Abnormal activity of membrane phospholipid synthetic enzymes in the brain of patients with Friedreich's ataxia and spinocerebellar atrophy type-1

Much evidence, derived from biochemical studies of both blood and autopsied brain, has suggested that phospholipid metabolism is abnormal in patients with Friedreich's ataxia (FA), a disorder characterized by severe neuronal loss in the spinal cord and lower brain stem with no, or only modest, damage in other brain regions. To establish the cause of our recent finding of reduced brain levels of phospholipids in FA, we assayed activities of 10 phospholipid-metabolizing enzymes in the autopsied cerebellar cortex of patients with the disorder and, for comparison, in a group of patients with spinocerebellar ataxia type 1 (SCA-1), a disease characterized, unlike FA, by marked neuronal loss in the cerebellar cortex. Enzyme activities were also measured in four brain areas which are relatively unaffected morphologically in both FA and SCA-1. We found that ethanolamine kinase activity was increased in multiple brain regions of patients with FA (increased 31%-137%) and, more modestly, in SCA-1 (increased 39%-60%), suggesting a nonspecific enhancement of phosphoethanolamine production in both disorders. In contrast, the activity of phosphoethanolamine cytidylyltransferase (PECT), the rate-limiting enzyme of phosphatidylethanolamine synthesis, was significantly and markedly decreased by 35%-78% in the cerebellar, frontal, and occipital cortices of patients with FA but was normal in SCA-1. Reduced PECT activity in FA may explain the lower brain levels of phosphatidylethanolamine in the disorder. Moreover, because decreased PECT activity in FA occurs in brain regions having no, or only modest, morphologic damage, this may represent a systemic change consequent to the frataxin gene defect. Our data also suggest that therapeutic intervention in FA designed to increase synthesis of membrane phospholipids may warrant further investigation.Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.FLWINinfo:eu-repo/semantics/publishe

Deterioration of long-term results following high tibial osteotomy in patients under 60 years of age

We have investigated, in a prospective study, the outcome of a valgus osteotomy of the tibia in patients less than 60 years of age with arthrosis of the medial compartment and a varus angle of no more than 177.7°. Included in the study were 44 high tibial osteotomies (HTO) performed in 42 patients from 1981 until 1996. There were 35 females (2 bilateral) and 7 males, with an average age of 51 years (range: 30–60 years). Only patients in the first three grades, according to Ahlback’s classification, were included. During a mean follow-up period of 10 years (range: 5–17 years), all but 2 patients experienced pain relief. The average loss of postoperative correction at 10 years was 2.4°. The average postoperative Hospital for Special Surgery Knee Rating System score (HSSK) for patients with excellent or good results was 83.5 points. Survivorship analysis showed a success rate of 80% and 66% at 10 and 15 years respectively, and over 52.8% at 17 years of follow-up. HTO results in redistribution of the main stresses towards normal levels, although normal values are never attained. This is probably the reason why patients experienced good results only in the medium term