Regional Distribution of Neurofibrillary Tangles and Senile Plaques in the Cerebral Cortex of Elderly Patients: A Quantitative Evaluation of a One-Year Autopsy Population from a Geriatric Hospital

Detailed analyses of the neuropathologic changes in the cerebralcortex of elderly individuals and Alzheimer's disease patientshave demonstrated that certain components of the neocorticaland hippocampal circuits are likely to be selectively vulnerable.Based on the distribution of neurofibrillary tangles (NFTs)and senile plaques, it has been proposed that a global cortico-corticaldisconnection leads to the loss of integrated functions observedin Alzheimer's disease. In order to investigate the distributionof lesions associated with aging as well as with the earliestsymptoms of senile dementia, we performed a quantitative neuropathologicavaluation of a large series of elderly patients representingthe entire autopsy population for the year 1989 from a geriatrichospital. Among the 145 cases quantitatively assessed, therewere 102 nondemented patients, 33 patients presenting clinicallywith globally intact intellectual function but early signs ofimpairment of specific cognitive functions, and 10 cases withsenile dementia of the Alzheimer type. All of the cases hadNFTs in layer II of the entorhinal cortex, regardless of theirclinical diagnosis, and most cases had some NFTs in the CA1field of the hippocampus. Severe pathologic changes within theinferior temporal neocortex were observed only in the dementedcases. The extent of amyloid deposition was not correlated withthe clinical diagnosis and seemed to be present in the neocorticalareas earlier than in the hippocampal formation. Also, severalcases contained NFTs without amyloid deposition, but amyloidnever occurred without NFTs. These results suggests that involvementof certain structures within the hippocampal formation is aconsistent feature of aging. Thus, involvement of the hippocampalformation may be a necessary, but not sufficient, conditionfor the clinical expression of dementia, which is likely tobe more closely related to the progressive degeneration of selectneuronal populations in the neocortex.     

Problems and needs for improving primary care of osteoarthritis patients: the views of patients, general practitioners and practice nurses

Background  

Osteoarthritis (OA) is highly prevalent and has substantial impact on quality of life as well as on healthcare costs. The general practitioner (GP) often is the first care provider for patients with this chronic disease. The aim of this study was to identify health care needs of patients with OA and to reveal possible obstacles for improvements in primary care management of OA patients.     

Phonological representations in children with SLI: a study of French.

The present research examined the quality of the phonological representations of French children with specific language impairment (SLI) and those with normal language development (NLD). Twenty-five children with SLI and 50 children with NLD matched on lexical age level participated in an auditory lexical decision task. The observations gathered in our study can be summarized as follows. First, children with a higher receptive lexical level performed better, and this was true both for children with NLD and children with SLI. Second, both children with NLD and those with SLI were more likely to reject pseudowords resulting from a modification affecting the number of syllables of a word than pseudowords resulting from a slight modification with the number of syllables unchanged. This difference, however, was greater for the children with SLI, who appeared to have much difficulty rejecting pseudowords resulting from slight modifications. Finally, the performance of children with SLI was particularly poor when presented with pseudowords resulting from a slight modification at the beginning or the end of a word. These findings are interpreted as supporting the hypothesis of an under-specification of phonological representations in children with SLI.     

Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis.

Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci -- in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis -- release hydrogen peroxide (H(2)O(2)) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H(2)O(2) production on regional cerebral blood flow (rCBF) and intracranial pressure (ICP). Compared to wild-type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H(2)O(2) defective SpxB(-) mutant (maximum increase, 135% +/- 17% versus 217% +/- 23% of the individual baseline; P<0.01) or after treatment of D39-induced meningitis with H(2)O(2)-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H(2)O(2)-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB(-), supporting the predominant role of bacterial H(2)O(2). We conclude that in addition to host-sided mediators, bacterial-derived H(2)O(2) acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.     

Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.     

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.