenic cascade. In conclusion, the present study demonstrates Nox4 involvement in PDGF-induced DNA synthesis in metanephric mesenchymal cells and provides the first evidence that PDGF-induced PI3-K activity enhances production of ROS by Nox4.
Prospective Diagnosis of the Initial Prodrome for Schizophrenia Based on the Structured Interview for Prodromal Syndromes: Preliminary Evidence of Interrater Reliability and Predictive Validity
Authors: Tandy J. Miller, Thomas H. McGlashan, Joanna Lifshey Rosen, Lubna Somjee, Philip J. Markovich, Kelly Stein, Scott W. Woods
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study was conducted to determine the interrater reliability and predictive validity of a set of diagnostic criteria for the prodrome of the first episode of schizophrenic psychosis when based on the Structured Interview for Prodromal Syndromes. METHOD: The subjects were patients referred for evaluation because of a suspected schizophrenia prodromal syndrome. For the reliability study, two to four raters independently diagnosed 18 patients on the basis of face-to-face or videotaped interviews. For the validity study, 6- and 12-month outcome data were collected for 29 patients. RESULTS: Agreement in differentiating prodromal from nonprodromal patients was 93%. The prodromal features had converted to schizophrenic psychosis for 46% of the prodromal patients at 6 months and for 54% at 12 months. CONCLUSIONS: In small groups of subjects, these diagnostic criteria for the schizophrenic prodrome and the Structured Interview for Prodromal Syndromes showed promising interrater reliability and predictive validity.
Chemotherapy Alone or Chemotherapy with Chest Radiation Therapy in Limited Stage Small Cell Lung Cancer
Authors: P. A. Bunn, A. S. Lichter, R. W. Makuch, M. H. Cohen, S. R. Veach, M. J. Matthews, A. J. Anderson, M. Edison, E. Glatstein, John D Minna
Journal: Annals of Internal Medicine (1987)

Study Objective: To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy. Design: Randomized trial with a median follow-up of 57 months. Setting: A single government institution—the National Cancer Institute. Patients: Consecutive sample of 96 patients with histologically confirmed small cell lung cancer that was confined to the hemithorax of origin or mediastinal and supraclavicular nodes, and which could be encompassed within a tolerable radiation portal ("limited stage"). All patients were followed until death or the end of the study period. Interventions: Chemotherapy: Cyclophosphamide, methotrexate, and lomustine in 6-week cycles alternating with vincristine, adriamycin, and procarbazine in 6-week cycles, for a total of 48 weeks. Radiation therapy: Chest irradiation to 40 Gy in 15 fractions over 3 weeks, given simultaneously with the first chemotherapy cycle. Measurements and Main Results: The combined therapy led to a significantly higher response rate (complete responses, 81%, compared with partial responses, 43%; 95% Cl for the difference, 20% to 56%), significantly improved local control of the chest tumor (p < 0.001), and significantly longer survival (p < 0.035) (median, 15.0 months, compared with 11.6 for chemotherapy alone). The combined therapy produced significantly more myelosuppression, weight loss, esophagitis, and pulmonary dysfunction. There were more infections and deaths from toxicity in the combined treatment group, but the differences between groups were not statistically significant. Conclusion: A regimen of combined chemotherapy and chest radiation therapy given concurrently is superior to chemotherapy given alone in inducing remission and prolonging survival in patients with limited stage small cell lung cancer, and the benefit of combined therapy is reduced by its greater toxicity.
Efficacy and Antivascular Effects of EphA2 Reduction With an Agonistic Antibody in Ovarian Cancer
Authors: Charles N. Landen, Chunhua Lu, Liz Y. Han, Karen T. Coffman, Elizabeth Bruckheimer, Jyotsnabaran Halder, Lingegowda S. Mangala, William M. Merritt, Yvonne G. Lin, Changhou Gao, Rosemarie Schmandt, Aparna A. Kamat, Yang Li, Premal Thaker, David M. Gershenson, Nila U. Parikh, Gary E. Gallick, Michael S. Kinch, Anil K. Sood
