Lack of association between hippocampal volume reduction and first-onset alcohol withdrawal seizure. A volumetric MRI study.

AIMS AND METHODS: Magnetic resonance imaging (MRI) of the hippocampus has been extensively studied in both neurological and psychiatric disorders. Furthermore, hippocampal volume reductions on MRI have been reported in patients with chronic alcoholism. The present volumetric MRI study was undertaken to determine whether an association exists between hippocampal volume reduction and first-onset alcohol withdrawal seizure. Until recently, no data as to whether hippocampal volume reductions in alcoholics might serve as a predictor of withdrawal seizures were available. RESULTS: We found the average hippocampal volumes measured by high resolution MRI to be significantly reduced in 52 alcoholics compared with 30 healthy controls. Besides a decrease of hippocampal volume in patients with chronic alcoholism, we could not find any significant correlation between the occurrence of seizures during alcohol withdrawal and the amount of hippocampal volume reduction in these patients. CONCLUSIONS: Thus, the alcoholism-related atrophy within the hippocampal formation in patients suffering from chronic alcoholism does not seem to be the source of convulsive activity in these patients. Neither does the amount of atrophy allow the occurrence of first-onset withdrawal seizures to be predicted.

[Glutamatergic neurotransmission in schizophrenics]. / Glutamaterge Neurotransmission bei Schizophrenien.

Glutamate is the most abundant amino acid in the brain, where it plays an important role as a well-established major excitatory neurotransmitter in the central nervous system. It has been suggested that reduced glutamate neurotransmission may be involved in the pathophysiology of schizophrenia. The glutamate hypothesis of schizophrenia postulates alterations in the glutamatergic system as an important neurobiochemical event in the pathophysiology of this group of psychotic disorders. An altered glutamate release from synaptosomes including a hypofunction of different glutamate receptors (i.e. NMDA receptors) from different brain areas have previously been reported. Furthermore, partial agonists at the glycine co-agonist site of the NMDA receptor might be a new approach in the treatment of schizophrenic symptoms but further studies are necessary to clarify the role and efficacy of these substances in schizophrenia. Changes in the glutamatergic cortico-striatal connections in schizophrenia could precipitate a potential perceptive overstimulation of the neocortex from thalamic input and an inhibiting influence of the striatum on the thalamus would modulate the information input of the cortex, thereby possibly counteracting the disturbed information processing which is relatively characteristic for schizophrenic psychoses.

Moderate alcohol consumption in social drinkers raises plasma homocysteine levels: a contradiction to the 'French Paradox'?

Evidence from observational studies suggests that elevated levels of homocysteine are associated with an increased risk of cardiovascular diseases. We assessed whether moderate alcohol intake in healthy social drinkers, suggested to be cardioprotective according to the 'French paradox', influences the cardiovascular risk factor homocysteine. A total of 60 normal nourished subjects who had no evidence of vascular disease or other risk factors for hyperhomocysteinaemia were assigned to receive mineral water or 30 g of alcohol per day (as beer, red wine or spirits) for a period of 6 weeks. Homocysteine levels of social drinkers, independent of which beverage was consumed, increased during the observation. We postulate that elevated levels of homocysteine in social drinkers with regular moderate alcohol intake are at risk of developing cardiovascular diseases, which contradicts the suggested cardioprotection of alcohol according to the 'French paradox'.

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.