Impairment of the blood-brain barrier can result in tacrolimus-induced reversible leucoencephalopathy following heart transplantation

Fatal leucoencephalopathy is a rare calcineurin inhibitor-related complication, especially in kidney and liver transplant recipients. The only means of clinical management reported so far is the discontinuation or reduction in the calcineurin inhibitor. We herein report a case of a 37-yr-old male who developed leucoencephalopathy 12 wk after heart transplantation and recovered after stabilization of metabolism and arterial blood pressure. The findings in this case support the hypothesis that tacrolimus-associated neurotoxicity is severely increased by an impairment of the blood-brain barrier. Withdrawal of tacrolimus was not necessary while other causes of endothelial injury were treated successfully.     

Inter-sequence and inter-imaging unit variability of diffusion tensor MR imaging histogram-derived metrics of the brain in healthy volunteers

BACKGROUND AND PURPOSE: Diffusion tensor MR imaging has the potential to improve our ability to monitor several neurologic conditions. As a preliminary step to the assessment of the role of diffusion tensor MR imaging in the context of longitudinal and multicenter studies, we evaluated the effect of sequence-, imaging unit-, and imaging-reimaging-induced variations on diffusion tensor MR imaging quantities derived from histogram analysis of a large portion of the central brain of healthy volunteers. METHODS: Each of eight healthy volunteers underwent imaging on two MR imaging units using three different pulsed gradient spin-echo single shot echo-planar pulse sequences (each of them having a different diffusion gradient scheme). Four additional healthy participants underwent imaging twice on the same imaging unit to assess imaging-reimaging variability. RESULTS: For mean diffusivity histograms, the differences between inter-sequence and inter-imaging unit coefficients of variation were significant for all the considered quantities with P values ranging from.003 to <.001. Also, the inter-imaging unit coefficient of variation for average fractional anisotropy was significantly higher than the corresponding inter-sequence coefficient of variation (P =.002). In general, inter-sequence mean diffusivity histogram-derived metrics (coefficients of variation ranging from 1.72% to 5.56%) were more reproducible than were fractional anisotropy histogram-derived metrics (coefficients of variation ranging from 5.45% to 7.34%). Imaging-reimaging variability was found to fall in the range of inter-sequence coefficients of variation for all the considered quantities. CONCLUSION: This study shows that inter-sequence, imaging-reimaging, and inter-imaging unit variabilities of diffusion tensor MR imaging-derived measurements are relatively low, suggesting that diffusion tensor MR imaging might provide additional measures of outcome with which to assess the evolution of brain structural damage in large scale studies of various neurologic conditions.     

Dislocated wrap after previous reduction aortoplasty causes erosion of the ascending aorta

We report a patient with bicuspid aortic valve and dilatation of the ascending aorta who had previous aortic valve replacement and reduction aortoplasty with wrapping. After 4 years, reoperation because of coronary artery disease and paravalvular leakage revealed an erosion of the aortic wall due to dislocation of the wrap. This complication confirms the need for secure anchoring and good fitting of the Dacron wrap to avoid alterations of the underlying aortic wall.     

Pulsatile mechanical cardiac assistance in pediatric patients with the Berlin heart ventricular assist device

Mechanical cardiac assistance for neonates, infants, children and adolescents may be accomplished with pulsatile ventricular assist devices (VAD) instead of extracorporeal membrane oxygenation or centrifugal pumps. The Berlin Heart VAD consists of extracorporeal, pneumatically driven blood pumps for pulsatile univentricular or biventricular assistance for patients of all age groups. The blood pumps are heparin-coated. The stationary driving unit (IKUS) has the required enhanced compressor performance for pediatric pump sizes. The Berlin Heart VAD was used in a total number of 424 patients from 1987 to November 2001 at our institution. In 45 pediatric patients aged 2 days-17 years the Berlin Heart VAD was applied for long-term support (1-111 days, mean 20 days). There were three patient groups: Group I: "Bridge to transplantation" with various forms of cardiomyopathy (N = 21) or chronic stages of congenital heart disease (N = 9); Group II: "Rescue" in intractable heart failure after corrective surgery for congenital disease (N = 7) or in early graft failure after heart transplantation (N = 1); and Group III: "Acute myocarditis" (N = 7) as either bridge to transplantation or bridge to recovery. Seventeen patients were transplanted after support periods of between 4 and 111 days with 12 long-term survivors, having now survived for up to 10 years. Five patients (Groups I and III) were weaned from the system with four long-term survivors. In Group II only one patient survived after successful transplantation. Prolonged circulatory support with the Berlin Heart VAD is an effective method for bridging until cardiac recovery or transplantation in the pediatric age group. Extubation, mobilization, and enteral nutrition are possible. For long-term use, the Berlin Heart VAD offers advantages over centrifugal pumps and ECMO in respect to patient mobility and safety.     

