Search PubMed⌕ Search

Biomedical subjects

W Oertel

Publications and source records attributed to W Oertel.

At least 19 recordsLinked to original sources
PubMed2003

The phenylalanine loading test in the differential diagnosis of dystonia.

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients with DRD and patients with other types of dystonia was observed. This indicates that Phe-L may be helpful in the differential diagnosis of dystonias.

Administration, Oral↗
PubMed2001

Reduced levels of amyloid beta-peptide antibody in Alzheimer disease.

OBJECTIVE: To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-beta-amyloid (Abeta) antibodies in the CSF of patients with AD and age-matched controls by employing a sensitive ELISA. BACKGROUND: Immunization with preaggregated amyloid beta-peptide (Abeta(1-42)) and administration of antibodies against Abeta into amyloid precursor protein APP(V717F)- transgenic mice (an animal model of AD) have recently been reported to dramatically reduce amyloid plaque deposition, neuritic dystrophy, and astrogliosis, most likely by enhancing Abeta clearance from brain. METHODS: A sensitive ELISA was performed to detect levels of naturally occurring anti-Abeta antibodies in the CSF of patients with AD and age-matched controls. Additionally, an immunoprecipitation assay was performed to confirm that naturally occurring anti-Abeta antibodies also exist in the human blood. RESULT: - Naturally occurring antibodies directed against Abeta were found in the CSF and plasma of patients with AD and healthy control subjects. Moreover, CSF anti-Abeta antibody titers are significantly lower in patients with AD compared with healthy control subjects. CONCLUSION: Naturally occurring antibodies directed against Abeta exist in human CSF and plasma. The CSF anti-Abeta antibody titers may be helpful in better understanding the effects of future immunologic therapies for AD.

Aged↗
PubMed2000

Treatment with the selective muscarinic agonist talsaclidine decreases cerebrospinal fluid levels of total amyloid beta-peptide in patients with Alzheimer's disease.

Brain amyloid load in Alzheimer's disease (AD) is, at least in genetic forms, associated with overproduction of amyloid beta-peptides (A beta). Thus, lowering A beta production is a central therapeutic target in AD and may be achieved by modulating such key enzymes of amyloid precursor protein (APP) processing as beta-, gamma-, and alpha-secretase activities. Talsaclidine is a selective muscarinic M1 agonist that stimulates the nonamyloidogenic alpha-secretase pathway in model systems. Talsaclidine was administered double-blind, placebo-controlled, and randomized to 24 AD patients and cerebrospinal fluid (CSF) levels of total A beta were quantitated before and after 4 weeks of drug treatment. We observed that talsaclidine decreases CSF levels of A beta significantly over time within the treatment group (n = 20) by a median of 16% as well as compared to placebo (n = 4) by a median of 27%. We conclude that treatment with selective M1 agonists may reduce A beta production and may thus be further evaluated as a potential amyloid-lowering therapy of AD.

Aged↗
PubMed2000

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts.

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD.

Adult↗
PubMed1999

Glial cell line-derived neurotrophic factor protects dopaminergic neurons from 6-hydroxydopamine toxicity in vitro.

Glial cell line-derived neurotrophic factor (GDNF) is a potent and specific neurotrophic factor for dopaminergic neurons. GDNF has been previously shown to protect dopaminergic neurons from lesion-induced degeneration in vivo. In this study we investigated the effect of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro. In dissociated cultures of embryonic rat mesencephalon, 6-OHDA exhibited a dose-dependent cytotoxicity on tyrosine hydroxylase (TH)-immunoreactive neurons. After pre-treatment with GDNF, however, 6-OHDA-induced loss of dopaminergic neurons was effectively reduced. It has been shown recently that GDNF signals through the receptor tyrosine kinase Ret and the GDNF receptor-alpha (GFR-alpha). By RT-PCR, we found both Ret- and GFR-alpha-genes to be expressed in the cultured mesencephalic cells. We propose that the neuroprotective effect of GDNF on 6-OHDA-treated dopaminergic neurons in vitro is most likely mediated by functional Ret receptor signaling pathways.

Animals↗
PubMed1999

A synthetic gene coding for the green fluorescent protein (GFP) is a versatile reporter in Chlamydomonas reinhardtii.

