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In the present study, we demonstrated the emergence of dalbavancin non-susceptible and teicoplanin-resistant Staphylococcus aureus small colony variants which were selected in vivo through long-term treatment with dalbavancin. A 36-year-old man presented with a cardiac device-related S. aureus endocarditis and received long-term therapy with dalbavancin. Consecutively, two glycopeptide/lipoglycopeptide susceptible and two non-susceptible S. aureus isolates were obtained from blood cultures and the explanted pacemaker wire. The isolates were characterized by: standard typing methods, antimicrobial susceptibility testing, auxotrophic profiling, proliferation assays, scanning and transmission electron microscopy, as well as whole genome sequencing. The isolated SCVs demonstrated a vancomycin-susceptible but dalbavancin non-susceptible and teicoplanin-resistant phenotype whereof the respective MICs of the last isolate were 16- and 84-fold higher than the susceptible strains. All four strains were indistinguishable or at least closely related by standard typing methods (spa, MLST, and PFGE), and whole genome sequencing revealed only eight sequence variants. A consecutive increase in cell wall thickness (up to 2.1-fold), an impaired cell separation with incomplete or multiple cross walls and significantly reduced growth rates were observed in the present study. Therefore, the mutations in pbp2 and the DHH domain of GdpP were identified as the most probable candidates due to their implication in the biosynthesis and metabolism of the staphylococcal cell wall. For the first time, we demonstrated in vivo induced dalbavancin non-susceptible/teicoplanin resistant, but vancomycin and daptomycin susceptible S. aureus SCVs without lipopeptide or glycopeptide pretreatment, thus, indicating the emergence of a novel lipoglycopeptide resistance mechanism.

Purpose Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland’s Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. Methods We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). Results Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. Conclusion While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

OBJECTIVE Epilepsy surgery is the recommended treatment option for patients with drug-resistant temporal lobe epilepsy (TLE). This method offers a good chance of seizure freedom but carries a considerable risk of postoperative language impairment. The extremely variable neurocognitive profiles in surgical epilepsy patients cannot be fully explained by extent of resection, fiber integrity, or current task-based functional MRI (fMRI). In this study, the authors aimed to investigate pathology- and surgery-triggered language organization in TLE by using fMRI activation and network analysis as well as considering structural and neuropsychological measures. METHODS Twenty-eight patients with unilateral TLE (16 right, 12 left) underwent T1-weighted imaging, diffusion tensor imaging, and task-based language fMRI pre- and postoperatively (n = 15 anterior temporal lobectomy, n = 11 selective amygdalohippocampectomy, n = 2 focal resection). Twenty-two healthy subjects served as the control cohort. Functional connectivity, activation maps, and laterality indices for language dominance were analyzed from fMRI data. Postoperative fractional anisotropy values of 7 major tracts were calculated. Naming, semantic, and phonematic verbal fluency scores before and after surgery were correlated with imaging parameters. RESULTS fMRI network analysis revealed widespread, bihemispheric alterations in language architecture that were not captured by activation analysis. These network changes were found preoperatively and proceeded after surgery with characteristic patterns in the left and right TLEs. Ipsilesional fronto-temporal connectivity decreased in both left and right TLE. In left TLE specifically, preoperative atypical language dominance predicted better postoperative verbal fluency and naming function. In right TLE, left frontal language dominance correlated with good semantic verbal fluency before and after surgery, and left fronto-temporal language laterality predicted good naming outcome. Ongoing seizures after surgery (Engel classes ID–IV) were associated with naming deterioration irrespective of seizure side. Functional findings were not explained by the extent of resection or integrity of major white matter tracts. CONCLUSIONS Functional connectivity analysis contributes unique insight into bihemispheric remodeling processes of language networks after epilepsy surgery, with characteristic findings in left and right TLE. Presurgical contralateral language recruitment is associated with better postsurgical language outcome in left and right TLE.

Much research has been done on bone cells, but only a few studies deal with biomaterial-induced effects on human osteoclasts, which may take on an important role in the successful regeneration of bone. In order to highlight such effects, human peripheral blood mononuclear cells (PBMCs) were extracted from venous blood, differentiated to osteoclasts and then cultured in, the presence of five particulate hydroxyapatite (HA)/β-tricalcium phosphate (TCP) biomaterials, on bovine bone slices and glass cover slips. The biomaterials, AlgOSS 50/50 (50 % HA/50 % TCP), AlgOSS 20/80 (20 % HA/80 % TCP), Algipore (98 % HA), Cerasorb (100 % TCP) and Bio-Oss (100 % HA) were chosen to assess their influence on cell morphology and numbers. Light microscopic evaluation was performed during ongoing cell culture. After 21 d of cultivation, the biomaterial-induced effects on osteoclastic resorption of the bone slices were evaluated by scanning electron microscopy (SEM). Osteoclast-like cells were identified by TRAP staining. All five biomaterials showed larger area fractions of resorbed bone than the control (5.6 ± 6.8 %), as measured on SEM images. The purely hydroxyapatite-based Algipore (9.8 ± 9.7 %) and Bio-Oss (7.9 ± 8.8 %) showed significantly elevated area fraction rates (p ≤ 0.05) of bone resorption. Light microscope evaluation revealed a significant, but inhibiting effect of Cerasorb (p = 0.05). These data indicated that introducing of small biomaterial hydroxyapatite particles may have improved the performance of bone substitute materials.

