[Addiction as loss of self-control? Current concepts on the development and treatment of addictive behaviors].
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Alcoholism↗
Biomedical subjects
A Beck
Publications and source records attributed to A Beck.
New angiographic measurement tool for analysis of small cerebral vessels: application to a subarachnoid haemorrhage model in the rat.
INTRODUCTION: Exact quantification of vasospasm by angiography is known to be difficult especially in small vessels. The purpose of the study was to develop a new method for computerized analysis of small arteries and to demonstrate feasibility on cerebral angiographies of rats acquired on a clinical angiography unit. METHODS: A new software tool analysing grey values and subtracting background noise was validated on a vessel model. It was tested in practice in animals with subarachnoid haemorrhage (SAH). A total of 28 rats were divided into four groups: SAH untreated, SAH treated with local calcium antagonist, SAH treated with placebo, and sham-operated. The diameters of segments of the internal carotid, caudal cerebral, middle cerebral, rostral cerebral and the stapedial arteries were measured and compared to direct measurements of the diameters on magnified images. RESULTS: There was a direct correlation between the cross-sectional area of vessels measured in a phantom and the measurements acquired using the new image analysis method. The spread of repeated measurements with the new software was small compared to the spread of direct measurements of vessel diameters on magnified images. Application of the measurement tool to experimental SAH in rats showed a statistically significant reduction of vasospasm in the SAH groups treated with nimodipine-releasing pellets in comparison to all the other groups combined. CONCLUSION: The presented computerized method for analysis of small intracranial vessels is a new method allowing precise relative measurements. Nimodipine-releasing subarachnoidal pellets reduce vasospasm, but further testing with larger numbers is necessary. The tool can be applied to human angiography without modification and offers the promise of substantial progress in the diagnosis of vasospasm after SAH.
Animals↗
Fine structure and phylogeny of green algal photobionts in the microfilamentous genus Psoroglaena (Verrucariaceae, lichen-forming ascomycetes).
According to the literature the microfilamentous thalli of lichen-forming ascomycetes of the genus Psoroglaena are assumed to harbour vivid green "prochlorophyte" cyanobacterial photobionts. As this would be the first report of terrestrial "prochlorophytes" we investigated the fine structure and two molecular markers (SSU rDNA and rbcL) of the photobionts of P. stigonemoides (Orange) Henssen and P. epiphylla Lücking. Both Psoroglaena spp. had unicellular green algal photobionts, representatives of the Trebouxiophyceae. The photobiont of P. stigonemoides is closely related to the non-symbiotic auxenochlorella protothecoides and to a Chlorella endosymbiont of the freshwater polyp Hydra viridis. The putative photobiont of P. epiphylla may be related to Chlorella luteoviridis, C. saccharophila, and a Pseudochlorella isolate. In contrast to other microfilamentous lichens, which derive their shape from filamentous green algae or cyanobacterial colonies overgrown and ensheathed by the fungal partner, Psoroglaena mycobionts position their unicellular photobiont in uni- or multiseriate rows which strongly resemble the situation in filamentous cyanobacterial colonies.
Ascomycota↗
MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience.
BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive thermal ablation technique, shown to be clinically effective in the treatment of uterine fibroids and is being evaluated as a method of thermal ablation of benign and malignant breast tumors. To evaluate the safety and initial efficacy of MRgFUS for the palliation of pain caused by bone metastases, in patients for whom other treatments are either not effective or not feasible. MATERIALS AND METHODS: Thirteen patients suffering from symptomatic bone metastases underwent MRgFUS procedure. Treatment safety was evaluated by assessing the incidence and severity of device-related complications up to 6 months after treatment. Effectiveness of pain palliation was evaluated by visual analog scale, pain questionnaires and changes in the patients' medication. RESULTS: Fifteen procedures were carried out. Mean follow-up was 59 days. Twelve patients received adequate treatment and were available for follow-up. Two patients died due to disease progression during the first month after treatment. No severe adverse events were recorded. The remaining 10 patients reported prolonged improvement in pain score and/or reduced analgesic dosage. CONCLUSION: MRgFUS may provide a safe and effective noninvasive alternative for the palliation of pain, caused by bone metastases.
Bone Neoplasms↗
Activity patterns of proteasome subunits reflect bortezomib sensitivity of hematologic malignancies and are variable in primary human leukemia cells.
