[Interventional treatment of benign prostatic hyperplasia : Embolization of the testicular vein]. / Interventionelle Therapie der benignen Prostatahyperplasie : Embolisation der V. spermatica.

CLINICAL/METHODICAL ISSUE: Embolization of the testicular veins (Gat-Goren technique) is an interventional procedure for the treatment of benign prostatic hyperplasia (BPH). STANDARD RADIOLOGICAL METHODS: In addition to standard urological procedures, such as transurethral resection of the prostate (TUR-P), arterial embolization of the prostate is considered as the interventional radiological method of choice. METHODICAL INNOVATIONS: Embolization of the testicular veins is technically identical to the embolization of varicoceles in infertile men and represents a less invasive treatment. PERFORMANCE: Embolization of the testicular veins can be performed as a low-risk intervention with low side effects. Variants of the venous anatomy can make the procedure more difficult. In current studies a good reduction of symptoms could be achieved in intermediate-term follow-up. ACHIEVEMENTS: The medium-term results are promising but data on long-term results and comparisons with alternative treatments are missing. PRACTICAL RECOMMENDATIONS: Embolization of the testicular veins is a minimally invasive method for the treatment of BPH. The procedure can be performed in an outpatient setting. In the intermediate course up to 6 months after treatment, promising results were demonstrated in recent studies. Randomized studies, data on long-term results and comparisons to alternative methods (e. g. arterial prostatic embolization and surgical procedures) are missing.

[High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. / Hochintensiver fokussierter Ultraschall (HIFU) zur Linderung tumorbedingter Schmerzen bei inoperablem Pankreaskarzinom : Evaluation anhand der Schmerzempfindungsskala (SES).

BACKGROUND: High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. OBJECTIVE: Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. MATERIAL AND METHODS: In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). RESULTS: The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p < 0.05 for all pain scales). CONCLUSION: US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer.

Novel Non-invasive Treatment With High-intensity Focused Ultrasound (HIFU).

Ultrasound is not only used for diagnostic purposes but it also can be applied therapeutically so far that nowadays high-intensity focused ultrasound (HIFU) even represents a novel non-invasive treatment modality for various solid tumors. HIFU works by causing selectively deep tissue destruction of target lesions within the body without harming adjacent and overlying structures. In this article, we present an overview on both the mode of action and requirements for a HIFU treatment as well as on the safety and the current status of indications and possible applications with regard to benign and malignant gynecological diseases. Based on numerous studies and original articles, HIFU proved to be an effective and low-risk treatment option particularly for uterine fibroids and adenomyosis, but it also seems to be effective for breast fibroadenomas or even for breast cancer in special cases and other rare entities.

Successful treatment of partial portal vein thrombosis (PVT) with low dose rivaroxaban.

In a 63-year-old cirrhotic patient, recanalisation of a partial portal vein thrombosis was achieved by a low dose of rivaroxaban (10 mg daily). After anticoagulant therapy was stopped, partial vein thrombosis recurred. Restarting rivaroxaban at a dose of 10 mg led to recanalisation. The patient did not suffer any complications; in particular no bleeding occurred during 8 months of treatment.

Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial.

BACKGROUND: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). RESULTS: Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/µl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in this trial.

The afterglow of GRB 050709 and the nature of the short-hard gamma-ray bursts.

The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates.

Photochemical regeneration of flavoenzymes - An Old Yellow Enzyme case-study.

Direct, NAD(P)H-independent regeneration of Old Yellow Enzymes represents an interesting approach for simplified reaction schemes for the stereoselective reduction of conjugated C=C-double bonds. Simply by illuminating the reaction mixtures with blue light in the presence of sacrificial electron donors enables to circumvent the costly and unstable nicotinamide cofactors and a corresponding regeneration system. In the present study, we characterise the parameters determining the efficiency of this approach and outline the current limitations. Particularly, the photolability of the flavin photocatalyst and the (flavin-containing) biocatalyst represent the major limitation en route to preparative application.

Endofacial competitive inhibition of the glucose transporter 1 activity by gossypol.

