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91.
Angie S. Price Amy K. Nelson Alip Ghosh Shyamasundaran Kottilil Joel V. Chua 《Journal of medical virology》2023,95(1):e28105
Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log10 IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination. 相似文献
92.
Charles M. Haberkern Anne M. Lynn Jeremy M. Geiduschek Mary Kay Nespeca Lawrence E. Jacobson Susan L. Bratton Maureen Pomietto 《Journal canadien d'anesthésie》1996,43(12):1203-1210
Purpose
To compare two doses of bolus epidural morphine with bolus iv morphine for postoperative pain after abdominal or genitourinary surgery in infants.Methods
Eighteen infants were randomly assigned to bolus epidural morphine (0.025 mg · kg?1 or 0.050 mg · kg?1) or bolus iv morphine (0.050–0.150 mg · kg?1). Postoperative pain was assessed and analgesia provided, using a modified infant pain scale. Monitoring included continuous ECG, pulse oximetry, impedance and nasal thermistor pneumography. The CO2 response curves and serum morphine concentrations were measured postoperatively.Results
Postoperative analgesia was provided within five minutes by all treatment methods. Epidural groups required fewer morphine doses (3.8 ± 0.8 for low dose [LE], 3.5 ± 0.8 for high dose epidural [HE] vs. 6.7 ± 1.6 for iv, P < 0.05) and less total morphine (0.11 ± 0.04 mg · kg?1 for LE, 0.16 ± 0.04 for HE vs 0.67 ± 0.34 for iv, P < 0.05) on POD1 Dose changes were necessary in all groups for satisfactory pain scores. Pruritus, apnoea, and haemoglobin desaturation occurred in all groups. CO2 response curve slopes, similar preoperatively (range 36–41 ml · min?1 · mmHg ETco 2 ?1 · kg?1) were generally depressed (range, 16–27 ml · min?1 · mmHg ETco 2 ?1 · kg?1) on POD1. Serum morphine concentrations, negligible in LE (<2 ng · ml?1), were similar in the HE and iv groups (peak 8.5 ± 12.5 and 8.6 ± 2.4 ng · ml?1, respectively).Conclusion
Epidural and iv morphine provide infants effective postoperative analgesia, although side effects are common. Epidural morphine gives satisfactory analgesia with fewer doses (less total morphine); epidural morphine 0.025 mg · kg?1 is appropriate initially. Infants receiving epidural or iv morphine analgesia postoperatively need close observation in hospital with continuous pulse oximetry. 相似文献93.
Point and Counterpoint
A rejoinder to Professor Bruening 相似文献94.
95.
Anne EG Lenferink Joanne Magoon Christiane Cantin Maureen D O'Connor-McCourt 《Breast cancer research : BCR》2004,6(5):R514
Introduction
This report describes the isolation and characterization of three new murine mammary epithelial cell lines derived from mammary tumors from MMTV (mouse mammary tumor virus)/activated Neu + TβRII-AS (transforming growth factor [TGF]-β type II receptor antisense RNA) bigenic mice (BRI-JM01 and BRI-JM05 cell lines) and MMTV/activated Neu transgenic mice (BRI-JM04 cell line). 相似文献96.
Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. 总被引:4,自引:0,他引:4
Jame Abraham Manish Agrawal Susan Bakke Ann Rutt Maureen Edgerly Frank M Balis Brigitte Widemann Louis Davis Bharat Damle Daryl Sonnichsen David Lebwohl Susan Bates Herb Kotz Tito Fojo 《Journal of clinical oncology》2003,21(9):1866-1873
PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. 相似文献
97.
Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. 总被引:7,自引:0,他引:7
Peter B Illei Valerie W Rusch Maureen F Zakowski Marc Ladanyi 《Clinical cancer research》2003,9(6):2108-2113
PURPOSE: Homozygous deletions at chromosome region 9p21 targeting the CDKN2A gene have been reported as a common cytogenetic abnormality in mesothelioma. MTAP, a gene approximately 100-kb telomeric to CDKN2A, encodes methylthioadenosine phosphorylase, an enzyme essential in the salvage of cellular adenine and methionine, and its codeletion with CDKN2A has been reported in other tumors. The aim of this study was to define the prevalence of homozygous deletion of CDKN2A alone or in combination with MTAP in a large series of pleural mesothelioma. EXPERIMENTAL DESIGN: We used a fluorescent in situ hybridization assay for CDKN2A and MTAP on interphase nuclei in imprints of frozen tissue from 95 cases of pleural mesothelioma. Histologically, the cases were classified as epithelial (71), biphasic (19) and sarcomatous (5). In each experiment, a 9p21 locus specific probe and a chromosome 9 centromeric probe were used and fluorescent in situ hybridization signals for both probes were simultaneously recorded in at least 100 nuclei. Cases were considered homozygously deleted if both 9p21 signals were lost in at least 20% of nuclei. RESULTS: Overall, 70 cases (74%) had homozygous deletion of CDKN2A. MTAP was codeleted in 64 of these cases (91%). No case with MTAP deletion without CDKN2A deletion was identified. Homozygous loss of CDKN2A was seen in 49 of 71 epithelial (70%), 16 of 19 biphasic (89%), and 5 of 5 sarcomatous (100%) mesotheliomas. CONCLUSIONS: Homozygous deletion of CDKN2A is seen in the majority of pleural mesotheliomas, and MTAP is codeleted in most of these cases. Previous cell line studies have shown that loss of MTAP renders cells dependent on de novo synthesis of purine derivatives. Thus, the particularly high prevalence of MTAP codeletion in mesothelioma makes it an ideal candidate for trials of targeted therapy using inhibitors of de novo AMP synthesis (e.g., L-alanosine). 相似文献
98.
Karen M Emmons Rita M Butterfield Elaine Puleo Elyse R Park Ann Mertens Ellen R Gritz Maureen Lahti Fredrick P Li 《Journal of clinical oncology》2003,21(2):189-196
PURPOSE: This article describes baseline data collection and the intervention design of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study. The purpose of this article is to evaluate demographic, psychosocial, and cancer-related factors that are associated with smoking behavior and mediators of smoking cessation. PATIENTS AND METHODS: This study includes 796 smokers from the Childhood Cancer Survivors Study database who were diagnosed with cancer before the age of 21, had survived at least 5 years, and were at least 18 years of age at the time of the baseline survey. Correlates of smoking behaviors included smoking rate, number of recent quit attempts, and nicotine dependence; two key mediators of smoking cessation, readiness to quit smoking and self-efficacy, were also assessed. RESULTS: Participants smoked, on average, 14 cigarettes/day; 53.2% were nicotine dependent, and 58% had made at least one quit attempt in the past year. Smoking behaviors were primarily associated with demographic variables; mediators of cessation were primarily associated with age at cancer diagnosis and perceived vulnerability to smoking-related illnesses. Severity of psychologic symptoms was associated with increased smoking rate, high nicotine dependence, and low self-efficacy. Support for quitting was related to smoking rate, number of quit attempts, readiness to quit smoking, and self-efficacy. CONCLUSION: These findings indicate that many cancer survivors who smoke are receptive to smoking cessation interventions. Factors related to mediators of smoking cessation might be particularly good targets for intervention. 相似文献
99.
Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. 总被引:13,自引:0,他引:13
Robert J Downey Tim Akhurst David Ilson Robert Ginsberg Manjit S Bains Mithat Gonen Heng Koong Marc Gollub Bruce D Minsky Maureen Zakowski Alan Turnbull Steven M Larson Valerie Rusch 《Journal of clinical oncology》2003,21(3):428-432
PURPOSE: Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy. PATIENTS AND METHODS: Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months. RESULTS: PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively). CONCLUSION: Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted. 相似文献
100.