Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells

Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM). Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines. Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels. There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons. Among 7 MM subgroups identified by unsupervised hierarchical cluster analysis, PRL-3 gene expression was significantly higher in the 3 groups denoted as "proliferation," "low bone disease," and "MMSET/FGFR3." PRL-3 protein was detected in 18 of 20 BM biopsies from patients with MM. Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells. In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.     

Sleep apnoea, anxiety, depression and somatoform pain: a community-based high-risk sample

Community-based studies that measure both psychiatric diagnoses and obstructive sleep apnoea (OSA) are lacking. This study reports current psychiatric disorders in community-dwelling adults at high risk for OSA identified by the Berlin Questionnaire. Furthermore, associations between OSA and current psychiatric disorders, unadjusted and adjusted for putative confounders, are reported. A subsample of the Akershus Sleep Apnoea Project consisting of 290 adults, aged 30-65 yrs, with positive Berlin Questionnaire screening underwent the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, version IV and polysomnography. Auxiliary analyses of depression are provided. The median apnoea/hypopnoea index score in the sample was 7.7 (interquartile range 2.4-22.2). Major depressive disorder, current anxiety and somatoform pain disorder were diagnosed in 12.4%, 14.8% and 19.3% of participants, respectively. At least one psychiatric disorder was diagnosed in 110 participants. The odds ratio of participants with OSA having a psychiatric disorder compared with participants without OSA was 0.54 (95% CI 0.33-0.88). A negative association did not exist among Berlin Questionnaire low-risk participants. In conclusion, more than one-third of participants in a community-based, Berlin Questionnaire high-risk sample were diagnosed with a psychiatric disorder. A negative association between OSA and psychiatric morbidity was found.     

Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection

OBJECTIVE: Three-dimensional (3-D) ultrasound is an intraoperative imaging modality used in neuronavigation as an alternative to magnetic resonance imaging (MRI). This article summarizes 4 years of clinical experience in the use of intraoperative 3-D ultrasound integrated into neuronavigation for guidance in brain tumor resection. METHODS: Patients were selected for inclusion in the study on the basis of the size and location of their lesion. Preoperative 3-D MRI data were registered and used for planning as in other conventional neuronavigation systems. Intraoperative 3-D ultrasound images were acquired three to six times, and tumor resection was guided on the basis of these updated 3-D images. RESULTS: Intraoperative 3-D ultrasound represents a good solution to the problem of brain shift in neuronavigation because it easily provides an updated, and hence more accurate, map of the patient's true anatomy in all phases of the operation. Ultrasound makes it possible to follow the progression of the operation, and it improves the radicality of tumor resection by detecting tumor tissue that would remain if the imaging technology had not been used (in 53% of the cases). Integration of 3-D ultrasound with navigation technology solves the orientation problem experienced previously with two-dimensional ultrasound in neurosurgery. The technology makes it possible to directly compare intraoperative ultrasound and MRI data regarding visualization of the lesion. Ultrasound image quality is useful for guiding surgical procedures. CONCLUSION: Intraoperative 3-D ultrasound seems to provide a time- and cost-effective way to update high-quality 3-D maps used in neuronavigation.     

Comparison of navigated 3D ultrasound findings with histopathology in subsequent phases of glioblastoma resection

Objective  The purpose of the study was to compare the ability of navigated 3D ultrasound to distinguish tumour and normal brain tissue at the tumour border zone in subsequent phases of resection. Materials and methods  Biopsies were sampled in the tumour border zone as seen in the US images before and during surgery. After resection, biopsies were sampled in the resection cavity wall. Histopathology was compared with the surgeon’s image findings. Results  Before resection, the tumour border was delineated by ultrasound with high specificity and sensitivity (both 95%). During resection, ultrasound had acceptable sensitivity (87%), but poor specificity (42%), due to biopsies falsely classified as tumour by the surgeon. After resection, sensitivity was poor (26%), due to tumour or infiltrated tissue in several biopsies deemed normal by ultrasound, but the specificity was acceptable (88%). Conclusions  Our study shows that although glioblastomas are well delineated prior to resection, there seem to be overestimation of tumour tissue during resection. After resection tumour remnants and infiltrated brain tissue in the resection cavity wall may be undetected. We believe that the benefits of intraoperative ultrasound outweigh the shortcomings, but users of intraoperative ultrasound should keep the limitations shown in our study in mind.     

Predictors and moderators of outcome in child and adolescent anxiety and depression: a systematic review of psychological treatment studies

The aim of this literature review was to examine pre-treatment child and adolescent characteristics as predictors and moderators of outcome in psychotherapy treatment trials of anxiety and depressive disorders. A literature search was conducted using several databases and resulted in 45 published studies (32 anxiety studies and 13 depression studies) meeting predefined methodological criteria. Ten client demographic (age, gender, ethnicity, IQ) and clinical factors (duration, type of diagnosis, pre-treatment severity, comorbidity) were examined across studies. The majority of findings showed non-significant associations between demographic factors (gender and age) with treatment outcome for both the anxiety and the depression treatment trials. Some important differences between the results of the anxiety and depression treatment trials were found. The majority of findings for the anxiety studies suggest that there are no demographic or clinical factors that predict or moderate treatment outcome. For the depression studies, however, the findings suggest that baseline symptom severity and comorbid anxiety may impact on treatment response. Overall, existing studies of pre-treatment patient variables as predictors and moderators of anxiety and depression treatment outcome provide little consistent knowledge concerning for what type of patients and under what conditions treatments work. Suggestions for future research are discussed.