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Biomedical subjects

J D Mitchell

Publications and source records attributed to J D Mitchell.

At least 91 records · Page 5Linked to original sources

Central nervous system sarcoidosis.

The presenting features, clinical course and outcome of 19 patients with a diagnosis of CNS sarcoidosis are described. In two-thirds of the patients the initial features of sarcoidosis were neurological; half of them had an acute monophasic illness and half a chronic progressive or relapsing course. A favourable outcome was recorded unexpectedly during a study period of one to 16 years for two-thirds of the patients. The course of the disease in four patients suggested multiple sclerosis thus emphasising the importance of considering the possibility of CNS sarcoidosis in patients with suspected demyelinating disease.

Adolescent↗

Trace elements in cerebrospinal fluid in motor neurone disease.

Concentrations of sodium, chlorine, potassium, chromium, iron, cobalt, zinc, rubidium, silver, caesium, and selenium in cerebrospinal fluid from 14 control subjects and 20 patients with motor neurone disease were measured by in vitro neutron activation analysis. No statistically significant correlation was found between the concentrations of any two elements other than sodium and chlorine in either the patient or control group (r = 0.9905; p less than 0.001). The mean cobalt concentration was significantly lower in the patients (p = 0.0015). No other statistically significant difference was shown. The relevance of this finding was examined in relation to current concepts of the pathogenesis of motor neurone disease and the role of cobalt in cellular metabolism.

Cobalt↗

Focal lymphocytic thyroiditis in Southampton.

The presence of focal collections of lymphocytes within the thyroid gland has been associated with autoimmune thyroiditis. In a prospective study 197 thyroid glands were examined from post mortems performed in two Southampton hospitals over a 12 month period. The mean thyroid mass was 19.5 g in women and 22.2 g in men. Varying degrees of focal lymphocytic thyroiditis were present in 54 per cent of women and 24 per cent of men. Morphometry showed that on average less than 4 per cent of the gland was infiltrated by lymphocytes. There was no significant relationship with age. A possible association between focal lymphocytic thyroiditis and circulating thyroid autoantibodies has been shown.

Aged↗

Fluorometric microassay of trypsin and enteropeptidase in children--comparison with a titrimetic assay.

Two trypsin assay methods for the estimation of this enzyme in duodenal fluid from children have been compared. Assay results for a fluorometric method based on the use of N-carbobenzoxy-diglycyl-L-arginyl-2-naphthylamide hydrochloride (GANA) as the trypsin substrate were found to correlate well (r = 0.91, P less than 0.001) with those obtained with a much less sensitive titrimetric assay which used benzoylarginine ethylester hydrochloride (BAEE) as substrate. The higher sensitivity of the fluorometric assay has allowed accurate determination of trypsin activity in 10 microliter aliquots of duodenal fluid. This low volume requirement makes the assay suitable for studies on infants of all ages and conserves duodenal fluid for use in other investigations often warranted during the assessment of childhood malabsorption. The fluorometric assay has also been used to monitor the separation of enteropeptidase from trypsin(ogen) by chromatography on Sephacryl S-200 in samples of duodenal fluid from two children. Different proteolytic pathway deficiencies were confirmed in these children.

Arginine↗

Patterns of Refsum's disease. Phytanic acid oxidase deficiency.

Four children each exhibiting a profound deficiency of phytanic acid oxidase activity in cultured skin fibroblasts but with very different phenotypes, are described. A consistently raised plasma phytanic acid value, generally considered to be pathognomonic for Refsum's disease (phytanic acid oxidase deficiency), was observed in three of these children but not in the fourth, who also showed no evidence of accumulation of phytanic acid in liver or fat biopsies. Our data suggest that the clinical diagnosis of Refsum's disease in children is more difficult because the full spectrum of clinical features usually observed in adults with the disorder is not always present. Moreover, a failure to detect a raised plasma phytanic acid value may not necessarily indicate normal fibroblast phytanic acid oxidase activity.

Adult↗

The recovery cycle of the pattern visual evoked potential in normal subjects and patients with multiple sclerosis.

The recovery cycle of amplitude and latency of the P100 of the chequerboard pattern reversal visual evoked response was studied in 16 normal subjects and 20 patients with multiple sclerosis. There was no clear-cut pattern of recovery with respect to amplitude but at interstimulus intervals of less than 40 msec the latency of the test response P100 tended to be significantly delayed, the magnitude of this delay being virtually constant at intervals of 20 msec or less. Only 8 of 40 eyes from the 20 multiple sclerosis patients showed a pattern of recovery of latency significantly different from the normal subjects. Possible mechanisms for these observations are discussed with particular reference to current concepts of the pathophysiology of multiple sclerosis.

Electroencephalography↗

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples.

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.

Amino Acid Metabolism, Inborn Errors↗

Weight-gain inhibition by lactose in Australian Aboriginal children. A controlled trial of normal and lactose hydrolysed milk.

Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital (49 admissions) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder. Infants fed the lactose hydrolysed milk gained 70% more weight than those receiving normal milk. Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage standard weight for age, the presence of diarrhoea on admission to the trial, and stool sugar concentrations. The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world.

Animals↗

Evaluation of a new mineral and trace metal supplement for use with synthetic diets.

In an earlier study (Alexander et al., 1974) it was shown that the mineral mixture used in association with a synthetic diet was deficient in zinc, copper, iron, and manganese. A new mixture containing appropriately increased amounts of these trace metals has now been evaluated by means of metabolic balance studies carried out on children with phenylketonuria. This new mixture was shown to be satisfactory for zinc, copper, and iron, but minor changes have been recommended for manganese.

Child↗

Transmission of rotavirus gastroenteritis from children to a monkey.

A pooled suspension of rotavirus was prepared from the stools of eight children with acute non-bacterial gastroenteritis. The suspension was infused into the duodenum and stomach of an infant monkey (Nemestrina macaque). Biopsy samples of duodenal mucosa were taken at several intervals after inoculation, examined by light and electron microscopy, and assayed for lysosomal activity. Virus-like particles were seen within and around microvilli and intracellularly within vesicles as early as 20 minutes after the infusion. On the fourth and fifth days, large lysosomal bodies containing numerous virus-like particles were found within epithelial cells of the duodenal villi. No such particles were seen in the pre-inoculation sample or at days 16 or 25 after infection. The present study would appear to be the first demonstration of the transmission of this human virus to another species.

Animals↗

Enzyme changes in human small bowel mucosa during culture in vitro.

Human jejunal biopsy slices were maintained in culture for up to 48 hours. At 24 hours there was good morphological preservation but by 48 hours there was ultrastructural evidence of damage to the enterocytes. During culture the tissue had lost a certain amount of protein. At the same time the levels of three brush border enzymes (alkaline phosphatase, alpha-glucosidase, and leucyl-beta-naphthylamidase) and one lysosomal enzyme (N-acetyl-beta-glucosaminidase) showed a progressive decrease. Alkaline phosphatase, alpha-glucosidase, and N-acetyl-beta-glucosaminidase accumulated in the medium throughout the experimental period to give a medium:tissue distribution ratio of between 2 and 9. Leucyl-beta-naphthylamidase had a medium:tissue ratio of 140 after 48 hours of culture suggesting a selective secretion of this enzyme by the tissue.

Adult↗