Electrocardiographic findings in motor neurone disease

The electrocardiogram was analyzed in 31 patients with motor neurone disease. ECG abnormalities were encountered in 27 of the patients. The dominating ECG changes consisted of ST-T wave changes and supraventricular arrhythmias. The underlying mechanisms are discussed in relation to the neurological symptomatology.     

F-wave velocity in motor neurone disease

The F-wave velocity in the central segment (axilla to spinal cord) was studied employing the "collison technique" described by Kimura (1974), and compared with the conduction velocity obtained with the usual methods. In 25 normal subjects the F-wave velocity increased proceeding proximally, reaching the maximum values in the central tract (64.86 +/- 2.23 m/sec in ulnar nerve). In 11 patients affected by motor neurone disease and 11 patients affected by amyotrophic lateral sclerosis the F-wave velocity decreased significantly proceeding proximally and the minimum values were found in the central tract (52.51 +/- 2.15 m/sec in MND and 48.64 +/- 5.60 m/sec in ALS). We therefore suggest the use of F-wave velocity as a more complete element for precise localization of the lesion in the central segment when the motoneurone is primarily involved.     

Oxidative stress and motor neurone disease

The effects of oxidative stress within post mitotic cells such as neurones may be cumulative, and injury by free radical species is a major potential cause of the age-related deterioration in neuronal function seen in several neurodegenerative diseases. There is strong evidence that oxidative stress plays an important role in the pathogenesis of motor neurone disease (MND). Point mutations in the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) are found in some pedigrees with the familial form of MND. How mutations in this ubiquitous enzyme cause the relatively selective cell death of specific groups of motor neurones is not clear, although a number of hypotheses have been forwarded. These include (1) the formation of hydroxyl radicals, (2) the catalysis of reactions of the nitrogen centred oxidant species peroxynitrite, (3) toxicity of copper or zinc and (4) protein aggregation. Some experimental support for these different hypotheses has been produced by manipulating cells in culture to express the mutant SOD1 proteins and by generating transgenic mice which over-express mutant SOD1. Observations in these model systems are, in some cases at least, supported by observations made on pathological material from patients with similar SOD1 mutations. Furthermore, there are reports of evidence of free radical mediated damage to neurones in the sporadic form of MND. Several lines of evidence suggest that alterations in the glutamatergic neurotransmitter system may also play a key role in the injury to motor neurones in sporadic MND. There are several important subcellular targets, which may be preferentially impaired within motor neurones, including neurofilament proteins and mitochondria. Future research will need to identify the aspects of the molecular and physiological phenotype of human motor neurones that makes them susceptible to degeneration in MND, and to identify those genetic and environmental factors which combine to cause this disease in individuals and in familial pedigrees.     

Health professionals'' responses to multiple sclerosis and motor neurone disease

The effect of vasopressin and oxytocin on the contractile activity of preparations isolated from the feline gastric corpus wall was investigated. Vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M), but not oxytocin, evoked concentration-dependent tonic contractions only of longitudinal muscle strips. At the same time, vasopressin (1.5 x 10(-9)-2.1 x 10(-7) M) potentiated the magnitude of amplitudes, but not the frequency, of spontaneous contractions. Both the vasopressin V1 receptor antagonist d(CH2)5-(Me)2-Tyr-AVP and the predominantly vasopressin V2 receptor antagonist d(CH2)5, D-Ile2, Ile4-AVP, the non-selective muscarinic receptor antagonist, atropine, the predominantly selective muscarinic M1 receptor antagonist, pirenzepine, the predominantly selective muscarinic M2 antagonist, methoctramine, the predominantly selective muscarinic M3 receptor antagonist, para-fluoro-hexahydro-siladifenidol, and the calcium channel blocker, nifedipine, but not the ganglion blocking agent, mecamylamine, depressed or blocked the tonic contractions induced by vasopressin. Among the antagonists, only atropine and nifedipine inhibited the spontaneous contractions. On the other hand, the anticholinesterase, physostigmine, potentiated both the vasopressin-induced tonic and spontaneous contractions. With regard to the receptors, the vasopressin-induced tonic contractions are mediated at least in part through vasopressin V1 and V2 receptors, non-selective muscarinic and selective muscarinic M1, M2 and M3 receptors. The increase in amplitudes of spontaneous contractions is mediated only via-nonselective muscarinic receptors. Vasopressin receptors appear to be located mostly pre-synaptically, although the direct effect of vasopressin on post-synaptic receptors cannot be excluded. The pA2 values suggests rather V1a than V1b vasopressin receptor subtype involvement in tonic contractions vasopressin had produced. The tonic as well as spontaneous contractions are calcium-dependent. In addition, these results point to the existence of non-selective muscarinic receptors, which participate in the regulation of both tonic and spontaneous contractions, while muscarinic M1, M2 and M3 receptors subserve only the tonic contractions.     