Background:Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment.Methods:323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated.Results:Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS.Conclusions:We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

Peripheral blood mononuclear cells (PBMCs) have been shown to produce and release a plethora of pro-angiogenetic factors in response to γ-irradiation, partially accounting for their tissue-regenerative capacity. Here, we investigated whether a certain cell subtype of PBMCs is responsible for this effect, and whether the type of cell death affects the pro-angiogenic potential of bioactive molecules released by γ-irradiated PBMCs. PBMCs and PBMC subpopulations, including CD4+ and CD8+ T cells, B cells, monocytes, and natural killer cells, were isolated and subjected to high-dose γ-irradiation. Transcriptome analysis revealed subpopulation-specific responses to γ-irradiation with distinct activation of pro-angiogenic pathways, cytokine production, and death receptor signalling. Analysis of the proteins released showed that interactions of the subsets are important for the generation of a pro-angiogenic secretome. This result was confirmed at the functional level by the finding that the secretome of γ-irradiated PBMCs displayed higher pro-angiogenic activity in an aortic ring assay. Scanning electron microscopy and image stream analysis of γ-irradiated PBMCs revealed distinct morphological changes, indicative for apoptotic and necroptotic cell death. While inhibition of apoptosis had no effect on the pro-angiogenic activity of the secretome, inhibiting necroptosis in stressed PBMCs abolished blood vessel sprouting. Mechanistically, we identified tumor necrosis factor (TNF) receptor superfamily member 1B as the main driver of necroptosis in response to γ-irradiation in PBMCs, which was most likely mediated via membrane-bound TNF-α. In conclusion, our study demonstrates that the pro-angiogenic activity of the secretome of γ-irradiated PBMCs requires interplay of different PBMC subpopulations. Furthermore, we show that TNF-dependent necroptosis is an indispensable molecular process for conferring tissue-regenerative activity and for the pro-angiogenic potential of the PBMC secretome. These findings contribute to a better understanding of secretome-based therapies in regenerative medicine.

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher’s exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Background:Health-related quality of life (HRQOL) is an important issue in the context of dementia care. The purpose of this study was to investigate the association between HRQOL and depressive symptoms in patients with subjective cognitive decline (SCD) and subtypes of mild cognitive impairment (MCI) and Alzheimer´s disease (AD).Methods:In this cross-sectional, observational study, a control group and four experimental groups (SCD, non-amnestic MCI, amnesticMCI, AD) were compared. Neuropsychological measurers (NTBV) and psychological questionnaires were used for data collection.Results:The control group scored higher than patients with SCD, naMCI, aMCI, or AD for the Mental Health Component Score (MHCS) of the Short Form of the Health Survey (SF-36). The Physical Health Component Score (PHCS) of the SF-36 differed only between some groups. Furthermore, cognitive variables were more strongly associated with the physical aspects of HRQOL, whereas depressive symptoms were more strongly related with the mental aspects of HRQOL.Conclusions:HRQOL and depressive symptoms are closely related in patients with cognitive impairments. Therefore, it is of great importance to assess patients with subjective impairment carefully in terms of depressive symptoms.

Background:Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls.Methods:Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls. Patients were categorized into groups according to two well-established classifications of MCI according to Petersen's (cognitively intact vs. amnestic MCI, aMCI, vs. non-amnestic MCI, non-aMCI) and Litvan's (cognitively intact vs. single-domain MCI, sMCI, vs. multi-domain MCI, mMCI) criteria. Patients and controls underwent individual assessments using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (Neuropsychological Test Battery Vienna, NTBV), the Beck Depression Inventory, and a measure of premorbid IQ (WST).Results:Cognitively intact PD patients and patients with MCI in PD (PD-MCI) showed significantly worse emotion recognition performance when compared to healthy controls. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohen's ds from 0.31 to 1.22). Moreover, emotion recognition performance was higher in women, positively associated with premorbid IQ and negatively associated with age. Depressive symptoms were not related to FER.Conclusions:The present investigation yields further evidence for impaired FER in PD. Interestingly, our data suggest FER deficits even in cognitively intact PD patients indicating FER dysfunction prior to the development of overt cognitive dysfunction. Age showed a negative association whereas IQ showed a positive association with FER.

Background: Subjective cognitive decline (SCD) may be an early indicator for an increased risk of dementia. The exact definition of SCD remains unclear and has recently become a major research interest. Objectives: To determine impairments in activities of daily living (ADL) and depressive symptoms in elderly individuals with SCD, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Methods: We included 752 consecutive patients suffering from SCD, non-amnestic (naMCI) or amnestic MCI (aMCI), AD, and 343 healthy controls into this prospective cohort study. A neuropsychological test battery, B-ADL and BDI-II was performed. Results: SCD patients showed a decreased performance in ADL compared to controls. Performance in ADL declined concurrently with cognitive abilities along the controls−SCD−naMCI−aMCI−AD continuum. Individuals with cognitive complains, no matter if SCD, MCI, or AD patients, reported more often depressive symptoms compared to healthy controls without complaints. Within all five cognitive subgroups, patients with depressive symptoms reported more difficulties in ADL in comparison to patients without depressive symptoms. Adjusting for depressive symptoms, there was no significant group difference between the control versus the SCD group (OR 1.1, CI 0.6–1.7). Conclusions: SCD is a heterogeneous clinical condition. Specific features such as slightly impaired ADL and depressive symptoms are associated with SCD. Clinical markers may serve as an indicator for preclinical AD and in combination with biomarkers guide to an early diagnosis of a progressive neurodegenerative disease.

Summary Objectives We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC). Materials and methods The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan–Meier curves and Cox regression models were used for survival analyses. Results A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders ( p = 0.032 and p = 0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival ( p = 0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients. Conclusion Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer.

Objective Matrix-associated chondrocyte transplantation is routinely used in joints of the extremities but not in the temporomandibular joint (TMJ). Study Design We report the first case series in 7 patients of a tissue engineering approach to regenerate severely degraded articulating surfaces in the TMJ by simultaneously completely resurfacing both the mandibular condyle and the articular eminence/glenoid fossa with a commercially available collagen sponge seeded with autologous cells stabilized within a fibrin matrix. To facilitate healing, we temporarily employed a silicone membrane to protect the engineered tissues. The indications for surgery were posttraumatic fibro-osseous ankylosis, ankylosing osteoarthritis, or late-stage osteoarthritis. Results Six of the patients were recalled for follow-up after 3 years 6 months to 12 years 1 month. The maximum incisal opening was 18.2 ± 9.2 mm (range, 9-33 mm) before and 31.2 ± 13.6 mm (range, 12-47 mm) at the latest follow-up. Histologic specimens taken at 4 months showed beginning differentiation of fibrocytes into chondrocytes, whereas at 3 and 11 years, mature hyaline cartilage—not typical for the TMJ—was present. Conclusions We conclude that the reconstruction of TMJ surfaces by matrix-associated chondrocyte transplantation may become a routine method for cartilage regeneration in the TMJ in the future.

