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K Sieradzan

Publications and source records attributed to K Sieradzan.

16 recordsLinked to original sources
PubMed1998

Efaroxan, an alpha-2 antagonist, in the treatment of progressive supranuclear palsy.

We have tested, in a prospective randomized, double-blind, placebo-controlled, crossover, 12-week study, the effects of 2 mg efaroxan, a potent alpha-2 antagonist, given three times per day to 14 patients with progressive supranuclear palsy. Efaroxan did not induce any significant change on any motor assessment criteria. The present data do not confirm the assumption that the blockade of alpha-2 receptors might be a useful pharmacologic strategy to improve patients with progressive supranuclear palsy.

Adrenergic alpha-Antagonists↗
PubMed1997

Clinical presentation and patterns of regional cerebral atrophy related to the length of trinucleotide repeat expansion in patients with adult onset Huntington's disease.

We correlated trinucleotide CAG repeat numbers in the huntingtin gene with the regional brain atrophy and clinical phenotype in 23 adult autopsy cases of Huntington's disease (HD). CAG repeat number (39-56, mean 45.4 +/- 4.6) correlated inversely (P < 0.0001) with age at onset and death, but not with disease duration or initial symptoms. Cross-sectional areas of the striatum, pallidum, thalamus, amygdala, hippocampus, and the cortical grey and white matter within the frontal, temporal and parietal lobes at four levels (genu of the corpus callosum, amygdala, accumbens, hippocampus) were measured morphometrically from the coronal brain slices using image analysis. None of these morphometric variables correlated with number of CAG repeats. Thus, tissue atrophy in advanced HD is unrelated to the underlying genetic defect.

Adolescent↗
PubMed1996

Motor response to acute dopaminergic challenge with apomorphine and levodopa in Parkinson's disease: implications for the pathogenesis of the on-off phenomenon.

OBJECTIVES: To evaluate the contribution of postsynaptic changes to motor fluctuations, three groups of parkinsonian patients with differing responses to treatment were acutely challenged with two dopaminergic drugs-apomorphine and levodopa-having different mechanisms of action. METHODS: Forty two patients with Parkinson's disease (14 untreated, eight with a stable response to levodopa, and 20 with levodopa induced motor fluctuations) were challenged on two consecutive days with apomorphine and levodopa. The latency, duration, and magnitude of motor response was measured. RESULTS: A progressive shortening of mean latency after levodopa challenge was found passing from the untreated to the stable and fluctuating groups; the difference between untreated and fluctuating patients was statistically significant (P < 0.01). Response duration after levodopa challenge was similar in untreated and stable patients, whereas it showed a significant shortening in patients with motor fluctuations (P < 0.05 v both untreated and stable patients). When subcutaneous apomorphine was given, untreated patients had a longer response duration than those who had developed motor fluctuations (P < 0.05). Although baseline disability was significantly greater in the fluctuating patients than in the untreated and stable patients, the severity of residual parkinsonian signs after both apomorphine and levodopa challenge was similar for all three groups; as a result, the degree of improvement in parkinsonian signs after dopaminergic stimulation was substantially greater in more advanced than in early cases. Linear regression analysis also indicated that latency and duration after apomorphine challenge did not significantly correlate with those after levodopa challenge, whereas magnitude of response to apomorphine showed a strong positive correlation with that after levodopa challenge (r = 0.9, P < 0.001). CONCLUSION: The progressive shortening of motor response after both apomorphine and levodopa suggests that pharmacodynamic factors play an important part in determining the duration of motor response and argue against altered central pharmacokinetics of levodopa being principally responsible for the on-off effect. The widening response amplitude and increasing off phase disability occurring during disease progression are also critical factors in determining the appearance of motor fluctuations.

Aged↗
PubMed1995

The therapeutic potential of moclobemide, a reversible selective monoamine oxidase A inhibitor in Parkinson's disease.

Dopamine is equally well deaminated oxidatively by monoamine oxidase (MAO) A and B types. Selegiline (L-deprenyl), a selective inhibitor of MAO-B, ameliorates the "wearing off" akinesia and delays the need for levodopa in mild, previously untreated Parkinson's disease. The therapeutic potential of selective inhibition of MAO-A in Parkinson's disease has not been examined in detail. MAO-A accounts for only about 20% of total MAO activity in the human basal ganglia, and it differs from MAO-B in distribution. In contrast to MAO-B, which is confined to the extraneuronal compartment, MAO-A is found both extraneuronally and within the presynaptic dopaminergic terminals. The inhibition of MAO-A might alter the intraneuronal handling of dopamine reuptaken from synaptic clefts and thereby prolong oral levodopa benefit. We have given moclobemide, a selective, reversible inhibitor of MAO-A, to nondepressed patients with Parkinson's disease receiving standard levodopa/peripheral decarboxylase inhibitor or levodopa with dopaminergic agonist (bromocriptine, pergolide). Selegiline was discontinued at least 8 weeks earlier. A standard oral levodopa challenge was performed at the patient's entry to the study and repeated on the 22nd day of moclobemide treatment (150 mg thrice daily). The overall time spent "on" and "off" before the onset of treatment and during the last week on the drug was estimated from the patients' diaries. Neuropsychological assessments were also made before and after 3 weeks of moclobemide to measure possible effects on cognitive performance and mood. In acute levodopa challenge, the latency of motor response was significantly shortened and its duration was prolonged during moclobemide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Idiopathic Parkinson's disease: epidemiology, diagnosis and management.