Proteasomal proteolysis relies on the activity of six catalytically active proteasomal subunits (beta1, beta2, beta5, beta1i, beta2i and beta5i). Applying a functional proteomics approach, we used a recently developed activity-based, cell-permeable proteasome-specific probe that for the first time allows differential visualization of individual active proteasomal subunits in intact primary cells. In primary leukemia samples, we observed remarkable variability in the amounts of active beta1/1i-, beta2/2i- and beta5/5i-type of subunits, contrasting with their constant protein expression. Bortezomib inhibited beta5- and beta1-type, but to a lesser extend beta2-type of subunits in live primary cells in vitro and in vivo. When we adapted the bortezomib-sensitive human acute myeloid leukemia cell line HL-60 to bortezomib 40 nM (HL-60a), proteasomal activity profiling revealed an upregulation of active subunits, and residual beta1/beta5-type of activity could be visualized in the presence of bortezomib 20 nM, in contrast to control cells. In a panel of cell lines from hematologic malignancies, the ratio between beta2-type and (beta1 + beta5)-type of active proteasomal polypeptides mirrored different degrees of bortezomib sensitivity. We thus conclude that the proteasomal activity profile varies in primary leukemia cells, and that the pattern of proteasomal subunit activity influences the sensitivity of hematologic malignancies toward bortezomib.
Animals↗
CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry.
Store-operated Ca2+ entry is mediated by Ca2+ release-activated Ca2+ (CRAC) channels following Ca2+ release from intracellular stores. We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx. A secondary patch-clamp screen identified CRACM1 and CRACM2 (CRAC modulators 1 and 2) as modulators of Drosophila CRAC currents. We characterized the human ortholog of CRACM1, a plasma membrane-resident protein encoded by gene FLJ14466. Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery.
Animals↗
Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up.
AIMS: The study was designed to evaluate Raf1, Aurora-A/STK15 and E-cadherin (E-CD) protein expression and their prognostic value in patients with pTa/pT1 tumours. MATERIALS AND METHODS: A tissue microarray of 105 pTa, and 141 pT1 tumours was constructed and sections were immunostained with these three antibodies. RESULTS: There were significant associations between Raf1 overexpression and tumour grade (p = 0.03), between Aurora-A overexpression/alterations of E-CD and tumour grade and stage (p < 0.001 and p < 0.001). In multiple Cox regression analysis, moderate/strong expression of E-CD seemed to be an independent factor in predicting slower tumour progression (p = 0.003) and Aurora-A overexpression (p = 0.022) displays an independent value in predicting tumour recurrences. CONCLUSION: Evaluation of E-CD and Aurora-A expressions in tissue of patients with pTa/pT1 UC have been proven to be useful in predicting tumours behavior and Raf1 protein expression seemed to have no potential use in this regard.
Adult↗
Prostaglandin-induced programmed cell death in Trypanosoma brucei involves oxidative stress.
Recently, we reported the induction of a programmed cell death (PCD) in bloodstream forms of Trypanosoma brucei by prostaglandin D(2) (PGD(2)). As this prostanoid is readily metabolized in the presence of albumin, we were prompted to investigate if PGD(2) metabolites rather than PGD(2) itself are responsible for the observed PCD. In fact, J series metabolites, especially PGJ(2) and Delta(12)PGJ(2), were able to induce PCD more efficiently than PGD(2). However, the stable PGD(2) analog 17phenyl-trinor-PGD(2) led to the same phenotype as the natural PGD(2), indicating that the latter induces PCD as well. Interestingly, the intracellular reactive oxygen species (ROS) level increased significantly under J series metabolites treatment and, incubation with N-acetyl-L-cysteine or glutathione reduced ROS production and cell death significantly. We conclude that PGJ(2) and Delta(12)PGJ(2) formation within the serum represents a mechanism to amplify PGD(2)-induced PCD in trypanosomes via ROS production.
Animals↗
Feasibility of ultra-low-dose multi-detector-row CT-colonography: detection of artificial endoluminal lesions in an in-vitro-model with optimization of image quality using a noise reduction filter algorithm.
