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Biomedical subjects

P R Burkhard

Publications and source records attributed to P R Burkhard.

At least 19 recordsLinked to original sources
PubMed2006

Changes of the cortex proteome and Apolipoprotein E in transgenic mouse models of Alzheimer's Disease.

Transgenic mice carrying human Amyloid Precursor Protein mutations present amyloid plaque deposition in the brain upon aging. In this study, we characterized the changes of cortex proteome and endogenous Apolipoprotein E in these mice. Differential analysis of two-dimensional electrophoresis images revealed spots altered upon aging, transgene addition and plaque deposition. Alpha-synuclein and cytochrome oxidase polypeptide Va were up-regulated in transgenic mice. Upon aging, expression of ATP synthase alpha, alpha enolase, UMP-CMP kinase, and dihydropyrimidinase like-2 protein was modified. These proteins and their modification probably play a role in the amyloid aggregate formation in these mice.

Alzheimer Disease↗
PubMed2006

[Pathogenic mechanisms of neurodegenerative diseases: amyotrophic lateral sclerosis].

Since its description by Charcot in 1869, the mechanism underlying the characteristic selective degeneration and death of motor neurons in amyotrophic lateral sclerosis (ALS) has remained a mystery. There is no effective remedy for this progressive, fatal disorder. Modern genetics have now identified two genes, SODI and ALS2 as primary causes of the disease and has implicated others as potential contributors. These insights have enabled development of model systems to test hypotheses of disease mechanism and potential therapies. Along with errors in the handling of synaptic glutamate and the potential excitotoxic response that it provokes, these model systems underscore the involvement of non-neuronal cells in disease progression and provide new therapeutic strategies.

Amyotrophic Lateral Sclerosis↗
PubMed2006

[Neuronal death and growth factors: new therapeutic approaches in Parkinson's disease].

Neurodegenerative disorders represent a major and growing cause of morbidity and mortality in our populations, and a therapeutic challenge for the years to come. This paper reviews the mechanisms implicated in neuronal death, focusing on the model of Parkinson's disease. Available data are critically presented, and oriented in a therapeutic perspective. Neuroprotective strategies are mentioned, along with stem cell transplantation, growth factor production and gene therapy.

Animals↗
PubMed2005

[Wilson's disease: Clinical presentations].

Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1: 30000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.

Adult↗
PubMed2005

[Current treatment of Parkinson's disease: problems and controversies].

Treating patients with Parkinson's disease is not an easy task for the physician who is facing a disease well responsive to symptomatic therapy, yet escaping any curative approaches. In spite of the large therapeutic armamentarium available, many issues remained unsolved, as indications of a particular therapeutic agent are only loosely defined and evolving according to various parameters such as disease progression and severity, the profile of potentially serious adverse effects, the physician's level of expertise and patient's expectations. The growing experience acquired with subthalamic nucleus deep brain stimulation has shown that indications for such a surgery have to be cautiously examined. After initial therapeutic enthusiasm, we are now at a time of problems and controversies.

Antiparkinson Agents↗
PubMed2005

Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

BACKGROUND: The simultaneous occurrence of bullous pemphigoid (BP) and multiple sclerosis (MS), two autoimmune diseases involving the skin and the central nervous system (CNS), respectively, has been described. OBJECTIVES: As the BPAG1 gene encodes the epithelial isoform of BP antigen 1 (BPAG1-e), a major autoantigen of BP, as well as additional variants expressed in the neurones of the CNS and peripheral nervous system and in Schwann cells, we tested the hypothesis that products of the BPAG1 gene act as shared autoantigens in both BP and MS. METHODS: The reactivity of cerebrospinal fluid (CSF) obtained from 18 patients with MS, 10 patients with other inflammatory CNS diseases and 20 normal controls was assayed by immunoblotting against two recombinant fragments of BPAG1-e encompassing regions that are also found in the neuronal variants BPAG1-n and BPAG1-a. RESULTS: The recombinant protein glutathione-S-transferase (GST)-BPAG1-e1-887 was recognized by five of 18 (27%) CSF samples obtained from patients with MS, two of 10 (20%) samples from patients with other inflammatory neurological diseases and five of 20 (25%) samples from normal controls. Furthermore, two of 18 (11%) CSF samples from patients with MS bound to GST-BPAG1-e1880-2649, whereas none of the samples obtained from patients with other inflammatory neurological diseases or from control subjects showed reactivity. CONCLUSIONS: These results raise the possibility that a subset of patients with MS develops an autoantibody response to the neuronal variants of BPAG1. These findings potentially open the avenue of neuronal BPAG1 variants being novel targets of autoantibodies in neurological diseases.

