Altered D(1) dopamine receptor trafficking in parkinsonian and dyskinetic non-human primates

Dyskinesias represent a debilitating complication of levodopa therapy for Parkinson's disease (PD). While we recently demonstrated that levodopa-induced dyskinesia results from increased dopamine D(1) receptor-mediated transmission, we also questioned the possible role of subcellular localization of D(1) and D(2) receptors in mediating these effects as we previously showed that D(1) receptors undergo differential trafficking in striatal neurons of non-dyskinetic PD patients. Taking advantage of a monkey brain bank, we here report changes affecting the cellular and subcellular distribution of D(1) and D(2) dopamine receptors within the striatum of three experimental groups: normal, parkinsonian and dyskinetic L-dopa-treated parkinsonian animals. Our studies at both light and electron microscopy levels show a recruitment of D(1) receptor at the plasma membrane of striatal neurons in the parkinsonian animals and a strong increase of D(1) expression both at the membrane and in cytoplasm of dyskinetic animals, whereas D(2) receptor distribution is only modestly affected in all conditions. Our results rule out the hypothesis of a pathological overinternalization of dopamine receptors in levodopa-induced dyskinesia but raise the possibility for involvement of D(1) receptors in the priming phenomenon through massive and sudden internalization in response to the first ever administration of L-dopa and for an altered homologous desensitization mechanism in dyskinesia leading to an increased availability of D(1) receptors at membrane. Further experiments including parkinsonian monkeys chronically treated with L-dopa that show no dyskinesia and parkinsonian monkeys treated only once with L-dopa are now necessary to confirm our hypothesis.     

Cardiorespiratory capacity after weight-supported treadmill training in patients with traumatic brain injury

BACKGROUND AND PURPOSE: The primary goal of body-weight-supported treadmill training (BWSTT) has been to improve the temporal and spatial characteristics of unsupported overground walking; however, little attention has been given to cardiorespiratory adaptations. The purpose of this case report is to describe the effects of BWSTT on cardiorespiratory fitness in 2 patients recovering from severe traumatic brain injury (TBI). CASE DESCRIPTION: Both patients were involved in motor vehicle accidents and were studied after admission to a postacute residential treatment program. Patient 1 was a 25-year-old man (initial Glasgow Coma Scale [GCS] score=3) who began observation and treatment 3 months after the injury. Patient 2 was an 18-year-old woman (initial GCS=6) who began observation and treatment 1 year after the injury. OUTCOMES: Each patient received 2 to 3 sessions of BWSTT per week. Aerobic capacity was measured while they ambulated on a treadmill without body-weight support before and after BWSTT. Both patients' submaximal and peak responses improved. For patient 1 and patient 2, total treadmill work performed increased 134% and 53%, respectively. Peak oxygen uptake increased 24% for patient 1 and 16% for patient 2. Estimated cardiac stroke volume (oxygen pulse) increased 32% and 26% for patient 1 and patient 2, respectively. DISCUSSION: The observations made on these 2 patients suggest that BWSTT has the potential to favorably change cardiorespiratory capacity after TBI.     

The multiple mini‐interview: how long is long enough?

Objectives  The multiple mini-interview (MMI) overcomes the limitations of the traditional panel interview by multiple sampling to provide improved objectivity and reliability. Reliability of the MMI is affected by number of stations; however, there are few data reporting the influence of interview duration on MMI outcome and reliability. We aimed to determine whether MMI stations can be shortened without affecting applicant rankings or compromising test reliability.
Methods  A total of 175 applicants were interviewed and assessed at 10 8-minute stations. Applicants were scored once after 8 minutes at five control stations and twice after 5 minutes and 8 minutes at five experimental stations. Scores at 5 and 8 minutes were compared using t -tests and correlation coefficients. Rankings of applicants based on 5- and 8-minute scores were compared using Spearman's rank order coefficient. The reliability of the MMI was examined for 5- and 8-minute scores using generalisability theory.
Results  Mean scores at 5 minutes were lower than mean scores at 8 minutes. Cumulative scores at 5 minutes were also lower. There were highly significant correlations between 5- and 8-minute scores at all experimental stations (0.82–0.91; P  < 0.01) and between the cumulative scores at 5 and 8 minutes (0.92; P  < 0.01). There was a strong correlation between applicant rankings based on cumulative 5- and 8-minute scores (Spearman's rank order coefficient 0.92). Reliability was not affected.
Conclusions  Reducing the duration of MMI stations from 8 to 5 minutes conserves resources with minimal effect on applicant ranking and test reliability.     

Use of StarClose for brachial artery closure after percutaneous endovascular interventions

The objective of this study was to evaluate a percutaneous extravascular closure device (StarClose, Abbott Vascular, Redwood City, CA) after brachial endovascular approach. From 2004 to 2006, 29 patients received StarClose for brachial closure. Primary endpoints were successful deployment and absence of procedure-related morbidity, secondary endpoints were brachial artery patency on duplex and absence of late (> 30 days) complications. The device was successfully deployed in all patients. In two patients (6.8%) local complications occurred: one patient developed a large hematoma successfully treated with prolonged compression and a second patient presented with brachial artery occlusion requiring operative intervention. After a mean follow-up of 7.5+/-7.2 months, all patients had a palpable brachial/radial pulse; none had signs of infection, distal embolization or neurological deficits. On ultrasound b-mode imaging, the clip was visible as a 4 mm echolucent area at the outer anterior wall of the artery. Based on the peak systolic velocity ratios between the site of StarClose and proximal brachial artery (mean 1.08+/-0.2), none of the studied patients had a significant stenosis at the site of closure. StarClose is safe and effective in providing hemostasis following interventional procedures through the brachial artery; further advantages include patients comfort and early discharge.     

Direct identification of chlamydiae from clinical samples using a DNA microarray assay: a validation study

While DNA microarrays have become a widely accepted tool for mRNA expression monitoring, their use in rapid diagnosis of bacterial and viral pathogens is only emerging. So far, insufficient sensitivity and high costs have been the major limiting factors preventing more widespread use of microarray platforms in direct testing of clinical samples. In the present study, a total of 339 samples, among them 293 clinical specimens from animals and humans, were examined by the ArrayTube (AT) DNA microarray assay to detect chlamydial DNA and identify the species of Chlamydia and Chlamydophila involved. Samples included nasal and conjunctival swabs, formalin-fixed, paraffin-embedded and fresh organ tissue, milk, feces and cell culture. Notably, the AT test was shown to detect mixed infections in clinical samples. The calculated median sensitivity of 0.81 over the entire panel of clinical samples was comparable to conventional 16S PCR, but slightly lower than real-time PCR and other PCR assays. However, when a panel of long-time stored swab samples was excluded from the calculation, the sensitivity was clearly higher (0.87) and equivalent to that of real-time PCR. Altogether, the data demonstrate the suitability of this DNA microarray assay for routine diagnosis.