Biomedical subjects
G A Rose
Publications and source records attributed to G A Rose.
Seasonal and geographic variations in urinary composition in England, Scotland and Wales.
Aliquots of 24 hour urine samples were collected from a series of normal doctors in various areas of England, Scotland and Wales. The total volume was recorded and aliquots sent in for analysis for sodium, potassium, urea, creatinine, calcium, phosphate, urate, magnesium and oxalate. Geographical variations in urinary composition were small except for a raised oxalate content in Scotland. Likewise, seasonal variations were small and not systematic with the notable exception of a summer rise in oxalate content in all areas.
Plasma level and renal clearance of oxalate in normal subjects and in patients with primary hyperoxaluria or chronic renal failure or both.
1. Plasma oxalate has been measured by a radioisotopic method applicable to all concentrations of plasma oxalate and renal function, and also by an enzymatic method which was only applicable to raised concentrations of plasma oxalate. 2. Where the two methods could be applied simultaneously, the agreement between them was good. 3. Plasma oxalate was 86% ultrafiltrable at concentrations of up to 44 micromol/l. 4. Oxalate clearance and the exchangeable oxalate pool were also measured. The ratio of oxalate clearance to creatinine clearance was greater than unity in most normal subjects and patients. 5. These methods were used in normal subjects and in patients with primary hyperoxaluria and/or chronic renal failure. A raised plasma oxalate concentration was found in both conditions. Chronic renal failure is probably the most common cause of a raised plasma oxalate.
Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child.
We report a third case of 2, 8-dihydroxyadenine stones in a child with a complete lack of the adenine salvage enzyme--adenine phosphoribosyltransferase (APRT). The propositus, a 20-month-old girl of consanguineous Arab parents, presented with multiple urinary tract infections and supposed 'uric acid' stones in the right renal pelvis and left ureter. Both parents and one brother were heterzygotes for the defect, in keeping with an autosomal recessive mode of inheritance. In contrast with the other purine salvage enzyme disorder of childhood with true uric acid stones (the Lesch-Nyhan syndrome), uric acid excretion was normal in all family members. As in our previous case, treatment with allopurinol, without alkali, has eliminated the urinary excretion of 2, 8-dihydroxyadenine: the stones were removed surgically. 2, 8-Dihydroxyadenine should be considered in any child thought to have uric acid stones and tests made to distinguish the two compounds.
Oxalate loading test: a screening test for steatorrhoea.
To investigate the possibility of measuring urinary oxalate output instead of faecal fat excretion as an outpatient screening test for steatorrhoea, we determined 24 hour urinary oxalate and five day faecal fat excretion before and during an oral load of sodium oxalate 600 mg daily (oxalate 4.44 mmol), in 32 patients with suspected malabsorption on a diet containing oxalate 30 mg (0.33 mmol), fat 50 g (180 mmol), and calcium 1 g (25 mmol). Nineteen patients proved to have steatorrhoea (mean faecal fat 62 mmol/24 h, range 19--186 mmol) of varying aetiologies. On the diet alone, urinary oxalate was raised in only nine of these patients (mean 0.25 mmol/24 h, range 0.08--0.59 mmol) (normal less than 0.20). By contrast, when the diet was supplemented with oral sodium oxalate, all 19 patients with steatorrhoea had hyperoxaluria (mean 0.91 mmol/24 h, range 0.46--1.44 mmol) (normal less than 0.44). There was a significant positive linear relationship between urinary oxalate and faecal fat when the 32 patients were on the high oxalate intake (r = 0.73, P less than 0.001), but not when they were on the low oxalate intake. Mean percentage absorption of orally administered oxalate was 5.8 +/- 0.99% (+/- 1 SD) in normal subjects and 14.7 +/- 6.0% (P less than 0.002) in patients with steatorrhoea. Measurement of urinary oxalate output during oral sodium oxalate loading appears to be a reliable and convenient screening test for steatorrhoea.
Changing social-class distribution of heart disease.
Analysis of mortality trends over 40 years in England and Wales showed that mortality from coronary heart disease had become progressively more common in working-class men and women than in those from the middle and upper classes. The change was most noticeable for men. Whereas in 1931 and 1951 heart disease was more common in men of social classes I and II, by 1961 it was more common in men of classes IV and V. This change in social-class distribution can only partly be explained by changes in diagnostic methods. The worsening mortality of classes IV and V correlated with relatively more smoking, a higher consumption of sugar, and a lower consumption of wholemeal bread in these classes. There was no correlation between change in heart disease and change in the social-class pattern of fat consumption.
A new urinary test for stone "activity".
Rapid evaporation of urine to osmolarity 1200 results in a high incidence of envelope Wedellite and calcium phosphate crystals. The Wedellite crystals closely resemble those seen in untreated urine samples of stone formers. The incidence of crystalluria produced by these tests is higher in the stone formers than in the normal subjects, reduced by thiazides and increased by cellulose phosphate; combined thiazide and cellulose phosphate therapy was most effective in reducing crystalluria. Simple calcium and oxalate concentration products were calculated and did not correlate well with incidence of calcium oxalate crystalluria. Although the product is important, inhibitors of crystal formation must be equally important. It is postulated, but not proven, that the evaporation tests may indicate normal subjects at risk to stone formation when exposed to chronic dehydration and whether a stone former is still metabolically active.
