Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients

Objective

Rapid eye movement (REM) sleep behavior disorder (RBD) is a risk factor for dementia in Parkinson disease (PD) patients. The objectives of our study were to prospectively evaluate the frequency of RBD in a sample of treatment-naïve, newly diagnosed PD patients and compare sleep characteristics and cognition in RBD and non-RBD groups.

Methods

Fifty-seven newly diagnosed PD patients were consecutively recruited in a university medical center. All patients underwent two overnight polysomnography (PSG) sessions and were diagnosed with RBD according to the International Classification of Sleep Disorders, Second Revision criteria. Daytime sleepiness was measured in a multiple sleep latency test (MSLT). Cognition was assessed in a standard neuropsychologic examination.

Results

Seventeen PD patients (30%) met the criteria for RBD. The RBD patients and non-RBD patients did not significantly differ in mean age, gender ratio, disease duration, motor symptom subtype and severity, total sleep time, percentage of REM sleep, apnea–hypopnea index, mean oxygen saturation, and importantly cognitive performance. However, non-RBD patients had a significantly shorter mean daytime sleep latency than RBD patients (15 vs 18 min, respectively; P = .014).

Conclusion

A high frequency of RBD was found in our sample of 57 newly diagnosed PD patients. At this stage in the disease, RBD was not found to be associated with other sleep disorders or cognitive decline. Follow-up is needed to assess the risk for developing dementia in early-stage PD patients with RBD.     

Multiple once-daily subcutaneous doses of pasireotide were well tolerated in healthy male volunteers: a randomized, double-blind, placebo-controlled, cross-over, Phase I study

A randomized, double-blind, placebo-controlled, cross-over, dose-escalating, single-center study was conducted to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of multiple once-daily (qd) subcutaneous (sc) doses of pasireotide in healthy male subjects. Subjects received pasireotide 50, 200, or 600?μg?sc?qd for 14?days and placebo in separate sequences. Thirty-three subjects were randomized. The most frequently reported drug-related adverse events were injection-site reactions (n?=?18), diarrhea (n?=?14) and nausea (n?=?10), which were mostly mild or moderate in intensity. Pasireotide 600?μg?sc was associated with pre- and post-prandial elevations in glucose levels relative to placebo; however, this effect was less pronounced on day 14 compared with day 1. PK steady state appeared to be achieved after 3?days of dosing and PK exposures had a moderate accumulation of 20-40?% across doses. Pasireotide demonstrated fast absorption (T (max,ss): 0.25-0.5?h), low clearance (CL/F (ss): 8.10-9.03?L/h), long effective half-life (T (?,eff): ~12?h, on average between 9.7 and 13.1?h for 50, 200, and 600?μg?sc?qd), and large volume of distribution (V (z)/F (ss): 251-1,091?L) at steady state. Dose proportionality was confirmed for C (max,ss); other PK parameters (C (max), AUC(0-24?h) and AUC(tau)) were approximately dose proportional. Growth hormone inhibition was observed with pasireotide 200 and 600?μg?sc?qd. Gallbladder volume increased post-prandially with pasireotide 200 and 600?μg?sc?qd, which appeared to correlate with reduced levels of cholecystokinin at these doses. Pasireotide was generally well tolerated up to the tested dose of 600?μg?qd, with a linear and time-independent PK profile after sc qd dosing in healthy subjects.     

Comparison of the roll-plate and sonication techniques in the diagnosis of microbial ureteral stent colonisation: results of the first prospective randomised study

Background

Microbial ureteral stent colonisation (MUSC) is one leading risk factor for complications associated with ureteral stent placement. As MUSC remains frequently undetected by standard urine cultures, its definitive diagnosis depends on microbiological investigation of the stent. However, a standard reference laboratory technique for studying MUSC is still lacking.

Materials and methods

A total of 271 ureteral stents removed from 199 consecutive patients were investigated. Urine samples were obtained prior to device removal. Stents were divided into four parts. Each part was separately processed by the microbiology laboratory within 6 h. Ureteral stents were randomly allocated to roll-plate or sonication, respectively, and analysed using standard microbiological techniques. Demographic and clinical data were prospectively collected using a standard case-report form.

Results

Overall, roll-plate showed a higher detection rate of MUSC compared with sonication (35 vs. 28 %, p < 0.05) and urine culture (35 vs. 8 %, p < 0.05). No inferiority of Maki’s technique was observed even when stents were stratified according to indwelling time below or above 30 days. Compared with roll-plate, sonication commonly failed to detect Enterococcus spp., coagulase-negative staphylococci (CoNS) and Enterobacteriaceae. In addition, sonication required more hands-on time, more equipment and higher training than roll-plate in the laboratory.

Conclusions

This prospective randomised study demonstrates the superiority of Maki’s roll-plate technique over sonication in the diagnosis of MUSC and that urine culture is less sensitive than both methods. The higher detection rate, simplicity and cost-effectiveness render roll-plate the methodology of choice for routine clinical investigation as well as basic laboratory research.     

Functional late outgrowth endothelial progenitors isolated from peripheral blood of burned patients

Background

Bioengineered skin substitutes are increasingly considered as a useful option for the treatment of full thickness burn injury. Their viability following grafting can be enhanced by seeding the skin substitute with late outgrowth endothelial progenitor cells (EPCs). However, it is not known whether autologous EPCs can be obtained from burned patients shortly after injury.

Methods

Late outgrowth EPCs were isolated from peripheral blood sampled obtained from 10 burned patients (extent 19.6 ± 10.3% TBSA) within the first 24 h of hospital admission, and from 7 healthy subjects. Late outgrowth EPCs were phenotyped in vitro.

Results

In comparison with similar cells obtained from healthy subjects, growing colonies from burned patients yielded a higher percentage of EPC clones (46 versus 17%, p = 0.013). Furthermore, EPCs from burned patients secreted more vascular endothelial growth factor (VEGF) into the culture medium than did their counterparts from healthy subjects (85.8 ± 56.2 versus 17.6 ± 14 pg/mg protein, p = 0.018). When injected to athymic nude mice 6 h after unilateral ligation of the femoral artery, EPCs from both groups of subjects greatly accelerated the reperfusion of the ischaemic hindlimb and increased the number of vascular smooth muscle cells.

Conclusions

The present study supports that, in patients with burns of moderate extension, it is feasible to obtain functional autologous late outgrowth EPCs from peripheral blood. These results constitute a strong incentive to pursue approaches based on using autotransplantation of these cells to improve the therapy of full thickness burns.     

Phonology and syntax in French children with SLI: A longitudinal study

Maillart and Parisse found out that French children with specific language impairment (SLI) presented strong difficulties in phonology when compared with normally‐developing children matched by MLU (NLD). Some of the youngest children from this study were followed to provide developmental information about their language deficit. Children were tested again in the same way as before (free spontaneous production) and matched by MLU against other NLD children. The previous phonological analysis was extended to include syntax as well as phonology. Percentage of words correct was computed for both phonology and syntax. An analysis of covariance (ANCOVA) was performed with children's age as covariate. Results showed a significant difference between SLI and NLD children for phonology but not for syntax. There was a trend that showed that the difference between SLI and NLD children tended to increase with age. The same analysis was performed separately for 9 frequent syntactic categories for phonology and for syntax. A significant difference was found for prepositions, nouns, subject pronouns, and verbs in phonology. Effects were found for determiners and prepositions in syntax. As well as confirming the importance of phonological difficulties in SLI, our results call for a developmental theory of phonological and syntactic deficits in SLI, where differences between SLI and NLD grow with age and where there is a timing difference between phonology (earlier) and syntax (later).