Summary Many studies investigating sleep and memory consolidation have evaluated full‐night sleep rather than alternative sleep periods such as daytime naps. This multi‐centre study followed up on, and was compared with, an earlier full‐night study (Schabus et al., 2004) investigating the relevance of daytime naps for the consolidation of declarative and procedural memory. Seventy‐six participants were randomly assigned to a nap or wake group, and performed a declarative word‐pair association or procedural mirror‐tracing task. Performance changes from before to after a 90‐min retention interval filled with sleep or quiet wakefulness were evaluated between groups. Associations between performance changes, sleep architecture, spindles, and slow oscillations were investigated. For the declarative task we observed a trend towards stronger forgetting across a wake period compared with a nap period, and a trend towards memory increase over the full‐night. For the procedural task, accuracy was significantly decreased following daytime wakefulness, showed a trend to increase with a daytime nap, and significantly increased across full‐night sleep. For the nap protocol, neither sleep stages, spindles, nor slow oscillations predicted performance changes. A direct comparison of day and nighttime sleep revealed that daytime naps are characterized by significantly lower spindle density, but higher spindle activity and amplitude compared with full‐night sleep. In summary, data indicate that daytime naps protect procedural memories from deterioration, whereas full‐night sleep improves performance. Given behavioural and physiological differences between day and nighttime sleep, future studies should try to characterize potential differential effects of full‐night and daytime sleep with regard to sleep‐dependent memory consolidation.

Purpose Epilepsy surgery is the most efficacious therapeutic modality for patients with medically refractory focal epilepsies, but surgical failures remain a challenge to the epilepsy treatment team. The aim of present study was to evaluate the postoperative outcome of patients who underwent reoperation after a failed epilepsy surgery on the temporal lobe. Methods We systematically analyzed the results of comprehensive preoperative evaluations before the first surgery, and before and after reoperation in 17 patients with drug resistant temporal lobe epilepsies. Results Overall, 13 of 17 patients (76.5%) improved after reoperation: five patients (29.4%) were completely seizure free after reoperation (median duration 60months, range 12–72); six patients (35.3%) were seizure free at least 12month before observation points (median duration 120.5months, range 35–155) and two patients (11.8%) had a decrease in seizure frequency. Four patients (23.5%) remained unchanged with respect to seizure frequency and severity. There was no correlation between the improvement in seizure outcome after reoperation and other clinical data except of the history of traumatic brain injury (TBI). The patients who had no history of TBI improved after reoperation, compared to patients with TBI ( p =0.044). The postoperative seizure outcome of patients with incongruent Video-EEG results before the first surgery ( p =0.116) and before reoperation ( p =0.622) was not poorer compared to patients with congruent Video-EEG results. Conclusions Reoperation can considerably improve the operative outcome of the first failed epilepsy surgery in patients with drug resistant temporal lobe epilepsies. Epilepsy centres should be encouraged to report the results of failed epilepsy surgeries.

Summary Background Awareness of subjective memory is an important factor for adequate treatment of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This study served to find out whether awareness of subjective memory complies with objective performance, if differences in awareness are observed longitudinally and whether decrease of awareness can serve as a predictor of AD in MCI patients. Methods Thirty-four patients with MCI seeking help in a memory outpatient clinic were included. All participants underwent thorough neuropsychological examination. Awareness of subjective memory was obtained by calculating difference scores between patient and informant ratings on a 16-item questionnaire concerning complaints about loss of memory in every-day life. Retesting was performed after a mean follow-up period of 24 months. Results Whole group analyses showed that awareness remained relatively stable across time. Self-reported memory complaints correlated with episodic memory at baseline and with performance on a language task at follow-up. Retests displayed decrease of awareness. At group level differences in awareness between both times of assessment were not significant for MCI and MCI patients converting to mild AD at follow-up. The predictive value of awareness was low. Conclusions Awareness of subjective memory deficit is linked to episodic memory function and decreases with decline of cognitive ability. Further studies evaluating predictive power of awareness of subjective memory should include a larger patient sample.

Objective Cyclic alternating pattern (CAP) is defined as periodic EEG activity during NREM sleep that reflects unstable sleep and represents a marker of instability of the sleep process. The aim of the present investigation was to analyze sleep quality of 28 healthy subjects (mean age 53.3 ± 21.3 years) over two consecutive nights and determine potential differences between them (“first-night effect”). Methods Evaluations comprised objective and subjective sleep variables as well as macrostructural and microstructural variables of sleep. Results Macrostructural analysis showed significant differences between the first and the second sleep laboratory night in REM latency (122.39 ± 60.46 min vs. 95.43 ± 36.60 min; T = 3.431; p = 0.002) and the amount of sleep stage 1 (42.60 ± 21.80 min vs. 39.70 ± 18.95 min; T = 2.223; p = 0.035). Microstructural analysis revealed a significant decrease in the CAP rate (1st night: 33.29%; 2nd night: 26.34%; T = 3.288; p = 0.003) and in the amount of subtype A2 (74.79 ± 43.47 vs. 58.50 ± 23.22; T = 2.185; p = 0.038). Subjective variables also demonstrated a significant increase of drive ( T = 2.564; p = 0.016). Conclusion Healthy subjects show hardly any macrostructural differences between the first and the second night in the sleep laboratory. On the microstructural level differences in CAP variables were found. Significance Microstructural analysis can be seen as a further approach to the classification of sleep and CAP turned out to be sensitive to environmental influences on sleep.

Purpose In this study we report our experiences with the treatment of midfacial fractures and various other indications in regions with low load bearing (eg, dysmorphias) using the biodegradable Osteosynthesis System (SonicWeld Rx by KLS Martin, Tuttlingen, Germany), comprising biomechanical and histological aspects. Patients and Methods Seventy-five patients were included in this study. We describe the application of this system for the treatment of fractures of the zygomamaxillary complex, frontal bone impression fractures, surgical treatment of mukocele in the frontal sinus, isolated fractures of the orbital floor, complex midfacial trauma and bone cap fixation, craniosynostoses, and fixation of a distracted bone fragment. Results The pin insertion could be finished with a total failure rate of lower than 5%. In 3 patients, soft tissue swellings in regions with less subcutaneous fat were observed 6 to 8 months postoperatively. No fracture dislocations occurred. Scanning electron micrograph of the experimentally acquired connection between the resorbable plate and 2 pins clearly demonstrates a tight and reliable fusion to bone, both at the cortical as well as at the spongy compartment. Conventional histology leads to corresponding findings as scanning electron micrography, and shows a close fusion between all components. Conclusion This retrospective study shows the general feasibility, sufficient mechanical stability, and efficient intraoperative handling of this angle-stable, ultrasonic-guided resorbable Osteosynthesis System (ResorbX and SonicWeld Rx) for a wide variety of indications in craniomaxillofacial surgery.

