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Biomedical subjects

M D Milne

Publications and source records attributed to M D Milne.

At least 19 recordsLinked to original sources

The effect of chelation therapy on the amino aciduria and peptiduria of Wilson's disease.

1. There is an excess urinary output of free amino acids and of urinary peptides in most cases of untreated Wilson's disease. Studies of 11 patients have shown that both these abnormalities are greatly improved by two years of standard chelation therapy. 2. The reduction in excretion of both free amino acids and peptides is purely quantitative, there being no significant change in the percentage composition of amino acids, either free or combined, in relation to their total urinary output. 3. Arguments are advanced that the peptiduria of the disease is usually due to a proximal renal tubular reabsorption defect, but in rare cases it may be due to excess bone breakdown or even to a combination of bone and renal tubular disease in the same patient.

Adolescent↗

Peptiduria in experimental Fanconi syndrome in rats.

1. The plasma concentrations and urinary output of proline and hydroxyproline contained in peptides were measured in normal rats and in rats with Fanconi syndrome produced by injection of sodium maleate. All animals received a prior injection of 10 mg of the dipeptide L-prolyl-L-hydroxy-proline to increase plasma and urinary peptide content. There was a significant increase of urinary output of the two imino acids contained in peptides and a fall in their plasma concentrations. 2. It is concluded that increased output of peptides derived from collagen degradation in the experimental Fanconi syndrome in rats is at least in part due to diminished tubular reabsorption of these compounds from the glomerular filtrate. The results are claimed to be relevant to the increased output of urinary peptides in the Fanconi syndrome in man.

Animals↗

Peptide excretion in experimental Fanconi syndrome in the rat.

A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides. 2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of beta-aminopropionitrile. 3. The fractional amino acid content of urinary peptides after maleate and beta-aminopropionitrile is shown to be significantly different from that in control animals. 4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.

Aminopropionitrile↗

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↗

Long-term assessment of extradural analgesia for the relief of pain in labour. II: Sense of "deprivation" after extradural analgesia in labour: relevant or not?

Ninety-nine mothers who received extradural analgesia, and 95 who received conventional methods of analgesia for the relief of pain in labour, were interviewed at 18-24 months following delivery. An increase of about 2% in the proportion of mothers experiencing a sense of "deprivation" in the long term in comparison with the findings recorded immediately after delivery was noted. This was not accompanied by the need to seek psychiatric treatment.

Adolescent↗

Amino acid imbalance in cystinuria.

After oral ingestion of a free amino acid mixture by three cystinuric patients, plasma increments of lysine and arginine were lower and those of many other amino acids were significantly higher than those found in control subjects. Similar results were obtained in control subjects after amino acid imbalance had been artificially induced by the omission of cystine, lysine, and arginine from the amino acid mixture. Especially high increments of alanine and proline provided the best evidence of amino acid imbalance caused by a temporary lysine and, to a lesser extent, arginine and cystine deficit. No such amino acid imbalance was found to occur in the cystinuric patients after ingestion of whole protein, indicating that absorption of oligopeptides produced by protein digestion provided a balanced physiological serum amino acid increment. This is considered to explain the lack of any unequivocal nutritional deficit in cystinuric patients despite poor absorption of the essential free amino acid, lysine.

Adult↗

Intestinal absorption of an arginine-containing peptide in cystinuria.

Separate tolerance tests involving oral intake of the dipeptide, L-arginyl-L-aspartate, and of a corresponding free amino acid mixture, were carried out in a single type 2 cystinuric patient. Absorption of aspartate was within normal limits, whilst that of arginine was normal after the peptide but considerably reduced after the amino acid mixture. The results are compared with the increments of serum arginine found in eight normal subjects after the oral intake of the free amino acid mixture. Analyses of urinary pyrrolidine and of tetramethylenediamine in urine samples obtained after the two tolerance tests in the patient support the view that arginine absorption was subnormal after the amino acid mixture but within normal limits after the dipeptide.

Alanine↗