Assessment of depth perception using psychophysical thresholds and stereoscopically evoked brain activity

Dynamic random-dot stereograms (dRDS) elicit brain activity generated exclusively by cortical neurons sensitive to binocular horizontal disparity. We studied 20 adults with stereovision deficiency but otherwise normal vision. Psychophysical thresholds were determined with static RDS and with the three-rod experiment. VEP was recorded from seven occipital channels. Stimuli were presented on a monitor by dRDS as stereoscopic checkerboard patterns that moved in depth with 8 depth reversals per second. Horizontal disparity ranged from 7 to 24.5 min of arc. Stimuli were displayed at the center, or in the left or right half field. We determined electrophysiological thresholds as well as the disparity where largest responses occurred. Subjective and electrophysiological thresholds showed a significant positive correlation. In addition, the right visual field was more sensitive to dRDS stimuli than other locations. Squint angle was related to the disparity thresholds. Our data illustrate correlations between clinical symptoms, perceptual deficiency, and VEP parameters.     

Reduced genital sensitivity in female patients with multiple system atrophy of parkinsonian type.

According to the consensus statement on the diagnosis of multiple system atrophy (MSA), erectile dysfunction is required for male patients to fulfil the urinary incontinence criterion. However, there is no equivalent item for female patients. We questioned 19 female patients with MSA of the parkinsonian type (MSA-P), 28 female patients with Parkinson's disease (PD), and 27 healthy controls on their genital sensitivity. A total of 47% of the MSA patients but only 4% of the PD patients and 4% of the control group admitted to reduced genital sensitivity, a highly significant difference (P < 0.001). Moreover, the appearance of reduced genital sensitivity in female MSA patients showed a close temporal relation to the onset of the disease. If these preliminary results can be confirmed and further specified in a larger sample, a historical item of reduced genital sensitivity in female patients might become a diagnostic feature for MSA, comparable to erectile dysfunction in male patients.     

Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Nonlinear excitation profiles for three-dimensional inflow MR angiography

An RF excitation pulse for three-dimensional (3D) time-of-flight (TOP) MR angiography (MRA) with a nonlinear excitation profile was numerically calculated under the condition of uniform vessel signal across the excitation volume (slab), and the superiority of the optform pulse as compared with conventional RF pulses and TONE pulses was demonstrated. For this purpose we acquired MRA of the lower leg and of the carotid and vertebral arteries in a 30-year-old healthy volunteer. Although the flow velocity ranges in these two anatomic locations are different by about a factor of 10, in both cases the corresponding optform pulse provided the best signal homogeneity at the highest level.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.