Interrater variability of sleep stage scorings has an essential impact not only on the reading of polysomnographic sleep studies (PSGs) for clinical trials but also on the evaluation of patients' sleep. With the introduction of a new standard for sleep stage scorings (AASM standard) there is a need for studies on interrater reliability (IRR). The SIESTA database resulting from an EU-funded project provides a large number of studies (n = 72; 56 healthy controls and 16 subjects with different sleep disorders, mean age +/- SD: 57.7 +/- 18.7, 34 females) for which scorings according to both standards (AASM and RK) were done. Differences in IRR were analysed at two levels: (1) based on quantitative sleep parameter by means of intraclass correlations; and (2) based on an epoch-by-epoch comparison by means of Cohen's kappa and Fleiss' kappa. The overall agreement was for the AASM standard 82.0% (Cohen's kappa = 0.76) and for the RK standard 80.6% (Cohen's kappa = 0.68). Agreements increased from RK to AASM for all sleep stages, except N2. The results of this study underline that the modification of the scoring rules improve IRR as a result of the integration of occipital, central and frontal leads on the one hand, but decline IRR on the other hand specifically for N2, due to the new rule that cortical arousals with or without concurrent increase in submental electromyogram are critical events for the end of N2.

We made osteotomies in the condylar neck in 12 adult sheep to simulate fractures, and joined the two ends with 2 poly(D,L)lactide (PDLLA) plates and 8 PDLLA screws 2mm in diameter. The animals were killed after 2, 6, and 12 months and bony healing was assessed macroscopically and histologically. The plates and screws remained intact and there was no displacement of the bony ends. The degrading plates, which were still visible in the specimens after 6 months, had been replaced by bone. At 12 months the PDLLA had been resorbed with no foreign body reaction and no resorption of underlying bone. The articular discs showed no signs of degeneration.

Background Health related quality of life (HRQOL) is an important issue in the context of dementia care. Objectives The purpose of this study was to investigate HRQOL in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) and its relation to Activity of Daily Living (ADL). Methods In this cross sectional study, four experimental groups (each n = 98), controls, SCD, naMCI and aMCI, were compared. For data collection, neuropsychological methods (NTBV) and psychological questionnaires (SF-36 and B-ADL) were used. Multivariate analysis of variance was calculated to detect differences in HRQOL between groups. Correlations between HRQOL and ADL were explored. Results The dimensions of HRQOL showed mainly consistent differences between the control and the SCD group and MCI subgroups. In almost every dimension of HRQOL, the control group scored higher than subjects with SCD, naMCI, or aMCI. The controls showed low to moderate negative correlations between HQROL and B-ADL in some dimensions of the HRQOL. In the SCD group, low negative correlations with ADL were observed in some HRQOL scales. Low to moderate correlations were found between each scale of the SF-36 and the B-ADL in both MCI subtypes. We found gender differences in HRQOL. Conclusion In conclusion, we could demonstrate that patients with SCD report reduced quality of life. This knowledge is important to get a better understanding of the individuals with SCD and may pave the way for the development of early intervention.

Several recently proposed criteria for assessing cognitive disorder require measuring the cognitive domain of visuo-constructional function. The aims of the present study were to develop a new test (Vienna Visuo-constructional Test-VVT) measuring visuo-constructional functions and to determine the reliability and validity of the VVT in patients with mild cognitive impairment (MCI), Parkinson's disease (PD), and Alzheimer's disease (AD). We further examined age and sex effects and the psychometric quality of the VVT.The study included 76 healthy controls and 103 patients who were referred to the Department of Neurology, Medical University of Vienna for neurocognitive assessment. An administering and scoring system for the VVT was developed.Internal consistency (Cronbach's alpha) was found to range from 0.82 for the healthy control group to 0.93 for the total patient group. There was no sex effect, but age had a negative effect on VVT performance. The VVT successfully differentiated healthy controls from MCI patients, AD patients, and PD patients, respectively.The VVT shows satisfactory validity and reliability and can be administered easily in clinical practice. It constitutes a new measure that can successfully be used to identify visuo-constructional problems in patients with cognitive dysfunction.

Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design.We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5.Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321).In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.

ObjectiveControlled data on predictors of subjective sleep quality in patients with memory complaints are sparse. To improve the amount of comprehensive data on this topic, we assessed factors associated with subjective sleep quality in patients from our memory clinic and healthy individuals.MethodsBetween February 2012 and August 2014 patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) from our memory clinic and healthy controls were recruited. Apart from a detailed neuropsychological assessment, the subjective sleep quality, daytime sleepiness and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory (BDI-II).ResultsOne hundred fifty eight consecutive patients (132 (84%) MCI patients and 26 (16%) SCD patients) and 75 healthy controls were included in the study. Pairwise comparison of PSQI scores showed that non-amnestic MCI (naMCI) patients (5.4 ± 3.5) had significantly higher PSQI scores than controls (4.3 ± 2.8, p = .003) Pairwise comparison of PSQI subscores showed that naMCI patients (1.1 ± 0.4) had significantly more "sleep disturbances" than controls (0.9 ± 0.5, p = .003). Amnestic MCI (aMCI) (0.8 ± 1.2, p = .006) and naMCI patients (0.7 ± 1.2, p = .002) used "sleep medication" significantly more often than controls (0.1 ± 0.6) Both, aMCI (11.5 ± 8.6, p < .001) and naMCI (11.5 ± 8.6, p < .001) patients showed significantly higher BDI-II scores than healthy controls (6.1 ± 5.3). Linear regression analysis showed that the subjective sleep quality was predicted by depressive symptoms in aMCI (p < .0001) and naMCI (p < .0001) patients as well as controls (p < .0001). This means, that more depressive symptoms worsened subjective sleep quality. In aMCI patients we also found a significant interaction between depressive symptoms and global cognitive function (p = .002).DiscussionDepressive symptoms were the main predictor of subjective sleep quality in MCI patients and controls, but not in SCD patients. Better global cognitive function ameliorated the negative effect of depressive symptoms on the subjective sleep quality in aMCI patients.