PURPOSE: To assess the most favorable slice thickness in Multi-Detector-Row CT-colonography (MDCTC), and the feasibility of dose reduction in an in-vitro-setting as well as the possibility of optimization of image quality using a noise reduction filter algorithm. - MATERIALS AND METHODS: 18 artificial lesions with sizes from 1 to 8 mm were randomly positioned in two cleansed pig colons. At a "Somatom Plus 4 Volume Zoom", six scanning protocols using a slice collimation of 2.5, 1, and 1 mm with a reconstructed slice thickness of 3, 3, and 1.25 mm were performed with tube currents of 100, and 10 mAs, respectively. Using a non-commercial software, a non-linear Gaussian filter was used to minimize image noise. Image noise was assessed before and after application of the filtering process. Using a threshold of -750 HU, two blinded readers analyzed the virtual colonography in respect to lesion location, size, and shape. Artifacts were noted. An automated detection system was evaluated. - RESULTS: Using 10 mAs, a ten-fold dose reduction was achieved. After application of the mathematical filter, image noise was reduced by 45-80% for 100 mAs, and by 50-70% for 10 mAs scans. Only with a slice thickness of 1.25 mm, all lesions could be detected. The definition of lesion size and shape was more accurate with higher mAs. Only minor noise artifacts were noted on low-dose images. The automated polyp detector marked not more than 60% of artificial lesions. - CONCLUSION: MDCTC benefits from narrow slice collimation. In an in-vitro-model, a significant dose reduction is achievable with preservation of a high lesion detection rate. The noise reduction filter algorithm improved image quality substantially.
Algorithms↗
FGFR3 and p53 protein expressions in patients with pTa and pT1 urothelial bladder cancer.
AIMS: This study is designed to evaluate the expression and prognostic value of FGFR3 protein expression in patients with pTa/pT1 tumours and to determine the significance of the combinations of FGFR3 and p53 protein expressions in bladder pathogenesis. MATERIALS AND METHODS: A tissue microarray (TMA) of 107 pTa, and 147 pT1 tumours was constructed. The TMA sections were immunostained with FGFR3 and p53 monoclonal antibodies. RESULTS: There were significant associations between loss of FGFR3 and tumour stage (p<0.001) and grade (p<0.001) and between p53 overexpression and tumour stage and grade (p<0.001 and p<0.001, respectively). There was no association between FGFR3 and p53 proteins (p=0.107). In addition, tumours with FGFR3+/p53- phenotype have slower recurrence rate than other (FGFR3+/p53+, FGFR3-/p53- and FGFR3-/p53+). CONCLUSION: 1-FGFR3 expression is significantly associated with two important prognostic factors; stage and grade. 2-FGFR3 protein expression is not an independent predictive factor for pTa/pT1 tumour recurrence and progression. 3-Tumours with FGFR3+/p53- phenotype seem to have a distinctive pathway in bladder tumorigenesis.
Adult↗
Variants in Apaf-1 segregating with major depression promote apoptosome function.
APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression.
Alleles↗
Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, break-apart probe fluorescence in situ (FISH) analysis in Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies.
AIMS: To compare the sensitivity and specificity of the recently commercially available FLI-1 monoclonal (FLI-1m) antibody with the currently used antibodies [CD99 and FLI-1 polyclonal (FLI-1p)] in the diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and to determine the diagnostic value of the EWSR1 (22q12) dual-colour, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique. MATERIALS AND METHODS: Forty-three cases of well-documented EWS/PNET and 15 non-EWS/PNET cases were retrieved from the archival files. Immunohistochemistry (IHC) for FLI-1p, FLI-1m and FISH analysis was performed. RESULTS: The most sensitive and specific test panel for the diagnosis of EWS/PNET is the combination of CD99 and FLI-1p. FISH had a very high specificity (100%) but only a moderate sensitivity (50%). CONCLUSION: The combination of CD99 and FLI-1p is the method of choice for the diagnosis of EWS/PNET. EWRS1 (22q12) dual-colour, break-apart rearrangement probe FISH should be used as a confirmatory test in addition to CD99 and FLI1-p due to its high specificity.
12E7 Antigen↗
Neuroprotective effects of the P2 receptor antagonist PPADS on focal cerebral ischaemia-induced injury in rats.
