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Biomedical subjects

A J Hudson

Publications and source records attributed to A J Hudson.

At least 19 recordsLinked to original sources
PubMed1992

Motor-evoked responses in primary lateral sclerosis.

Primary lateral sclerosis (PLS) may be distinguished on the basis of clinical and pathological features from amyotrophic lateral sclerosis (ALS). The former is featured by a much longer clinical course, exclusively upper motor neuron findings, losses of precentral pyramidal neurons, and preservation of anterior horn cells. Electrophysiological studies of 7 PLS cases have shown normal peripheral motor conduction, absent or very delayed motor-evoked potentials, the occasional late development of denervation activity in distal muscles, and normal somatosensory-evoked potentials.

Aged↗
PubMed1992

Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci.

Hypokalemic periodic paralysis (HOKPP) is an autosomal dominant neuromuscular disorder characterized by flaccid paralysis accompanied by lowered serum potassium levels. We have tested polymorphic markers linked to the adult skeletal muscle sodium channel (SCN4A) locus at 17q23-q25, the T-cell receptor beta (TCRB) locus at 7q35, and the H-Ras cellular proton-cogene locus (HRAS) at 11p15.5 for linkage with the affected phenotype in a single multigenerational pedigree. No evidence for genetic linkage to HOKPP was found at any of the candidate loci.

Chromosome Mapping↗
PubMed1992

Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria.

Eight patients with a homogeneous syndrome of progressive symmetric spinobulbar spasticity were studied. Clinical features were limited to those associated with dysfunction of the descending motor tracts and included spastic quadriparesis, pseudobulbar affect, spastic dysarthria, hyper-reflexia and bilateral Babinski signs. Lower motor neuron findings were absent and higher cognitive function preserved. Median age of onset was 50.5 yrs and median disease duration was 19 yrs. Neuropathologic features (including morphometric analysis) in the single autopsied case confirmed the selective involvement of the motor cortex. There was complete absence of Betz cells from layer 5 of the precentral cortex and the remaining pyramidal cells were significantly smaller than those seen in normal controls. Magnetic resonance imaging (MRI) revealed atrophy of the precentral gyrus and positron emission tomography (PET) scans showed diminished glucose [18F]fluorodeoxyglucose uptake in the pericentral cortex. Magnetic motor cortex stimulation revealed markedly prolonged central motor conduction times. The literature is reviewed and diagnostic criteria for primary lateral sclerosis based on clinical, laboratory and imaging features are proposed.

Aged↗
PubMed1992

Linkage analysis of candidate loci in autosomal dominant myotonia congenita.

Electrophysiologic studies in patients with autosomal dominant myotonia congenita (ADMC) have implicated defects of both muscle membrane sodium and chloride channels. An adult skeletal muscle sodium channel (ASkM1) gene maps to chromosome 17q23-25, and defects in this gene are almost certainly responsible for at least three variants of hyperkalemic periodic paralysis (HPP)--myotonic HPP, nonmyotonic HPP, and paramyotonia congenita. A gene for a muscle chloride channel has not yet been mapped in humans, but has been identified in the mouse. The gene for the cystic fibrosis transmembrane regulator (CFTR), which has chloride channel properties, is located on chromosome 7q31. This region is syntenic with the area of mouse chromosome 6 that contains the muscle chloride channel gene, a defect in which is responsible for the ADR phenotype, a murine model of myotonia. We performed linkage analysis using chromosome 17q polymorphisms at D17S74, SCN4A, and GH1, two chromosome 7q31 restriction fragment length polymorphisms, and a dinucleotide repeat polymorphism within the CFTR gene (CFTR-DNR), in three pedigrees with ADMC. The lod scores obtained show that the locus for ADMC is not at ASkM1 and is excluded from a region of at least 24 cM on either side of the CFTR gene.

Chromosome Mapping↗
PubMed1992

Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35.

The chromosomal localization of the gene for Thomsen disease, an autosomal dominant form of myotonia congenita, is unknown. Electrophysiologic data in Thomsen disease point to defects in muscle-membrane ion-channel function. A mouse model of myotonia congenita appears to result from transposon inactivation of a muscle chloride-channel gene which maps to a region of mouse chromosome 6. The linkage group containing this gene includes several loci which have human homologues on human chromosome 7q31-35 (synteny), and this is a candidate region for the Thomsen disease locus. Linkage analysis of Thomsen disease to the T-cell-receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected and 23 unaffected individuals) by using a PCR-based dinucleotide repeat polymorphism in the TCRB gene. Two-point linkage analysis between Thomsen disease and TCRB showed a maximum cumulative lod score of 3.963 at a recombination fraction of .10 (1-lod support interval .048-.275). We conclude that the Thomsen disease locus is linked to the TCRB locus in these families.

Base Sequence↗
PubMed1992

Absence of HTLV-I and HTLV-II proviral genome in the brains of patients with multiple sclerosis and amyotrophic lateral sclerosis.

