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Biomedical subjects

A C Ludolph

Publications and source records attributed to A C Ludolph.

At least 109 records · Page 6Linked to original sources
PubMed1992

Inhibition of energy metabolism by 3-nitropropionic acid activates ATP-sensitive potassium channels.

3-Nitropropionic acid (1 mM), which inhibits succinate dehydrogenase activity and reduces cellular energy, produces in the pyramidal cell layer of the hippocampal region CA1 a hyperpolarization for variable lengths of time before evoking an irreversible depolarization. Hyperpolarization is caused by an increased potassium conductance that is attenuated by glibenclamide (1-10 microM), a selective antagonist of ATP-sensitive potassium channels; in contrast, diazoxide (0.5 mM), an agonist at this channel, induces a hyperpolarization in CA1 neurons of rat hippocampal slices. The transient hyperpolarization after prolonged (ca. 1 h) application of 3-NPA is followed by a depolarization that is incompletely reversed by brief application of the glutamate antagonists (D-2-amino-5-phosphonopentanoic acid (APV), 6,7-dichloroquinoxaline-2,3-dione (CNQX), 3-(+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), 7-chloro-kynurenic acid (7Cl-KYN)). Early application of glibenclamide (within the initial 5 min) blocked or reduced hyperpolarization and accelerated the depolarization. These data suggest that metabolic inhibition by 3-NPA initially activates ATP-sensitive potassium channels. Events other than activation of glutamate receptors participate in the final depolarization resulting from uncoupling of oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed1992

Are human neurodegenerative disorders linked to environmental chemicals with excitotoxic properties?

At the present time, it seems unlikely that progressive neurodegenerative diseases, such as ALS, Parkinson's disease, and dementia of the Alzheimer type, are triggered by environmental agents with excitotoxic potential. These include excitotoxic agents that behave as glutamate agonists or disrupt energy metabolism: both types elicit permanent but self-limiting neuronal diseases with patterns of neuronal deficit that reflect selective chemical exposure (MPP+ and parkinsonism), differential susceptibility to energy dysmetabolism (NPA and dystonia), or the distribution of glutamate-receptors (domoic acid and memory loss). If environmental agents play an etiologic role in progressive neurodegenerative diseases, they are likely to target a critical, irreplaceable neuronal molecule that is required to maintain long-term neuronal integrity.

Alzheimer Disease↗
PubMed1992

The relation between functional deficits, motor and sensory conduction times and MRI findings in syringomyelia.

Opinions about the relation between the dimensions of the syrinx and the severity and distribution of symptoms in patients with syringomyelia are controversial. Therefore, this study investigates the relation of clinical symptoms, a disability score, quantified (1- and 2-dimensional) radiological findings (magnetic resonance imaging, MRI) and electrophysiological data (somatosensory and motor evoked potentials) in 22 patients with syringomyelia. There was a close relation between clinical symptoms and electrophysiological data. By both electrophysiological methods subclinical deficits could be detected. Furthermore, the results disclosed that the clinical symptoms, the degree of disability and the duration of the disease are not related to the dimensions of the syrinx or the electrophysiological results obtained by investigating the long ascending and descending spinal tracts of the lower limbs. Our findings suggest that, besides the syrinx, other factors not directly visible in the MRI are responsible for the development and progress of clinical symptoms.

Adolescent↗
PubMed1992

Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study.

In this study the regional cerebral glucose utilization and the neuropsychological performance of patients with amyotrophic lateral sclerosis (ALS) was investigated. Special attention was given to neuropsychological tests thought to mirror frontal lobe dysfunction. The regional cerebral glucose utilization was studied in 18 patients using high-resolution positron emission tomography. Clinically all patients displayed upper and lower motor neurone signs. In ALS patients glucose metabolism was significantly reduced in the frontal and in the entire cortex compared with controls; no changes were seen in the cerebellum. Comprehensive neuropsychological assessment of ALS patients compared to a pair matched control group revealed mild frontal dysfunction which in part significantly correlated with reduced glucose metabolism in the cortex and subcortical structures. We conclude that in patients with ALS, glucose consumption is decreased in parts of the brain other than the motor cortex accompanied by mild neuropsychological deficits based on the tests employed in this study.

