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Biomedical subjects

G A Rose

Publications and source records attributed to G A Rose.

At least 55 records · Page 3Linked to original sources

Procedure for the measurement of calcium oxalate and phosphate crystals in urine.

A method is described for the chemical measurement of calcium oxalate and phosphate crystal formation in urine. The crystals were centrifuged, washed and the oxalate measured by an immobilised oxalate oxidase technique and the phosphate by a standard centrifugal analyser procedure. The methods proved precise and recoveries were good. Calcium oxalate crystal formation after evaporation is time-dependent and this parameter must therefore be standardised. Values for normal urinary calcium oxalate crystal concentration after concentration are given.

Calcium Oxalate↗

Reduction of the urinary risk factors of urolithiasis with magnesium and tartrate mixture: a new treatment.

Magnesium and tartrate each reduce calcium oxalate crystal formation in urine. Since the effects are additive, a palatable mixture of magnesium and tartrate salts was devised and fed to 6 healthy volunteers. There were no side effects. There was a moderate fall in urinary calcium, moderate rises in urinary magnesium, tartrate and citrate, and no change in urinary oxalate. Hence there are good grounds for supposing that this mixture could be used to prevent urinary stone recurrence.

Calcium↗

Medical investigation and treatment of urinary stones: a search for new ideas.

The main threads of recent research into the cause and treatment of calcium oxalate/phosphate stones are reviewed. Little progress has been made in recent years, and two main reasons can be identified. First, there has been too much emphasis upon calcium and too little emphasis upon urinary oxalate as causative factors. Second, there has been too much emphasis upon the physical chemistry of simple solutions and too little emphasis upon the study of whole urine.

Calcium↗

Measurement of plasma oxalate in healthy subjects and in patients with chronic renal failure using immobilised oxalate oxidase.

A continuous flow assay using immobilised oxalate oxidase was used to measure the level of oxalate in plasma ultrafiltrate obtained from healthy subjects and from patients with chronic renal failure. The levels of oxalate in plasma from normal subjects ranged from 1.3-3.1 mumol/l (mean 2.03; SD = 0.52) with females showing a higher (p less than 0.05) level (mean 2.25 mumol/l) than males (mean 1.87 mumol/l). The mean oxalate/creatinine clearance ratio in fourteen healthy subjects was greater than unity, thus indicating a net tubular secretion of oxalate. At physiological pH, L-ascorbate was converted to oxalate in whole blood following venepuncture, in plasma and in plasma ultrafiltrate. Reduction of the spontaneous generation of oxalate in the samples prior to analysis was achieved by acidification and treatment with sodium nitrite. A linear correlation (r = 0.92; p less than 0.001) was found between plasma oxalate and plasma creatinine in patients with chronic renal failure.

Adult↗

Bladder stone disease in children in Afghanistan.

Of 132 children with bladder stones seen in 1 year, 94% were boys and 73% were aged between 1 and 5 years. Significant malnutrition and evidence of vitamin deficiency were absent. Wheat bread was the dietary staple, while the intake of milk and dairy products, eggs and meat was very low. Analysis of 29 stones showed them to consist mainly of calcium oxalate and uric acid, with small amounts of calcium phosphate and magnesium ammonium phosphate in some cases. The composition of the surface and central parts of the stones, examined in 20 cases, was usually different. The nucleus was formed almost entirely of calcium oxalate and uric acid in four and three cases respectively, whereas the surface layers were composed of other ingredients. In another case the nucleus was composed entirely of xanthine, which indicated a diagnosis of xanthinuria.

Afghanistan↗

Mild metabolic hyperoxaluria and its response to pyridoxine.

Three cases of mild metabolic hyperoxaluria (with glycollaturia) are described. They showed different types of response to pyridoxine. One responded to low dose, one responded at first to low dose but became resistant, and the third showed temporary response to high dose. One case also had primary hyperparathyroidism and one had medullary sponge kidneys and hypercalciuria. It is important to measure urinary oxalate (and glycollate) in all cases of calcium oxalate urolithiasis.

Adult↗

Idiopathic hypercalciuria. Urate and other ions in urine before and on various long term treatments.