Gossypol is a natural disesquiterpene that blocks the activity of the mammalian facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1, Chinese hamster ovary cells overexpressing GLUT1, and human erythrocytes, gossypol inhibited hexose transport in a concentration-dependent fashion, indicating that blocking of GLUT1 activity is independent of cellular context. With the exception of red blood cells, the inhibition of cellular transport was instantaneous. Gossypol effect was specific for the GLUT1 transporter since it did not alter the uptake of nicotinamide by human erythrocytes. Gossypol affects the glucose-displaceable binding of cytochalasin B to GLUT1 in human erythrocyte ghost in a mixed noncompetitive way, with a K(i) value of 20 microM. Likewise, GLUT1 fluorescence was quenched approximately 80% by gossypol, while Stern-Volmer plots for quenching by iodide displayed increased slopes by gossypol addition. These effects on protein fluorescence were saturable and unaffected by the presence of D-glucose. Gossypol did not alter the affinity of D-glucose for the external substrate site on GLUT1. Kinetic analysis of transport revealed that gossypol behaves as a noncompetitive inhibitor of zero-trans (substrate outside but not inside) transport, but it acts as a competitive inhibitor of equilibrium-exchange (substrate inside and outside) transport, which is consistent with interaction at the endofacial surface, but not at the exofacial surface of the transporter. Thus, gossypol behaves as a quasi-competitive inhibitor of GLUT1 transport activity by binding to a site accessible through the internal face of the transporter, but it does not, in fact, compete with cytochalasin B binding. Our observations suggest that some effects of gossypol on cellular physiology may be related to its ability to disrupt the normal hexose flux through GLUT1, a transporter expressed in almost every kind of mammalian cell and responsible for the basal uptake of glucose.

The secretory carrier membrane protein family: structure and membrane topology.

Secretory carrier membrane proteins (SCAMPs) are integral membrane proteins found in secretory and endocytic carriers implicated to function in membrane trafficking. Using expressed sequence tag database and library screens and DNA sequencing, we have characterized several new SCAMPs spanning the plant and animal kingdoms and have defined a broadly conserved protein family. No obvious fungal homologue has been identified, however. We have found that SCAMPs share several structural motifs. These include NPF repeats, a leucine heptad repeat enriched in charged residues, and a proline-rich SH3-like and/or WW domain-binding site in the N-terminal domain, which is followed by a membrane core containing four putative transmembrane spans and three amphiphilic segments that are the most highly conserved structural elements. All SCAMPs are 32-38 kDa except mammalian SCAMP4, which is approximately 25 kDa and lacks most of the N-terminal hydrophilic domain of other SCAMPs. SCAMP4 is authentic as determined by Northern and Western blotting, suggesting that this portion of the larger SCAMPs encodes the functional domain. Focusing on SCAMP1, we have characterized its structure further by limited proteolysis and Western blotting with the use of isolated secretory granules as a uniformly oriented source of antigen and by topology mapping through expression of alkaline phosphatase gene fusions in Escherichia coli. Results show that SCAMP1 is degraded sequentially from the N terminus and then the C terminus, yielding an approximately 20-kDa membrane core that contains four transmembrane spans. Using synthetic peptides corresponding to the three conserved amphiphilic segments of the membrane core, we have demonstrated their binding to phospholipid membranes and shown by circular dichroism spectroscopy that the central amphiphilic segment linking transmembrane spans 2 and 3 is alpha-helical. In the intact protein, these segments are likely to reside in the cytoplasm-facing membrane interface. The current model of SCAMP1 suggests that the N and C termini form the cytoplasmic surface of the protein overlying a membrane core, which contains a functional domain located at the cytoplasmic interface with little exposure of the protein on the ectodomain.

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PURPOSE: Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. MATERIALS AND METHODS: 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. RESULTS: Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). CONCLUSION: US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. KEY POINTS: • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670.

Persistence and reactivation of human adenoviruses in the gastrointestinal tract.

