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Biomedical subjects

A Eisen

Publications and source records attributed to A Eisen.

At least 19 recordsLinked to original sources
PubMed1992

Quality control in nerve conduction studies with coupled knowledge-based system approach.

Contemporary equipment used for nerve conduction studies is usually capable of computerized measurement of latency, amplitude, duration, and area of nerve and muscle action potentials and resulting conduction velocities. Abnormalities can be due to technical error or disease. Identification of technical error is a major element of quality control in electromyography, and artificial intelligence could be useful for this purpose. We have developed a coupled knowledge-based prototype system (QUALICON) to assess the correctness of recording and stimulating characteristics in routine conduction studies. QUALICON extracts numeric features from CMAPs or SNAPs, which are translated into symbolic form to drive a Bayesian network. The network uses high-level knowledge to infer the quality of stimulating and recording electrode placement as well as polarity and stimulus strength making recommendations as to the likely technical error when abnormal potentials are detected. A preliminary assessment shows that QUALICON performs as well as manual assessment performed by professionals.

Action Potentials↗
PubMed1992

Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron?

It is proposed that the primary cell involved in amyotrophic lateral sclerosis (ALS) is the corticomotoneuron. The spinal motoneuron becomes affected as a result of antegrade effects. This hypothesis does not negate most of the presently popular theories regarding the pathogenesis of ALS, but directs focus to one cell type--the corticomotoneuron. It takes cognizance of the complex, monosynaptic, corticomotoneuronal-spinomotoneuronal connections that have evolved in primates, and especially in man. It might explain the lack of any natural or thus far induced animal model which closely mimics the human disease. Threshold measurements to transcotical magnetic stimulation might be used to test the hypothesis. Replication of ALS in an animal is only likely to succeed in a nonhuman primate.

Amyotrophic Lateral Sclerosis↗
PubMed1992

Amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease: phylogenetic disorders of the human neocortex sharing many characteristics.

Features common to amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are reviewed. Shared epidemiological aspects include an increasing frequency which is proportional for each disease. We draw attention to geographic non-uniform distribution which, for ALS and PD, correlates positively with latitude. Clinical and pathological overlap occurs in the same patients, and in members of the same family. A high early morning plasma cysteine/sulphate ratio possibly related to the development of proteinacious inclusions, as well as ubiquinated neuronal inclusions, characterize ALS, PD and AD. HLA-DR (the human group II major histocompatibility class) staining is marked in ALS, PD and AD and may represent autoimmunity-incited by-products of neuronal degeneration. Based upon demonstrated glutaminergic connections between the neocortex and anterior horn cells, the entorhinal cortex and the basal ganglia we hypothesize that ALS, AD and PD are phylogenetic disturbances of the neocortical cell. The postsynaptic neuron may degenerate secondarily to anterograde effects of deranged glutamate metabolism. Future therapeutic strategies should be directed to agents that decrease transmission induced by excitatory amino-acids.

Alzheimer Disease↗
PubMed1992

Transcranial magnetic stimulation for detection of preclinical cervical spondylotic myelopathy.

Twenty-three patients, mean age 50.4 years, with cervical radiculopathy at C7 or more rostrally, were studied with electromyography, CT scans (in 16 cases) and transcranial magnetic stimulation. None had overt evidence of myelopathy. Motor evoked potentials (MEPs) were recorded from the hand muscles (C8/T1), and latency, amplitude, and the MEP/CMAP ratio and central motor delay between the hand motor cortex and the lower cervical spine were measured. One or more of these were abnormal in 15 of 23 cases (65%). The most common abnormality was a reduced MEP/CMAP ratio. The findings indicate that physiologic dysfunction of the spinal cord, caudal to a radiculopathy, frequently accompanies a radiculopathy and may antedate overt cervical spondylotic myelopathy. This may be valuable in directing more timely surgical intervention.

Action Potentials↗
PubMed1991

Neuropathic pain behavior in rats depends on the afferent input from nerve-end neuroma including histamine-sensitive C-fibers.

Sciatic and saphenous neurectomy in rats produces nerve-end neuromas, known to be a source of afferent input. Concurrently rats self-injure the denervated hindpaw ('autotomy'), a behavior related to neuropathic pain in humans. Here we show that surgical resection of the neuromas in various groups of rats, each at a different postoperative time (days 22, 33, 48) suppress autotomy. This recalls the pain relief in humans following resection of painful neuromas. We also show that daily injections of astemizole, a peripheral anti-histamine which blocks histamine H1-receptors, suppress autotomy. Since mostly C-fibers in rat neuroma are sensitive to histamine, these results corroborate the suggestion that autotomy is driven by afferent neuroma input, mainly in histamine-sensitive C-fibers.