24 h urine compositions of male stone formers with idiopathic hypercalciuria prior to treatment were compared with those of male general practitioners without urolithiasis. Urinary urate was slightly higher in the stone formers than in the normals but this was not statistically significant. Furthermore, when results were corrected for the higher creatinine excretions of the stone formers then the reverse was true and statistically significant. All subjects with urinary urate over 7.0 mmol/24 h were separately studied. In these groups the normals had higher urate and creatinine excretions than the stone formers but when results were corrected for creatinine the difference in the urate excretions disappeared. In long term follow up studies urinary calcium was lowered by diet and more so by diet supplemented with either Bendrofluazide or cellulose phosphate. Each drug raised urinary oxalate slightly and this was statistically significant, while both drugs together caused an even bigger rise in oxalate excretion. An unexpected finding was a rise in urinary urate with cellulose phosphate.

Bendroflumethiazide↗

Relationship of stone growth and urinary biochemistry in long-term follow-up of stone patients with idiopathic hypercalciuria.

One hundred and twenty-four male stone formers with idiopathic hypercalciuria were followed up for 4 to 27 years (mean 12.2). Twenty-eight received restricted calcium diet alone, 52 also received bendrofluazide, 11 cellulose phosphate, and 33 received mixtures of those drugs. Although urinary calcium values fell in all groups, the stone recurrence rate remained unacceptably high. Patients on cellulose phosphate fared worst and this drug seems unsatisfactory as a sole agent. Urinary calcium was highest in patients without stone recurrences, but in patients with stone activity a higher stone recurrence rate was associated with higher urinary calcium and lower urinary volume.

Bendroflumethiazide↗

Continuous-flow assay for urinary oxalate using immobilised oxalate oxidase.

A continuous-flow assay for measuring oxalate in urine is described. Covalently attached oxalate oxidase (EC 1.2.3.4) is used to oxidize the oxalate anion to carbon dioxide and hydrogen peroxide. The formed hydrogen peroxide is measured colorimetrically (A580) with an established reaction using horseradish peroxidase (EC 1.11.17), 3-methyl-2-benzothiazolinone hydrazone (MBTH) and 3-dimethylaminobenzoic acid (DMAB). Ascorbate interference is eliminated by treating the urine sample with sodium nitrite prior to assaying. The assay is accurate (mean recovery of added oxalate in spiked urine sample is 93 +/- 11%), sensitive (detection limit 1.0 mumol/L), reproducible (within-batch CV 3.5%; between-batch CV 5%) and relatively rapid (15 samples/h). This assay correlates well (R = 0.99) with another established enzymatic method (using oxalate decarboxylase).

Adolescent↗

Tamm-Horsfall mucoprotein promotes calcium phosphate crystal formation in whole urine: quantitative studies.

Fresh samples of human urine adjusted to pH 6.8 were rapidly evaporated at 37 degrees C to 1,250 mosmol/kg. The calcium phosphate precipitated was washed and the calcium measured by flame atomic absorption spectrophotometer. This procedure was found to be reasonably reproducible. When macromolecules were first removed by ultrafiltration the precipitated calcium was reduced by 76.9%. Addition of human Tamm-Horsfall mucoprotein (T-H) to the urine ultrafiltrates prior to evaporation largely but not completely restored the precipitated calcium. Clumping of crystals was studied quantitatively by passage through a nylon mesh. Mean retention on the mesh was strikingly reduced after ultrafiltration and increased by addition of T-H to the ultrafiltrates. These findings support the view that T-H triggers calcium phosphate crystal formation and clumping in whole urine.

Calcium Phosphates↗

Urinary chemiluminescence--an evaluation of its use in clinical practice.

It has been proposed that a substance, as yet unidentified, is excreted in the urine and acts as a chemical carcinogen. This substance during oxidative reactions will exhibit urinary chemiluminescence (UCL) and it is this release of energy in the form of light which activates the intracellular changes responsible for carcinogenesis. One hundred and seventy-seven people, 110 patients being followed up endoscopically for transitional cell carcinoma of the bladder (TCCB) and 67 controls, had their UCL measured. The UCL estimations confirmed previously reported trends where those with active disease had the highest UCL (84) and the controls had the lowest (55). These results did not reach statistical significance and the wide variations of the results do not allow UCL, as yet, to be of practical clinical use.