Previous studies have failed to provide serological evidence to incriminate a retroviral infection in the cause of multiple sclerosis. Gene amplification techniques have also failed to identify retroviral footprints in DNA from peripheral blood leukocytes. Here we provide evidence that proviral DNA of HTLV-I and HTLV-II is not found in the central nervous system tissues of patients with multiple sclerosis, patients with amyotrophic lateral sclerosis and controls.

Amyotrophic Lateral Sclerosis↗
PubMed1991

Familial amyotrophic lateral sclerosis, 1850-1989: a statistical analysis of the world literature.

We present clinical and pathologic data on four previously unreported familial ALS pedigrees and review and analyze by descriptive and exploratory statistical techniques all published cases of familial ALS (1850-1989). In contrast to the age-dependent incidence of sporadic ALS, the age of onset of familial ALS is normally distributed about a mean of 45.7 years (std. dev. 11.3 years). Survival curves for the familial ALS data also demonstrate a skewed distribution with a median survival time of 24 months with 74% surviving at 12 months, 48% at 24 months and 23% surviving at 60 months. The patient characteristics of age at onset of disease, sex and focus of disease onset are unrelated variables and age at onset of disease is the only predictor of survival (Cox's proportional hazard model, chi-square 14.74, p = 0.0001). By applying accelerated failure time models with a log-normal baseline distribution, estimated probabilities for survival adjusted by age at onset were calculated. It was found that the older the age at disease onset, the shorter the survival.

Adult↗
PubMed1991

Amyotrophic lateral sclerosis/parkinsonism/dementia: clinico-pathological correlations relevant to Guamanian ALS/PD.

In a recent report on the clinical and pathological features of Guamanian ALS/PD and post-encephalitic parkinsonism/ALS a number of similarities were described, notably in the distribution of neurofibrillary tangles throughout the nervous system. In this account additional pathological features which these disorders share (and which differ from classical ALS, Parkinson's and Alzheimer's diseases) are described. These include atrophy of the globus pallidus and the entire substantia nigra, viz. pars compacta and pars reticulata. Moreover, neither Lewy bodies nor senile plaques are features of the Guamanian and post-encephalitic disorders. The significance of these observations and their relationship, more generally, to parkinsonism, ALS and dementia are discussed.

Alzheimer Disease↗
PubMed1991

Changes in sizes of cortical and lower motor neurons in amyotrophic lateral sclerosis.

It has been suggested that the degeneration of lower motor neurons in amyotrophic lateral sclerosis (ALS) is a transneuronal event, secondary to the loss of corticospinal and corticobulbar neurons. In an attempt to test this hypothesis, the cross-sectional areas of pyramidal cells in layer 5 of the foot and tongue areas of the precentral gyri were measured in 12 cases of the classical sporadic form of ALS, and in 10 control subjects. The areas of motor neurons in the hypoglossal nuclei and in the ventral horns of segment L4 of the spinal cord were also measured. The number of neurons per 20 microns section of ventral horn or hypoglossal nucleus provided a more reliable index of severity of lower motor neuron loss at the time of death than did a semiquantitative score derived from clinical observations. Cortical neurons and lower motor neurons were significantly smaller in the cases of ALS than in the controls. In the cortex this change included, but was not confined to, the largest neurons. These observations indicate that shrinkage precedes neuronal death. There was no correlation, positive or negative, between the numbers of surviving lower motor neurons and the mean sizes of pyramidal cells in layer 5 of the corresponding areas of the precentral gyri. The absence of such a correlation indicates that functionally related cortical and lower motor neurons probably degenerate independently, and not from a transsynaptic effect. Neuronal shrinkage has been observed in other diseases in which interconnected systems of neurons degenerate. The possible association of shrinkage with cytoskeletal degradation is discussed.

Adult↗
PubMed1990

Similarities of guamanian ALS/PD to post-encephalitic parkinsonism/ALS: possible viral cause.

Guamanian amyotrophic lateral sclerosis with parkinsonism-dementia (ALS/PD) has been the subject of intensive study since its discovery in 1947 because of its extraordinarily high incidence in a small ethnic group (Chamorros) whose dietary lack and customs have suggested possible causes. As yet, these and other suspected causes have eluded proof. Because of marked similarities between Guamanian ALS/PD and late onset post-encephalitic (encephalitis lethargica) parkinsonism and ALS it is suggested that they have a common cause. The parkinsonism and ALS in the two disorders are clinically very similar and neuropathological studies have shown a very similar distribution of neurofibrillary tangles in neurons. Some clinical differences, such as ocular features in the post-encephalitic cases and dementia in Guamanian ALS/PD, can be explained by differences in the severity of infection and the interval between the encephalitis and onset of sequelae. Although unproven, influenza A (HswilN1 strain) has long been suspected as the cause of encephalitis lethargica because of simultaneous pandemics of the two diseases in the 1920s. Because influenza A can persistently infect cells and has a marked propensity to mutate it is an optimal candidate among other RNA viruses for delayed nervous system infection as a possible cause of ALS/PD.