Background The purpose of this study was to assess the impact of standard anticoagulation and intermittent catheter irrigation on clot formation on intraarterial chemotherapeutical catheters. Methods Sixteen nonheparinized catheters were placed in the carotid vessels of 10 patients. Ten catheters were perfused with chemotherapeutic drugs; six catheters were not perfused. Patients received LMWH anticoagulation; catheters were irrigated with boluses of heparinized saline daily. Catheters were retrieved for SEM evaluation after a mean intravessel placement interval of 21 days. Results All samples demonstrated accumulation of thrombotic debris on luminal sides and outsides of catheters. Obliteration was seen in three samples. Detachment of thrombus fragments was present in several specimens. No significant dependence of clot formation on placement interval and chemotherapeutic perfusion was calculated. Conclusions Standard anticoagulation was ineffective in clot prevention. Heparinized catheters might potentially reduce the risk of clot formation. A delivery system should be engaged for continuous irrigation of catheters with heparinized saline. © 2002 Wiley Periodicals, Inc. Head Neck 24: 566–574, 2002

To study the role of neutrophils in host defense, using human endothelial cells in migration studies in the presence of ketamine (0.3, 3, and 30 microg/mL).Prospective, controlled study.University research laboratories.Seven independent experiments from different donors were done, investigating the influence of ketamine (0.3, 3, and 30 microg/mL) to the migration of human leukocytes through human endothelial cell monolayers.Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant (3 microg/mL), higher (30 microg/mL), and lower (0.3 microg/mL) concentrations of ketamine. The amount of leukocyte migration after 3 hrs was measured in a fluorometer.Human endothelial cells isolated from umbilical veins were cultured on microporous membranes (polyethylene-terephthalat membranes) until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells under the clinically relevant concentration of ketamine was reduced to 59+/-9.8% (SD) (p.05) when leukocytes but not the endothelial cell monolayers were preincubated with ketamine. Leukocyte migration was reduced to 92+/-7.3% (p.05) when only monolayers of endothelial cells were treated with ketamine, and to 52+/-8.8% (p.05) when both leukocytes and monolayers of endothelial cells were treated with ketamine. The higher and lower concentrations showed a dose-dependent effect.We investigated the cellular interaction between both cell systems, leukocytes and endothelial cells, simultaneously in the presence of ketamine. Ketamine is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different dosages revealed a dose-dependent effect. The current model allowed treatment of one cell type, either leukocyte or endothelial cell. Ketamine inhibits the function of leukocytes more than the function of endothelial cells.

Free/pedicled myocutaneous flaps used as functional replacement after radical dissection of advanced stage squamous cell carcinomas of the oral cavity/oropharynx were examined by immunohistochemistry (APAAP-technique). Biopsies from eight patients were taken at the time of surgery and at 3 and 5 months post-operatively. Fifteen monoclonal antibodies were used to detect surface antigens as markers of phenotypic changes of immune competent cells. In post-operative biopsies all antigens investigated increased significantly. Significantly higher numbers of CD45RO+ (P < 0.01) and CD45RA+ (P < 0.001) leukocytes were detectable. The majority of these leukocytes were TcR alpha/beta +/CD3+ T-cells, which increased in the CD4 (P < 0.05) and the CD8 (P < 0.001) subset. In addition, B-cells (P < 0.05), granulocytes (P < 0.05), NK cells (CD16+ lymphocytic cells; P < 0.05) and mature macrophages (25F9+cells; P < 0.01) were increased. Intra- and subepidermally a significantly (P < 0.01) higher number of dendritic-/Langerhans cells (CD1a+) was detectable. In post-operative biopsies, the activation-associated antigens ICAM-1, VCAM and HLA-DR were expressed on significantly more mononuclear-/endothelial cells and on keratinocytes. Our findings indicate that the myocutaneous flaps still contained cells with immunological capacities.

An electroneutral thiazide-sensitive Na-Cl cotransport pathway (TSC) has been localized functionally to the distal convoluted tubule (DCT), although the TSC has also been detected in the connecting tubule (CNT), the cortical collecting duct, and the medullary collecting tubule as well. The present experiments were designed to localize expression of message for the TSC in rat and human kidney. A riboprobe, generated from the mouse TSC, was used for in situ hybridization. Simultaneous immunocytochemistry, using antibodies to Tamm-Horsfall protein, band 3, and the Na+/Ca2+ exchanger, permitted delineation of specific nephron segments. In rat, message for the TSC was highly expressed in DCT cells but not elsewhere. The transition from thick ascending limb to DCT was abrupt, whereas the transition to CNT was gradual. In the more distal region of rat DCT (DCT-2), which contained few intercalated cells, both TSC message and Na+/Ca2+ exchanger immunoreactivity were present. Treatment of rats with furosemide for 5 days increased expression of TSC message within the DCT but did not induce its expression elsewhere. In humans, expression of TSC message was also highest in cells of the DCT. In humans, however, expression extended well into the CNT. These experiments indicate that the TSC is expressed predominantly by DCT cells in both rat and humans, although expression extends into the CNT cells in humans. They also show that the TSC and Na+/Ca2+ exchanger are coexpressed by a subpopulation of DCT cells near the junction with the CNT.

During an archaeological excavation in Altenberg/Linz (Upper Austria), the well-preserved skeletal remains of a mature male dated the 13th century AD were recovered. Several elements of the skeleton yielded alterations caused by trauma: beside a malunion of the left ulna which was accompanied by shortening of the diaphysis, a luxation and deformation of the left radial head was observed (Monteggia-type lesion, Bado-type I). Moreover, at the anterior aspect of the corresponding humerus, a chalice-shaped, newly built bone structure that framed the displaced capitulum radii was visible. This structure formed a sort of “alternative joint” that functionally even allowed some movements, although considerably restricted in regard to flexion/extension and even more in pronation/supination. To verify the assumption of a “single event”, we not only investigated the concerned skeletal portions by gross-anatomical examination, but also by non-invasive conventional radiological, micro-computed tomographical, and histological techniques. Particular morphological features, injuries at the calvarium, and fractures of other postcranial elements imply the scenario of a close combat; although survived, the traumata obviously resulted in partial invalidity.

