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Olaf Eberhardt

Publications and source records attributed to Olaf Eberhardt.

5 recordsLinked to original sources
PubMed2006

Stenting of vertebrobasilar arteries in symptomatic atherosclerotic disease and acute occlusion: case series and review of the literature.

PURPOSE: Two of three patients with vertebrobasilar stroke harbor a stenosis of the vertebral or basilar arteries. The best treatment for secondary prophylaxis in vertebrobasilar occlusive disease has not been defined. In patients with high-grade stenoses, and especially those refractory to medication, stenting offers the chance to restore normal flow and prevent major strokes. METHODS: We provide data regarding outcome and complications on 20 consecutive patients who underwent vertebrobasilar stenting at our institution (9 V0, 2V3, 5 V4, and 4 basilar artery lesions). Furthermore, we provide a comprehensive overview of the literature on >600 cases of vertebrobasilar stenting, including all published cases up to 2005. RESULTS: Primary interventional success was achieved in all cases, with a mean residual stenosis of 3% +/- 4% in V0, 5% +/- 4% in V3/4, and 7% +/- 3% in basilar artery lesions. No peri-interventional neurologic complications and no transient ischemic attack or stroke at follow-up were noted in patients with vertebral ostial lesions, whereas two transient and three permanent clinical deteriorations occurred in patients with V4 or basilar artery lesions, some of which had presented with acute stroke. Patency rate was 100% at the last examination. According to published data on proximal vertebral artery stenting, mortality is 0.3%, the rate of neurologic complications is 5.5%, and the risk of posterior stroke at follow-up is 0.7%. Interventions for distal vertebral or basilar artery disease carry a 3.2% mortality risk, a 17.3% risk for neurologic complications and a 2% risk for stroke at follow-up. CONCLUSIONS: Stenting of the vertebral origin can be performed safely and with a low rate of cerebral ischemic events at follow-up, although restenosis may occur. Larger comparative trials are needed. Treatment decisions in distal vertebrobasilar disease have been made on an individual basis.

Adult↗
PubMed2003

Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease.

Synphilin-1 is linked to the pathogenesis of Parkinson's disease (PD) based on its identification as an alpha-synuclein (PARK1) and parkin (PARK2) interacting protein. Moreover, synphilin-1 is a component of Lewy bodies (LB) in brains of sporadic PD patients. Therefore, we performed a detailed mutation analysis of the synphilin-1 gene in 328 German familial and sporadic PD patients. In two apparently sporadic PD patients we deciphered a novel C to T transition in position 1861 of the coding sequence leading to an amino acid substitution from arginine to cysteine in position 621 (R621C). This mutation was absent in a total of 702 chromosomes of healthy German controls. To define a possible role of mutant synphilin-1 in the pathogenesis of PD we performed functional analyses in SH-SY5Y cells. We found synphilin-1 capable of producing cytoplasmic inclusions in transfected cells. Moreover we observed a significantly reduced number of inclusions in cells expressing C621 synphilin-1 compared with cells expressing wild-type (wt) synphilin-1, when subjected to proteasomal inhibition. C621 synphilin-1 transfected cells were more susceptible to staurosporine-induced cell death than cells expressing wt synphilin-1. Our findings argue in favour of a causative role of the R621C mutation in the synphilin-1 gene in PD and suggest that the formation of intracellular inclusions may be beneficial to cells and that a mutation in synphilin-1 that reduces this ability may sensitize neurons to cellular stress.

Acetylcysteine↗
PubMed2003

Apoptotic mechanisms and antiapoptotic therapy in the MPTP model of Parkinson's disease.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model constitutes the best-characterized toxin paradigm for Parkinson's disease, faithfully replicating most of its clinical and pathological hallmarks. Many lines of evidence point to a significant contribution of apoptosis to cell death after application of 1-methyl-4-phenylpyridinium (MPP(+)) in cell culture or MPTP in vivo. This holds true for apoptotic DNA strand breaks, activation of the JNK pathway and caspases, induction of Par-4 protein and the protection conferred by interference with p53, Apaf-1 or Bax signalling. In MPTP models, intervention in upstream events of apoptosis, e.g. by inhibition of the JNK pathway, provides morphological and functional rescue. In contrast, inhibition of the propagation and execution phase of apoptosis, e.g. by inhibition of caspases, blocks or delays cell death but may not recover neuronal function. At this stage, the combination of an anti-apoptotic together with a neurorestorative therapy may be promising.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Parkinson's disease: one biochemical pathway to fit all genes?

Although originally discounted, hereditary factors have emerged as the focus of research in Parkinson's disease (PD). Genetic studies have identified mutations in alpha-synuclein and ubiquitin C-terminal hydrolase as rare causes of autosomal dominant PD and mutations in parkin as a cause of autosomal recessive PD. Functional characterization of the identified disease genes implicates the ubiquitin-mediated protein degradation pathway in these hereditary forms of PD and also in the more common sporadic forms of PD. Subsequent identification of further loci in familial PD and diverse genetic factors modulating the risk for sporadic PD point to substantial genetic heterogeneity in the disease. Thus, new candidate genes are expected to encode proteins either involved in ubiquitin-mediated protein degradation or sequestrated in intracytoplasmic protein aggregations. Future identification of disease genes is required to confirm this hypothesis, thereby unifying the clinical and genetic heterogeneity of PD, including the common sporadic form of the disease, by one biochemical pathway.

Animals↗