Reactivation of persistent human adenoviruses (HAdVs) is associated with high morbidity and mortality in paediatric haematopoietic stem cell transplant (HSCT) recipients. Although invasive HAdV infections mainly arise from the gastrointestinal (GI) tract, the specific sites of HAdV persistence are not well characterised. We prospectively screened biopsies from 143 non-HSCT paediatric patients undergoing GI endoscopy and monitored serial stool specimens from 148 paediatric HSCT recipients for the presence of HAdV by real-time PCR. Persistence of HAdV in the GI tract was identified in 31% of children, with the highest prevalence in the terminal ileum. In situ hybridisation and immunohistochemistry identified HAdV persistence in lymphoid cells of the lamina propria, whereas biopsies from five transplant recipients revealed high numbers of replicating HAdV in intestinal epithelial cells. The prevalence of HAdV species, the frequencies of persistence in the GI tract and reactivations post transplant indicated a correlation of intestinal HAdV shedding pre-transplant with high risk of invasive infection. HAdV persistence in the GI tract is a likely origin of infectious complications in immunocompromised children. Intestinal lymphocytes represent a reservoir for HAdV persistence and reactivation, whereas the intestinal epithelium is the main site of viral proliferation preceding dissemination. The findings have important implications for assessing the risk of life-threatening invasive HAdV infections.

Three-Dimensional Isotropic Fat-Suppressed Proton Density-Weighted MRI at 3 Tesla Using a T/R-Coil Can Replace Multiple Plane Two-Dimensional Sequences in Knee Imaging.

PURPOSE: To evaluate whether a 3 D proton density-weighted fat-suppressed sequence (PDwFS) of the knee is able to replace multiplanar 2D-PDwFS. MATERIALS AND METHODS: 52 patients (26 men, mean age: 41.9 ±â€Š14.5years) underwent magnetic resonance imaging (MRI) of the knee at 3.0 Tesla using a T/R-coil. The imaging protocol included 3 planes of 2D-PDwFS (acquisition time (AT): 6:40 min; voxel sizes: 0.40 - 0.63 × 0.44 - 0.89 × 3mm³) and a 3D-PDwFS (AT: 6:31 min; voxel size: 0.63 × 0.68 × 0.63mm³). Homogeneity of fat suppression (HFS), artifacts, and image sharpness (IS) were evaluated on a 5-point scale (5[excellent] - 1[non-diagnostic]). The sum served as a measure for the overall image quality (OIQ). Contrast ratios (CR) compared to popliteal muscle were calculated for the meniscus (MEN), anterior (ACL) and posterior cruciate ligaments (PCL). In 13 patients who underwent arthroscopic knee surgery, two radiologists evaluated the presence of meniscal, ligamental and cartilage lesions to estimate the sensitivity and specificity of lesion detection. RESULTS: The CR was higher in the ACL, PCL and MEN in 3D- PDwFS compared to 2D-PDwFS (p < 0.01 for ACL and PCL; p = 0.07 for MEN). Compared to 2 D images, the OIQ was rated higher in 3D-PDwFS images (p < 0.01) due to fewer artifacts and HFS despite the lower IS (p < 0.01). The sensitivity and specificity of lesion detection in 3D- and 2D-PDwFS were similar. CONCLUSION: Compared to standard multiplanar 2D-PDwFS knee imaging, isotropic high spatial resolution 3D-PDwFS of the knee at 3.0 T can be acquired with high image quality in a reasonable scan time. Multiplanar reformations in arbitrary planes may serve as an additional benefit of 3D-PDwFS. KEY POINTS: • 3D-PDwFS of the knee is acquired with high image quality• 3D-PDwFS can be achieved in only one measurement with a reasonable scan time• 3D-PDwFS with the advantage of multiplanar reformation may replace 2D-PD-weighted knee MRI Citation Format: • Homsi R, Gieseke J, Luetkens JA et al. Three-Dimensional Isotropic Fat-Suppressed Proton Density-Weighted MRI at 3 Tesla Using a T/R-Coil Can Replace Multiple Plane Two-Dimensional Sequences in Knee Imaging. Fortschr Röntgenstr 2016; 188: 949 - 956.

Differential signalling for enhanced hexose uptake by interleukin (IL)-3 and IL-5 in male germ cells.

We studied the expression and function of the IL (interleukin)-3 and IL-5 family of receptors in male germ cells. RT (reverse transcription)-PCR showed expression of mRNAs encoding the alpha and beta subunits of the IL-3 and IL-5 receptors in human testis, and the presence of IL-3 and IL-5 receptors alpha and beta proteins was confirmed by immunoblotting with anti-alpha and anti-beta antibodies. The immunolocalization studies showed expression of these receptors in the germ line in the human testis and in human and bovine ejaculated spermatozoa. Functional studies with bull spermatozoa indicated that IL-3 signalled for increased uptake of hexoses in these cells at picomolar concentrations compatible with expression of functional high-affinity IL-3 receptors in these cells. In contrast, IL-5 failed to induce increased hexose uptake in bull spermatozoa. Experiments using HL-60 eosinophils that express functional IL-3 and IL-5 receptors confirmed that IL-3, but not IL-5, signalled for increased hexose uptake. Our findings suggest that differential signalling for increased hexose uptake by heteromeric high-affinity IL-3 and IL-5 receptors in mammalian spermatozoa is a property that depends on the identity of the alpha-subunit forming part of the alphabeta-complex and is not a property specific to the germ cells.

