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31.
Emma J. Kilford Iroise Dumontheil Nicholas W. Wood Sarah-Jayne Blakemore 《Social cognitive and affective neuroscience》2015,10(6):777-782
The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val158Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function. 相似文献
32.
33.
E. Niclas Jonsson Rujia Xie Scott F. Marshall Rosalin H. Arends 《British journal of clinical pharmacology》2016,81(4):688-699
AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V
1), peripheral volume (V
2), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day–1, 2.71 l, 1.98 l, 0.371 l day–1, 8.03 μg day–1 and 27.7 ng ml–1, respectively. Inter‐individual variability (IIV) was included on CL, V
1, V
2 and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V
1 and V
2 significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit. 相似文献
34.
Simeprevir added to peginterferon and ribavirin lessens time with fatigue,depressive symptoms and functional limitations in patients with chronic hepatitis C compared with peginterferon and ribavirin: results from 1161 patients in the QUEST‐1, QUEST‐2 and PROMISE studies
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J. Scott L. Gilles M. Fu E. Brohan C. Panter R. Arbuckle W. Jessner M. Beumont 《Journal of viral hepatitis》2015,22(8):639-650
The value of adding simeprevir (SMV) vs placebo (PBO) to peginterferon and ribavirin (PR) for treatment of chronic hepatitis C virus infection was examined using patient‐reported outcomes (PROs); further, concordance of PROs with virology endpoints and adverse events (AEs) was explored. Patients (n = 768 SMV/PR, n = 393 PBO/PR) rated fatigue (FSS), depressive symptoms (CES‐D) and functional impairment (WPAI: Hepatitis C Productivity, Daily Activity and Absenteeism) at baseline and throughout treatment in three randomised, double‐blind trials comparing the addition of SMV or PBO during initial 12 weeks of PR. PR was administered for 48 weeks (PBO group) and 24/48 weeks (SMV group) using a response‐guided therapy (RGT) approach. Mean PRO scores (except Absenteeism) worsened from baseline to Week 4 to the same extent in both groups but reverted after Week 24 for SMV/PR and only after Week 48 for PBO/PR. Accordingly, there was a significantly lower area under the curve (baseline–Week 60, AUC60) and fewer weeks with clinically important worsening of scores in the SMV/PR group at any time point. Incidences of patients with fatigue and anaemia AEs were similar in both groups, but FSS scores showed that clinically important increases in fatigue lasted a mean of 6.9 weeks longer with PBO/PR (P < 0.001). PRO score subgroup analysis indicated better outcomes for patients who met the criteria for RGT or achieved sustained virological response 12 weeks post‐treatment (SVR12); differences in mean PRO scores associated with fibrosis level were only observed with PBO/PR. Greater efficacy of SMV/PR enabled reduced treatment duration and reduced time with PR‐related AEs without adding to AE severity. 相似文献
35.
36.
Dan-Feng Xu Bing Wu Jin-Xin Wang Jian Yu Jian-Xin Xie 《World Journal of Clinical Cases》2021,9(5):1096-1102
BACKGROUNDGuillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS.CASE SUMMARYA 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up.CONCLUSIONGBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms. 相似文献
37.
Ahmed M. Abu El-Asrar Ajmal Ahmad Eef Allegaert Mohammad Mairaj Siddiquei Priscilla W. Gikandi Gert De Hertogh 《Ocular immunology and inflammation》2020,28(4):575-588
ABSTRACT
Purpose
To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163+ M2 macrophages in proliferative diabetic retinopathy (PDR). 相似文献38.
39.
Purpose
Chest wall pain is an uncommon but bothersome late complication following lung stereotactic body radiation therapy. Despite numerous studies investigating predictors of chest wall pain, no clear consensus has been established for a chest wall constraint. The aim of our study was to investigate factors related to chest wall pain in a homogeneous group of patients treated at our institution.Patients and methods
All 122 patients were treated with the same stereotactic body radiation therapy regimen of 48 Gy in three fractions, seen for at least 6 months of follow-up, and planned with heterogeneity correction. Chest wall pain was scored according to the Common Terminology Criteria for Adverse Events classification v3.0. Patient (age, sex, diabetes, osteoporosis), tumour (planning target volume, volume of the overlapping region between planning target volume and chest wall) and chest wall dosimetric parameters (volumes receiving at least 30, 40, and 50 Gy, the minimal doses received by the highest irradiated 1, 2, and 5 cm3, and maximum dose) were collected. The correlation between chest wall pain (grade 2 or higher) and the different parameters was evaluated using univariate and multivariate logistic regression.Results
Median follow-up was 18 months (range: 6–56 months). Twelve patients out of 122 developed chest wall pain of any grade (seven with grade 1, three with grade 2 and two with grade 3 pain). In univariate analysis, only the volume receiving 30 Gy or more (P = 0.034) and the volume of the overlapping region between the planning target volume and chest wall (P = 0.038) significantly predicted chest wall pain, but these variables were later proved non-significant in multivariate regression.Conclusion
Our analysis could not find any correlation between the studied parameters and chest wall pain. Considering our present study and the wide range of differing results from the literature, a reasonable conclusion is that a constraint for chest wall pain is yet to be defined. 相似文献40.
L.‐Q. Zheng X.‐C. Han Y. Huang H.‐W. Li X.‐D. Niu J. Li 《Clinical and experimental dermatology》2015,40(3):293-297
Porocarcinoma is an unusual, locally aggressive and potentially fatal neoplasm. Several cutaneous malignancies have been described in association with porocarcinoma, including squamous cell carcinoma, basal cell carcinoma and tricholemmal carcinoma. Previous reports have indicated that the occurrence of malignant tumours in combination with porocarcinoma is extremely rare, in particular with regard to Bowen disease (BD). We report an uncommon case of porocarcinoma occurring synchronously in a single BD lesion in a 63‐year‐old woman with multiple BD lesions. The clinical and histological findings confirmed this diagnosis. 相似文献