After acute injury of the central nervous system extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations as a result of cell damage and subsequent increase in membrane permeability. Released ATP may act as a toxic agent, which causes cellular degeneration and death, mediated through P2X and P2Y receptors. Mechanisms underlying the various effects of purinoceptor modulators in models of cerebral damage are still uncertain. In the present study the effect of P2 receptor inhibition after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats was investigated. Rats received either the non-selective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) or artificial cerebrospinal fluid (ACSF) as control by the intracerebroventricular route. First, these treatments were administered 10 min before MCAO and subsequently twice daily for 1 or 7 days after MCAO. The functional recovery of motor and cognitive deficits was tested at an elevated T-labyrinth. The PPADS-treated group showed a significant reduction of paresis-induced sideslips compared with ACSF-treated animals. Infarct volume was reduced in the PPADS group in comparison with the ACSF group. A significant decrease in intermediately and profoundly injured cells in favour of intact cells in the PPADS group was revealed by quantification of celestine blue/acid fuchsin-stained cells in the peri-infarct area. The data provide further evidence for the involvement of P2 receptors in the pathophysiology of cerebral ischaemia in vivo. The inhibition of P2 receptors at least partially reduces functional and morphological deficits after an acute cerebral ischaemic event.
Animals↗
Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei.
In a previous study, a three-dimensional (3D) MRI atlas of the human cerebellar nuclei was introduced based on findings in one healthy human subject [Dimitrova, A., Weber, J., Redies, C., Kindsvater, K., Maschke, M., Kolb, F.P., Forsting, M., Diener, H.C., Timmann, D., 2002. MRI atlas of the human cerebellar nuclei. NeuroImage 17, 240-255]. The present MRI investigation was designed to study variability of the anatomy of the dentate/interposed nuclei in a larger group of healthy subjects. Similar to our previous study, iron-induced susceptibility artifacts were used to visualize the cerebellar nuclei as hypointensities on MR images. Data of 63 healthy subjects (27 female, 36 male; mean age 45.3+/-13.4 years, age range 22--71 years) were included. A 3D axial volume of the cerebellum was acquired using a T2*-weighted FLASH sequence on a Siemens Sonata 1.5 T MR scanner. Each volume was registered, re-sampled to 1.00 x 1.00 x 1.00 mm(3) voxel size and spatially normalized into a standard proportional stereotaxic space using SPM99. Dentate/interposed nuclei were traced on axial images and saved as regions of interest using MRIcro-software by two independent examiners. A probabilistic 3D MRI atlas of the cerebellar dentate/interposed nuclei is presented based on findings in all subjects.
Adolescent↗
Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis.
BACKGROUND: Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome. OBJECTIVES: To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared to placebo or antipsychotics, to control disturbed behaviour and reduce psychotic symptoms. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (October 2002 and April 2005), inspected reference lists of included and excluded studies and contacted authors of relevant studies. SELECTION CRITERIA: We included all randomised clinical trials comparing benzodiazepines, alone or in combination with antipsychotics, with placebo or sole use of antipsychotics, for people with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality assessed them and extracted data. For binary outcomes we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI), and weighted number needed to treat or harm (NNT/NNH) statistics. For continuous outcomes we estimated a weighted mean difference between groups. If heterogeneity was found, we used a random effects model. MAIN RESULTS: We included eleven studies with a total of 648 participants. When comparing benzodiazepines with placebo, sedation was equally prevalent (n=102, 1 RCT, RR 1.67 CI 0.4 to 6.6), however, fewer people allocated lorazepam remained excited at 24 hours (n=102, RR 0.62 CI 0.4 to 1.0, NNT 5 CI 3 to 59). The lorazepam and placebo group experienced similar non-significant, low levels of adverse effects. In the comparison of benzodiazepines versus use of antipsychotics without use of anticholinergics/antihistamines, people allocated benzodiazepines did not clearly need additional medication compared with those given antipsychotics (n=216, 2 RCTs, RR 1.28 CI 0.5 to 3.2). Numbers sedated were also equivocal between groups (n=324, 6 RCTs, RR 0.76 CI 0.5 to 1.2) as were mental state ratings. Extrapyramidal symptoms were significantly higher in the antipsychotic treatment group (n=391, 7 RCTs, RR 0.17 CI 0.1 to 0.4, NNT 6 CI 2 to 17). Two trials (total n=83) comparing lorazepam plus haloperidol with lorazepam alone found no clear difference for the need of additional medication (n=83, 2 RCTs, RR 1.02 CI 0.8 to 1.3) or 'not improved' at one hour (n=20, 1 RCT, RR 1.47 CI 0.66 to 3.25). There was no difference in the incidence of extrapyramidal symptoms (n=83, 2 RCTs, RR 1.94 CI 0.2 to 20.3). Finally when the benzodiazepine plus antipsychotic combination was compared with antipsychotics alone (2 RCTs, n=95) there was no difference between groups in the need for additional medications (n=67, 1 RCT, RR 0.95 CI 0.8 to 1.2) or for mental state measures. Extrapyramidal symptoms were significantly lower for people receiving both benzodiazepines and antipsychotics compared with those receiving antipsychotics alone (n=95, 2 RCTs, RR 0.45 CI 0.2 to 0.9, NNH 2 CI 1 to 5). There was no significant difference in the number of participants unfit for early discharge (n=28, 1 RCT, RR 0.90 CI 0.54 to 1.5). AUTHORS' CONCLUSIONS: There is insufficient data from these studies to support or refute the use of benzodiazepines with or without antipsychotics where emergency drugs are needed. The sole use of older antipsychotics unaccompanied by anticholinergic drugs may be problematic, but studies in this review are not large enough to identify any serious adverse effects of benzodiazepines such as respiratory depression. Larger, more informative studies are needed before definite conclusions can be drawn as to the efficacy of benzodiazapines.