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: EphA2 is an oncoprotein and tyrosine kinase receptor that is overexpressed in ovarian and many other cancers. We investigated the effects of reduced EphA2 levels on tumor growth and the tumor microenvironment in an orthotopic ovarian cancer model. Methods: The effect of the EphA2-agonistic monoclonal antibody EA5, alone or in combination with paclitaxel, on the growth of ovarian cancer cells (SKOV3ip1, HeyA8, and HeyA8MDR [taxane–platinum resistant]) was determined in vitro and in vivo by immunoblotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and immunohistochemical analysis. Expression of EphA2 and markers of angiogenesis (CD31, vascular endothelial growth factor [VEGF], and basic fibroblast growth factor), proliferation (proliferating cell nuclear antigen), and endothelial cell apoptosis (CD31–terminal deoxynucleotidyl transferase biotin–deoxyuridine triphosphate nick-end labeling colocalization) and phosphorylation of Src were analyzed by immunoblotting, immunohistochemistry, immunofluorescence, and in situ hybridization in tumors from treated mice. Statistical tests were two-sided. Results: EA5 antibody treatment led to a more than 90% reduction in EphA2 expression in HeyA8 tumors in vivo. In mice bearing orthotopic SKOV3ip1 or HeyA8 tumors, 4 weeks of EA5 treatment resulted in tumors that weighed 31% and 45% less, respectively, than those in control (IgG-treated) mice (95% confidence interval [CI] = −0.09% to 71% and 20% to 70%, P = .27 and .01, respectively). Combination therapy with EA5 and paclitaxel reduced tumor weight by 77% and 80% (95% CI = 63% to 91% and 68% to 91%), respectively, compared with paclitaxel alone and by 92% and 88% (95% CI = 87% to 97% and 80% to 94%), respectively, compared with IgG alone. Combination therapy also reduced the weight of HeyA8MDR tumors by 47% (95% CI = 24% to 72%) compared with paclitaxel. Mice bearing SKOV3ip1 or HeyA8 tumors that were treated with combination therapy survived longer than those treated with paclitaxel alone (median survival = 144 versus 69 days and 46 versus 37 days, respectively). EA5-treated tumors had reduced microvascular density, proliferation, and VEGF protein and mRNA levels, with increased endothelial cell apoptosis. EphA2 was associated with Src, which was rapidly dephosphorylated after EA5 treatment. Conclusions: EA5 in combination with paclitaxel decreased tumor growth in an orthotopic ovarian cancer mouse model through antiangiogenic mechanisms associated with reduced levels of VEGF and phosphorylated Src. Humanized antibody constructs against EphA2 are worthy of future study.
Physical Exertion, Exercise, and Sudden Cardiac Death in Women
Authors: William Whang, JoAnn E. Manson, Frank B. Hu, Claudia U. Chae, Kathryn M. Rexrode, Walter C. Willett, Meir J. Stampfer, Christine M. Albert
Journal: JAMA (2006)

Exercise is associated with a lower risk of cardiovascular events but may transiently increase the risk of ventricular arrhythmias. Its short-term and long-term associations with risk of sudden cardiac death among women are unclear.To compare the risk of sudden cardiac death in women during moderate to vigorous exertion with the risk of sudden cardiac death during lighter or no exertion; and to assess the long-term association between moderate to vigorous exercise and sudden cardiac death.Prospective, nested case-crossover study of 288 cases of sudden cardiac death within the Nurses' Health Study (1980-2004); and a prospective cohort analysis of 69,693 participants without prior cardiovascular disease followed up from 1986-2004.Risk of sudden cardiac death associated with moderate to vigorous exertion.The absolute risk of sudden cardiac death associated with moderate to vigorous exertion was exceedingly low at 1 per 36.5 million hours of exertion. In case-crossover analyses, the risk of sudden cardiac death was transiently elevated during moderate to vigorous exertion (relative risk [RR], 2.38; 95% confidence interval [CI], 1.23-4.60; P = .01) compared with the risk during lesser or no exertion. Habitual moderate to vigorous exertion modified this transient risk (P = .005 for interaction) and the risk was no longer significantly elevated among those who exercised 2 or more hours per week. In the cohort analyses, an increasing amount of moderate to vigorous exercise was associated with a lower long-term risk of sudden cardiac death in age-adjusted and multivariable models that excluded biological intermediates (P = .006 for trend). This relationship was attenuated when biological intermediates were included (P = .06 for trend); however, the reduction in risk remained significant among women who exercised 4 or more hours per week (adjusted RR, 0.41; 95% CI, 0.20-0.83; P = .01) compared with women who did not exercise.These prospective data suggest that sudden cardiac death during exertion is an extremely rare event in women. Regular exercise may significantly minimize this small transient risk and may lower the overall long-term risk of sudden cardiac death.