Treatment of benign prostatic hyperplasia by occlusion of the impaired urogenital venous system - first experience.

PURPOSE: To effect regression of benign prostatic hyperplasia (BPH), Gat et al. (Andrologia 2008) proposed to occlude incompetent spermatic veins to reduce increased hydrostatic pressure on the prostatic venous plexus and prevent reflux with androgen rich blood from the testicles. Our aim was to implement this treatment strategy in clinical practice and to report about first results. METHODS: Embolization of the spermatic veins was performed in 30 patients with BPH. In 16 patients, we obtained follow-up data from at least 6 months. The sonographic transabdominal prostatic volume, prostate-specific antigen (PSA) and peripheral total testosterone levels were determined before and 6 months after the intervention. Subjective symptomatology was assessed using standardized questionnaires (International Prostate Symptom Score [IPSS] and Quality of Life score [QoL]) before and 6 months after the procedure. RESULTS: The age of all treated patients was 46 - 77 years. The age of the 16 patients who received follow-up was 51 - 77 years. IPSS (median 18 [IQR 20.75 - 14.50] vs. 9 [IQR 11.00 - 7.25], p < 0.0001) and QoL score (4 [IQR 5 - 3] vs. 2 [IQR 3 - 1], p < 0.001) were significantly decreased 6 months after the intervention. The subjective improvement of symptoms did not correspond with prostatic volumes, which did not change significantly (54.31 ±â€Š30.90 vs. 50.50 ±â€Š29.26 ml, p = n. s.). 4/16 patients had a measurable post-void urine volume, which decreased in two patients 6 months after the procedure, remained unchanged in one patient, and was no longer detectable in one patient. 4 of the 11 had a sonographically detectable varicocele before the intervention, and one patient had a trabeculated bladder. Both the peripheral total testosterone levels (4.55 ±â€Š1.27 vs. 3.93 ±â€Š1.00 ng/ml; p = n. s.) and PSA levels (3.74 ±â€Š2.83 vs. 4.06 ±â€Š3.34 ng/ml; p = n. s.) showed no significant differences. CONCLUSION: Interventional occlusion of the spermatic veins in patients with BPH is a feasible outpatient procedure with a low complication rate. Intermediate results are satisfactory. Mid- and long-term results and pathophysiologic mechanisms need to be further elucidated.

Differential impairments in recalling people's names: a case study in search of neuroanatomical correlates.

The case of a patient with selective left hemispheric medial and lateral temporal lobe damage is described. The patient was of slightly supra-average intelligence and had no problems in normal memory functions, but was severely anomic with respect to people's names. One month post-onset, this deficit held for names of colleagues and friends she had gotten to know during the last 10 years prior to the infarct and for all names confronted with post-infarct. On the other hand, learning of face-name associations was preserved and was independent of the ability to generate context-specific information for the subjects whose names were requested. The results support the existence of category-specific naming impairments, and, moreover, indicate a deficit that has to be differentiated with regard to memory systems. A time-limited, but prolonged engagement of interconnected left medial and adjacent lateral temporal lobe structures in ecphory is stressed for context-restricted information such as proper names.

Exposure to hazardous substances and male reproductive health: a research framework.