Adolescent↗

Prostaglandin synthetase inhibitors and their effect on urinary calcium excretion and other parameters in idiopathic hypercalciuria.

The treatment of idiopathic hypercalciuric stone formers with the prostaglandin synthetase inhibitors flurbiprofen and indomethacin has been studied in two phases. Ten patients were studied in a metabolic unit for 14 days that included a control period of 7 days on a controlled intake of dietary calcium, followed by treatment with flurbiprofen 50 mg tds. Three patients were studied along similar lines and were treated with indomethacin 25 mg tds. A significant reduction in urinary calcium excretion was noted during the 7-day control period during which dietary calcium intake was reduced to 700 mg daily. No further significant reduction in urinary calcium excretion was observed during the treatment with either flurbiprofen or indomethacin. Thirteen patients then continued to take flurbiprofen 50 mg tds for between 1 and 12 months. A small but not statistically significant reduction in urinary calcium excretion was noted by the third month of treatment, but this was not sustained. This study confirms the benefit of dietary restriction of calcium as the primary approach to the treatment of idiopathic hypercalciuria. Neither flurbiprofen nor indomethacin reduced urinary calcium excretion to significant levels. Their routine use for the treatment of idiopathic hypercalciuria cannot be recommended from the evidence of this study.

Adult↗

Effect of macromolecules and of sodium dodecyl sulphate upon precipitation of calcium oxalate and phosphate from whole urine.

Different proportions of mixtures of whole urine and its ultrafiltrate were evaporated to 1,250 mosm/kg to study crystal formation of calcium oxalate at pH 5.3 and calcium phosphate at pH 6.8. At both pH values there was a direct linear relationship between proportion of whole urine and crystal formation. When sodium dodecyl sulphate was added to whole urine before evaporation, calcium oxalate and calcium phosphate crystal formation were reduced to 64.3 and 53% respectively of the values of whole urine. This favours the proposition that crystal formation is promoted by polymeric uromucoid.

Calcium Oxalate↗

Effect of different fractions of macromolecules upon triggering of calcium oxalate and calcium phosphate crystal formation in whole urine.

Macromolecules were removed from whole urine samples by sequential ultrafiltration using molecular weight cut-offs of 300,000, 100,000 and 10,000 dalton. The whole urine samples and ultrafiltrates were evaporated to 1,250 mosm/kg at pH 5.3 and 6.8 to study calcium oxalate and calcium phosphate crystal formation, respectively. While all the ultrafiltrates removed Tamm-Horsfall proteins and most of the crystal formation, there was some 10% of the crystal-promoting powers in the macromolecules in the fraction between molecular weight 100,000 and 300,000 dalton. This demonstrates the existence of a second crystal-promoting substance in the macromolecules of whole urine.

Calcium Oxalate↗

Pyrophosphate does not influence calcium oxalate or calcium phosphate crystal formation in concentrated whole human urine.

1) Low pyrophosphate urine was generated by passage through a nylon coil bearing immobilised inorganic pyrophosphatase. High pyrophosphate urine was made by addition of inorganic pyrophosphate. 2) Urine samples of low, normal, and high pyrophosphate content were rapidly evaporated at 37 degrees C to 1,050 or 1,250 mosmol/L and the crystals formed studied by microscope, isotope and chemical methods. 3) Urinary pyrophosphate level had no significant effect upon calcium oxalate crystals formed in whole urine at pH 5.3 or 6.1, or calcium phosphate crystals formed at pH 6.8.

Calcium Oxalate↗

Raising urinary citrate lowers calcium oxalate and calcium phosphate crystal formation in whole urine.

Crystal formation in whole urine was studied by the technique of rapid evaporation to 1,250 mosmol/l with and without raising citrate concentration by 40-50%. The added citrate reduced calcium oxalate crystal formation at pH 5.3 by about 25% and reduced calcium phosphate crystal formation at pH 6.8 by some 42%. These results support the view that citrate is important in maintaining calcium in solution in whole urine, and that raising the urinary citrate could be effective treatment for calcium oxalate/phosphate urolithiasis.

Calcium Oxalate↗