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Erik Oudman Tanja C.W. Nijboer Albert Postma Jan W. Wijnia Sandra Kerklaan Karen Lindsen 《Neuropsychological rehabilitation》2013,23(6):888-913
Patients with Korsakoff's syndrome show devastating amnesia and executive deficits. Consequently, the ability to perform instrumental activities such as making coffee is frequently diminished. It is currently unknown whether patients with Korsakoff's syndrome are able to (re)learn instrumental activities. A good candidate for an effective teaching technique in Korsakoff's syndrome is errorless learning as it is based on intact implicit memory functioning. Therefore, the aim of the current study was two-fold: to investigate whether patients with Korsakoff's syndrome are able to (re)learn instrumental activities, and to compare the effectiveness of errorless learning with trial and error learning in the acquisition and maintenance of an instrumental activity, namely using a washing machine to do the laundry. Whereas initial learning performance in the errorless learning condition was superior, both intervention techniques resulted in similar improvement over eight learning sessions. Moreover, performance in a different spatial layout showed a comparable improvement. Notably, in follow-up sessions starting after four weeks without practice, performance was still elevated in the errorless learning condition, but not in the trial and error condition. The current study demonstrates that (re)learning and maintenance of an instrumental activity is possible in patients with Korsakoff's syndrome. 相似文献
105.
Boelens MC van den Berg A Vogelzang I Wesseling J Postma DS Timens W Groen HJ 《Journal of clinical pathology》2007,60(6):608-614
BACKGROUND: Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis. AIM: To screen for altered expression of epithelial adhesion genes in lung cancer development. METHODS: Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels. RESULTS: 43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion-that is, integrin alpha3 (ITGA3), integrin beta4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell-matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell-cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas. CONCLUSIONS: Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested. 相似文献
106.
Mahmoud Hashim Boris M. Pfeiffer Robert Bartsch Maarten Postma Bart Heeg 《Value in health》2018,21(1):9-17
Background
In previous studies, correlation between overall survival (OS) and surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) was poor. This can be biased by crossover and postprogression treatments.Objectives
To evaluate the relationship between these two surrogate endpoints and OS in advanced NSCLC studies that did not allow for crossover or reported balanced post-progression treatments.Methods
A systematic review in patients with advanced NSCLC receiving second- and further-line therapy was performed. The relationship between the absolute difference in ORR or median PFS (mPFS) and the absolute difference in median OS (mOS) was assessed using the correlation coefficient (R) and weighted regression models. The analysis was repeated in predefined data cuts based on crossover and balance of postprogression treatments. When the upper limit of R’s 95% confidence interval (CI) was more than 0.7, the surrogate threshold effect (STE) was estimated.Results
In total, 146 randomized clinical trials (43,061 patients) were included. The mean ORR, mPFS, and mOS were 12.2% ± 11.2%, 3.2 ± 1.3 months, and 9.6 ± 4.1 months, respectively. The correlation coefficients of ORR and mPFS were 0.181 (95% CI 0.016–0.337) and 0.254 (95% CI 0.074–0.418), respectively, with mOS. Nevertheless, in trials that did not allow crossover and reported balanced postprogression treatments, the correlation coefficients of ORR and mPFS were 0.528 (95% CI 0.081–0.798) and 0.778 (95% CI 0.475–0.916), respectively, with mOS. On the basis of STE estimation, in trials showing significant treatment effect size of 41.0% or more ORR or 4.15 or more mPFS months, OS benefit can be expected with sufficient certainty.Conclusions
Crossover and postprogression treatments may bias the relationship between surrogate endpoints and OS. Presented STE calculation can be used to interpret treatment effect on either ORR or PFS when used as primary endpoints. 相似文献107.
MJ Ramdass P Harnarayan N Mooteeram A Nath V Naraynsingh S Budhooram T Dookie R Henry 《Annals of the Royal College of Surgeons of England》2014,96(2):121-126
Introduction
This study aimed to determine whether ethnic differences show different patterns of arterial disease in the lower limb.Methods
A prospective analysis of 100 consecutive patients with 160 lower limb arteriograms was performed looking at the pattern of disease with relation to ethnicity in Trinidad and Tobago.Results
There were 53 male and 47 female patients with an age range of 43–90 years (mean: 66 years). Of the 100 patients, 45 were of East Indian descent, 36 of Afro-Caribbean descent, 14 of mixed descent and 5 had other backgrounds. There were 32 smokers and 69 diabetics.The most commonly affected artery in East Indians was the anterior tibial artery (ATA, 70%) followed by the peroneal artery (60%), superficial femoral artery (SFA, 60%), posterior tibial artery (PTA, 57%) and tibioperoneal trunk (TPT, 39%). In Afro-Caribbeans, the most commonly affected artery was the ATA (79%) followed by the PTA (74%), peroneal artery (66%) and TPT (55%). The mixed group showed the PTA (85%) to be most diseased followed by the peroneal artery (75%), ATA (70%), SFA (70%), dorsalis pedis artery (DPA, 60%) and TPT (50%). Overall, the most diseased vessel in all groups was the ATA (73%) followed by the PTA (66%), peroneal artery (64%), SFA (59%), TPT (46%), DPA (38%), popliteal artery (31%) and medial plantar artery (MPA, 29%), with the proximal vessels not being affected severely.Conclusions
Ethnic divisions were only statistically significant (p<0.05) with East Indians showing worse disease in the profunda femoris artery and Afro-Caribbeans showing worse disease in the PTA, DPA and MPA. This suggests that environmental factors may play a significant role in the disease process including smoking and dietary factors rather than purely genetics. 相似文献108.
MJ Hwang A Bhangu CE Webster DM Bowley MX Gannon SS Karandikar 《Annals of the Royal College of Surgeons of England》2014,96(5):343-347
Introduction
In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.Methods
A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.Results
The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).Conclusions
Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk. 相似文献109.
MJ Bown 《Annals of the Royal College of Surgeons of England》2014,96(6):405-414
Introduction
An individual’s genetic background plays a significant role in his or her chances of developing an abdominal aortic aneurysm (AAA). This risk is likely to be due to a combination of multiple small effect genetic factors acting together, resulting in considerable difficulty in the identification of these factors.Methods
Methods for the identification of genetic factors associated with disease are usually based on the analysis of genetic variants in case-control studies. Over the last decade, owing to advances in bioinformatics and laboratory technology, these studies have progressed from focusing on the examination of a single genetic variant in each study to the examination of many millions of variants in a single experiment. We have conducted a series of such experiments using these methods.Results
Our original methods using candidate gene approaches led to the initial identification of a genetic variant in the interleukin-10 gene associated with AAA. However, further studies failed to confirm this association and highlighted the necessity for adequately powered studies to be conducted, as well as the need for confirmatory studies to be performed, prior to the acceptance of a variant as a risk for disease. The subsequent application of genomic techniques to our sample set, in a global collaboration, has led to the identification of three robustly verified risk loci for AAA in the LRP1, LDLR and SORT1 genes.Conclusions
Genomic studies of AAA have led to the identification of new pathways involved in the pathogenesis of AAA. The exploration of these pathways has the potential to unlock new avenues for therapeutic intervention to prevent the development and progression of AAA. 相似文献110.
Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits
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PA Baldock S Lin L Zhang T Karl Y Shi F Driessler A Zengin B Hörmer NJ Lee IPL Wong EJD Lin RF Enriquez B Stehrer MJ During E Yulyaningsih S Zolotukhin ST Ruohonen E Savontaus A Sainsbury H Herzog 《Journal of bone and mineral research》2014,29(10):2238-2249
Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research. 相似文献