Adult↗
PubMed1992

Neurological outcome in 22 treated adolescents with hyperphenylalaninemia. A clinical and electrophysiological study.

We examined clinically and electrophysiologically 22 adolescents suffering from hyperphenylalaninemia. Three of 16 treated patients showed slight impairment of proprioception; their examination was otherwise unremarkable. Subclinical deficits were present in the central motor and sensory pathway. In addition, we had evidence of a minor sensory neuropathy: 32% of the 22 patients had subclinical deficits in the visual system. However, in contrast to earlier reports we saw no relation to the degree of metabolic control. Our results suggest that treated adolescent patients with hyperphenylalaninemia show neurological dysfunction that may be related to morphological, as well as pharmacological changes.

Adolescent↗
PubMed1992

MRI in ALS.

Explore the source record for details and available documents.

Amyotrophic Lateral Sclerosis↗
PubMed1992

[Clinical studies of writer's cramp in 30 patients].

30 patients with writer's cramp were examined by a neurologist and a psychiatrist. The syndrome was frequently associated with a postural tremor. We found no evidence for a peripheral causation. Electromyographical recordings showed co-contractions of agonists and antagonists as well as individual patterns of increased muscle activity during writing. CT and MRI scans were normal in most patients. The psychiatric examination revealed a history of situational stress at the onset of the disease and also some abnormalities in the biography and personality traits. Since the latter findings were not consistently present we have no evidence that the disease is a neurotic manifestation. We consider it likely that secondary psychoreactive processes may have some significance in the individual patient.

Diseases in Twins↗
PubMed1991

Disturbed myelination in patients with treated hyperphenylalaninaemia: evaluation with magnetic resonance imaging.

Cranial magnetic resonance imaging (MRI) was performed in nine treated adolescents with hyperphenylalaninaemia (HPA) in order to analyse possible changes in myelination. Three patients suffered from type I HPA, four from type II and two from type III (persistent HPA). Images were obtained with a 1.5 T unit using spin-echo-sequences. In all patients with type I or type II HPA, abnormal findings in the cerebral white matter were demonstrated including band-like and/or confluent patchy areas of high signal intensity predominantly in the peritrigonal region, with anterior and posterior periventricular extension and/or involvement of the subcortical white matter. The extent of MRI changes did not correlate with the initiation, duration or quality of dietary treatment. There was also no consistent relationship between electrophysiological changes and white matter abnormalities on MRI. Our findings suggest a disturbance of myelination in patients with treated HPA. These results correspond well with earlier neuropathological and biochemical studies in untreated patients.

Adolescent↗
PubMed1991

3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin.

3-Nitropropionic acid (3-NPA)--a suicide inhibitor of succinate dehydrogenase--is a widely distributed plant and fungal neurotoxin known to induce a damage to basal ganglia, hippocampus, spinal tracts and peripheral nerves in animals. Recent reports from Northern China indicate that 3-NPA is also likely to be responsible for the development of putaminal necrosis with delayed dystonia in children after ingestion of mildewed sugar cane. This article discusses the role of 3-NPA in the causation of the disease in China, its neurotoxic effects in animals and the potential role for this compound as a probe of selective neuronal vulnerability.

Animal Diseases↗
PubMed1991

Functional and morphological deficits in late-treated patients with homocystinuria: a clinical, electrophysiologic and MRI study.