Adenine phosphoribosyltransferase deficiency presenting with supposed 'uric acid' stones: pitfalls of diagnosis.
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Seasonal variations in urinary crystals.
Individual urine samples from normal subjects and stone-formers with idiopathic hypercalciuria have been examined for crystals both qualitatively and quantitatively at 37 degrees C. The group as a whole showed a rise in incidence of urinary crystals in the summer months of June to August inclusive. This rise was seen most clearly in overnight urines, collected on rising in the morning, and the patients appeared to be at risk overnight during the summer. In the untreated patients the summer rise in incidence of phosphate crystals was quite dramatic but was only small in the cellulose phosphate treated group, who showed a rather constant and raised incidence of oxalate crystals right through the year. Seasonal crystal incidence has been compared with seasonal changes in urinary composition. The rise in crystal incidence during the summer was associated with increased creatinine concentration in the same urine samples and with increased oxalate concentration in 24-hour urine collections.
Aluminium hydroxide gels and intestinal phosphorus absorption.
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The causes and medical treatment of renal calculi.
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Biochemical aspects of urinary stones.
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Urinary oxalate in summer and winter in normal subjects and in stone-forming patients with idiopathic hypercalciuria, both untreated and treated with thiazide and/or cellulose phosphate.
Urinary oxalate excretion has been measured by a specific enzymatic method in normal subjects and stone formers with idiopathic hypercalciuria. In every group studied urinary oxalate was higher in the summer than in the winter. These differences were slight and not significant in normal subjects but were considerable and statistically significant in the stone formers both untreated and when treated with thiazide. Thiazides raise urinary oxalate only very slightly but cellulose phosphate leads to large rises in urinary oxalate both in the summer and the winter. The highest values of urinary oxalate were seen in the summer in patients treated with cellulose phosphate. The mean rise in this group was 70% above normal and this must be viewed with some anxiety.
Studies on the chemical nature of urinary chemiluminescence.
Studies on the nature of the chemicals responsible for urinary chemiluminescence have been carried out. Urinary chemiluminescence can be increased slightly by sulphatase, more by glucuronidase but most of all by boiling for 1 hour at pH 1. It is suggested that most of the chemicals responsible for urinary chemiluminescence are bound as non-chemiluminescent precursors to sulphate, glucuronic acid and in other ways. Both the chemiluminescent material and the inactive precursors are freely ultrafiltrable with molecular weights below 500. A survey of various chemicals has revealed considerable chemiluminescence in certain metabolites of naphthylamines and known to cause bladder cancer but little or no chemoluminescence in the tryptophane metabolites that have been thought to cause bladder cancer.
The thermogravimetric analysis of renal stones (in clinical practice).
Thermogravimetric (TG) analysis has been used as a routine technique for renal tract stone analysis. The results obtained in a consecutive series of 502 renal stones are described and evaluated. The technique is easy, rapid and gives quantitative information about stone composition. Results were compared with quantitative data obtained by standard chemical methods. Correlation coefficients for oxalate and urate were o-947 and 0-97 respectively. The comparison also showed that 63% of the stones could have been correctly analysed by TG analysis alone; in an additional 31%, TG analysis provided helpful information. TG analysis permits the identification of the proportions of mono- and dihydrate of oxalate present in calcium oxalate. It is confirmed that the centres of calcium oxalate calculi are richer in dihydrate than the exterior surfaces.
Crystalluria in normal subjects and in stone formers with and without thiazide and cellulose phosphate treatment.
Quantitative and qualitative studies have been made of the urinary crystals from a series of normal subjects and from stone formers with idiopathic hypercalciuria with and without treatment with thiazide diuretics and/or cellulose phosphate. The results obtained from mid-morning unprepared subjects seemed more helpful than those obtained following overnight collections or after a dry breakfast. Crystalluria was more common in stone formers than in normal subjects, but was seen in both groups. The most striking difference between these 2 groups was the almost complete absence of aggregation of oxalate crystals in the normal subjects. Cellulose phosphate greatly reduced phosphate crystals but resulted in a large increase in small oxalate crystals but without change in the incidence of aggregation of oxalate crystals. Thiazides also reduced occurrence of phosphate crystals but only gave a very small increase in oxalate crystals and also without change in aggregation of oxalate crystals.
The influence of calcium content of water, intake of vegetables and fruit and of other food factors upon the incidence of renal calculi.
An area of high incidence of renal calculi in Northern England and Scotland has been found to coincide with an area of soft water supply. However, in Wales and South West England the equation of soft water with high incidence of urolithiasis is lacking, and an enquiry into regional variations in diet reveals that a high intake of fruit and vegetables may protect against renal calculi.
A simplified and rapid enzymatic method for determination of urinary oxalate.
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