Amyotrophic Lateral Sclerosis↗
PubMed1988

Motor unit estimates in the biceps-brachialis in amyotrophic lateral sclerosis.

A newly developed technique for estimating the number of motor units in the biceps-brachialis muscles and for studying the innervation patterns of motor units in the same muscles has been applied to the study of 17 patients with amyotrophic lateral sclerosis (ALS). Although severe motor unit losses were seen in many ALS cases, in most there were clear indications of increases in innervation densities, linked potentials, and blocking. This technique provides a powerful new tool for quantitatively assessing the extent of motor unit losses and the accompanying changes in innervation patterns in ALS.

Adult↗
PubMed1988

Evaluation of six screening methods for detecting significant bacteriuria.

Six screening methods for the successful detection of significant bacteriuria--electrical impedance (Malthus), automated acridine-orange staining (Autotrak), particle counting (Ramus), bioluminescence, nitrite and leucocyte test strip (BM Nephur), and microscopy--were evaluated. All had excellent predictive values for a negative result (97%-100%) but were less accurate in predicting a positive result (31%-83%). All methods had high sensitivities (83%-100%) but lower levels of specificity (68%-79%). Bioluminescence was the method with the highest specificity (79%) and the lowest rate of false positive results (15%). It would be inappropriate to decide on treatment and management on the basis of the positive results achieved with any of the methods evaluated, but all methods tested could be used for screening out negative results.

Bacteriological Techniques↗
PubMed1988

Otolaryngologic manifestations of amyotrophic lateral sclerosis.

Otolaryngological manifestations were examined in a series of 250 patients diagnosed as having ALS between 1976 and 1986. Surgical intervention was only required in 10 cases due to excessive drooling and aspiration. Five patients had submandibular gland excisions with only limited improvement in respect to drooling. One case having a unilateral tympanic neurectomy had significantly better drooling control. Cricopharyngeal myotomy is helpful when dysphagia is predominantly due to cricopharyngeal spasm. In our series, tympanic neurectomy and chorda tympanectomy provide the better control of drooling for these patients and has the added advantage of being performed under local anesthesia.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Outpatient management of amyotrophic lateral sclerosis.

The patient with ALS can be managed almost entirely as an outpatient by a team consisting of a nurse, physiotherapist, occupational therapist, speech pathologist, nutritionist, respirologist, social worker, and certain other consultants from time to time. The team's goal is to maintain physical function and extend the useful life of the patient through the skills that the team members are trained to provide. Pulmonary function tests, especially spirometry, should be done at regular intervals and a modified barium swallow should also be done at least once in cases with dysphagia. It is possible with these tests to anticipate and even correct a number of hazards, such as upper airway obstruction and aspiration. Some patients are candidates for gastrostomy and tympanic and chorda tympani neurectomy, but full knowledge of their pulmonary function is essential before undertaking any operative procedure. Death in ALS is due to pulmonary failure and the choice of respirator care requires careful deliberation with the family. The neurologist and ALS team should work in close cooperation with the home care personnel in the patient's own community. Does the care of the ALS patient in any way affect survival? In the attempt to answer this question we have estimated the survival of ALS patients in southwestern Ontario, most of whom have visited our clinic over the period of 1978 to 1985, inclusive. As shown in Figure 4, there was an apparent decline in the annual mortality rate over this period, although there was no significant change in the incidence of ALS in this region.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyotrophic Lateral Sclerosis↗
PubMed1987

The role of insulin resistance in the pathogenesis of myotonic muscular dystrophy.

A study of glucose, insulin, lipids and lipoproteins in myotonic dystrophy (MyD) has shown elevation of fasting plasma insulin, triglycerides and very low density lipoproteins (VLDL) but no significant difference from normal in the fasting plasma glucose, total cholesterol or low and high density lipoproteins. Elevation of the total triglyceride and VLDL levels showed a direct relationship to hyperinsulinaemia. Insulin binding to cultured MyD fibroblasts under optimal conditions was significantly reduced but there was no difference in receptor affinity between MyD and control cells. In contrast to insulin binding, LDL binding to MyD fibroblasts was normal although there was a tendency to reduced LDL binding at 37 degrees C that may reflect mildly reduced lipid metabolism. The alterations in lipids and insulin in MyD are compatible with insulin resistance. Laboratory and clinical findings in MyD were compared with other inherited insulin-resistant diseases. MyD showed marked similarity to a group of disorders that have mild insulin resistance and mildly elevated plasma insulin in contrast to others with severe hyperinsulinaemia and insulin resistance. It is suggested that at least some clinical features of MyD may be due to diminished overall effect of insulin or other trophic factors on cell metabolism.

Adolescent↗