Purpose The present study was conducted to evaluate the effect of platelet-rich plasma (PRP) on new bone formation and remodeling after grafting of the maxillary sinus with an algae-derived hydroxyapatite AlgOss/C Graft/Algipore. Materials and Methods Fourteen consecutive patients with severely atrophic maxillae underwent uni- or bilateral grafting of the maxillary sinus with a mixture of collected bone, algae-derived hydroxyapatite AlgOss/C Graft/Algipore (ratio 1:10), and a combined addition of PRP and thrombin (Tissucol Kit; Baxter, Vienna, Austria) to allow for fast clotting. After an average healing period of 7.1 months bone samples were retrieved. Patients from a former consecutive series treated without PRP served as control group. Statistical analysis was done by Welch 2-sample t test and mixed linear model testing. Results In the coronal specimen portions, mean values for newly formed bone area, biomaterial area and marrow space of 32.2% ± 10.4%, 20.1% ± 13.0%, and 47.7% ± 8.5% were found with PRP, respectively. In the control group the corresponding values were 27.6% ± 13.4%, 20.3% ± 12.9%, and 52.1% ± 9.3%. In the apical specimen portions in the PRP group, the newly formed bone area, biomaterial area, and marrow space was 25.7% ± 15.0%, 23.4% ± 14.9%, and 50.9% ± 12.5%, respectively. The corresponding values in the control group were 17.0% ± 8.6%, 34.5% ± 11.2%, and 48.5% ± 8.5%. Conclusions Statistical evaluation of the samples proved significantly better overall resorption of algae-derived hydroxyapatite AlgOss/C Graft/Algipore and increased new bone formation when PRP was used, especially in the apical region.

The aim of this paper was to assess the prevalence of morning headaches in the Austrian general population and to analyse their relationship to daytime functioning and quality of sleep. In a nationwide survey, we recruited 1000 adults (478 men, 522 women, age over 14 years). For this study, we selected all subjects with self-reported morning headaches as well as controls matched for age, sex, size of hometown, level of education and marital status. Forty-eight persons reported morning headaches making a prevalence of 5% in the Austrian general population. Compared to controls, subjects with morning headaches reported more often daytime sleepiness (50% vs. 18.8%, p = 0.003), difficulties in staying awake (47.9% vs. 18.8%, p = 0.005) and falling asleep involuntarily (29.2% vs. 8.3%, p = 0.019). Moreover, they reported a longer sleep onset latency (26.5 ± 27.5 vs. 13.5 ± 13.5 min, p = 0.005), and more often sleep disturbances (58.3% vs. 14.6%, p < 0.001), tossing and turning around during the night (50.0% vs. 8.0%, p < 0.001), problems with sleep maintenance (64.6% vs. 22.9%, p < 0.001) and the symptom of restless legs (20.8% vs. 2.1%, p = 0.01). In addition, subjects with morning headaches felt less often refreshed in the morning (18% vs. 51%, p < 0.001) and reported regular use of medication more often (64.6% vs. 29.2%, p = 0.001) than controls. After correction for multiple testing, the differences in sleep maintenance, sleep disturbances and regular use of medication remained statistically significant. In conclusion, this is the first Austrian population-based controlled study to show that morning headaches afflict one out of 20 persons and are related to self-reported sleep problems.

Although obesity traditionally has been considered a condition of low risk for osteoporosis, this classic view has recently been questioned. The aim of this study was to assess bone microarchitecture and turnover in a mouse model of high-fat diet-induced obesity. Seven-week-old male C57BL/6J mice (n = 18) were randomized into 3 diet groups. One third (n = 6) received a low-fat diet for 24 weeks, one third was kept on an extended high-fat diet (eHF), and the remaining was switched from low-fat to high-fat chow 3 weeks before sacrifice (sHF). Serum levels of insulin, leptin, adiponectin, osteocalcin, and cross-linked telopeptides of type I collagen (CTX) were measured. In addition, bone microarchitecture was analyzed by micro-computed tomography; and lumbar spine bone density was assessed by dual-energy x-ray absorptiometry. The CTX, body weight, insulin, and leptin were significantly elevated in obese animals (sHF: +48%, +24%, +265%, and +102%; eHF: +43%, +52%, +761%, and +292%). The CTX, body weight, insulin, and leptin showed a negative correlation with bone density and bone volume. Interestingly, short-term high-fat chow caused similar bone loss as extended high-fat feeding. Bone volume was decreased by 12% in sHF and 19% in eHF. Bone mineral density was 25% (sHF) and 27% (eHF) lower when compared with control mice on low-fat diet. As assessed by the structure model index, bone microarchitecture changed from plate- to rod-like appearance upon high-fat challenge. Trabecular and cortical thickness remained unaffected. Short-term and extended high-fat diet-induced obesity caused significant bone loss in male C57BL/6J mice mainly because of resorptive changes in trabecular architecture.

Background:The goals of this study were to establish prevalence of subjective memory complaints (SMC) and depressive symptoms (DS) and their relation to cognitive functioning and cognitive status in an outpatient memory clinic cohort.Methods:Two hundred forty-eight cognitively healthy controls and 581 consecutive patients with cognitive complaints who fulfilled the inclusion criteria were included in the study.Results:A statistically significant difference (p < 0.001) between control group and patient group regarding mean SMC was detected. 7.7% of controls reported a considerable degree of SMC, whereas 35.8% of patients reported considerable SMC. Additionally, a statistically significant difference (p < 0.001) between controls and patient group regarding Beck depression score was detected. 16.6% of controls showed a clinical relevant degree of DS, whereas 48.5% of patients showed DS. An analysis of variance revealed a statistically significant difference across all four groups (control group, SCI group, naMCI group, aMCI group) (p < 0.001). Whereas 8% of controls reported a considerable degree of SMC, 34% of the SCI group, 31% of the naMCI group, and 54% of the aMCI group reported considerable SMC. A two-factor analysis of variance with the factors cognitive status (controls, SCI group, naMCI group, aMCI group) and depressive status (depressed vs. not depressed) and SMC as dependent variable revealed that both factors were significant (p < 0.001), whereas the interaction was not (p = 0.820).Conclusions:A large proportion of patients seeking help in a memory outpatient clinic report considerable SMC, with an increasing degree from cognitively healthy elderly to aMCI. Depressive status increases SMC consistently across groups with different cognitive status.