The use of Chlamydomonas reinhardtii as a model system has been hindered by difficulties encountered in expressing foreign genes. We have synthesised a gene encoding green fluorescent protein (GFP) adapted to the codon usage of C. reinhardtii (cgfp). After verifying the gene was functional in Escherichia coli, the cgfp was fused in frame to the phleomycin resistance gene ble from Streptoalloteichus hindustanus and expressed in C. reinhardtii under control of the rbcS2 promoter and intron sequences. The GFP-fluorescence was seen only in the nucleus demonstrating the nuclear accumulation of the Ble-GFP fusion protein. The cgfp was also fused to the chlamyopsin gene, cop, and expressed in C. reinhardtii under control of the cop promoter. The eyespot became fluorescent indicating that the opsin-GFP fusion protein was correctly directed into the eyespot along with the endogenous unmodified opsin. We conclude that cgfp provides a useful tool to visualize protein synthesis and localisation in vivo in C. reinhardtii and possibly in related green algal species.

Algal Proteins↗
PubMed1998

Electrical stimulation of the posteroventral pallidum influences internally guided saccades in Parkinson's disease.

Chronic electrical stimulation of the posteroventral internal pallidum, a recently developed treatment option in advanced Parkinson's disease (PD), improves bradykinesia, rigidity and medication-induced dyskinesia. Apart from disturbances of the somatic motor system, PD is also characterized by disturbances of saccadic eye movements with hypometric and delayed internally guided saccades. We examined these internally guided eye movements (memory-guided and anti-task saccades) in a patient with bilaterally implanted stimulation electrodes, when stimulation was turned on and off. The electrical stimulation not only improved the bradykinesia and rigidity, but also the internally guided saccades by shortening the latency of the anti-saccades and increasing the gain of the memory-guided saccades. This finding supports the idea that the oculomotor pathways through the basal ganglia are organized like the somatic motor pathways and that stimulation of the posteroventral pallidum influences both.

Electric Stimulation↗
PubMed1998

What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group.

OBJECTIVES: Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS: Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4, and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS: Seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes. CONCLUSION: Magnitude and duration of improvement was greatest after injections of 1000 units Dysport; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport is recommended in patients with cervical dystonia, with upward titration at subsequent injection sessions if clinically necessary.

Adult↗
PubMed1998

[Psychosomatic aspects of idiopathic spasmodic torticollis. Results of a multicenter study].

Idiopathic spasmodic torticollis (IST) is one of the most frequent dystonic movement disorders. Its classification as a focal dystonia, as well as its treatment with botulinum toxin resulted in groups of patients being regularly seen by neurologic specialists. In a multicentre study, we investigated psychosocial changes, coping and psychopathology, and their interrelations with signs, symptoms and course. 256 patients were included in the study (59.3% women, 40.7% men). The mean age was 49.1 years. Rotating torticollis occurred more often than latero-retrocollis and antero-retrocollis. A family history of IST was seen in 3.1% of the total sample. 34% of the patients had additional dystonic symptoms. Most frequently, these affected the upper extremities (13%), less often the legs. 19.1% of the patients had experienced a period of complete remission. The General Symptom Index of the SCL 90-R in 27% of the patients ranged above the double standard deviation of the normal controls, indicating a clinically significant psychopathology.

Adaptation, Psychological↗
PubMed1996

Acute MPTP treatment produces no changes in mitochondrial complex activities and indices of oxidative damage in the common marmoset ex vivo one week after exposure to the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause a Parkinsonian syndrome in man and non-human primates. Hypotheses concerning the pathogenetic mechanisms of MPTP toxicity on nigro-striatal dopaminergic neurons relate to impairment of mitochondrial function and oxidative stress. However, surprisingly few primate studies addressed these issues ex vivo. Thus, the present study assessed the enzyme activities of the respiratory chain, GSH/GSSG and ubiquinol/ubiquinone content in the MPTP primate model (common marmoset, Callithrix jacchus; 2 mg MPTP-hydrochloride/kg body wt were injected subcutaneously (s.c.) on four consecutive days; animals were sacrificed 7 days after last MPTP exposure). Activities of respiratory chain enzymes were measured in crude homogenates of the caudate nucleus, because the probable toxic metabolite of MPTP, MPP+, is transported into dopaminergic neurons via the dopamine uptake system in striatal synapses and mitochondria are concentrated in axonal terminals. Since MPP+ can damage membranes of axonal terminals of nigro-striatal neurons we measured GSH/GSSG contents in the putamen and ubiquinol/ubiquinone concentrations in the substantia nigra and putamen as indices of oxidative damage. At the time of sacrifice MPTP-induced deficits comprised severe behavioural Parkinsonian symptoms, profound depletion of striatal dopamine and its major metabolites as well as pronounced loss of nigro-striatal neurons. Despite these severe lesions, acute MPTP treatment had no effect on any of the enzymes of the respiratory chain in the caudate nucleus and indices of oxidative damage in both the substantia nigra and putamen. These results suggest that factors other than mitochondrial impairment and/or oxidative stress may be involved in MPTP neurotoxicity in primates. Alternatively, early compensatory mechanisms and/or transient effects could account for the reported results and will be discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Neurotoxicity induced by prenatal exposure to MPTP on the monoaminergic and peptidergic systems of the marmoset brain.