Seven late-treated patients between the ages of 10-30 years suffering from homocystinuria were examined clinically and electrophysiologically; four had MRI. The clinical examination showed extrapyramidal features and slight impairment of proprioception. Electrophysiological evaluation revealed normal results in the acoustic and central motor system; a minor, possibly vitamin B6 related, sensory neuropathy was detected by peripheral conduction studies. MR imaging showed small focal areas of gliosis in the white matter, generalized cortical atrophy in two patients, but only one small cortical infarct. No changes in the basal ganglia were detected. These results support the view that neurological signs and symptoms in patients suffering from homocystinuria are related to morphological findings, as well as pharmacological effects.

Adolescent↗
PubMed1991

Slow toxins, biologic markers, and long-latency neurodegenerative disease in the western Pacific region.

The western Pacific parkinsonism-dementia and amyotrophic lateral sclerosis complex is a prototypical neurodegenerative disorder found among inhabitants of Guam, New Guinea (Irian Jaya, Indonesia) and Japan (Kii Peninsula, Honshu). Nonviral environmental factors peculiar to the affected populations seem to play a prominent etiologic role. Although cause-effect relationships cannot be established by epidemiologic studies alone, we have shown in all three affected population groups that individuals develop the amyotrophic lateral sclerosis variant of this disorder after heavy exposure to the raw or incompletely detoxified seed of neurotoxic cycad plants. Since long periods may elapse between cycad exposure and the appearance of neurological disease in humans, cycads may harbor a "slow toxin" that causes the postmitotic neuron to undergo slow irreversible degeneration. Two cycad neurotoxins are recognized, one of which (cycasin) is known to have long-latency effects (tumorigenesis) on mitotic neurons and replicating cells in other tissues. This paper explores the possible relationship between tumorigenesis and long-latency neurotoxicity, and discusses possible biologic markers of cycad exposure and subclinical neurodegenerative disease.

Biomarkers↗
PubMed1991

Long-latency neurodegenerative disease in the western Pacific.

The western Pacific parkinsonism-dementia and amyotrophic lateral sclerosis complex is a prototypical neurodegenerative disorder found among inhabitants of Guam, New Guinea (Irian Jaya, Indonesia) and Japan (Kii Peninsula, Honshu). Nonviral environmental factors peculiar to the affected populations seem to play a prominent etiologic role. Although cause-effect relationships cannot be established by epidemiologic studies alone, we have shown in all three affected population groups that individuals develop the amyotrophic lateral sclerosis variant of this disorder after heavy exposure to the raw or incompletely detoxified seed of neurotoxic cycad plants. Since long periods may elapse between cycad exposure and the appearance of neurological disease in humans, cycads may harbor a "slow toxin" that causes the postmitotic neuron to undergo slow irreversible degeneration. Two cycad neurotoxins are recognized, one of which (cycasin) is known to have long-latency effects (tumorigenesis) on mitotic neurons and replicating cells in other tissues. This paper explores the possible relationship between tumorigenesis and long-latency neurotoxicity, and discusses possible biologic markers of cycad exposure and subclinical neurodegenerative disease.

Biomarkers↗
PubMed1989

N-isopropyl-p-123I-amphetamine single photon emission computer tomography in motor neuron disease.

N-Isopropyl-p-123I-amphetamine (123I-IMP) single photon emission computer tomography studies were performed on 17 patients suffering from amyotrophic lateral sclerosis (ALS). All patients displayed varying degrees of impaired fixation of 123I-IMP in the whole brain. These findings were not related to the clinical variants of ALS and the age of the patients. A correlation between the severity of the disease and the degree of impaired fixation could be observed. In addition, patients suffering from ALS for longer periods showed more pronounced impairment of 123I-IMP fixation.

Adult↗
PubMed1989

Cerebellar atrophy following acute intoxication with phenytoin.

A patient developed marked cerebellar atrophy after a single suicidal intoxication with 7 grams phenytoin. The clinical signs of cerebellar dysfunction subsided very slowly and incompletely within 18 months. We documented the cerebellar atrophy by CTs 4 weeks and 1 year after the intoxication, and we suggest that a single severe acute intoxication with phenytoin may directly cause cerebellar degeneration.

Adult↗