Corrigendum to: 'Identification and characterization of a mouse homologue of the spinal muscular atrophy-determining gene, survival motor neuron'
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Journal Article↗
Biomedical subjects
A Bergin
Publications and source records attributed to A Bergin.
Cerebrospinal fluid free choline in movement disorders of paediatric onset.
We measured free choline in cerebrospinal fluid (CSF) of 78 patients with movement disorders of paediatric onset and various controls as a putative index of central phospholipid metabolism. Most of the disorders studied were myoclonic disorders, such as progressive myoclonus epilepsy, the opsoclonus-myoclonus syndrome, and essential myoclonus, but other movement disorders, interictal seizure disorders, and different neurological and nonneurological disorders were also included. There were no significant differences in CSF choline concentrations in myoclonic disorders or other movement disorders compared with controls. The CSF choline levels were lowest in children with seizure disorders including progressive myoclonus epilepsy. In progressive myoclonus epilepsy, the CSF choline values resembled other epileptic disorders rather than other myoclonic disorders. When all the data were analysed collectively, no significant relation of CSF choline was found to patient age, gender, aliquot of CSF measured, or the length of time the sample was stored at -70 degrees C. Separate analyses of data from children and adults showed a trend toward a biphasic relation between patient age and CSF choline which could be pursued in developmental studies of normal subjects. Reduced CSF choline may indicate increased choline incorporation into brain phospholipids, disturbances of choline metabolism, decreased choline release, or non-neural factors.
Acetylcholine↗
Relaxation therapy in Tourette syndrome: a pilot study.
To evaluate the feasibility and efficacy of behavioral relaxation therapy as treatment for Tourette syndrome, 23 patients were recruited from a university-based pediatric Tourette syndrome referral clinic. Individuals were randomized and stratified according to initial tic severity and the presence of attention-deficit hyperactivity disorder into either relaxation therapy or a minimal therapy (control) group. Sixteen patients, mean age 11.8 years (S.D. 2.8 years), completed the 3-month study, which included weekly, hour-long, individual training sessions for 6 weeks. Individuals (n = 7) in the relaxation therapy group demonstrated a significantly increased ability to relax, compared with the minimal therapy (awareness and quiet time training) group. At 6 weeks, tic findings, based on five established tic severity scales, revealed greater improvement in the relaxation treatment group, but values failed to reach statistical significance. No difference between therapy groups was apparent at the 3-month evaluation. The acquired ability to relax did not significantly affect behavioral measures on the Child Behavioral Checklist. On the basis of this pilot study, relaxation therapy appears to have a limited role in the treatment of tics in Tourette syndrome.
Adolescent↗
Identification and characterization of a mouse homologue of the spinal muscular atrophy-determining gene, survival motor neuron.
Spinal muscular atrophy (SMA), the second most common fatal, autosomal recessive disease of infants, manifests as generalized muscle weakness. The most severe form (Type I, Werdnig-Hoffmann disease) is associated with quadriplegia, respiratory muscle paralysis and death in infancy. Less severe forms are classified as Type II and Type III, based on age of onset and ultimate motor disability. Some spinal motor neurons show chromatolysis and the number of these cells is decreased. Recently, SMA has been mapped to chromosome 5q11.2-13.3 (Gilliam et al., 1990), a region that contains three candidate genes: Survival Motor Neuron (SMN) (Lefebvre et al., 1995); Neuronal Apoptosis Inhibitory Protein (NAIP) (Roy et al., 1995); and p44, a subunit of transcription factor II H (TFIIH) (Carter et al., 1995; Bürglen et al., 1997). Homozygous deletions or deleterious mutations in SMN are present in all SMA patients, and in some affected individuals, deletions have been identified in one or both of the other genes. These extensive deletions may be associated with a more severe phenotype. We have identified and characterized the mouse homologue of SMN, MoSMN, which is 82% identical to SMN at the amino-acid level. Unlike the duplicated human SMN, MoSMN is present in single copy. Like its human counterpart, MoSMN is ubiquitously expressed, but unlike SMN, MoSMN does not appear to be alternatively spliced. In-situ hybridization analysis of the mouse nervous system revealed that MoSMN mRNA is expressed in spinal cord and throughout the brain, with relatively higher levels of expression in the hippocampus and cerebellum.
Alternative Splicing↗
The effects of loxiglumide on food intake in normal weight volunteers.
The aim of this paper was to investigate the effects of the CCK, a receptor antagonist loxiglumide on food intake, hunger and fullness in humans. A double blind, placebo controlled, cross-over test was carried out, with subjects taking one loxiglumide or one placebo tablet three times a day, 15 min before main meals or at comparable intervals. The work was carried out at the Centre for Human Nutrition, Northern General Hospital, University of Sheffield, on 11 healthy, normal weight, male and female volunteers. The following were measured: weighted-intake measurement of food intake during drug and placebo treatment; laboratory test of food intake on day three of each treatment; hunger and fullness ratings throughout this meal. A small, non-significant, increase in food intake as measured by the weighed intake diaries (8577 +/- 636 vs 7895 +/- 569 kJ (2049 +/- 152 vs 1886 +/- 136 kcal); P = 0.17) was seen during loxiglumide treatment, but no effect on food consumption from the evening test meal was observed and no effect on feelings of hunger and fullness before or after this meal was seen. These results do not support the hypothesis that, in the free feeding situation, endogenously released CCK is involved in the reduction of food intake or inhibition of hunger. However, a different dose of route of administration or a larger group of subjects may reveal an effect of loxiglumide on feeding in humans.