Increased frequency of HLA A2/DR4 and A2/DR8 haplotypes in young saskatchewan aboriginal people with diabetic end-stage renal disease

AIMS: To determine the association of HLA with diabetic end-stage renal disease (DESRD) in Saskatchewan aboriginal people. METHODS: This was a retrospective study of HLA profiles in four groups of Saskatchewan residents with ESRD diagnosed from 1980 to 1998: aboriginal people with and without DESRD, and non-aboriginal people with and without DESRD. The aboriginal DESRD group was also subdivided into those 50 years of age. Frequencies of individual and combinations of HLA antigens were compared between groups and subgroups. RESULTS: HLA data were available for 634 subjects. Young aboriginal people with DESRD had a higher frequency of HLA-A2 than older AB DESRD subjects (69 vs. 36%; p = 0.03), and of HLA-DR4 and/or DR8 compared to older AB DESRD subjects (91 vs. 68%; p = 0.07) and AB non-DESRD subjects (91 vs. 67%; p = 0.03). Over 65% of young AB DESRD subjects had either an A2/DR4 or A2/DR8 haplotype (odds ratio 5.09 [confidence intervals 1.35, 20.15] versus older AB DESRD subjects; odds ratio 3.32 [confidence intervals 1.20, 9.3] versus AB non-DESRD subjects). Forty percent of young AB DESRD subjects were homozygous for at least one of A2, DR4 or DR8. CONCLUSIONS: Our findings suggest that DESRD in young AB subjects with T2DM has a genetic basis related to HLA.     

Referral paths, patient profiles and treatment adherence of older alcoholic men

We sought factors affecting completion by older men of 1-year outpatient treatment for alcohol dependence. We retrospectively studied clinical datasets of 110 men, age > or =55 years, consecutively admitted over 4 years, examining the association of 18 referral, treatment and patient variables with completion of treatment. We found that referral source was the most significant correlate of completion. Legal and self/family referrals were far more likely to complete treatment than patients referred by health or social services. Referral groups had distinctive profiles. Legal referrals were the healthiest. Self/family referrals were most likely to be married, to have had prior alcoholism treatment (a factor also associated with treatment completion), and to suffer currently from depression. Health/social services referrals showed the highest levels of psychosocial and physical dysfunction. Referral pathways deserve special consideration by programs treating older alcoholics. Special strategies for engaging dysfunctional older patients in alcoholism treatment are discussed.     

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.     

Magnetic drug targeting--biodistribution of the magnetic carrier and the chemotherapeutic agent mitoxantrone after locoregional cancer treatment

Magnetic Drug Targeting means the specific delivery of chemotherapeutic agents to their desired targets, e.g. tumors, by using magnetic nanoparticles (ferrofluids) bound to these agents and an external magnetic field which is focused on the tumor. This type of target directed drug injection attempts to concentrate a pharmacologic agent by enhancing its efficacy while simultaneously minimizing deleterious side effects. In previous studies, we have been able to demonstrate the efficacy of this type of localized intraarterial chemotherapy in VX2 squamous cell carcinoma among rabbits [Alexiou, C., Arnold, W., Klein, R.J., Parak, F.G., Hulin, P., Bergemann, C., Erhardt, W., Wagenpfeil, S. and Lübbe, A.S. "Locoregional cancer treatment with Magnetic Drug Targeting", Cancer Res. 60 (2000) 6641-6648]. In the present investigation, we have studied the biodistribution of ferrofluids and chemotherapeutic agent by measuring the amount in the tumor, peritumoral area, various organs and body fluids (e.g. blood and urine), with and without Magnetic Drug Targeting. We compared results to that of administering a chemotherapeutic agent soley. An external magnetic field was directed toward the tumor for 60 min. Biodistribution of ferrofluids in the tumor was investigated using histological cross sections and measured semi-quantitatively using 123I-labeled nanoparticles and quantitatively by the use of radioactive 59Fe-ferrofluids. Mitoxantrone was quantitatively measured using HPLC-analysis. The strength of the external magnetic field was 0.6 Tesla (permanent magnet) in the 123iodine study and 1.7 Tesla (electromagnet) in the 59Fe-study and HPLC-analysis. The concentration of the ferrofluids (FFs) in the tumor region i.e. the tumor tissue and the surrounding area, which was under the influence of an external magnetic field, was found to be much higher than in the absence of one. In contrast to systemic chemotherapy, a much higher concentration of mitoxantrone in the tumor and the peritumoral area (region surrounding the tumor < or = 1 cm), by using only 50% and 20% of the normal dose was seen. Thus, the higher concentration of mitoxantrone could explain the therapeutic efficacy of Magnetic Drug Targeting in treatment of VX2 squamous cell carcinoma in rabbits in our previous studies with the advantage of no adverse clinical side effects.