The neurotoxicity induced by incidental prenatal exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in three marmosets. The baby marmosets exposed in utero to MPTP looked normal in the first few weeks of life but around 8 to 10 weeks of life they started to behave abnormally and were sacrificed when they were 20 weeks old. A marked reduction in DA levels was found in the baby marmosets prenatally exposed to MPTP as compared to the corresponding age-matched controls and this was highly significant in the caudate nucleus, putamen, and nucleus accumbens. Serotonin content was normal in the caudate and putamen and was only significantly reduced in the nucleus accumbens, hypothalamus, and cingulate cortex. Met-enkephalin levels were reduced in the caudate nucleus, putamen, and globus pallidus. Substance P content tended to be lower in all regions examined; however, the decrease was only statistically significant in the substantia nigra. These results indicate that prenatal exposure to MPTP induces a marked and long-lasting alteration in monoaminergic and peptidergic systems of the primate brain. This observation may provide a new insight into the role of toxins in the etiology of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Psychosocial aspects of Parkinson's disease.

Although Parkinson's disease has a definite neurologic basis, patients and relatives experience a multitude of stresses, only partly related to motor symptoms. Subjective and behavioral problems may be regarded as secondary disease symptoms. In an integrated approach, patients and relatives receive psychological counseling and learn new coping strategies for everyday situations. Results show that even elderly patients can make use of structured psychological interventions and change dysfunctional behaviors and cognitions. Measures specifically adjusted to Parkinson's disease are aimed at helping patients make better use of the beneficial effects of medication and counteract the possible negative effects of social and emotional stressors. Relatives need information about the disease and training to cope adequately with difficult caring situations. Future evaluation of medical treatment of Parkinson's disease should consider the interaction of psychological factors and symptom intensity. This interaction may result in momentary changes in the effects of medication because of psychological conditions. In the early stages of the disease, medication has the most positive effect, and psychological interventions should also have the most benefit.

Aged↗
PubMed1992

Neurotoxic effect of prenatal exposure to MPTP on the dopaminergic systems of the marmoset brain.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was incidentally administered to pregnant marmosets during the whole gestational period, except for the last 15 days before term. The infant monkeys were killed 5 months after birth, and dopamine and its metabolites were measured in the striatum and the nucleus accumbens. Prenatal exposure to MPTP produced a marked dopamine depletion in these brain regions of the offspring, showing that MPTP is able to cross the placental barrier in primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

The competitive NMDA antagonist CGP40.116 enhances L-dopa response in MPTP-treated marmosets.

Experiments in MPTP-treated non-human primates testing potential antiparkinsonian action have shown both, beneficial and adverse effects of gutamate receptor antagonists. To investigate this matter further, the novel competitive NMDA antagonist CGP40.116 was administered systemically to three adult MPTP-treated marmosets. When coadministered subcutaneously with a subthreshold dose of L-DOPA, 2 mg/kg, CGP40.116 25-250 micrograms/kg, increased locomotor activity. However, when administered alone, CGP40.116 had no effect on locomotor activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

[The dependence of rapid voluntary contractions on the tremor phase in parkinsonism].

Parkinsonian patients sometimes have problems to produce really fast motor responses. Often, these are significantly delayed in comparison to those of normal controls. In patients with tremor-at-rest, this delay might be induced by some attraction of the movement execution to the tremor oscillator, according to a hypothesis of Hallet et al. (1977). This study now examined the phase relationship between the on-going tremor and the onset of fast voluntary contractions in Parkinson's disease (PD), quantitatively. Five patients with prominent tremor-at-rest performed rapid isometric index finger abductions under self paced (SP) and reaction time (RT) conditions, and force and surface EMG signals from the FDI muscle were analyzed. In both conditions the SP and the RT, data showed that the onset of the contraction mostly occurs during the descending phase of the tremor oscillation and, accordingly, the phasic EMG burst synchronously with the tremor bursts confirming the above mentioned hypothesis.

Aged↗