Depressive symptoms in patients with hypersomnia measured with Beck Depression Inventory.

BACKGROUND: Patients with central hypersomnia (HCO) often show symptoms of depression. Despite of many studies conducted in this field, the link between these two disorders remains unclear. In order to contribute data to this research, we examined the question of which depressive symptoms characterize these patients. Furthermore, we investigated the differences between HCO who were more or less depressed regarding insomnia, sleep quality and daytime tiredness. METHODS AND MATERIAL: The retrospective analysis assesses the presence and kind of depressive symptoms as measured by the Beck Depression Inventory (BDI) in 168 HCO including narcolepsy type I (NAR1), narcolepsy type II (NAR2) and idiopathic hypersomnia (HYP). Sleep parameters from one night of polysomnography, scores of questionnaires for insomnia and for daytime sleepiness, and data from sustained attention tests were compared between HCO with and without depression, as determined by BDI scores (cut off >12). RESULTS: According to BDI scores 52% exhibited no depression. The BDI items pertaining to tiredness and work inhibition exhibited elevated scores, whereas those pertaining to suicidality showed low scores. No difference was found between depressed and non-depressed HCO with regard to daytime vigilance performance or daytime sleepiness. However, depression was associated with older age, higher insomnia scores, and a shorter sleep time on polysomnography. CONCLUSION: A potential interpretation of our findings is that depressive symptoms in HCO may be a consequence of restricted life quality due to hypersomnia. Thus, therapeutical effort should focus more intensely on coping strategies.

Incidence and outcome of atlanto-occipital dissociation at a level 1 trauma centre: a prospective study of five cases within 5 years.

BACKGROUND: Prospective evaluation of atlanto-occipital dissociations (AODs) at a level 1 trauma centre within 5 years. METHODS: Over a period of 5 years (2005-2009), all CT scans of the skull base and the upper cervical spine due to traumatic injuries were prospectively entered into a database. Furthermore, in cases of confirmed AOD all empirical data were prospectively collected. A more detailed data analysis of all AOD patients was conducted 2 years post-trauma. If required, another prospective follow-up was performed. RESULTS: 2,616 CT scans were performed in total. Out of these, there were five male patients with confirmed AOD. Thus, the total incidence was 0.2 %. AOD was associated with occipital condyle fractures in three out of the five cases. Three out of five patients (60 %) died due to the severity of the injury. It was possible to stabilise two patients surgically with a clinical/radiological follow-up 2 years post-surgery. At that time, one patient had an incomplete tetraplegia and was wheelchair ridden without needing ventilation, while the other patient suffered from post-traumatic stress disorder, but was able to walk and live alone. CONCLUSIONS: AOD is a rarely seen injury, even in a level 1 trauma centre, and is associated with high morbidity and mortality. However, it is possible for adults to survive this severe occipito-cervical injury after surgical repair while maintaining the ability to walk. All the results and recommendations are still based on a low level of evidence, due to the low incidence of this injury.

Occipital condyle fractures. Prospective follow-up of 31 cases within 5 years at a level 1 trauma centre.

PURPOSE: Prospective investigation of incidence and outcome of occipital condyle fractures (OCF) in a level 1 trauma centre. METHODS: Over a period of 5 years, we prospectively recorded all cases of OCF, and performed a 1-year post-injury radiological and clinical follow-up using CT imaging, SF-36 and Neck Disability Index, respectively. RESULTS: A total of 31 patients with OCF were identified. Based on a total of 2,616 CT scans that had been performed during this period, the incidence was 1.19%. There were 27 unilateral and 4 bilateral OCFs. Furthermore, 3 out of 31 patients (9.7%) were additionally diagnosed with atlanto-occipital dislocation (AOD), one of which was dorsally stabilised in a surgical procedure. All other patients were treated conservatively. 5 out of 31 patients (16.1%) died due to the severity of associated injuries. 22 out of 31 patients (70.9%) were prospectively followed-up for 1 year after trauma. During this period, CT imaging showed bony consolidation of fractures in all cases except for one, with no evidence of secondary dislocation or nonunion. Evaluation of the Neck Disability Index showed moderate disability. The SF-36 questionnaire showed an impaired quality of life in all areas; however, these were determined by associated injuries and independent of the type of fracture. CONCLUSIONS: Both unilateral and bilateral OCFs represent a stable injury regardless of the type of fracture. If AOD has been diagnosed in addition, it requires surgical stabilisation-independent of the OCF-and it is a significant predictor for poor outcomes. The patients quality of life 1 year after trauma has not been affected by the OCF, but by the overall pattern of the injury and by comorbidities. Based on our results, we introduce a new, simple and practical classification for OCFs.

Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers.

METHODS: We examined gene expression profiles of tumor cells from 29 untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), and 9 small cell lung cancer (SCLC)) in comparison to 5 samples of normal lung tissue (NT). The European and American methodological quality guidelines for microarray experiments were followed, including the stipulated use of laser capture microdissection for separation and purification of the lung cancer tumor cells from surrounding tissue. RESULTS: Based on differentially expressed genes, different lung cancer samples could be distinguished from each other and from normal lung tissue using hierarchical clustering. Comparing AC, SCC and SCLC with NT, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed (estimated false discovery rate: < 2.6%). Different lung cancer subtypes had distinct molecular phenotypes, which also reflected their biological characteristics. Differentially expressed genes in human lung tumors which may be of relevance in the respective lung cancer subtypes were corroborated by quantitative real-time PCR. Genetic programming (GP) was performed to construct a classifier for distinguishing between AC, SCC, SCLC, and NT. Forty genes, that could be used to correctly classify the tumor or NT samples, have been identified. In addition, all samples from an independent test set of 13 further tumors (AC or SCC) were also correctly classified. CONCLUSION: The data from this research identified potential candidate genes which could be used as the basis for the development of diagnostic tools and lung tumor type-specific targeted therapies.

Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor.

BACKGROUND: Pegylated granulocyte colony-stimulating factor (G-CSF) has recently been introduced as a new compound for mobilization of CD34(+) hematopoietic stem and progenitor cells. In this study, we compared the molecular and functional characteristics of CD34(+) cells mobilized by pegylated G-CSF with those mobilized by unconjugated G-CSF. DESIGN AND METHODS: Gene expression of immunomagnetically enriched CD34(+) cells from leukapheresis products of patients who were given pegylated-G-CSF or unconjugated G-CSF was analyzed using Affymetrix HG Focus microarrays and quantitative reverse transcriptase polymerase chain reaction. Flow cytometry and fluorescence activated cell sorting was conducted to assess the CD34(+) subset composition and to obtain Lin(-), CD34(+), CD38(-) hematopoietic stem cells. Cell cycle assays and clonogenic assays were performed for functional corroboration. RESULTS: Pegylated G-CSF and unconjugated G-CSF mobilized CD34(+) and hematopoietic stem cells with different molecular phenotypes and functional properties. The CD34(+) cells mobilized by pegylated G-CSF had higher expression levels of genes indicative of early hematopoiesis, including HOXA9, MEIS1 and GATA3. We found lower expression of genes characteristic of erythroid and later stages of myeloid differentiation and a lower functional burst-forming unit erythroid/colony-forming unit-granulocyte-macrophage ratio. Consistently, greater numbers of hematopoietic stem cells and common myeloid progenitors and fewer megakaryocyte-erthrocyte progenitors were found in the pegylated-G-CSF-mobilized CD34(+) cells. Additionally, sorted pegylated-G-CSF-mobilized hematopoietic stem cells displayed higher expression of HOXA9 in comparison to G-CSF-mobilized hematopoietic stem cells. In line with the gene expression data, CD34(+) cells mobilized by pegylated G-CSF, as well as sorted hematopoietic stem cells, showed a significantly greater cell cycle activity. CONCLUSIONS: Stimulation with pegylated-G-CSF or G-CSF results in different expression of key regulatory genes and different functional properties of mobilized hematopoietic stem cells as well as their progeny, a finding that might be relevant for the application of these cells in blood stem cell transplantation.

Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts.

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.