Nucleotide Excision Repair Pathway Genes and Oral Premalignant Lesions
Authors: Yunfei Wang, Margaret R. Spitz, J. Jack Lee, Maosheng Huang, Scott M. Lippman, Xifeng Wu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Oral premalignant lesions (OPL) are associated with tobacco exposure and an increase in risk of oral cancer. Nucleotide excision repair (NER) is one of the major DNA repair pathways involved in the removal of tobacco carcinogen adducts. Polymorphisms in NER genes may cause variations in DNA repair capacity and increase susceptibility to both premalignant lesions and cancer. Experimental Design: In this case-control study of 144 OPL patients and 288 controls, we genotyped 11 polymorphisms in 8 major NER genes, including XPA [A23G at 5′ untranslated region (UTR)], XPD (Asp312Asn, Lys751Gln), XPC (Ala499Val, Lys939Gln), XPG (His1104Asp), XPF (Pro662Ser), ERCC6 (Met1097Val, Arg1230Pro) Rad23B (Ala249Val), and CCNH (Val270Ala). Results: We found significant or borderline-significant associations between OPL risk and the polymorphisms XPA (A23G), XPD (Lys751Gln), XPC (Ala499Val), Rad23B (Ala249Val), and XPD (Asp312Asn), with adjusted odds ratios (ORs) of 1.97 [95% confidence interval (95% CI), 1.27-3.06], 1.60 (95% CI, 1.02-2.51), 0.63 (95% CI, 0.40-1.00), 0.67 (95% CI, 0.41-1.07), and 1.42 (95% CI, 0.90-2.23), respectively. When further stratified analyses were done, the decreased risk conferred by the XPC (Ala499Val) variant allele was more evident in older individuals (OR, 0.50; 95% CI, 0.24-1.03), in women (OR, 0.46; 95% CI, 0.21-1.01), in ever smokers (OR, 0.59; 95% CI, 0.33-1.05), and in never drinkers (OR, 0.42; 95% CI, 0.18-1.00). Finally, we found joint effects between these NER gene variants and smoking status. For example, when never smokers with the XPA 23A genotypes were used as the reference group, the ORs for never smokers with the XPA 23G genotype, smokers with the 23A genotype, and smokers with 23G genotypes were 2.19 (1.07-4.46), 2.64 (1.42-4.89), and 5.04 (2.62-9.69), respectively. Gene-gene and gene-smoking interaction for OPLs risk were also confirmed by multifactor dimensionality reduction (MDR) analysis in our study. MDR analysis revealed that a model containing ever smoking, XPA (A23G), XPC (Ala499Val), and XPD (Asp312Asn) was the best model to predict OPL risk with maximum average cross-validation consistency and minimum prediction error (P &amp;lt; 0.001). Conclusion: Our results suggest that polymorphisms in NER genes may contribute to genetic susceptibility to OPLs and may therefore contribute to the development of oral cancer.
PDGF-C Mediates the Angiogenic and Tumorigenic Properties of Fibroblasts Associated with Tumors Refractory to Anti-VEGF Treatment
Authors: Yongping Crawford, Ian Kasman, Lanlan Yu, Cuiling Zhong, Xiumin Wu, Zora Modrusan, Josh Kaminker, Napoleone Ferrara
Journal: Cancer Cell (2009)
The gallium scan predicts relapse in patients with Hodgkin's disease treated with combined modality therapy
Authors: F.B. Hagemeister, R. Purugganan, D.A. Podoloff, M. Hess, M.A. Rodriguez, P. McLaughlin, F. Swan, J.E. Romaguera, F. Cabanillas
Journal: Annals of Oncology (1994)
Phase I Trial of Iodine-131 Tositumomab With High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Relapsed Non-Hodgkin's Lymphoma
Authors: Julie M. Vose, Philip J. Bierman, Charles Enke, Jordan Hankins, Gregory Bociek, James C. Lynch, James O. Armitage
Journal: Journal of Clinical Oncology (2004)

To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT.The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%.There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.
TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases
Authors: Chi Young Ok, Keyur P Patel, Guillermo Garcia-Manero, Mark J Routbort, Jie Peng, Guilin Tang, Maitrayee Goswami, Ken H Young, Rajesh Singh, L Jeffrey Medeiros, Hagop M Kantarjian, Rajyalakshmi Luthra, Sa A Wang
Journal: Journal of Hematology & Oncology (2015)

TP53 mutation is more prevalent in therapy-related myeloid neoplasms (t-MN) than their de novo counterparts; however, the pattern of mutations involving TP53 gene in t-MN versus de novo diseases is largely unknown.We collected 108 consecutive patients with therapy-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (t-AML). Clinical, hematological, and cytogenetic data were collected by searching the electronic medical record. TP53 sequencing was performed in all patients using a clinically validated next-generation sequencing-based gene panel assay. A previously published patient cohort consisting of 428 patients with de novo MDS/AML was included for comparison.We assessed 108 patients with t-MN, in which 40 patients (37%) had TP53 mutations. The mutation frequency was similar between t-MDS and t-AML; but significantly higher than de novo MDS/AML (62/428 patients, 14.5%) (p<0.0001). TP53 mutations in t-MN were mainly clustered in DNA-binding domains, with an allelic frequency of 37.0% (range, 7.1 to 98.8). Most mutations involved single nucleotide changes, of which, transitions (65.9%) were more common than transversions (34.1%). Missense mutations were the most frequent, followed by frameshift and nonsense mutations. This TP53 mutation pattern was strikingly similar to that observed in de novo MDS/AML. TP53 mutations in t-MN were associated with a complex karyotype (p<0.0001), a higher number of chromosomal abnormalities (p<0.0001), and an inferior overall survival in affected patients (6.1 vs 14.1 months) by univariate (p<0.0001) and multivariate analyses (p=0.0020).Our findings support the recent notion that heterozygous TP53 mutation may be a function of normal aging and that mutated cells are subject to selection upon exposure to cytotoxic therapy. t-MN carrying TP53 mutation have an aggressive clinical course independent of other confounding factors.