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Biomedical subjects

H A Simmonds

Publications and source records attributed to H A Simmonds.

At least 235 records · Page 13Linked to original sources
PubMed1978

Purine metabolism in adenosine deaminase deficiency.

Deoxyadenosine was identified in the urine of a second child with almost undetectable levels of adenosine deaminase (ADA) in erythrocyte lysates. Deoxyadenosine excretion thus appears to be characteristic of ADA deficiency: the acid lability of deoxyadenosine (responsible for the frequent confusion of this abnormal urinary metabolite with adenine) may be used in screening for this defect by isotachophoresis. The deoxynucleotides dATP, dADP and dAMP found initially in the child's erythrocytes (in comparable amounts to ATP, ADP and AMP) disappeared after a successful marrow graft from an unrelated donor, as did the urinary deoxy metabolites. Erythrocyte ADA activity decreased after the marrow graft but was still greater than 10% of normal congruent to 10 weeks after the last red cell transfusion.

Adenosine Deaminase↗
PubMed1978

Absence of oroticaciduria in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency.

Orotic acid excretion was normal when tested by three methods in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. These results do not support the speculation, based on the oroticaciduria observed by others, that the immunodeficiency in these disorders results from the inhibition of pyrimidine biosynthesis. An alternative hypothesis is discussed.

Adenosine Deaminase↗
PubMed1977

Complete deficiency of adenine phosphoribosyltransferase. Report of a family.

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).

Adenine↗
PubMed1977

Metabolism of intravenous adenine in the pig.

1. Adenine administered either parenterally or orally is less toxic to the pig than to other species; doses of 100 mg/kg are rapidly catabolised and excreted largely as soluble purine end-products in the urine. 2. The low toxicity is explained by the excretion of less than 1% of the dose as 2,8-dihydroxyadenine. 3. These results suggest that adenine dosages which give rise to kidney damage must be above a threshold-like level which varies in the different mammalian species, and is higher in the pig than in the rat, dog, rabbit or man.

Adenine↗
PubMed1977

Purine excretion in complete adenine phosphoribosyltransferase deficiency: effect of diet and allopurinol therapy.

1. Abnormal amounts of adenine, 8-hydroxyadenine and 2,8-dihydroxyadenine are found in the urine of homozygotes for APRTase deficiency and are diagnostic of this condition. 2. The renal complication is due to the excessive amounts of 2,8-dihydroxyadenine excreted since it is removed by allopurinol which blocks 2,8-dihydroxyadenine formation. 3. Uric acid metabolism and the excretion of the other minor purine bases is normal, at least in childhood, in homozygotes for APRTase deficiency. 4. Patients with the defect appear to be very sensitive to dietary purine. At least some of the adenine metabolites may have a dietary origin.

Adenine↗
PubMed1977

Thiopurinol: dose-related effect on urinary oxypurine excretion.

1. The important fact which emerges from these studies both without and with dietary purine supplementation is that thiopurinol dose possess apparent in vivo xanthine oxidase inhibitory activity but the dose must be increased well above therapeutic levels for this effect to manifest. 2. The considerable reduction in total endogenous urinary purine excretion at these high doses substantiates an additional inhibitory effect of thiopurinol on de novo purine synthesis. 3. Thiopurinol, like its analogue allopurinol, is also capable of reducing the absorption of dietary purine administered in the form of guanine in the pig.

Allopurinol↗
PubMed1976

Uric acid excretion by the pig kidney.

The handling of uric acid by the pig kidney has been investigated during continuous urate infusion in unrestrained, unanesthetized animals. Urate-to-inulin clearance rates in excess of 1 were found under all experimental conditions, demonstrating only net secretion by the pig kidney. The demonstration of a secretory maximum was precluded owing to a progressive reduction in the GFR associated with high rates of urate infusion. Urate clearance was independent of urine flow rate up to 10 ml/min. The administration of probenecid inhibited urate secretion, but urate-to-inulin clearance ratios below unity were not observed. Pyrazinamide or pyrazinoic acid, at doses which either inhibited secretion or promoted uricosuria in other species, did not alter urate excretion in the pig. Probenecid together with pyrazinamide exerted the same inhibitory effect on urate secretion as probenecid alone. Pyrazinoic acid was reabsorbed at all infusion rates. It is concluded that the pig kidney eliminates uric acid by filtration and secretion only.

Animals↗
PubMed1975

Experimental crystal nephropathy (one year study in the pig).

An acute crystal nephropathy was produced in pigs by feeding a mixture of guanine and allopurinol. The pathogenesis of the lesion produced was studied by serial histology and renal function tests over 12 months. Tubular blockage by the crystals produced erosion of the basement membrane and an accompanying interstitial nephritis. Tubular degeneration around the crystal mass transferred the crystals to the interstitium. Despite rapid subsequent disappearance of these crystals the interstitial nephritis was still evident nine months later. An early return of renal function to near normal was not sustained beyond nine months. It was shown that even brief periods of intratubular crystal deposition caused irreversible changes, resulting eventually in a reduction in kidney size, nephron population and renal function.

Allopurinol↗