PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics. 相似文献
AIM: To assess the efficacy and safety of a heavy silicone oil (Densiron 68) in the management of inferior retinal detachment recurrence.
METHODS: A retrospective non-comparative consecutive case series study. Forty-nine cases of complex inferior retinal detachment were treated using Densiron 68 heavy silicone oil (HSO) as the endotamponade. Our main purpose was anatomic reattachment following Densiron 68 removal. Functional outcomes, rate of recurrences, the presence of inflammatory complications and intraocular pressure alterations were evaluated.
RESULTS: Forty-nine patients affected by complex retinal re-detachment were recruited. The mean follow-up was 7.6 (±1.5) mo. The mean best corrected visual acuity after Densiron 68 removal was 0.95 logMAR, standard error (SE: 0.068). Retinal reattachment was 61.2% after first surgery and 81.6% after second surgery. Nineteen cases (38.8%) had recurrences when intraocular heavy silicon oil was in situ, 26.3% (5 cases) of which involved the inferior retina.
CONCLUSION: Densiron 68 ef?ciently fills the inferior retinal periphery and might lower the risk of inferior proliferative vitreoretinopathy development, in particular after a standard silicon oil tamponade that reduces the proliferative process in the upper quadrants of the retina. 相似文献
Fibrin sealants or fibrin glue are products made from human plasma proteins, which mimic the final pathway of the coagulation cascade. Its application to stimulate the healing process has been a topic of debate in the literature. The use of fibrin sealants in phonosurgery has been empirical; there have been no studies that investigate the action of fibrin sealant in Reinke's space.AimTo evaluate the effect of fibrin glue in healing of the vocal folds of pigs after surgical manipulation.Materials and MethodsThis was a prospective and experimental study. Six animals had both vocal folds incised. Sealant was applied in one of them; the other served as a control. After three months, the animals were sacrificed and a collagen count was carried out.ResultsThe side on which glue was applied had an average of 27.8% against 20.4% of the side without glue.ConclusionThe collagen concentration in the samples where the fibrin sealant was applied was significantly higher compared to samples without glue. Thus, the presence of a fibrin sealant stimulates fibrogenesis in this tissue. 相似文献
Eight outbreaks of acute and subacute fasciolosis are reported in sheep in the municipality of Santa Vitória do Palmar, southern Brazil, in areas used for irrigated rice cultivation, which are subject to frequent flooding. Two outbreaks occurred mid-winter during July and August, and six occurred during spring and early summer. Morbidity ranged from 3 to 66.7 %, and mortality ranged from 3 to 50 %. Clinical signs included weight loss, mucosal pallor, apathy, depression, muscle tremors, and drooling; these were followed by death within approximately 24 h. Some sheep were found dead. Gross lesions were characterized by an irregular liver capsule with fibrin deposition and hemorrhages. The liver parenchyma contained hemorrhagic tracts or irregular clear areas alternated with dark hemorrhagic areas. Histologically, hemorrhagic dark red tracts of necrotic liver parenchyma and an inflammatory infiltrate were noted; these lesions coincided with the presence of immature flukes. Langhans-type giant cells, fibrous tissue, and bile duct cell proliferation were observed in subacute cases. Chronic fasciolosis is a well-known disease to farmers in southern Brazil; nevertheless, acute and subacute fasciolosis, which are more difficult to diagnose and treat, may cause important economic losses. Efficient control of fasciolosis requires integration of measures to treat infections in the definitive host, to reduce the population of snails of the genus Lymnaea, and to avoid contact between the parasite and host by appropriate pasture management. 相似文献
Aim. To study any discriminative properties of SF-36 and QQL-EPM in stable and non-controlled moderate asthmatic patients. Methods. A total of 63 asthmatic patients were assessed regarding asthma symptoms, FEV1 % predicted value, PEF, ED visits and hospitalizations, QQL-EPM and SF-36 questionnaires. Results. QQL-EPM highlighted significance in all domains to distinguish stable from non-controlled patients (p = 0.0001) while SF-36 was only significant in 3 of its 7 domains (p = 0.009). Conclusion. The study showed that the specific quality of life questionnaire for asthma (QQL-EPM) demonstrates better discriminative properties that characterize asthma control when compared with the more generic SF-36 questionnaire. 相似文献
The Sexual Inhibition Scales and Sexual Excitation Scales (Janssen et al., 2002a), based on the dual control model by Bancroft and Janssen (2000), are part of a 45-item self-report questionnaire evaluating individual tendencies to sexual inhibition or excitation according to three factors: two inhibition factors, SIS1, threat of performance failure, and SIS2, threat of performance consequences, and one excitation factor, SES. In this paper, we aimed to validate and explore psychometric properties of the SIS/SES in a sample of 2260 Italian men and women aged 18 to 75 years. Confirmatory factor analyses showed that the three-factor structure proposed in the original version of the scales fit with our sample. Moreover, our data confirmed the results of the original validation sample: Women scored higher on the SIS and lower on the SES than men did, but no significant differences appeared in the factor scores by age group, except for a gender × age interaction, where younger women had higher SIS2 scores. The SIS/SES appeared to be an effective, appropriate cross-cultural measurement of human sexuality in Italian samples, also shedding light on sexual arousal differences in women and men in our country. We also discuss clinical and therapeutic aspects.
The ACE I/D polymorphism has been associated with longevity, although not consistently. The objective of this study was to detect the possible unequal distribution of the alleles and genotypes of this polymorphism among centenarians and younger segments of the population. Relevant data were extracted from studies in the literature, comparing genotype and allele frequencies between centenarians and younger controls. The association of ACE I/D polymorphism with exceptional longevity was analyzed in a total of 1803 centenarians and 10,484 controls using the chi-square test with the Yates correction. We conducted combined analyses for all ethnic groups studied in the literature (Caucasian, Chinese and Korean) as well as for Caucasians only. The DD genotype (odds ratio (OR): 1.25 (95% confidence interval (CI): 1.02–1.54), P = 0.032) and the D-allele were more frequent in Caucasian centenarians compared with their younger controls (OR: 1.16 (95% CI: 1.05–1.28), P < 0.001). Similar findings were obtained when all ethnic origin groups were included in the analyses, with no evidence of publication bias or heterogeneity (P > 0.05). The present meta-analysis indicates that the ACE D-allele and the DD genotype might confer a modest, albeit significant advantage to reach exceptional longevity. 相似文献