Background: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). Methods: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21–86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. Results: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen’s kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). Conclusion: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.

Background. In voice rehabilitation for laryngectomized patients, voice prosthetic biofilm formation is still an unsolved problem. Design and materials of voice prostheses have been altered by manufacturers to improve function and extend the lifetime of devices. The goal of the study was to investigate biofilm formation on Provox 2 and Phonax, recently introduced voice prostheses made of thermoplastic polyurethane. Methods. Five laryngectomized patients were equipped with both Phonax and Provox 2 voice prostheses. Microbial colonization was analyzed using standard microbiological methods. Biofilm formation and material infiltration were illustrated using scanning electron microscopy, fluorescence microscopy, and thin-section light microscopy. Results. Although no differences in quality or quantity of microbial colonization were assessed, microscopic imaging revealed differences in material surfaces, biofilm composition, and infiltration morphologies; the polyurethane material seems to destabilize biofilm architecture by inhibition of hypheal Candida growth forms. Conclusions. Polyurethane material for voice prostheses seems to reduce biofilm stability and infiltrative processes. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

FOR APPROXIMATELY 40 YEARS THE ONLY WIDELY ACCEPTED STANDARD FOR DESCRIBING THE HUMAN SLEEP PROCESS WAS THE MANUAL OF SLEEP CLASSIFICATION by Rechtschaffen and Kales.1 On the basis of these scoring rules, sleep recordings are divided into 7 discrete stages (wake, stage 1, stage 2, stage 3, stage 4, stage REM, and movement time). Even though in many cases this standard is useful, the rules of Rechtschaffen and Kales have also been criticized for leaving plenty of room for subjective interpretation, which leads to a great variability in the visual evaluation of sleep stages.2,3 Last but not least, the standard rules were developed for young healthy adults4,5 and do not necessarily directly apply to elderly subjects and patients. The American Academy of Sleep Medicine (AASM)6 modified the standard guidelines for sleep classification by Rechtschaffen and Kales and developed a new guideline for terminology, recording method, and scoring rules for sleep-related phenomena. The manual is the result of a review of literature, analysis and consensus which addresses 7 topics: digital analysis and reporting parameters, visual scoring, arousal, cardiac and respiratory events, movements and pediatric scoring. One of the major changes is a change in terminology: in the AASM classification, sleep stages S1 to S4 are referred to as N1, N2, and N3, with N3 reflecting slow wave sleep (SWS, RK stage REM is referred to as stage R. According to the AASM manual, a minimum of 3 EEG derivations, sampling activity from the frontal, central, and occipital regions, has to be recorded. The recommended derivations are F4-M1, C4-M1, and O2-M1 (right-sided active electrodes and a reference over the left mastoid, rather than the ear).7 The new manual also deals with the definition of the sleep-wake transition, sleep spindles, K-complexes, slow wave sleep, and REM sleep, as well as arousals and major body movements. In summary, the major changes of the new manual comprise EEG derivations, the merging of stages 3 and 4 into N3, the abolition of stage “movement time,” the simplification of many context rules as well as the recommendation of sampling rates and filter settings for polysomnographic (PSG) reporting and for user interfaces of computer-assisted sleep analysis.6 To date there are no studies evaluating the effects of the new standard on sleep scoring data. The aim of the present investigation was to describe in detail differences between visual sleep scoring according to the Rechtschaffen and Kales classification and scoring based on the new AASM guidelines in normal subjects of different age groups and sleep-disturbed patients.

PURPOSE: Osteonecrosis of the jaws is described as an intraoral complication after administration of intravenous nitrogen-containing bisphosphonates. In a retrospective study, patients with osteonecrosis of the jaws after bisphosphonate treatment were evaluated with regard to diagnostic investigations and therapeutic management. PATIENTS AND METHODS: Seventeen patients with osteonecrosis of the jaws after bisphosphonate treatment who were referred to our department between July 2004 and June 2005 were included in this study. Computer tomography, magnetic resonance imaging, scintigraphy, bacteriology and biopsy were used in diagnostic evaluation. All patients were treated surgically. RESULTS: The reasons for bisphosphonate treatment were multiple myeloma in 12 patients, breast cancer with bone metastasis in four patients and histiocytosis X in one patient. Five patients had received intravenous pamidronate and 12 patients zoledronic acid. The median number of treatment cycles for pamidronate was 36 times (range 4–100) in 38 months (range 4–100). Zolendric acid was given 23.5 times (range 5–39) in 26 months (range 5–39). Nine patients had a lesion in the mandible, eight in the maxilla. Clinical symptoms were exposed bone, pain and local inflammation of the mucosa. Computer tomography showed sclerotic areas in the osteonecrosis zone. The biopsy did not show a metastatic lesion. Sequestrectomy and decortication was adequate in the follow-up. CONCLUSION: Nitrogen-containing bisphosphonates appear to be associated with the risk of developing osteonecrosis of the jaws. To reduce this risk, patients should be evaluated by a dentist before beginning treatment with intravenous bisphosphonates.

Grafting of the maxillary sinus is an established treatment modality to provide sufficient bone for the fixation of dental implants. We stated the hypothesis that the porous fluorohydroxyapatitic (FHA) biomaterial FRIOS Algipore could be used as a suitable biomaterial for sinus grafting in severely atrophic maxillae. To investigate the accuracy of our hypothesis, 69 trephine specimens from 26 patients who received maxillary sinus grafting with FRIOS Algipore were retrieved during the installation of dental implants. The specimens were processed undecalcified and subjected to histomorphological and histomorphometrical examination. After a mean healing time of 7 months, 23.0% (+/-8.3) new bone had formed around the implanted particles. Bone formation was also evident within the pores of the particles. Statistical analysis indicated that bone formation originated from the sinus floor. Particles provided scaffolding for the promotion of newly formed bone towards apical sinus portions. Mineral dissolution from the walls of the pores was observed prior to and during bone apposition. Thereafter, portions of the particles were resorbed during bone remodeling and replaced by newly formed bone. The present investigation shows that the biomaterial FRIOS Algipore is a suitable biomaterial for sinus grafting of severely atrophic maxillae.