Since the introduction of levodopa therapy for idiopathic Parkinson's disease over 20 years ago, there has been an awakening of research interest in this chronic neuro-degenerative disorder. This paper describes current understanding of the role of genetic and environmental factors in the aetiology of idiopathic Parkinson's disease and problems associated with both diagnosis and management. It briefly outlines both pharmacological and non-pharmacological options for treatment. Despite an increasing armoury of available treatments, the optimum management for this condition remains controversial.

Antiparkinson Agents↗
PubMed1993

Observations on the survival of grafted embryonic motoneurons in the spinal cord of developing rats.

The sciatic nerve of newborn rats was injured unilaterally. Small solid grafts of ED-12 embryonic spinal cord prelabeled with 5-bromo-2'-deoxyuridine (BrDUr) were inserted into the host's hemicord on the side of the sciatic nerve injury on PD5-12. Each graft was connected to a neuromuscular implant, which in group 1 consisted of the soleus muscle and its nerve taken from the healthy leg of the same rat pup, whereas in group 2 the soleus neuromuscular implant was taken from an immunocompatible adult rat. Six to 12 weeks later the neurons extending axons into the nerve-muscle implants were retrogradely labeled with fast blue and diamidino yellow. The embryonic origin of these neurons was ascertained by visualizing BrDUr using an immunocytochemical method. The grafts survived well and contained many BrDUr-positive neurons. No retrogradely labeled neurons were found in group 1 animals. In group 2 (animals with adult implants) numerous retrogradely labeled neurons were present in the host's neuropil. Despite the access to the target there were no BrDUr-positive cells of embryonic origin that contained the retrograde labels. Indeed no motoneuron-like cells of embryonic origin were seen in the host neuropil in any of the animals which received a graft at the age of 5-12 days. This contrasts with previous studies where the grafts were introduced into the adult spinal cord and motoneuron-like cells of embryonic origin were present in the host neuropil. Thus, it appears that the environment of the developing spinal cord is unfavorable for survival of embryonic motoneurons.

Amidines↗
PubMed1993

The ability of developing spinal neurons to reinnervate a muscle through a peripheral nerve conduit is enhanced by cografted embryonic spinal cord.

The ability of neurons in the spinal cord of rats aged 5-12 days to reinnervate a muscle via a peripheral nerve bridge was examined and the possible influence of the cografted ED-12 embryonic spinal cord was tested. The soleus muscle was transferred paravertebrally and connected to the contralateral L4-L5 hemicord by its nerve. In some experiments embryonic spinal cord was grafted at the same level. Six to 12 weeks later fast blue and diamidino yellow were injected into the muscle or applied on the cut nerve bridge. The animals were perfused after 3-4 days and their spinal cords were examined using fluorescent microscopy, but retrogradely labeled neurons were only rarely seen. The embryonic spinal cord grafts survived well but had no influence on the outcome of these experiments. However, when neuromuscular implants from adult immunocompatible rats were used instead of the immature autologous ones, a variety of neurons including motoneurons extended their axons into the implants. The numbers of retrogradely labeled neurons were significantly higher in the spinal cords with embryonic grafts. These retrogradely labeled neurons were in the host's grey matter and only exceptionally in the grafts. Thus, the developing neurons can extend their axons outside the spinal cord into the implants of adult soleus muscle and nerve, but immature nerve-muscle implants fail to attract and/or support axonal outgrowth. The reinnervation potential of the host's spinal neurons was enhanced by cografting of embryonic spinal cord.

Animals↗
PubMed1993

Possible consequences of disruption of neuromuscular contacts in early development for motoneurone survival.

Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnatal development after axonal injury, and (3) as a consequence of disease such as SMA. Interactions with the target emerges as an important factor for survival of developing motoneurones. The evidence for the target dependence od of developing motoneurones will be presented and the mechanisms by which the muscle may regulate motoneurone survival discussed. Results that argue for the following proposal will be given: with maturation of the CNS motor activity in all mammals increases as do the functional demands on the motoneurones. The target muscle's role is to induce changes in the motoneurone to make it competent to respond to increased amounts of glutamate from excitatory inputs and thus allow it to carry out the tasks associated with its increased activity. A failure of the muscle to induce these changes in the motoneurone's phenotype in time may lead to motoneurone death. In addition new approaches that could (1) improve motoneurone survival, and (2) use embryonic grafts to replace the lost cells will be discussed.

Animals↗
PubMed1991

Factors influencing survival of transplanted embryonic motoneurones in the spinal cord of adult rats.

