[Clozapine in treatment of neuropsychiatric diseases in the elderly]. / Clozapin in der Behandlung neuropsychiatrischer Erkrankungen im Alter.

The atypical antipsychotic clozapine has been reported to be effective in otherwise refractory psychoses. This, and its low potential for inducing extrapyramidal side effects and tardive dyskinesia, predestines this drug for the treatment of psychotic disorders in late life. However, not much is known about the efficacy, safety and pharmacokinetics of clozapine in the treatment of aged patients. There are some studies and reports available about clozapine in the treatment of psychosis in patients suffering from dementia, schizophrenia and Parkinson's disease, which are reported here. They give some evidence that even low doses of clozapine are effective in controlling psychotic symptoms in the elderly. To avoid side effects, patient-specific factors and changes of pharmacokinetics in the elderly have to be considered. However, side effects including sedation, delirium, posturnal hypotension and the risk of agranulocytosis in particular limits the use of clozapine in elderly patients.

Loss of functional hemispheric asymmetry in Alzheimer's dementia assessed with near-infrared spectroscopy.

In a total of 10 patients with dementia of the Alzheimer-type (DAT) and in 10 healthy controls near-infrared spectroscopy (NIRS), a new non-invasive optical method, was used to measure the changes of concentrations of oxy- (O2HB) and deoxyhemoglobin (HHB) in left and right hemispheric prefrontal brain tissue areas during performance of the Verbal Fluency Test (VFT). On a neuropsychological level, the healthy subjects performed better in the VFT than patients with DAT. Statistical analysis of the relative concentrations of O2HB and HHB measured with NIRS during performance of the VFT revealed a significant interaction of the hemispheric effects with the diagnosis. A possible interpretation of this finding is that a good performance in the VFT relies on a predominantly left hemispheric activation observed in controls, whereas a low number of correct responses is associated with a loss of this asymmetric activation in patients with DAT. Although both, patients and controls, performed better in the category version of the VFT, the metabolic effects of this task were significantly less pronounced than in the letter version. This indicates that different energy demands, according to the type of access to the memory stores, may be interpreted as the result of a less energy-demanding access to categorically stored information and adds further evidence to the view that memory departments in humans are organized according to categorical principles.

Advanced glycation endproducts-associated parameters in the peripheral blood of patients with Alzheimer's disease.

Advanced glycation endproducts (AGEs), structural components of beta-amyloid plaques and neurofibrillary tangels, have been implicated in the pathogenesis of Alzheimer's disease. AGE levels, measured by fluorescence, and their precursor molecules such as glucose and its Amadori product, fructosylamine, were measured to examine the question whether the reported increased level of AGEs in the brain is reflected in an increase in AGE-associated parameters in peripheral blood. Lactoferrin, proposed to play an important role in the interaction of AGEs with their receptors, was determined by ELISA. All AGE-associated parameters showed trends to lower values in patients with Alzheimer's disease compared with non-demented controls. Albumin and total iron were not significantly different between the groups. In contrast to diabetes and renal failure, where high levels of AGEs and their precursors are present in tissue as well as in peripheral blood, elevated CNS AGE levels in patients with Alzheimer's disease are manifested without detectable peripheral changes.

Immune responses in vitro, XIV. Undetectability of Mlsb- and Mlsc-encoded products on F1 cells possessing Mlsa or Mlsd.

The Mls locus was originally defined to have four alleles; three controlled products that were detectable in primary mixed leukocyte reactions (MLR), whereas one, b, was described as being null. Recently, other investigators postulated that the Mls locus is nonpolymorphic, being composed of the b null allele and of a singly expressed allele previously thought to be the a and d alleles. We previously reported that products controlled by Mlsa and Mlsd were antigenically distinct and therefore are not controlled by the same allele, and the product of Mlsb on cells of three different strains was easily detectable by Mlsa and Mlsd responding cells. Thus the b allele is not null. In the present report evidence is presented which indicates that both Mlsb and Mlsc encoded products were undetectable by MLR when in the presence of Mlsa or Mlsd. This was demonstrated by the inability of Mlsa/Mlsc and Mlsa/Mlsb F1 cells to stimulate Mlsa responding cells and Mlsd/Mlsc and Mlsd/Mlsb cells to stimulate Mlsd cells; the positive response of Mlsa/Mlsb and Mlsd/Mlsb F1-hybrid cells to Mlsb-encoded products; and the reactivity of Mlsa/Mlsc and Mlsd/Mlsc F1 hybrid cells to Mlsc-encoded determinants.