Background and purpose: The goal of this study was to establish the prevalence of subjective memory complaints (SMCs) and depressive symptoms (DS)s and their relation to cognitive functioning in patients with Parkinson’s disease (PD). Methods: In all, 248 controls and 104 PD patients were included in the study. The PD group was subdivided into three PD subtypes with mild cognitive impairment (MCI) according to the Petersen criteria and three PD subtypes with MCI according to the Litvan criteria. Results: Substantial SMCs were reported by 7.7% of controls and 16.3% of the PD patients (P < 0.001). A clinically relevant degree of DSs was evident in 16.6% of controls compared with 40.4% in the PD group (P < 0.001). An analysis of variance revealed a statistically significant difference for SMCs across all Petersen groups as well across all Litvan groups. Two-factor analyses of variance with the factors cognitive status (MCI subtype) and depressive state (depressed versus not depressed) and SMCs as dependent variable revealed significant results. Conclusions: Approximately 15% of PD patients seeking help in a movement disorder clinic report significant SMCs, with an increasing degree from cognitively healthy PD to PD-MCI. Significant DSs increase SMCs across all cognitive status groups.

Objective: To test propotol and the solvent of propofol on leukocyte function in the presence of endothelial cell monolayers. The interactions of leukocytes with endothelial cells play a tremendous role during inflammation. Previous studies have investigated the influence of propofol on leukocytes. Design: Prospective, controlled study. Setting: University research laboratories. Subjects: Seven independent experiments were performed to investigate the influence of propofol (0.4, 4, and 40 ng/mL) on the migration of human leukocytes through human endothelial cell monolayers. Moreover, the authors tested the solvent of propofol on leukocyte migration. Interventions: Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant higher and lower concentrations of propofol. The amount of leukocyte migration after 3 hrs was measured with a fluorometer. Measurements and Main Results: Human endothelial cells isolated from umbilical veins were cultured on microporous membranes until they formed an endothellal cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells using the clinically relevant concentration of propofol was reduced to 93% ± 3.8% (SD; p

Effect of anticoagulation on blood membrane interactions during hemodialysis. Background Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation—conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis—on membrane-associated coagulation activation. Methods Fifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments. Results Using UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 ± 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 ± 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 ± 0.6 of 20 points, P Conclusion The results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.

UNLABELLED The interactions between blood and vascular wall cells are essential for understanding pathophysiological processes, e.g., during inflammation. The influence of anesthetics on leukocyte function is well documented. An inhibitory effect of thiopental, midazolam, and ketamine on leukocyte chemotaxis in a Boyden chamber chemotaxis assay (i.e., endothelial cells were not included) has been demonstrated. Little is known, however, about the influence of sufentanil on the inflammatory processes. To reach their targets in the tissue in vivo, leukocytes must interact with endothelial cell monolayers (ECMs). The aim of the current study was to investigate the influence of sufentanil on the migration of leukocytes through an ECM. Human umbilical vein endothelial cells were cultured to achieve a monolayer. Isolated polymorphonuclear leukocytes and ECM were preincubated with different concentrations of sufentanil. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenylalanine was measured (n = 7). Sufentanil significantly reduced the amount of leukocyte migration through ECM to 77%+/-7.8% (P < 0.05 compared with control). Endothelial cells as well as leukocytes contributed to this effect: treatment of both cell types showed an additive effect. Although lower concentrations showed no effect, high concentrations reduced leukocyte migration through ECM to 61%+/-7.1%. IMPLICATIONS Leukocytes play an important role during inflammation, and anesthetics influence leukocyte functions, e.g., respiratory burst or chemotaxis. The effect of sufentanil on transendothelial leukocyte migration has not been investigated. Therefore, we used a migration assay including endothelial cell monolayers. Sufentanil showed a reducing effect on transendothelial leukocyte migration.

The interactions between blood and vascular wall cells are essential for the understanding of pathophysiologic processes, e. g. inflammation. The influence of the anesthetic drug thiopental on leukocyte function is well documented. Recently, an inhibitory effect of thiopental on leukocyte chemotaxis in a Boyden chamber assay (i. e. endothelial cells were not included) was demonstrated. In vivo, leukocytes have to interact with endothelial cell monolayers to invade the tissue. The influence of thiopental on a monolayer of endothelial cells has not yet been investigated. The aim of the current study was to investigate the influence of thiopental on the migration of leukocytes through endothelial cell monolayers (ECM). Human umbilical vein endothelial cells (HUVEC) were isolated and cultured on microporous membrane filters to achieve a monolayer. Isolated polymorphonuclear leukocytes (PMNL) as well as ECM were preincubated with different concentrations of thiopental. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenyla-lanine was measured (n=7). Thiopental was able to reduce the amount of leukocyte migration through ECM significantly. In conclusion, we could show that thiopental is able to reduce the migration of PMNL through ECM significantly.

A thiazide-sensitive Na-Cl cotransporter contributes importantly to mammalian salt homeostasis by mediating Na-Cl transport along the renal distal tubule. Although it has been accepted that thiazide-sensitive Na-Cl cotransport occurs predominantly along the distal convoluted tubule in rats and mice, sites of expression in the rabbit have been controversial. A commonly accepted model of rabbit distal nephron transport pathways identifies the connecting tubule, not the distal convoluted tubule, as the predominant site of thiazide-sensitive Na-Cl cotransport. The thiazide-sensitive Na-Cl cotransporter has been cloned recently. The present experiments were designed to localize sites of thiazide-sensitive Na-Cl cotransporter mRNA expression along the rabbit distal nephron. Nonradioactive in situ hybridization with a thiazide-sensitive Na-Cl cotransporter probe was combined with immunocytochemistry with an antibody that recognizes distal convoluted tubule cells and with a Na+/Ca2+ exchanger antibody that recognizes only connecting tubule cells. The results indicate that thiazide-sensitive Na-Cl cotransporter mRNA is highly expressed by cells of the distal convoluted tubule and not by connecting tubule cells. Segments that stain with the Na+/Ca2+ exchanger antibody (connecting tubules) do not demonstrate thiazide-sensitive Na-Cl cotransporter mRNA expression. We conclude that the predominant site of thiazide-sensitive Na-Cl cotransporter mRNA expression in rabbit distal nephron is the distal convoluted tubule and that sites of mRNA expression of electroneutral Na and Cl transport are similar in rabbits, rats, and mice.