Adolescent↗
Effect of food and anti-cholinergic drugs on the pattern of rectosigmoid contractions.
The colonic response to a meal is often used to test the effect of drugs on colonic motility, but this test is hindered by its inconsistency. This study has used multiple manometric sensors situated in the rectosigmoid region to investigate whether recording of the site and type of contraction offers a clear discrimination of the colonic response to a meal and the effect of drugs. Two studies were carried out on 16 healthy volunteers. Before the meal, rectosigmoid motility consisted mainly of isolated contractions occurring in a single manometric channel. The motility index increased in every subject after the meal (p < 0.05), but this increase entirely consisted of a massive increase in contractions occurring simultaneously in three or more manometric channels (multiple channel contractions), the number increasing from 9 per hour preprandially to 57 per hour (p < 0.01). There was a concomitant decrease in the number of the single channel contractions from 65 to 56 per hour. In a second study an infusion of an antispasmodic drug, mebeverine hydrochloride, into the sigmoid colon of healthy volunteers stopped the postprandial increase in the multiple channel contractions and prevented the significant rise in the motility index. The decrease in single channel contractions was unaffected. These results show that the colonic response to a meal consists of a change in the pattern of rectosigmoid contractions and suggest that multiple channel contractions may be a more sensitive indicator of the effect of a meal on the rectosigmoid colon than the motility index.
Adult↗
Adrenoleukodystrophy: phenotypic variability and implications for therapy.
X-linked adrenoleukodystrophy (ALD) is a relatively common disorder that shows a great deal of phenotypic variability. Approximately half of the patients have the rapidly progressive childhood cerebral form that is associated with an inflammatory response in brain and leads to total disability or death during the first decade. Twenty five per cent or more of the patients have adrenomyeloneuropathy (AMN), a form that progresses slowly, involves the spinal cord mainly, shows little or no inflammatory response, manifests in adulthood, and is compatible with a near-normal life span. The two forms of the disease occur frequently within the same kindreds and nuclear families. Segregation analysis based on 3862 individuals in 89 kindreds points to the existence of an autosomal modifier locus with a likelihood ratio of 20:1. In addition, we present preliminary results of three types of therapy. Two hundred and four patients have received a dietary regimen that combines the administration of oils containing mono-unsaturated fatty acids (oleic and erucic) with the restricted intake of very long-chain fatty acids. This regimen normalizes the levels of satured very long-chain fatty acids in plasma within 4 weeks. It appears to improve peripheral nerve function in patients with AMN, and a large-scale trial is in progress to determine whether it can prevent the onset of neurological involvement in patients who have the biochemical abnormality of ALD but are neurologically intact. We report early results of bone marrow transplantation in 14 patients. There is encouraging but still preliminary evidence that transplantation can arrest the progression of the disease in patients with mild neurological involvement. There is urgent need to develop methods to combat the rapid progression of the cerebral forms of the disease, which so far has resisted therapeutic intervention, including immunosuppression or the administration of immunoglobulin.
Adolescent↗
Peroxisomal disorders.
The concept that there are human disease states that are associated with abnormal peroxisomal function is of recent origin. This is due in part to the relatively recent discovery of the organelle itself by de Duve in 1983, and to the earlier belief that it was a vestigial structure in mammals. The recognition that the organelle is significant in mammals was ushered in by Paul Lazarow's observation that rat peroxisomes catalyze the beta-oxidation of fatty acids. By 1981, more than 40 enzymes had been localized to the peroxisome, and the number continues to grow. Respect for the physiological role of the peroxisome in man has been heightened by our recent recognition that peroxisome malfunction causes profound disturbances. The Zellweger cerebro-hepato-renal syndrome represents the most serious peroxisomal disease. It is associated with malfunction of virtually every organ, and children with the disease usually do not survive beyond the 4th month. Application of newly developed diagnostic techniques has shown that the clinical spectrum and frequency of peroxisomal disorders are greater than had been realized. Eleven separate peroxisomal disorders have now been identified. Our laboratory alone has identified more than 2000 patients. Disturbances of very long chain fatty acid and ether phospholipid metabolism are present in 9 of the 11 peroxisomal disorders. In this presentation, we will provide an overview of the peroxisomal disorders, with emphasis on disturbances of fatty acid and ether lipid metabolism.
Adrenoleukodystrophy↗
Clinical aspects of adrenoleukodystrophy and adrenomyeloneuropathy.