Animals↗
PubMed1991

Age-dependent decline in motor evoked potential (MEP) amplitude: with a comment on changes in Parkinson's disease.

Peak-to-peak measurement of the maximum amplitude motor evoked potential (MAXMEP) elicited by 20 consecutive transcranial magnetic stimuli recorded from the contracting thenar and hypothenar muscles measured 9.8 +/- 2.0 mV and 7.25 +/- 2.9 mV respectively (P less than 0.01). The ratio of MAXMEP/CMAP measured 92.6 +/- 25.8% and 54.8 +/- 12.3% respectively (P less than 0.001). Repeat studies showed good individual reproducibility. Amplitudes declined linearly with age (r = -0.836 for thenar MAXMEP P less than 0.001). It is argued that MAXMEP related to age is more meaningful than the MEP/CMAP wave ratio and is proportional to the number of fast conducting cortical motor neurons excited. In 7/18 patients with Parkinson's disease (PD) MAXMEP was increased; in 2 other patients MAXMEP was decreased for their age.

Adult↗
PubMed1991

Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties.

HU211 is a novel synthetic derivative of tetrahydro-cannabinol (THC), the active marijuana ingredient. The stereochemistry of HU211 is enantiomeric to that of THC. In contrast to THC, HU211 is not psychotropic. This agent exhibits other types of biological activities; it is a non-competitive NMDA receptor blocker and has antinociceptive activity when injected with cupric chloride. This study examined its effects in autotomy, a behavioral model of neuropathic pain. Autotomy, a behavior of self-mutilation of denervated areas, was induced in Sabra rats by cutting the sciatic and saphenous nerves. We found that injections of HU211 (2.5 mg/kg) with cupric chloride (0.8 mg/kg) every 2nd day markedly suppressed autotomy during the injection period by delaying its average onset day and reducing the incidence of severe autotomy. Moreover, suppression of autotomy was retained in the postinjection period (for at least 30 days) but only when the drug was injected intraperitoneally. Lesser effects were achieved by subcutaneous injections. Cupric chloride or HU211 alone were ineffective. The general behavior and open field motor activity indicated that the effects of HU211 with Cu++ on autotomy were not due to sedation or ataxia but presumably due to antinociception mediated by NMDA receptor blockade.

Animals↗
PubMed1991

Two monomers of yeast transcription factor ADR1 bind a palindromic sequence symmetrically to activate ADH2 expression.

ADR1 is a transcription factor from Saccharomyces cerevisiae that regulates ADH2 expression through a 22-bp palindromic sequence (UAS1). Size fractionation studies revealed that full-length ADR1 and a truncated ADR1 protein containing the first 229 amino acids, which has the complete DNA-binding domain, ADR1:17-229, exist as monomers in solution. However, two complexes were formed with target DNA-binding sites. UV-cross-linking studies suggested that these two complexes represent one and two molecules of ADR1 bound to DNA. Studies of ADR1 complexes formed with wild-type UAS1, asymmetrically altered UAS1, and one half of UAS1 showed that ADR1 can bind to one half of UAS1 and gives rise to a complex containing one molecule of ADR1. Dimethyl sulfate interference studies were consistent with this interpretation and in addition indicated that purine contact sites in each half of UAS1 were identical. Increasing the distance between the two halves of UAS1 had at most a minor effect of the thermodynamics of formation of the two complexes. These data are more consistent with ADR1 binding as two independent monomers, one to each half of UAS1. However, binding of two ADR1 monomers at UAS1 is apparently essential for transactivation in vivo. Further, we have identified a stretch of 18 amino acid residues amino terminal to the zinc two-finger domains of ADR1 which is essential for DNA-binding activity. Single amino acid substitutions of residues in this region resulted in severely reduced DNA-binding activity.

Alcohol Dehydrogenase↗
PubMed1990

Positron emission tomographic scanning demonstrates a presynaptic dopaminergic lesion in Lytico-Bodig. The amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam.

