Pain assessment in patients with possible vascular dementia

PREVIOUS studies comparing Alzheimer's disease (AD) patients with the normal elderly suggest that AD patients experience less pain. In the present study, pain reporting in 20 patients with possible vascular dementia (VaD) was compared to 20 nondemented elderly who had comparable pain conditions. It was hypothesized that, due to de-afferentiation, the possible VaD patients would experience more pain than the cognitively intact elderly. Pain assessment was conducted using three visual analogue scales, (1) the Coloured Analogue Scale (CAS) for Pain Intensity, (2) the CAS for Pain Affect, and (3) the Faces Pain Scale (FPS); a verbal pain questionnaire, Number of Words Chosen--Affective (NWC-A) of the McGill Pain Questionnaire; and an observation scale, the Checklist of Nonverbal Pain Indicators (CNPI). Results showed a significant increase in the scores on the CAS for Pain Affect and the FPS in the demented patients compared to the control group. There was a tendency for an increase in scores on the CNPI in the VaD group. These results suggest that patients with possible VaD suffer more pain than healthy elderly without cognitive impairment.     

Summary of the Dutch College of General Practitioners' "Gout" Standard

The typical form of acute gout can be clinically diagnosed. The term 'complicated gout' is used if there are more than three acute attacks of gout per year, tophi or urate stones in the urinary tracts. In the case of recurrent probable acute gout, a diagnostic fine needle aspirate from the joint during an attack is indicated. First choice treatment of acute gout consists of NSAIDs. Colchicine is the second choice treatment and the third choice treatment consists of corticosteroids. Excessive alcohol use should be limited. Treatment of chronic gout depends on the uric acid excretion in the 24-hour urine. If the level of excretion is too low, the first choice should be benzbromarone, and if the uric acid output is too high, allopurinol should be the treatment of first choice. Increased fluid intake is recommended; maintenance treatment with colchicine is not advised. Consultation with or referral to a rheumatologist is indicated in the case of doubt about the diagnosis of 'acute gout' or 'complicated gout', or (suspected) bacterial arthritis and insufficient treatment effect.     

Sodium channel beta1-subunit expression is increased in reactive astrocytes in a rat model for mesial temporal lobe epilepsy

As several epilepsy syndromes are associated with changes in sodium channel subunits we investigated the expression of beta1 sodium channel protein in a rat epilepsy model. In this model a chronic epileptic syndrome develops after electrically induced status epilepticus (SE). Many neuropathological characteristics of mesial temporal lobe epilepsy can be reproduced (cell loss, gliosis and synaptic reorganization). In control hippocampus beta1 subunit protein was moderately expressed in neurons and weakly expressed in resting astrocytes. beta1 sodium channel immunoreactivity increased markedly within 1 week after SE mainly in astrocytes that were colocalized with vimentin (marker for reactive astrocytes). This up-regulation was still present in reactive astrocytes of chronic epileptic rats (> 3 months after SE). Considering the fact that the beta1 subunits may function as cell adhesion molecules interacting with extracellular matrix, the observed increase in reactive astrocytes might subserve a function in cellular and synaptic reorganization during epileptogenesis.     

The Role of a Computerised Case-based Testing Procedure in Practice Performance Assessment

Introduction: For postgraduate training of doctors there is a need for valid and reliable instruments to assess their daily performance. Various instruments have been suggested, some of which use incognito simulated patients (SPs). These methods are resource intensive. Computerised Case-based testing (CCT) is logistically simpler and may still predict performance well. The research question was to evaluate the predictive validity of CCT for performance.Methods: Seventeen rheumatologists were each visited by eight incognito SPs presenting various rheumatological complaints, and scoring the performance of the rheumatologists using a predefined checklist. From this checklist a panel of experts identified essential items. In addition the rheumatologists sat a CCT test containing 55 cases with a total of 121 items.Results: Negative correlations were found between the SP scores and the CCT scores. This was unexpected. Therefore, background variables on experience were used to compare both methods. The correlation between these and CCT were high and positive and with the SP scores high and negative. This pattern did not differ when using the essential items of the checklist. Reliabilities of the SP scores were markedly high.Discussion: Although CCT was not predictive of SP scores, it was related to working experience. There are good reasons to assume that although SP-scores were more authentic, they were less valid than CCT scores, mainly because they focussed more on thoroughness than on efficiency in data gathering. The results underpin the assumption that for valid performance assessment the most important issue is what information about the candidate is collected and now how authentic the method is.     

Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain

PURPOSE: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)-binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)-related proteins. Recently, upregulation of different MDR proteins has been shown in human epilepsy-associated conditions. This study investigated the expression and cellular distribution of BCRP in human control and epileptic brain, including a large number of both neoplastic and nonneoplastic specimens from patients with chronic pharmacoresistant epilepsy. METHODS: Several epileptogenic pathologies, such as hippocampal sclerosis (HS), focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumor, oligodendroglioma astrocytoma, and glioblastoma multiforme were studied by using Western blot and immunocytochemistry. RESULTS: With Western blot, we could demonstrate the presence of BCRP in both normal and epileptic human brain tissue. In contrast to P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) 2, BCRP expression levels did not change in tissue from patients with HS, compared with control hippocampus. No BCRP immunoreactivity was observed in glial or neuronal cells, including reactive astrocytes and dysplastic neurons in FCD. BCRP expression was, however, increased in tumor brain tissue. Immunocytochemistry demonstrated that BCRP was exclusively located in blood vessels and was highly expressed at the luminal cell surface and in newly formed tumor capillaries. This localization closely resembles that of P-gp. The higher expression observed in astrocytomas by Western blot analysis was related to the higher vascular density within the tumor tissue. CONCLUSIONS: These results indicate a constitutive expression of BCRP in human endothelial cells, representing an important barrier against drug access to the brain. In particular, the strong BCRP expression in the microvasculature of epileptogenic brain tumors could critically influence the bioavailability of drugs within the tumor and contribute to pharmacoresistance.     

Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats

PURPOSE: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain. METHODS: Expression of multidrug resistance-associated proteins MRP1 and MRP2 and breast cancer-resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high-performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid. RESULTS: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels. CONCLUSIONS: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.