Adrenoleukodystrophy (ALD) is an X-linked recessive disorder that affects mainly the nervous system white matter and the adrenal cortex. It is associated with an abnormal accumulation of saturated very long chain fatty acids and can be diagnosed by demonstrating an excess of these substances in plasma or red cells. Our laboratory has identified more than 900 hemizygotes and 1,000 heterozygotes. Approximately 50% of the hemizygotes have a rapidly progressive childhood or adolescent form of the disease. Twenty-five percent of males have a slowly progressive paraparesis in adulthood, but often are not diagnosed correctly. The illness may also present as Addison disease without apparent neurological involvement. Approximately 15% of heterozygotes develop moderately severe spastic paraparesis. It is important to diagnose ALD promptly because of the urgent need for genetic counseling and the availability of promising therapeutic interventions.
Addison Disease↗
Adrenoleukodystrophy.
X-linked adrenoleukodystrophy (ALD) is a disorder of very long chain fatty acid (VLCFA) metabolism that can be diagnosed by demonstrating increased levels of VLCFA in plasma and, prenatally, by similar assays in cultured amniocytes or chorionic vilus samples. ALD causes Addison disease frequently in men and occasionally in women. Prompt diagnosis is important for genetic counseling and for the institution of therapies aimed to prevent or ameliorate the progressive neurologic disability that often is associated with this illness.
Adrenoleukodystrophy↗
Trisomy 18: a nine year review.
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Chromosomes, Human, Pair 18↗
Cardiac constriction due to malignant disease of the pericardium.
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Adult↗
Valve replacement for aortic valve disease.
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Adolescent↗
The value of radioimmunoassay of parathyroid hormone in diagnosis of hyperparathyroidism, renal calculi, hypercalcaemia and metabolic bone disease.
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Adult↗
The effect of various methods of eye immobilization on corneal topography.
BACKGROUND: Accurate, predictable, and safe refractive surgery requires immobilization of the eye. We measured the effects of current eye fixation techniques on human cadaver eyes. MATERIALS AND METHODS: Central to our study was a device specially designed to secure cadaver eyes and stabilize intraocular pressure. Topographical measurements were made with a modified Model 2 Corneal Analysis System (EyeSys Technologies, Houston, Tex) mounted vertically to allow analysis of a cadaver eye mounted in the artificial orbit. The effect on human cadaver eyes of six fixation instruments was assessed: forceps, U-shaped fixation forceps, a full Hofman-Thornton ring, a VISX vacuum fixation ring, a Meditec suction ring, and a new instrument, the Eye Fixation Speculum. RESULTS: The circular vacuum fixation rings caused minimal distortion, resulting in less than 1.00 diopter (D) of change. Forceps and U-shaped fixation forceps, which apply force at one or two points, caused significantly more distortion. Single-point fixation forceps distorted the cornea at the point of application a mean of +5.50 +/- 3.50 D, and, at 180 degrees from the point of instrument application, a mean of +2.00 +/- 1.90 D. U-shaped forceps apply force at two points, 90 degrees and 270 degrees, from the axis of instrument application. At these axes, the cornea was distorted a mean of +9.40 +/- 3.70 D and +8.30 +/- 3.10 D, respectively. CONCLUSIONS: Single- and multi-point fixation instruments, due to an asymmetric application of fixation force, significantly distort the cornea. Ring fixation instruments, which apply a more equally distributed force, cause less distortion.
Cornea↗
Zimbabwe: a nursing story.
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Dehydration↗
MR findings in adult-onset adrenoleukodystrophy.
PURPOSE: To describe the MR findings of brain and spinal cord in adult-onset adrenoleukodystrophy. METHODS: One hundred sixty-four adult patients ranging from 19 to 74 years of age (119 men and 45 women) with clinically and biochemically proved adrenoleukodystrophy underwent MR of the brain. In 30 patients the spinal cord also was evaluated with MR. RESULTS: The brain MR findings were abnormal in 54 of 119 males and in 9 of 45 female heterozygotes and consisted of varying degrees of demyelination of the cerebral white matter in 40 patients, corpus callosum in 25 patients, corticospinal tracts in 46 patients, visual tracts in 31 patients, and auditory tracts in 18 patients. The thoracic spinal cord showed diffuse atrophy in 18 of 20 men and in 8 of 10 women. CONCLUSION: It is important to recognize the MR findings of adult-onset adrenoleukodystrophy, because not uncommonly the clinical and MR findings of adrenoleukodystrophy are misdiagnosed as multiple sclerosis, olivopontocerebellar or spinocerebellar atrophy, amyotrophic lateral sclerosis, or dementia. Analysis of the MR findings and correlation of the clinical findings has permitted a tentative subdivision of adult-onset adrenoleukodystrophy population into four subtypes that appear to differ in respect to prognosis and possibly pathogenesis. MR evaluation of the brain in adrenoleukodystrophy also is helpful in patient selection for experimental therapy, which is most effective if offered in the early stage of the disease.
Adrenoleukodystrophy↗