The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy

Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias.     

HLA antigens, psoriasis and acute anterior uveitis in Bechterew's syndrome (ankylosing spondylitis)

One hundred and twenty-two consecutively hospitalized patients with ankylosing spondylitis (AS) were reexamined. Ninety-two per cent were HLA B27 positive. Of the HLA B27 negative patients, 60% were found to have psoriasis, as opposed to 11 % of the HLA B27 positive patients. Acute anterior uveitis (AAU) was found only in HLA B27 positive patients, and more frequently in males than in females. The genetic and clinical heterogeneity of AS, together with the overlapping clinical criteria for AS and psoriatic spondylitis, may make the term "Bechterew's syndrome" preferable. Based on these findings and previous reports, we conclude that (i) AAU is a manifestation of Bechterew's syndrome in HLA B27 positive patients, (ii) HLA B27 negative patients without any obvious accompanying manifestations may suffer from psoriatic spondylitis, and (iii) genetic predisposition to psoriasis in persons who are HLA B13, B17 and B37 negative, may interact with the genetic predisposition to Bechterew's syndrome in HLA B27 positive persons and produce Bechterew's syndrome with psoriasis or psoriasis-like skin eruptions.     

The alpha2 agonist, clonidine, improves spatial working performance in Parkinson's disease.

Previous work has shown that the dopaminergic defect in Parkinson's disease is involved, to some extent, in the "frontal"-like impairment in spatial working memory and attentional set-shifting functions. We investigated whether an alpha2 agonist, clonidine (0.5 and 2 microg/kg, per os), could alleviate spatial working memory and attentional set-shifting defect in Parkinson's disease patients. We observed that 2 microg/kg clonidine stimulated spatial working memory accuracy, but had no effect on attentional set shifting or visual recognition memory. Clonidine was also effective in stimulating spatial working memory after withdrawal of dopaminergic drugs, and when this was done, its effect was greater in severe Parkinson's disease patients. In contrast, clonidine failed to stimulate visual recognition memory. These results suggest that disrupted activation of alpha2 adrenoceptors may contribute to the impairment of spatial working memory in Parkinson's disease.     

Fixation of femoral shaft osteotomy with intramedullary metallic or absorbable rod: an experimental study on growing dogs.

The purpose of this study was to examine the effects of an intramedullary self-reinforced polyglycolic acid (SR-PGA), self-reinforced poly-L-lactic acid (SR-PLLA) and a metallic rod on growing bone and their applicability in the fixation of a femoral shaft osteotomy in growing dogs. In 5 dogs, 12 weeks of age, a SR-PGA rod and in another 5 dogs a SR-PLLA rod, both 4.7 mm in diameter and 60 mm in length, were introduced into the intramedullary cavity of the right femur to fix a femoral shaft osteotomy. In a third group of 5 dogs the femoral shaft osteotomy was fixed with an intramedullary metallic rod of equal size. The follow-up intervals were 1, 3, 6, 12, 24 and 48 weeks. Solid union of the osteotomy without secondary displacement was seen radiographically 6 weeks after the operation in all dogs. Neither an intramedullary SR-PGA-, SR-PLLA- nor metallic rod caused any significant disturbance to the longitudinal growth of the operated femur. Narrowing of the femoral neck and a slight valgization of the angle between the femoral neck and shaft without any functional disability was seen 48 weeks after the operation.     

Degeneration and electron microscope analysis of the synaptic glomeruli in the lateral geniculate body

Summary Optic fibers of retinal origin terminate in the lateral geniculate body exclusively in the so called glomerular synapses. They can be recognized on the basis of their unusually large irregular mitochondria having very few cristae. In the cat the structure of the optic terminal profiles is rather dense. The majority of terminals in most glomeruli originate from axons of other source. Relatively large axon terminal profiles of unusually light structure cannot be brought to degeneration by any interference with extraneous pathways. From Golgi information it becomes obvious that they originate from local Golgi 2nd type neurons. Small rather dense axonal profiles of the glomeruli can occasionally be traced back by degeneration to the occipital cortex (parastriate), although most of the descending cortical afferents of the lateral geniculate body terminate outside the glomeruli on more proximal parts of the dendrites. — Axo-axonic synapses are very frequent. If an optic terminal is involved, it appears that by structural standards it is presynaptic to the non optic. As judged, however, from the numerous axoaxonic contacts persisting after enucleation, many of the contacts are established between non optic axon terminals. — The progress of secondary degeneration and particularly the removal from the glomeruli of degeneration fragments is unexpectedly rapid. — The possible functional significance of these findings, especially also with regards to presynaptic inhibition, is discussed.     

Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart

Even though sequencing of the mammalian genome has led to the discovery of a large number of ionic channel genes, identification of the molecular determinants of cellular electrical properties in different regions of the heart has been rarely obtained. We developed a high-throughput approach capable of simultaneously assessing the expression pattern of ionic channel repertoires from different regions of the mouse heart. By using large-scale real-time RT-PCR, we have profiled 71 channels and related genes in the sinoatrial node (SAN), atrioventricular node (AVN), the atria (A) and ventricles (V). Hearts from 30 adult male C57BL/6 mice were microdissected and RNA was isolated from six pools of five mice each. TaqMan data were analysed using the threshold cycle ( C _t) relative quantification method. Cross-contamination of each region was checked with expression of the atrial and ventricular myosin light chains. Two-way hierarchical clustering analysis of the 71 genes successfully classified the six pools from the four distinct regions. In comparison with the A, the SAN and AVN were characterized by higher expression of Navβ1, Navβ3, Cav1.3, Cav3.1 and Cavα2δ2, and lower expression of Kv4.2, Cx40, Cx43 and Kir3.1. In addition, the SAN was characterized by higher expression of HCN1 and HCN4, and lower expression of RYR2, Kir6.2, Cavβ2 and Cavγ4. The AVN was characterized by higher expression of Nav1.1, Nav1.7, Kv1.6, Kvβ1, MinK and Cavγ7. Other gene expression profiles discriminate between the ventricular and the atrial myocardium. The present study provides the first genome-scale regional ionic channel expression profile in the mouse heart.