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101.
Carlos M. Villaln Eduardo Ramírez‐San Juan Araceli Snchez‐Lpez Guadalupe Bravo Edwin W. Willems Pramod R. Saxena David Centurin 《Basic & clinical pharmacology & toxicology》2003,92(4):165-172
Abstract: The present study investigated the effects of dopamine on the canine external carotid circulation. One min. intracarotid artery (i.c.) infusions of dopamine (10–310 μg min.?1) produced dose‐dependent decreases in the canine external carotid conductance without affecting blood pressure or heart rate. This effect was mimicked by the D1/2‐like receptor agonist apomorphine (1–310 μg min?1), but not by the D2‐like receptor agonist, bromocriptine (31–310 μg min.?1). In contrast, fenoldopam (1–310 μg min.?1, intracarotid), a D1‐like receptor agonist, produced dose‐dependent increases in external carotid conductance. The vasoconstrictor response to dopamine was abolished after intravenous administration of the antagonists, phentolamine (α1/2; 2000 μg kg?1) or rauwolscine (α2; 100 μg kg?1), but remained unaffected after prazosin (α1; 100 μg kg?1) or haloperidol (D2‐like; 1000 μg kg?1). Interestingly, after phentolamine not only were the vasoconstrictor responses to dopamine abolished, but even a dose‐dependent vasodilator component was unmasked. These vasodilator responses to dopamine remained unchanged after intravenous haloperidol or propranolol (1000 μg kg?1 each). On the other hand, the vasodilator responses to fenoldopam, which remained unchanged after intravenous saline (0.1 ml kg?1), propranolol (1000 μg kg?1) or vagosympathectomy, were abolished by the D1‐like receptor antagonist, SCH‐23390 (10 μg kg?1). Lastly, the responses to dopamine and fenoldopam were not significantly altered after intraperitoneal pretreatment with reserpine (5 mg kg?1; ?24 hr). The above results suggest that the canine external carotid vasoconstrictor responses to dopamine: (i) are mainly mediated by α2‐adrenoceptors; and (ii) overshadow a vasodilator component, which involves vascular D1‐like receptors. 相似文献
102.
Anthony T C Chan Brigette B Y Ma Y M Dennis Lo S F Leung W H Kwan Edwin P Hui Tony S K Mok Michael Kam Lisa S Chan Samuel K W Chiu K H Yu K Y Cheung Karen Lai Maria Lai Frankie Mo Winnie Yeo Ann King Philip J Johnson Peter M L Teo Benny Zee 《Journal of clinical oncology》2004,22(15):3053-3060
PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC. 相似文献
103.
Bradley R Pieters Augustinus A M Hart Nicola S Russell Edwin P M Jansen Johannes L Peterse Jacques Borger Emiel J Th Rutgers 《Radiotherapy and oncology》2003,67(2):159-164
BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome. 相似文献
104.
Ruth Plummer Charlotte Rees Andrew Hughes Philip Beale Martin Highley Jose Trigo Sathyarathnarn Gokul Ian Judson Hilary Calvert Ann Jackman Fraser Mitchell Robert Smith Edwin Douglass 《Clinical cancer research》2003,9(4):1313-1322
PURPOSE: ZD9331 is a novel, direct-acting antifolate cytotoxic that does not require polyglutamation for activity, and is a specific thymidylate synthase inhibitor. This Phase I trial aimed to determine the maximum tolerated dose of ZD9331, given as a 30-min i.v. infusion on days 1 and 8 of a 21-day cycle. Pharmacokinetic parameters and tumor response were also assessed. EXPERIMENTAL DESIGN: A total of 71 patients, with a range of solid malignancies and refractory to standard therapies (44% had received > or =3 prior chemotherapy regimens), were treated. The most common malignancies were colorectal cancer (35% of patients) and ovarian cancer (31%). ZD9331 was escalated from 4.8 mg/m(2)/day. RESULTS: Dose-limiting toxicity occurred at 162.5 mg/m(2) ZD9331, with grade 4 thrombocytopenia, grade 4 neutropenia lasting > or =7 days, and grade 3 nonhematologic toxicity. Plasma clearance of ZD9331 was slow and dose-dependent; however, ZD9331 pharmacokinetics were nonlinear. Pharmacodynamics of ZD9331 were determined by measurement of plasma deoxyuridine, which increased at all of the dose levels; dose-related increases in plasma deoxyuridine were significant (P = 0.003) on day 5. Stable disease was observed in 37% of patients; 23% of ovarian cancer patients had a > or =50% reduction in CA125 levels. CONCLUSIONS: The maximum tolerated dose of this schedule was 130 mg/m(2). The toxicity profile at this dose was acceptable, with 7 of 28 patients treated developing grade 3/4 neutropenia and thrombocytopenia, 2 grade 4 diarrhea, and 2 grade 3/4 rash. This schedule was convenient and demonstrated activity in extensively pretreated patients; therefore, this is the recommended dose for study in Phase II trials. 相似文献
105.
Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. 总被引:3,自引:0,他引:3
John W Smith Edwin B Walker Bernard A Fox Daniel Haley Ketura P Wisner Teri Doran Brenda Fisher Lisa Justice William Wood John Vetto Holden Maecker Annemiek Dols Sybren Meijer Hong-Ming Hu Pedro Romero W Gregory Alvord Walter J Urba 《Journal of clinical oncology》2003,21(8):1562-1573
PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results. 相似文献
106.
Caroline Y. Yang Peter E. Andersen Edwin C. Everts James I. Cohen 《The Laryngoscope》1998,108(7):1006-1008
Objective: Although there is a generalized understanding of the relatively low overall incidence of nodal disease from purely glottic carcinoma, the exact role for elective neck treatment in the management of this disease remains controversial. The purpose of this study was to identify the incidence of occult nodal disease (including paratracheal) in patients who have glottic carcinoma without significant extra-glottic extension and to identify which patients are at risk for this. A retrospective chart review of 92 such patients who had either undergone neck dissection or been observed for a minimum of 2 years was performed. Results: For the 92 patients, neck treatment consisted of observation in 68 patients, paratracheal node dissection in four, unilateral neck dissection in four, unilateral neck dissection and excision of paratracheal nodes in 14, and bilateral neck dissection with paratracheal node excision in two. Of the 24 nodal dissections performed, four were positive for occult metastatic disease. No patient in the observation group developed nodal disease. Conclusion: The incidence of occult nodal disease in NO glottic carcinoma is low, 0% in early stage disease (T1–T2) and 19% in late stage disease (T3–T4). Nodes at highest risk included only the paratracheal, level II, and level III. Elective neck treatment should only be undertaken for advanced (T3–T4) disease and even then is of questionable benefit. If undertaken, it should have a low potential morbidity, such as selective neck dissection or radiation. Computed tomography was not useful in staging the neck for this subset of patients. 相似文献
107.
Mary Feng Siavash Jabbari Alexander Lin Carol R Bradford Douglas B Chepeha Theodoros N Teknos Francis P Worden Christina Tsien Matthew J Schipper Gregory T Wolf Laura A Dawson Avraham Eisbruch 《Radiotherapy and oncology》2005,77(1):32-38
BACKGROUND AND PURPOSE: Predictive factors for local-regional (LR) failures after parotid-sparing, Intensity modulated (IMRT) or 3D conformal radiotherapy for head and neck (HN) cancers were assessed. PATIENTS AND METHODS: One hundred and fifty-eight patients with mostly stages III-IV HN squamous cell carcinoma underwent curative bilateral neck irradiation aimed at sparing the parotid glands. Patient, tumor, and treatment factors were analyzed as predictive factors for LR failure. RESULTS: Twenty-three patients had LR recurrence (19 in-field and four marginal). No differences were found in the doses delivered to the PTVs of patients with or without in-field recurrences. In univariate analysis, tumor site was highly predictive for LR failure in both postoperative and definitive RT patients. In postoperative RT patients, pathologic tumor size, margin status, extracapsular extension (ECE) and number of lymph node metastases, were also significantly predictive. Multivariate analysis showed tumor site (oropharynx vs. other sites) to be a significant predictor in all patients, and involved margins and number of involved lymph nodes in postoperative patients. CONCLUSIONS: Clinical rather than dosimetric factors predicted for LR failures in this series, and were similar to those reported following standard RT. These factors may aid in the selection of patients for studies of treatment intensification using IMRT. 相似文献
108.
Harald J J Moonen Edwin J C Moonen Lou Maas Jan W Dallinga Jos C S Kleinjans Theo M C M de Kok 《Food and chemical toxicology》2004,42(6):869-878
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.4 ng/g) or low (1.7 ng/g) dose of PhIP. Urinary PhIP excretion levels were found to reflect recent dietary exposure levels, with average levels of 174% (high dose group) and 127% (low dose group), as compared to pre-feed levels. Urinary caffeine metabolite ratios were significantly different between the two NAT2 genotypes, whereas for CYP1A2, the apparent difference in metabolic ratios between the genotypes was statistically non-significant. Significant correlations were firstly found between the CYP1A2-164A-->C (CYP1A2*1F) polymorphism and differential urinary PhIP excretion levels. Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility. 相似文献
109.
110.
Victor R. Pendleton Edwin Willems Paul Swank Walker S. Carlos Poston G. Ken Goodrick Rebecca S. Reeves 《Eating disorders》2013,21(4):351-360
This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress. 相似文献