Acute Disease↗
Axillary recurrences after sentinel node (SLN) biopsy without complete axillary dissection in breast cancer patients.
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Breast Neoplasms↗
[Trauma surgery in the elderly].
The indications for the surgical treatment of fractures in elderly patients should consider the individual's general health status, the specific pattern of injury, and the ability of the patient to actively participate in the rehabilitation process. Intramedullary systems are the gold standard for shaft and metaphyseal fractures due to the decreased operative trauma and the possibility of early weight bearing and functional treatment. Minimally invasive locking plate systems can frequently be applied, offer decreased risk of secondary fracture displacement, and have great advantages in the treatment of periprosthetic fractures with firm implants. The possible reasons for falls should be diagnosed in order to allow their prevention. An exact assessment of the severity of osteoporosis in important in allowing adequate treatment for associated pain and for decreasing the risk of future osteoporosis related fractures.
Accidental Falls↗
[Comparison of radiation dose and image quality of Siremobil-IsoC(3D) with a 16-slice spiral CT for diagnosis and intervention in the human pelvic bone].
PURPOSE: To compare the image quality of 16-slice computed tomography with the image quality of Siremobil-IsoC (3D) of the pelvic region and to measure simultaneously the radiation dose before and after implantation of a sacroiliac screw (SI-screw) MATERIALS AND METHODS: The pelvic region of 8 human cadavers was examined in the Siremobil-IsoC (3D) at five different levels. We used a standard protocol for the 16-slice CT of the complete pelvic region before and after insertion of a pelvic screw, followed by stepwise reduction of the tube current to find the tube current that equalizes the image quality of both modalities. We controlled the image quality by judging important structures such as neuroforamen, nerves, sacroiliacal joint space, intervertebral space, osteophytes, iliopsoas muscle, acetabular surface, fovea centralis, hip joint and os pubis. The image quality was judged by three radiologists and three trauma surgeons using a ranking from 1 to 5. The dose was measured with an endorectally placed NOMEX Dosimeter, to obtain the gonadal dose. RESULTS: The medium score for all viewers of the Siremobil-IsoC (3D) examinations was between 3 and 4.3. The medium score for all CT-examinations with a tube current of 250 mA was between 1.3 and 2.2. The reduction of tube current down to 80 mA hardly influenced the marks for the analyzed structures. Under 80 mA, bony structures, even after implantation of a SI-screw, were still marked as good, but soft tissue differentiation was getting worse. For the examination of the pelvis, the average dose-length product for the IsoC (3D) was 41.2 mGy x cm. The medium dose-length product for CT was 389 mGy x cm for 250 mA, 125 mGy x cm for 80 mA and 82 mGy x cm for 60 mA. CONCLUSION: The Siremobil-IsoC (3D) is sufficient for therapeutic intraoperative purpose, but the image quality is not sufficient for diagnostic purpose. The higher dose-length product of a CT examination is justifiable because of a better overview, shorter examination time and qualitative superiority. An advantage of the Siremobil-IsoC (3D) is the intraoperative availability with acceptable 3D image quality compared to conventional fluoroscopy.
Bone Screws↗