Motor neurone disease: a progressive disease requiring a coordinated approach

1. Such a variety of causes are implicated for MND that it is unlikely a single cause exists. 2. There is no actual treatment for the disease other than alleviating symptoms and improving function by the use of aids and appliances. 3. Care of people with MND is highly specialised, requiring multidisciplinary cooperation to ensure effective patient care. 4. Nurses owe it to their patients to acquaint themselves with the disease and support networks available.     

CNS tissue Cu/Zn superoxide dismutase (SOD1) mutations in motor neurone disease (MND)

DNA extracted from CNS tissue of 79 cases of motor neurone disease (MND) was screened by single strand conformation analysis (SSCA) and heteroduplex analysis (HA) for mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The aims were to determine whether somatic mutations of SOD1 may underlie some cases of MND and to characterize the genetic abnormalities by sequencing, for subsequent correlation with the molecular pathological phenotype. In 3 cases a point mutation was found in exon 4: E100G in one familial case, and I113T in two cases (one familial, one sporadic). Two cases had previously undescribed mutations in the 3' untranslated region (3'UTR) of SOD1 and one case had a single base substitution in the intronic sequence upstream from exon 2. None of these patients had a positive family history. Non-CNS tissue was available for 3 out of the 6 cases in whom changes were found. In all 3 the same changes were consistently found in both CNS and non-CNS tissue, excluding the presence of somatic mutations in SOD1. We investigated many MND blood samples and normal controls for the presence of the 3'UTR deletions. We found the 4 bp deletion in 1/90 sporadic MND patients and 1/209 non-MND controls. If the 3'UTR deletions are pathogenic, they would have to operate via a loss of the function mechanism, and further work is necessary to define their significance.     

Root stimulation studies in the evaluation of patients with motor neuron disease

Nerve root stimulation may be employed in patients with motor neuron disease (MND) to rule out motor neuropathy with conduction block. The diagnostic utility of these studies is unknown, in part because the range of amplitude changes across nerve root segments in patients with active neuronal degeneration has not been well studied. We reviewed root stimulation studies in 32 patients (59 nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range similar to values reported for normal subjects; there was no suggestion of conduction block based on our usual criteria.     

Mechanisms of normal and abnormal neurulation: evidence from embryo culture studies

In this paper we estimate the size of several categories of "Israeli" immigrants in the United States. According to the 1990 U.S. census, there were about 95,000 Israeli-born immigrants in the United States in that year. Using the language and ancestry information available in the Public Use Microdata Sample (PUMS) of the 1990 census, we estimate that of this total, about 80,000 are Jews and 15,000 are Palestinian Arabs born in Israel. In addition to the Israeli-born, we present a range for the number of Jewish immigrants from Israel who are not Israeli-born (about 30,000-56,000). Thus our estimate for the total number of Jewish immigrants from Israel in the United States in 1990 is between 110,000 and 135,000. Fertility information available in the PUMS, also enable us to provide estimates for the number of second-generation Israelis in the United States in the 1990 (about 42,000). Finally, using both the 1980 and 1990 PUMS, we provide estimates for the rate of return migration among Israeli-born Jewish immigrants in the United States.     