We performed positron emission tomography using 18F-6-fluorodopa on four Guamanians with an amyotrophic lateral sclerosis syndrome, eight Guamanians with parkinsonism, and seven clinically normal Guamanians; the results were compared with those of nine Vancouver control subjects. The Guamanian subjects had all been exposed to similar Chamorro lifestyles. The scans were analyzed using a graphic method that calculates a constant for whole striatal 18F-6-fluorodopa uptake. The parkinsonian subjects all had significantly reduced striatal 18F-6-fluorodopa uptake. The group with amyotrophic lateral sclerosis had significantly reduced uptake that was intermediate between that of the control group and the parkinsonian group. Two Guamanian normal subjects had reduced striatal 18F-6-fluorodopa uptake. The nigrostriatal dopaminergic lesion in Guamanian parkinsonism is similar to that found in idiopathic parkinsonism. The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.

Adult↗
PubMed1990

Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid.

Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients. Autopsy studies have shown glutamate contents to be significantly decreased in brain and spinal cord in ALS. These observations suggested that a systemic abnormality of glutamate metabolism might underlie the pathogenesis of ALS. We report here the findings of our studies of amino acid concentrations in patients with the sporadic form of ALS. Glutamate concentrations were normal in the fasting plasma of a great majority of the patients with ALS. Concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined. beta-N-Methylamino-L-alanine, a plant neurotoxin possibly responsible for causing the Guamanian form of ALS, was not detectable in the plasma or CSF of any of our patients. Our findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids.

Adult↗
PubMed1990

Cortical magnetic stimulation in amyotrophic lateral sclerosis.

Forty patients with ALS underwent cortical magnetic stimulation. Twelve had marked pseudobulbar signs; in these motor evoked potentials (MEPs) could not be elicited. Mean MEP latencies in the others, who had predominantly lower motor neuron signs, measured 23.3 +/- 2.1 msec (thenar), 18.7 +/- 5.3 msec (EDC), and 13.4 +/- 2.9 msec (biceps), respectively. These values were significantly longer (P greater than 0.001) compared with normal values (n = 35), which measured 20.2 +/- 1.6, 14.2 +/- 1.7, and 9.4 +/- 1.7 msec, respectively. MEP amplitude was often markedly reduced (less than 15% of the M wave) compared with a normal mean of 39.5 +/- 13.0%. Overall abnormal MEPs (delayed, absent, or reduced in amplitude) approached 100%. It is argued that measuring central motor delay, which was not significantly different in the patients compared with normals, is subject to error in ALS.

Adult↗
PubMed1990

Acute sensory neuronopathy with preserved SEPs and long-latency reflexes.

A case of spontaneous acute sensory neuronopathy is described in a previously healthy 19-year-old male. He had marked sensory ataxia with relative sparing of cutaneous sensation. There was no recovery over 4 years. Sural nerve biopsy showed modest axonal loss. Sensory evoked potentials were mildly abnormal in the face of absent sensory nerve action potentials. The long-latency (R2) reflex was preserved whereas the short-latency (R1) reflex was absent. The findings indicate that loss of large-diameter (group Ia) ganglion cells are primarily responsible for this syndrome.

Acute Disease↗
PubMed1990

Parkinson's disease, motoneuron disease and Alzheimer's disease: origins and interrelationship.

The cause of neurodegenerative disease is considered. For Alzheimer's disease, Parkinson's disease, and motoneuron disease, accumulating evidence over the last 3 years indicates that (a) the usual etiological mechanisms involve a subclinical lesion which kills some neurons and reduces the life expectation of their surviving neighbors, and (b) there may be more than one cause for each of the idiopathic syndromes now termed AD, PD, and MND.

Alzheimer Disease↗
PubMed1989

The relationship between Alzheimer's disease, Parkinson's disease and motor neuron disease.

We argue against the dominant status assigned to conventional microscopy in the categorization of disorders such as Alzheimer's disease, Parkinson's disease and ALS. As an example we criticize the emphasis that has been placed on correlating the presence of Lewy bodies with the diagnosis of Parkinson's disease. In essence, we submit that Parkinson's disease can exist without Lewy bodies, and Lewy bodies can exist without Parkinson's disease. Nevertheless, we consider that the newer techniques available to histology have led to an important concept that constitutes a shared feature for Alzheimer's disease. Parkinson's disease and ALS; they are all characterized by the deposition of cytoskeletal debris in tissue, so they may perhaps be collectively termed the "Cytoskeletal Disorders".

Aged↗