The survival of transplanted embryonic motoneurones in the initially intact spinal cord of adult rats was studied and compared to that previously observed in the motoneurone-depleted cord. Embryonic (ED 11-12) spinal grafts prelabeled with 5-bromo-2'-deoxyuridine (BrDUr) were placed in the intact lumbar cord of the hosts. To provide a target for grafted embryonic motoneurones and to guide their axons to it, the contralateral extensor hallucis longus (EHL) muscle with its nerve attached was transferred paravertebrally. The nerve stump was implanted in the cord at the site of transplantation. Eight to 14 weeks later BrDUr-labeled motoneurone-like cells had migrated outside the grafts into the host's neuropil, preferentially into the anterior horn. Following injection of HRP into the implanted EHL muscle 6-17 weeks after transplantation a few retrogradely labeled motoneurones were seen in the host's anterior horn around the grafts. The lumbar cord of the rats with neuromuscular implants but without embryonic grafts had no retrogradely labeled cells. However, most animals, both with and without embryonic grafts, had retrogradely labeled motoneurones in the thoracic cord, which may contribute to the reinnervation of the implanted muscle. Thus, although some embryonic motoneurones can survive, migrate into the proper location, and probably innervate a host muscle when transplanted into the intact spinal cord, their number was significantly fewer than that in the motoneurone-depleted cord. The results show that reduction of the host's motoneurone pool increases chances of their survival.

Animals↗
PubMed1991

Transplants of embryonic motoneurones to adult spinal cord: survival and innervation abilities.

One goal of transplantation experiments involving damaged spinal cords is to reconstruct a functional innervation to muscles in the periphery. Embryonic spinal cord grafts have been shown to survive transplantation into adult spinal cord lacking motoneurones. Motoneurones from the graft appear to be able to innervate muscle tissue by being encouraged to grow across a bridge of peripheral nerve. Integration of grafted motoneurones appears to involve their migration from the graft into the host ventral horn, thus replacing depleted host neurones. These results suggest possible strategies of research that might lead to treatments of spinal cord injuries and disorders in which motoneurone loss occurs, such as amyotrophic lateral sclerosis, spinal muscular atrophies and poliomyelitis.

Animals↗
PubMed1991

Grafts of embryonic tissue into spinal cord: a possible strategy for treating neuromuscular disorders.

The article describes various approaches used to bring about repair of damaged spinal cord by using embryonic grafts of neuronal tissue. One approach is to stimulate the host's neuronal elements to grow and regenerate. Indeed embryonic grafts have been found to reduce the effects of spinal cord injury, and promote regrowth of axons across a lesion site at least to a limited extent. Attempts have also been made to restore the loss of supraspinal influences with grafts from embryonic brain, and transplants of aminergic neurones have been shown to compensate for the loss of aminergic supraspinal inputs. Finally, it is possible to replace loss of highly specialised cells such as motoneurones by grafts of embryonic spinal cord. Grafted embryonic motoneurones are able to survive within adult host cord although both their chances of survival and maturation seem improved by prior depletion of the host motoneurones. They are able to innervate a skeletal muscle via its peripheral nerve if this is co-implanted at the site of grafting but no axon growth has yet been detected into the host ventral root. However, grafted embryonic neurones are able to migrate away from the graft to sites once occupied by missing motoneurones in the host anterior horn. Within the context of the treatment of neuromuscular disease, the research described suggests possible stratagems for the treatment of disorders such as amyotrophic lateral sclerosis, spinal muscular atrophies or poliomyelitis either by employing grafts that could release neuroactive substances which might prevent existing cells from dying, or even by replacing missing motoneurones with transplanted embryonic motoneurones.

Fetal Tissue Transplantation↗
PubMed1989

Replacement of missing motoneurons by embryonic grafts in the rat spinal cord.

The ventral quadrant of embryonic spinal cord with its motoneurons prelabelled by 5-bromo-2'-deoxyuridine was grafted into the spinal cord of adult rats. The ventral horn of the host had been previously partially depleted of its own motoneurons by a neonatal nerve lesion. To enhance the chances of survival of the transplanted embryonic motoneurons a target muscle was provided for their axons. Two to three months after the grafts were inserted into the cord nuclei containing 5'-bromo-2'-deoxyuridine were found in the graft and in the host's spinal cord. Many of the stained nuclei were much larger than those of embryonic motoneurons, and their size distribution was similar to that of nuclei from control motoneurons. Retrograde labelling with horseradish peroxidase, injected into the target muscle provided for the embryonic motoneurons, showed that some motoneurons had reached the muscle and presumably made contact with it. Physiological and histological examination of the target muscle showed that it was innervated and that it contained at least three different types of muscle fibres. Thus embryonic motoneurons can survive and develop in the adult spinal cord. Moreover, they seem to be able to make functional connections with skeletal muscle fibres. The heterogeneity of the muscle indicates that the motoneurons that supply them are able to differentiate into various types of cells.

Animals↗
PubMed1987

Progressive supranuclear palsy with lower motor neuron involvement. A case report.

The clinical picture of progressive supranuclear palsy is relatively constant, including supranuclear ophthalmoplegia, pseudobulbar palsy, axial dystonia in extension, parkinsonian signs, postural instability and dementia. A case is reported, which is unusual in having flexor dystonia of the neck and marked signs of lower motor neuron involvement.

Aged↗