COMT Val 158 Met polymorphism is associated with cognitive flexibility in a signal discrimination task in schizophrenia.

BACKGROUND: Associations between the well-known functional single nucleotide polymorphism Val (158)Met in the gene encoding catechol- O-methyltransferase (COMT) and cognitive do-mains affected in schizophrenia are inconsistent regarding directionality and specific impact and call for a more fundamental cognitive endophenotype. Recent studies suggest that the COMT genotype contributes to cognitive flexibility, a fundamental cognitive ability that potentially influences an individual's performance in a variety of other neurocognitive tasks. METHODS: We investigated the association between COMT Val (158)Met genotype and cognitive flexibility as assessed by signal discrimination in the Continuous Performance Test - Identical Pairs version in a cohort of 111 German schizophrenic patients. RESULTS: COMT genotype was significantly associated with signal discrimination index d' in schizophrenia. The Val/Val genotype was associated with the highest and the Met/Met genotype with the lowest scores; heterozygous individuals displayed an intermediate performance. CONCLUSIONS: Our data suggest that allelic variation at the COMT Val (158)Met locus may influence signal discrimination capacity in schizophrenia and confirm that Val loading, probably due to decreased prefrontal dopamine availability, is associated with greater cognitive flexibility, which in turn may influence other cognitive measures that have been associated with COMT to date.

Electroconvulsive monotherapy in confusion psychosis: a potential standard regimen?

We report on the successful use of continuation electroconvulsive therapy (ECT) as prophylactic treatment of relapse in a case of confusion psychosis. The 20-year-old patient exacerbated in an almost annual rhythm and had been characterized as pharmacologically treatment-resistant since he failed to respond to any psychopharmacological therapy including sufficient clozapine as well as mood-stabilizing and sedating pharmacological treatments. After the diagnosis of confusion psychosis, the patient received ECT as monotherapy and showed a marked reduction of symptoms. Continuation ECT was then conducted for 7 months after the patient was discharged from hospital. Two years later, our patient is still in remission while continuation ECT has been tapered; no prophylactic psychotropic medication was prescribed in the last 2 years. Implications of this case on the therapy of confusion psychosis as well as on the diagnostic classification of confusion psychosis within our current systems are discussed.

Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens.

Clozapine-induced agranulocytosis (CA) is still among the least understood adverse drug reactions in psychopharmacology. In particular, its genetic background is far from being clarified. Within the framework of a case-control study, we performed human leukocyte antigen (HLA) genotyping and haplotype analyses in 42 non-Jewish Caucasian schizophrenic patients (N=42) suffering from CA and 75 non-Jewish Caucasian schizophrenic patients treated with clozapine without developing CA. While controlling for age (P<0.0001) and sex (P=0.835), testing of the alleles from both HLA-loci resulted in borderline results for Cw2 (P=0.085, odds ratio (OR)=0.36, 95% confidence interval (CI): 0.08-1.23), Cw7 (P=0.058, OR=2.0, 95% CI: 0.87-4.63) and DRB5*0201 (P=0.005, adjusted OR=22.15). For haplotype analysis, we obtained significant association results with CA for the two-locus haplotypes HLA-Cw-B (P=0.022) and HLA-DRB5-DRB4 (P=0.050), and for the three-locus haplotype HLA-Cw-B-DRB5 (P=0.030). The complex nature of CA implies that many genes might play a role, but currently, only HLA associations with CA are identified as clinically relevant.

P300 is enhanced in responders to vagus nerve stimulation for treatment of major depressive disorder.

BACKGROUND: Vagus nerve stimulation (VNS) is a new therapy option for treatment of otherwise therapy-refractory major depressive disorder. However, the mechanism of central nervous action is poorly understood. Electroencephalographic (EEG) studies may be of interest since chronic peripheral current application to the vagus nerve may exert lasting neurophysiologically detectable effects on central electrical activity. In an exploratory study, we investigated the effects of VNS on auditory event-related potentials (ERP). METHODS: Thirteen depressive patients (mean Hamilton depression score (HAMD) at baseline=24.2) receiving VNS were investigated prior to implantation and 10 weeks after standard cycling VNS. Stimulation intensity was 0.94+/-0.46 mA, pulse width 0.250 mus, and frequency 20 Hz. 1 h prior to follow-up investigation, VNS was turned off. Auditory ERP were elicited using a standard auditory oddball paradigm and were recorded with 29-channel EEG. RESULTS: Post VNS, grand averages of the auditory ERP did not show significant differences as compared to baseline recording. However, differential effects were found when separating ERP of responders (N=5, mean HAMD post VNS=8.8) and non-responders (N=8, mean HAMD post VNS=22.4). In VNS responders only, P300 at midline electrodes Fz and Cz was significantly increased and correlated with HAMD scores. CONCLUSION: Auditory ERP seem to provide a useful tool for investigating VNS-induced changes concerning information processing in major depressive disorder. In our sample, enhancement of P300 distinguished VNS responders from non-responders 10 weeks after therapy onset. Our findings may be relevant for the understanding of both neurophysiological mechanism of action of VNS and pathophysiology of depression.

