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Biomedical subjects

J M Walshe

Publications and source records attributed to J M Walshe.

18 recordsLinked to original sources
PubMed1978

The urinary excretion of radiocopper in presymptomatic and symptomatic Wilson's disease, heterozygotes and controls: its significance in diagnosis and management.

Radiocopper (64Cu, 67CU), given intravenously, has been used to study the pattern of excretion of copper in patients with presymptomatic, symptomatic and treated Wilson's disease, together with heterozygotes for the Wilson's disease gene and a control group of patients with a variety of neurological lesions mimicking Wilson's disease. Urine was collected for three periods after injection, 0 to 8 hours, 8 to 24 hours, at which time a test dose of penicillamine was given, and from 24 to 30 hours. Stable (endogenous) copper was also estimated on these samples and specific activity was determined. This was multiplied by a correction factor to allow for variations in dose and body weight. The findings for stable copper in urine were largely predictable. Controls and heterozygotes had the least copper excretion, the amounts rising in the presymptomatic to a peak in the symptomatic patients. Institution of therapy was associated with a fall in copper excretion pro rata with time. The most important radiochemical findings were as follows. Heterozygotes excreted less of the injected copper than controls both under basal conditions and after penicillamine. Presymptomatic patients excreted less radiocopper than heterozygotes after penicillamine although the excretion during the basal 24 hour period was very much greater. Patients with symptomatic Wilson's disease had by far the highest excretion of radiocopper in all three time periods which fell after treatment, pro rata with time, as had been found for stable copper. These results were subjected to computer analysis. There was no overlap between the various groups with the exception of a single control subject who had combined pyramidal and extrapyramidal system degeneration of obscure aetiology. This patient was classified by the computer study as 'heterozygote'. These findings lend further support to the hypothesis that the loss of a single gene for copper balance can be detected with a high degree of accuracy and also that presymptomatic patients can be selected from a sibship for prophylactic treatment without the risk of subjecting healthy heterozygotes to unnecessary and potentially hazardous long-term therapy.

Adolescent↗
PubMed1977

Peptiduria in the Fanconi syndrome.

Peptide excretion has been studied in 20 cases of Wilson's disease and in maleate-induced Fanconi syndrome in the rat, ligand-exchange column chromatography being used to separate peptides from free amino acids. There is a statistically significant increase in urinary peptides in both types of the Fanconi syndrome. In both man and the rat, a large fraction of the excreted peptides has been shown to contain hydroxyproline, and therefore to be derived from collagen degradation. In both groups there is a close correlation between the output of hydroxyproline and that of total peptide-bound amino acids. Arguments are advanced that the peptiduria is due to increased urinary clearance of plasma peptides rather than to a metabolic cause. Peptides excreted in patients with the Fanconi syndrome are shown to have a different proportionate amino acid composition to those in urine specimens from normal controls. The mean size of urinary peptides derived from collagen must be at least five or six amino acids per peptide chain. Maleate-induced Fanconi syndrome in the rat is thought to be a close analogue of the syndrome in man, and further results obtained in the animal model may well be directly applicable to human disease.

Animals↗
PubMed1977

The effect of certain chelating compounds on the urinary excretion of copper by the rat: observations on their clinical significance.

1. A screening procedure is described to assess rapidly the clinical potential of chelating agents for the treatment of Wilson's disease. 2. Rats were used as the test animal; they were kept in metabolic cages and the urine was collected in copper-free containers. The compounds investigated were given by mouth as a standard dose of 100 mg. Copper was determined by atomic absorption spectrophotometry. 3. Basal urine copper excretion was 65-1 +/- SE 2-93 nmol/24 h (4-1 microgram +/- 0-185). After penicillamine this rose to 367-1 nmol and after trien to 305-9 nmol. 4. Certain compounds caused a reduction in the amount of copper excreted in the urine, probably by forming insoluble chelates with the metal, hence rendering it unavailable for excretion at the glomerulus.

Animals↗
PubMed1977

Arthropathy of Wilson's disease. Study of clinical and radiological features in 32 patients.

The principal clinical features and radiological findings relating to the locomotor system have been studied in 32 consecutive hospital admissions of patients with Wilson's disease. 5 of these patients were recently diagnosed and had as yet received no treatment, while 27 were routine admissions for follow-up and biochemical supervision of their illness. No patient was specifically included or excluded from the series because of the presence or absence of locomotor symptoms. The most common radiological abnormality was a generalized increase of radiolucency, interpreted as skeletal demineralization (21 cases), followed by premature osteoarthrosis (8 cases). Changes in the spine were common and included osteochondritis, reduction of intervertebral joint spaces, osteoarthrosis, and a tendency to squaring of vertebral bodies. Other bony changes included fluffy irregularity of femoral trochanters, osteochondritis dissecans of the knees, osteophytic protrusions at bone ends, and bunches of tongue-like osteophytes at joint margins. The symptoms associated with these radiological abnormalities comprised back pain and stiffness with restricted movement, pain and stiffness of knees, hips, and wrists, and tenderness to pressure over margins of affected joints. Joint hypermobility was also observed in 9 patients. Episodes of acute polyarthritis with serological changes were seen in 5 cases; all these episodes appeared to be related directly to treatment with penicillamine.

Adolescent↗
PubMed1977

Pregnancy in Wilson's disease.

The effect of pregnancy has been studied in 10 mothers with Wilson's disease. Three were presymptomatic but had the typical biochemical lesion, two of these were receiving penicillamine treatment at the time of conception, the third had yet to be diagnosed. The remaining seven mothers had had symptoms of Wilson's disease and had been receiving treatment for periods ranging from two and a half to 19 years. These mothers had 15 pregnancies between them, 13 went to full term but two ended prematurely at 26 and 30 weeks. In only one did pregnancy have an unfavourable effect on the Wilson's disease; this mother had been on penicillamine for only two and a half years in a suboptimal dose because of drug induced thrombocytopoenia. In addition she had extensive oesophageal varices and pregnancy was complicated by toxaemia. The other nine patients remained well and two had three pregnancies each. On six occasions penicillamine was taken throughout pregnancy, but in seven it was discontinued from the sixth to the twelfth week. All 15 babies were normal but one died of extreme prematurity (26 weeks gestation). Pregnancy does not appear to be contraindicated in well treated Wilson's disease and penicillamine does not seem to pose an undue risk to the foetus.

Ceruloplasmin↗
PubMed1976

Urinary excretion of peptides and of hydroxyproline in Wilson's disease.

1. A study has been made of peptide excretion in twenty cases of Wilson's disease, ligand-exchange column chromatography being used to separate peptides from free amino acids. Previous reports of excess of peptide output in the disease were confirmed and the excess was shown to be highly significant statistically. 2. A considerable fraction of the excess of peptide output was shown to consist of hydroxyproline-containing peptides derived from collagen degradation. 3. The method of rank correlation showed that the difference both in free amino acid and peptide-bound amino acid output in cases of Wilson's disease and in control subjects was mainly quantitative; the pattern of amino acid excretion was qualitatively similar in both groups. 4. Evidence is presented that the increase copper output in the urine in the disease is not secondary to peptiduria.

Adolescent↗