The discovery in the mid-1970s that occupational exposures to pesticides could diminish or destroy the fertility of workers sparked concern about the effects of hazardous substances on male reproductive health. More recently, there is evidence that sperm quantity and quality may have declined worldwide, that the incidence of testicular cancer has progressively increased in many countries, and that other disorders of the male reproductive tract such as hypospadias and cryptorchidism may have also increased. There is growing concern that occupational factors and environmental chemical exposures, including in utero and childhood exposures to compounds with estrogenic activity, may be correlated with these observed changes in male reproductive health and fertility. We review the evidence and methodologies that have contributed to our current understanding of environmental effects on male reproductive health and fertility and discuss the methodologic issues which confront investigators in this area. One of the greatest challenges confronting researchers in this area is assessing and comparing results from existing studies. We elaborate recommendations for future research. Researchers in the field of male reproductive health should continue working to prioritize hazardous substances; elucidate the magnitude of male reproductive health effects, particularly in the areas of testicular cancer, hypospadias, and cryptorchidism; develop biomarkers of exposure to reproductive toxins and of reproductive health effects for research and clinical use; foster collaborative interdisciplinary research; and recognize the importance of standardized laboratory methods and sample archiving.

A thermodynamic and mutational analysis of an RNA purine loop as a protein binding site.

The thermal stability and protein binding of a 36 nucleotide RNA hairpin containing an internal loop were studied under various solution conditions. Yeast ribosomal protein L32 binds to its transcript and small RNAs which reproduce the L32 transcript's secondary structure have been examined. Replacement of the internal loop with canonical base pairs did not affect the salt dependence of the melting temperature suggesting that both molecules adopt a linear shape. Several electrostatic contacts are formed on binding to a ribosomal fusion protein, but Mg+2 is not required for binding. The RNA protein complex is stable up to 50 degrees C. Two internal loop deletion mutants have similar thermodynamic stabilities and chemical and enzymatic reactivities, but fail to bind the fusion protein. However, several of the internal loop bases of the deletion mutants are moderately reactive to chemical agents whereas the wild type loop sequence displayed a mixed pattern of protection and hyperreactivity.

Susceptibility of various areas of the nervous system of hens to TOCP-induced delayed neuropathy.

Sensitivity of in-life parameters, biochemical endpoints, and susceptibility of various areas of the chicken nervous system to delayed neuropathy induced by tri-orthocresyl phosphate (TOCP) was assessed. Groups of hens were exposed to a single oral dose of TOCP of 0, 50, 200 or 500 mg/kg and the animals observed for 21 days. Perfusion fixed, paraffin embedded tissue sections were stained with Bodian's silver and Luxol blue and semi-thin epoxy sections with toluidine blue. Sciatic and tibial nerves, lumbosacral, midthoracic, and upper cervical spinal cord, medulla oblongata and cerebellum were examined using a semiquantitative scoring system. In pair-dosed hens inhibition of brain and spinal cord neurotoxic esterase (NTE) and cholinesterase and of plasma and erythrocyte cholinesterases was determined 24 hr and 48 hr after administration. At all dose levels NTE in brain and spinal cord and plasma cholinesterase was inhibited markedly. Quantitative inhibition of NTE was seen also in absence of neuropathy. Ataxia and body weight loss occurred in high-dose animals only, while dose-related neuropathy was seen in the distal tibial nerve, medulla oblongata and cerebellum. Ataxia was correlated best with neuropathy in peripheral nerves while degeneration of nerve fibers in the cerebellum, seen best in mid-longitudinal sections, was the most sensitive histological indicator of TOCP-induced delayed neuropathy. The particular susceptibility of spinocerebellar neurons was recognized long ago, but often has been neglected in delayed neurotoxicity studies and respective guidelines. Optimal sensitivity of toxicity tests is a prerequisite for risk assessment, can be cost efficient, and nowadays should be a main interest of animal welfare in order to reduce animals' suffering. Based on these data, determination of NTE inhibition together with histopathological examination of longitudinal sections of distal tibial nerves, mid-longitudinal sections of rostral cerebellum and cross sections of upper cervical spinal cord represents an optimally sensitive and cost efficient test requirement.

Response preparation begins before mental rotation is finished: evidence from event-related brain potentials.

Behavioral data (response time (RT) and accuracy) and psychophysiological data (event-related brain potentials of ERPs, and lateralized readiness potential or LRP) were studied in an experiment in which rotated alphanumeric characters were presented normally or mirror-reversed. In half of the trials, character classification (letter versus digit) determined whether or not the response was to be executed (go versus nogo) and parity determined the responding hand. In the other half, classification determined the responding hand and parity determined go versus nogo. LRP data indicated that response preparation occurred before mental rotation was finished. These data contradict strictly sequential discrete models of information processing and suggest continuous flow of information.