Electroconvulsive monotherapy in the treatment of acute confusion psychosis. A case report.

This report focuses on the successful treatment of a most acute case of confusion psychosis according to the concept of Karl Leonhard. The 18-year-old patient was hospitalized three times before the current episode and his case has been characterized as pharmacologically treatment-resistant psychosis since he failed to respond to any psychopharmacological therapy including sufficient clozapine medication. In the patient's history, typical and atypical antipsychotic as well as mood-stabilizing and sedating pharmacological treatments have been conducted. However, only adverse effects could be observed. When receiving electroconvulsive monotherapy (ECT), the patient showed a marked reduction of symptoms while experiencing no adverse effects. The implications of this finding are discussed with regard to Leonhard's diagnostic system.

[Development of animal welfare legislation for the European Community]. / Entwicklung der Tierschutzrechtsetzung der EG.

Animal welfare is of increasing importance for the European Community, which is reinforced by the Protocol to the EC Treaty on protection and welfare of animals. After the recent improvements to the legislation on the protection of pigs, the next priority for the Commission is the further development of the standards of animal transportation, particularly since a report of the Commission pointed out shortcomings in the enforcement of the existing rules in this area.

The use of gelatin-resorcin-formalin glue in acute aortic dissection type A.

OBJECTIVES: The Gelatin-resorcin-formalin (GRF) glue is widely used in the surgical treatment of dissecting aneurysms. This paper is focused on our experience with the GRF glue in cases, operated for acute aortic dissection type A. METHODS: Between September 1990 and December 1997, 164 patients were operated on for acute aortic dissection type A. In 148 patients GRF was used to reinforce the dissected layers proximal (n = 106) or distal (n = 144) of the grafted aortic segment. An intervention at the aortic valve was necessary in 93 instances. In 111 patients, an open distal anastomosis for replacement of the proximal aortic arch was performed. Thirty-seven additional patients underwent subtotal or total aortic arch replacement. RESULTS: Early postoperative mortality was 26.2% (43/164 patients). Another 16 patients died late postoperatively. Actuarial survival rates are 69.9% at 1 year, 62.5% at 3 years, 59.4% at 5 years and 56.1% at 7 years, post-operatively. Twenty-two reoperations were performed in 20 patients (16.5%). Nine of these patients had developed complications in aortic segments that underwent reconstruction by use of GRF during the primary intervention. Aortic root redissection was found in 7/9 patients intraoperatively, whereas 1/9 patients presented with a rupture near the distal graft to aortic anastomosis. CONCLUSIONS: The introduction of GRF glue has greatly facilitated the reconstruction of dissected aortic wall layers adjacent to the vascular graft. However, the use of the adhesive for aortic root reconstruction in acute aortic dissection type A may bear a significant risk of late postoperative proximal aortic redissection. Complications associated with the GRF glue are likely to be due to the toxic effects of the formalin component. Therefore, care should be taken that the amount of formalin administered to the glue components remains as low as possible.

[Early dyskinesia with administration of clozapine (Leponex)]. / Frühdyskinesie unter der Gabe von Clozapin (Leponex).

A 51-year old, female patient suffering from schizophrenic disorder was treated with clozapine (Leponex). Four hours after the first parenteral, drug administration, she developed an acute dyskinesia.

Hypertension in chronic idiopathic glomerulonephritis: analysis of 311 biopsied patients.

Prevalence of hypertension and relation of hypertension to renal function, type of glomerulonephritis or histological features were evaluated in 311 patients with idiopathic chronic glomerulonephritis. The overall prevalence of hypertension was 49.8%. At least in women, prevalence of hypertension was increased even at serum creatinine levels less than 1.1 mg dl-1 compared with the local general population. Prevalence of hypertension was 2.12 and 8.6 fold higher at serum creatinine 1.1-1.4 mg dl-1 in males and females respectively. In patients with untreated hypertension, a relation was found between mean blood pressure and subsequent decline of estimated GFR. Furthermore, in patients with arterial sclerosis, but not in patients without, a significant relation was found between blood pressure and subsequent increase in serum creatinine.