Central motor conduction in motor neuron disease

Central motor conduction time (CMCT) to abductor digiti minimi (ADM) and tibialis anterior (TA) was measured in 21 patients of motor neuron disease (MND). In the upper limb, the motor pathways were inexcitable in 13 and central motor conduction time (CMCT-ADM) was prolonged in 7 sides. In the lower limbs the motor pathways were inexcitable in 10 and CMCT-TA was prolonged in 14 sides. The CMCT abnormalities did not follow a constant pattern but were randomly distributed and were asymmetric in the upper limbs in 7 and lower limbs in 3 patients. Asymmetric and randomly focal abnormalities in central motor conduction in our patients are consistent with asymmetric and focal neuronopathy in MND.     

The reorganization of motor units in motor neuron disease

We studied 78 patients with motor neuron disease (MND) using concentric needle electromyography. Analysis on weak and maximal effort was performed using our own, fully automated, computer method, EMG-LAB. In addition to the conventional parameters of single motor unit action potentials (MUAPs) and interference pattern, new criteria were applied: the range of the acting motor units and the functional recruitment order. A total of 375 muscles of MND patients and 120 control muscles were investigated. The electromyographic data were analyzed separately in five groups of muscles, classified A, B, C, D, and E according to their clinical condition. Those results allowed us to discern six neurophysiological stages (N(0,1,2,3,4,5)) from the early to the most advanced phase. It has been confirmed that reinnervation in MND is adequate to compensate for the loss of over 50% of motor neurons but it is only a transitory phase in the morbid course. At stages N(O-5), the electrophysiological data reflect structural and functional integrity of the functioning motor units. Evaluation of not only single MUAPs but also of the full range of acting motor units and their recruitment order allowed a deeper look into the underlying pathophysiological mechanisms.     

Series effects in motor performance studies.

It was hypothesized that a series effect would operate in a study designed to determine the optimal work surface height for the performance of a simple motor task. Under Condition A, Ss performed the task at each of 6 work surface hieghts, comprising the lower ? of the range of heights used in an earlier study. Under Condition B, Ss performed at 6 heights comprising the upper ? of the range. Systematic differences were observed in the performance of the 2 groups at the 4 heights they had in common. The differences in motor performance were attributed to a series effect stemming from differences in judgments Ss made concerning what the optimal height should be. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms of aortic injury in fatalities occurring in motor vehicle collisions

We analyzed footprints on the surface of a sand dune to estimate maximal running speeds and the incidence of bipedality in nature, as well as to investigate the effects of incline on the escape locomotion of the lizard Callisaurus draconoides. Previous laboratory tests predicted that inclines would negatively affect sprinting performance in C. draconoides. Although physiologists commonly assume that escape locomotion will be near maximal capacity, we found that only 11% of all strides were greater than 90% of maximal speed of C. draconoides. Escape paths averaged 10 m in length and were generally straight. Approximately 30% of the strides taken by C. draconoides were bipedal, and this value was three times greater than previously found for the closely related species Uma scoparia. The modal value of bipedal stride lengths was greater than that for quadrupedal strides. Inclines negatively affected velocity of only the first meter of C. draconoides escape paths. The location of nearest cover had better predictive value for the initial orientation of C. draconoides escapes than incline. On steep slopes (>15 degrees), C. draconoides avoided running directly downhill and uphill and primarily ran horizontally, whereas on shallow slopes, lizards exhibited approximately equal amounts of horizontal, direct uphill, and direct downhill running.     

Ocular motor abnormalities in Huntington's disease

We review here the eye movements in patients with Huntington's disease (HD), concentrating upon saccades as they show the most prominent abnormalities. Inability to suppress reflexive glances to suddenly appearing novel visual stimuli and delayed initiation of voluntary saccades, including predictive saccades, are early and consistent findings. These two abnormalities can be interpreted in the context of a model, based upon the idea that the frontal lobes and basal ganglia contribute more to the control of voluntary than to reflexive types of saccades. Most patients eventually also show slow saccades but they are most prominent when the disease is early-onset. Slowing of saccades may reflect involvement of both the higher-level cerebral centers that trigger saccades and the areas in the brain stem that produce premotor saccade commands. The study of eye movements in HD has led to a fruitful interaction between basic science and clinical investigation, and has served as a paradigm for examining higher-level defects in saccadic eye movement control in patients with various degenerative, neurological diseases or with focal cerebral hemispheral lesions.     