Autoantibodies↗
PubMed2004

Suicide after successful deep brain stimulation for movement disorders.

The authors observed a high rate of suicide (6/140 patients, 4.3%) in a large cohort of patients with movement disorders treated with deep brain stimulation (DBS). Apparent risk factors included a previous history of severe depression and multiple successive DBS surgeries, whereas there was no relationship with the underlying condition, DBS target, electrical parameters, or modifications of treatment. Paradoxically, all patients experienced an excellent motor outcome following the procedure. The authors propose that patients at high risk for suicide should be excluded from DBS surgery.

Adult↗
PubMed2004

Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years.

The effects of subthalamic nucleus deep brain stimulation were studied in 52 consecutive patients (13 over age 70, 15 under age 60, 24 age 60 to 70). All groups had improvement of motor fluctuations and dyskinesia. Patients over age 70 had worsening of Unified Parkinson's Disease Rating Scale motor scores on medication, despite less medication reduction. Their activities of daily living and axial subscores worsened, particularly in those with preoperative gait difficulties.

Age Factors↗
PubMed2004

L-dopa-induced dyskinesia improvement after STN-DBS depends upon medication reduction.

The authors studied the long-term evolution of levodopa-induced dyskinesia (LID) after levodopa challenge in two groups of six STN-deep brain stimulation-treated Parkinson disease (PD) patients, one requiring medication after surgery and the other not. A dramatic (96%) reduction of LID severity was obtained in the six postoperatively untreated patients compared to a moderate improvement (47%) in the treated group (p < 0.03). These data support dopaminergic stimulation and striatal desensitization as major determinants of LID in PD.

Aged↗
PubMed2004

Phenotypic heterogeneity of dopa-responsive dystonia in monozygotic twins.

The clinical expression of dopa-responsive dystonia (DRD) was found to be different in a pair of affected monozygotic twins. An earlier onset was associated with a more disabling course of disease. Whereas monozygosity was genetically proven, the search for pathogenic mutations in the GTP-cyclohydrolase-1 gene was negative. The contribution of environmental factors appeared minimal. Intrafamilial variability of DRD phenotype may be related to yet unknown non-Mendelian epigenetic or proteomic factors.

Adult↗
PubMed2003

How do parkinsonian signs return after discontinuation of subthalamic DBS?

OBJECTIVE: To study the reappearance of the clinical signs of PD when subthalamic nucleus (STN) deep brain stimulation (DBS) was turned off. METHOD: The authors studied 35 patients treated with STN DBS 6.7 +/- 3.3 months (mean +/- SD) after implantation. All were clinically improved. Twenty-four had not required any antiparkinsonian medication for many months and 11 were in "practically defined off" conditions when studied. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were assessed at baseline and 5, 15, 30, 60, 90, 120, 150, 180, and 240 minutes after switching off STN DBS. RESULTS: A sequential pattern of return of parkinsonian signs was observed, with a fast worsening of tremor within minutes, followed by a smoother, slower worsening of bradykinesia and rigidity over half an hour to an hour, and finally a slow and steady worsening of axial signs over 3 to 4 hours. Ninety percent of the UPDRS motor score worsening was reached after 2 hours. When switching STN DBS "on" again, all motor UPDRS subscores improved with a similar pattern, but faster than their rate of worsening, especially for axial signs. CONCLUSIONS: STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.

Disease Progression↗
PubMed2002

Effect on mood of subthalamic DBS for Parkinson's disease: a consecutive series of 24 patients.

A series of 24 consecutive PD patients were prospectively studied prior to and within 6 months postoperatively for mood, motor, and cognitive status to investigate the effects on mood of subthalamic deep brain stimulation (DBS) in PD. In six patients (25%), mood state worsened significantly, and three were transiently suicidal despite clear motor improvement. Caregivers and patients should be educated about the potential impact of this neurosurgical procedure on mood.

Adult↗
PubMed2002

Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14.

Detailed autopsy findings are reported for a patient with dopa-responsive dystonia genetically related to the dopa-responsive dystonia locus DYT14 on chromosome 14q13. Substantia nigra and locus ceruleus showed a normal abundance of severely hypomelanized dopaminergic neurons and no Lewy body. In the nigra, the reduction of melanin pigment was found to be asymmetric between the two sides and uneven within neurons, and the lateral aspect of the nigra appeared more affected than the medial, in a pattern similar to the neuronal loss in PD. Dopa-responsive dystonia has a unique neuropathologic signature that seems to be independent of its genotype.

Aged↗