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221.
Najat C Daw Wayne L Furman Clinton F Stewart Lisa C Iacono Mark Krailo Mark L Bernstein Janet E Dancey Rose Anne Speights Susan M Blaney James M Croop Gregory H Reaman Peter C Adamson 《Journal of clinical oncology》2005,23(25):6172-6180
PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued. 相似文献
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223.
The 55-kD bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived polypeptide belonging to a family of
lipid and endotoxin binding proteins. BPI is composed of two functionally distinct structural domains: a potently antibacterial
and antiendotoxin ∼ 20-kD aminoterminal half, and an opsonic carboxy-terminal portion. In multiple animal models, a recombinant
amino-terminal fragment of BPI (rBPI21) is nontoxic and protects against gram-negative bacteria and endotoxin. In humans, rBPI21 is also nontoxic and nonimmunogenic and has undergone phase II/III clinical trials with apparent therapeutic benefit. 相似文献
224.
Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane. 总被引:4,自引:0,他引:4
Thomas J Spencer Joseph Biederman Bertha K Madras Darin D Dougherty Ali A Bonab Elijahu Livni Peter C Meltzer Jessica Martin Scott Rauch Alan J Fischman 《Neuropsychopharmacology》2007,62(9):1059-1061
BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. METHOD: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-na?ve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD. 相似文献
225.
Charlotte J. Harden Bernard M. Corfe J. Craig Richardson Peter W. Dettmar Jenny R. Paxman 《Nutrition Research》2009
This cross-sectional analysis evaluated the effect of age and body mass index (BMI) on Three-Factor Eating Questionnaire scores in males. Subjects (n = 60) were recruited according to BMI status. Each completed the 51-item Three-Factor Eating Questionnaire. The group was split at the median age to produce a “younger” and “older” group for statistical analysis. A 2-way between-groups analysis of variance revealed a significant main effect of BMI on disinhibition (P = .003) and hunger (P = .041) with higher levels found in overweight males compared to healthy-weight counterparts. A significant main effect of age on hunger (P = .046) demonstrated older males were less susceptible to hunger than younger males. These insights provide a better understanding of eating behavior across the male life cycle and may assist health professionals to better guide men in weight management in the light of rising overweight/obesity. 相似文献
226.
227.
Helen J. Michielsen Marcel A. Croon Tineke M. Willemsen Jolanda De Vries Guus L. Van Heck 《Stress and health》2007,23(2):121-130
The main objective of this study was to examine the psychosocial stress model developed by Taylor and Aspinwall with emotional exhaustion as the outcome variable. Respondents, 409 men and 346 women, who had a paid job for at least 20 hours per week, completed questionnaires concerning demographic variables, personality, temperament, work pressure, workload, perceived social support, appraisal, coping, and emotional exhaustion. Structural equation analyses provided only partial support for the validity of the model. First, on theoretical and statistical grounds, one more path linking external resources to social support was added. Second, contrary to expectations, coping styles did not predict emotional exhaustion. To conclude, when coping is measured retrospectively, it does not add to our understanding of emotional exhaustion. It is suggested that future studies should be longitudinal and include objective measures of stressors and psychosocial health outcomes in addition to self‐reports. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
228.
229.
M G De Maeseneer T E Philipsen C P Vandenbroeck P R Lauwers J M Hendriks S G De Hert P E Van Schil 《European journal of vascular and endovascular surgery》2007,34(3):361-366
BACKGROUND: Neovascularisation at the sapheno-femoral junction (SFJ) ligation site in the groin may occur within one year after great saphenous vein (GSV) surgery. Several anatomical and prosthetic barrier techniques have been proposed to prevent this evolution. OBJECTIVE: A prospective study examined whether closing the cribriform fascia could reduce the incidence of postoperative neovascularisation in the groin. PATIENTS AND METHODS: Patients with primary varicose veins and incompetence at the level of the SFJ were included. After SFJ ligation in 235 limbs of 193 patients an anatomical barrier was constructed by closing the cribriform fascia. Postoperative duplex scanning was performed after 2 and 12 months. Results were compared with historical control groups in which either a silicone patch saphenoplasty or no barrier technique had been performed. RESULTS: After one year, 10 limbs had developed recurrent thigh varicose veins and duplex scan showed neovascularisation at the SFJ ligation site in 15 of 223 re-examined limbs (6.7%). This was comparable to the group of 191 limbs with silicone patch saphenoplasty (5.2%) (P=0.526) and superior to the group of 189 limbs without barrier (14.8%) (P<0.01). CONCLUSION: Interposition of an anatomical barrier by closing the cribriform fascia after SFJ ligation reduced ultrasound detected neovascularisation at the SFJ after one year. In primary varicose vein operations application of an anatomical barrier technique (without prosthetic patch) is an alternative option to prevent postoperative neovascularisation. 相似文献
230.