Oculomotor abnormalities in motor neuron disease

OBJECTIVE: To assess whether giving a leaflet containing norms of self-control to diabetics receiving insulin treatment results in a metabolic improvement. The HbA1c was established prior and subsequent to giving out the leaflet. The written norms contained in the leaflet were highlighted from the wider range of instructions obtained from diabetes education. DESIGN: A longitudinal intervention study with no random allocation. SETTING: Hospital care in a specialised Endocrinology clinic. PATIENTS AND OTHER PARTICIPANTS: 122 types 1 and 2 diabetics, treated with various insulin diets, who had received prior diabetes education and carried out blood self-controls. Cases of meta-diabetic syndrome, serious illnesses and those without apparent hypoglycaemia symptoms were excluded. INTERVENTIONS: Giving out of a leaflet with written norms of self-control. MEASUREMENTS AND MAIN RESULTS: The averages, standard deviations and 95% confidence intervals of the basal HbA1c and of those at four-monthly check-ups were calculated. Basal 8.07 (CI 7.75 - 8.39); 4th month 6.88 (CI 6.74 - 7.17); 8th month 6.59 CI 6.29 - 6.90); 12th month 6.60 (CI 6.23 - 6.94); 16th month 6.06 (CI 5.63 - 6.49); 20th month 5.40 (CI 3.04 - 7.75). Averages were compared by the Student T test and all values had p < 0.005 against the basal. CONCLUSIONS: Following the written norms produced a clear metabolic improvement, represented by the significant fall of HbA1c. Therefore, though without ignoring the overall context of treatment and diabetes education, it is proposed that the relationship of the most practical features of insulin dosing to written norms of self-control should be emphasised.     

Genes for normal behavioral variation: recent clues from flies and worms

Interrelations between intranasal detection sensitivity for odor (H2S) and pain (CO2), nasal-airway volume (acoustic rhinometry), and body temperature were studied in young, healthy men across the diurnal cycle. The results showed a weak but statistically significant negative correlation between nasal volume and odor threshold and a weak but positive correlation between body temperature and odor threshold.     

Mechanisms by which vegetable consumption reduces genetic damage in humans

A previous intervention study had shown that consumption of carotenoid-containing vegetable juices reduces oxidative DNA damage in lymphocytes of 23 male subjects. It was the aim of this study to elucidate the potential mechanisms involved. Specifically, we studied the modulation of protein expression and determined susceptibility factors. Cryopreserved lymphocytes from the study were analyzed for genetic polymorphisms of glutathione S-transferase (GSTM1, GSTP1, and GSTT1) using multiplex PCR, GSTP1-protein with an ELISA, total protein by a colorimetric enzyme reaction, and DNA-repair enzymes with the Comet Assay. Analyses of the genotoxicity data revealed a more steady state of protection for GSTM1*+ than for GSTM1*0 (15 and 8 of 23, respectively) genotypes. Increased expression of cytosolic protein was observed in 11 of 23 subjects, increased expression of GSTP1 in 6 of 23 subjects, and capacity of repair of oxidized DNA bases in 9 of 21 subjects. GSTP1 induction was independent of the GSTP1 genotype (GSTP1a or GSTP1b/c alleles). Kinetics of induction of cytosolic protein and of GSTP1 were compared in one GSTM1*+ and one GSTM1*0 subject and showed an efficacy of tomato and carrots, but not of spinach. Reduced genetic DNA damage in lymphocytes may be due to the enhancement of cytosolic GSTP1, and DNA-repair proteins by tomato and carrot juices. Enhancement of cytosolic proteins may be indicative of increased gene expression by vegetable juices, some of which may be associated with protective activities.     

Mechanisms of cell death in Alzheimer's disease

Molecular mechanisms involved in neuronal degeneration in Alzheimer's disease remain still unknown. A toxic effect induced by beta amyloid, oxidative stress, excitotoxicity and alterations in signal transduction mechanisms are the main factors linked to neuronal death. In addition, it has been suggested that apoptosis may also participate as a part of the cascade of events resulting in neurodegeneration.