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Biomedical subjects

W G Robertson

Publications and source records attributed to W G Robertson.

At least 37 records · Page 2Linked to original sources

Relationship between plasma calcium fractions, other bone-related variables, and serum follicle-stimulating hormone levels in premenopausal, perimenopausal, and postmenopausal women.

The study comprises 186 untreated normal premenopausal, perimenopausal, and postmenopausal women in whom we measured serum follicle-stimulating hormone and a number of bone-related plasma and urinary variables. The calcium fractions in the plasma were calculated from the total calcium, albumin, globulin, anion gap, and bicarbonate concentrations. With a level of follicle-stimulating hormone within the reference range (up to 20 U/L) to define the premenopausal state, we confirmed previously reported menopausal rises in plasma calcium, phosphate, alkaline phosphatase, and bicarbonate, and in urinary calcium and hydroxyproline. However, inspection of the data, and t testing at different follicle-stimulating hormone criteria showed that these changes in bone-related variables did not generally occur until the level of follicle-stimulating hormone exceeded approximately 50 U/L. The plasma alkaline phosphatase level rose earlier than the other variables and was significantly elevated in subjects with follicle-stimulating hormone values above 30 U/L. The rise in plasma calcium was mainly a result of a rise in the ultrafiltrable fraction, which in turn was accounted for by rises in the ionized and complexed fractions, of which the complexed fraction was the most significant and proportionately the largest. The rise in the complexed fraction was accounted for by the increase in plasma bicarbonate.

Adult↗

The kidney-ureter stone sexual paradox: a possible explanation.

The greater frequency of renal stones seen on excretory urograms in women, compared with the greater frequency of ureteral stones in men has been termed a sexual paradox. We assessed stone composition and weight, and sex as possible explanatory factors. A total of 4,014 renal and ureteral calculi was analyzed. For the 3,119 calculi in which only calcium oxalate and/or phosphate was detected by infrared and wet chemical analysis, there was a strong relationship between the oxalate-to-phosphate weight ratio and sex (p less than 0.0001). The mean weight for phosphate stones was 330 mg. but for oxalate stones it was 107 mg. Male-to-female ratios were 2.7, 2.2 and 1.8 for stone weight groups of 20 or less, 21 to 100 and more than 100 mg. The male-to-female ratio was 0.87 for the 171 stones containing magnesium ammonium phosphate; the average weight was 508 mg. for men and 1,560 mg. for women. The tendency for phosphate stones to be heavier and relatively more common in women compared to predominantly oxalate stones may partly account for the sexual paradox.

Calcium Oxalate↗

Long-term results of open and closed sphincterotomy for anal fissure.

Three hundred fifty patients who underwent open or closed lateral internal anal sphincterotomy for acute or chronic anal fissure between January 1981 and June 1985 were reviewed. Minimum follow-up was 14 months (mean, 37 months). No patient underwent an additional procedure at the time of sphincterotomy. Twenty-one failed to heal or developed a recurrence in the interval (6 percent). Five of these individuals were found subsequently to have Crohn's disease. Excluding these patients, the incidence of nonhealing was 4.6 percent. Eight patients (2.3 percent) developed postoperative infections requiring drainage, one half of which were associated with fistulas. Sixty patients (17 percent) complained of incontinence for flatus or feces. For two thirds, this was transient. There was no statistically significant difference in rate of healing or morbidity when comparing the open with the closed method.

Abscess↗

Observations on in vitro and in vivo calcium oxalate crystalluria in primary calcium stone formers and normal subjects.

Fresh urine samples from stone formers (SF) and normal subjects (N) were rapidly evaporated at 37 degrees C to 1200 mosmol/kgH2O and the particle size distribution of the formed particles studied by Coulter Counter and chemical methods. No significant difference was found between the two groups in their relative supersaturation of calcium oxalate at the point of spontaneous precipitation. SF and N urines seem to have an equal driving force for particle precipitation. The major difference between them was in the volume of particles with diameters greater than 11.4 microns. SF urines showed an approximately 5-fold increase in total particle volume (after evaporation) and N urines had about a 2-fold increase over the volume in the freshly voided urine samples. The total volume of large particles (greater than 11.4 micron) increased more than 7-fold in SF urine while only a 2-fold increase was detected in the normal urines after evaporation.

Adult↗

Diet and calcium stones.

Urolithiasis is a worldwide problem which appears to be aggravated by the high-dairy-produce, highly energy-rich and low-fibre diets consumed in most industrialised countries. Together these factors lead to urine with a high risk of calcium oxalate and uric acid crystalluria. Epidemiological evidence points, in particular, to a high-meat protein intake as being the dominant factor within this combination. Such a diet not only increases the risk of stones in the population as a whole through its general effect on the urinary risk factors for stones but also may select out certain individuals who are metabolically more sensitive to this dietary stimulus and who show an exaggerated biochemical response to it. On the basis of epidemiological and biochemical studies, a move towards a more vegetarian, less energy-rich diet would be predicted to reduce the risk of stone formation in the population.

Calcium Oxalate↗

Are we really operating on diverticulitis?

The results of elective surgery for diverticulitis in 100 consecutive patients were reviewed. Follow-up was possible in 82 individuals. Seventy-seven (94 percent) were improved. There was no inflammatory change apparent on histologic examination of the resected specimens in 24 percent of patients. These individuals were less likely to have favorable results. There are a number of preoperative factors which may predict the likelihood of a successful surgical outcome.

Adult↗

Modifiers of calcium oxalate crystallization found in urine. II. Studies on their mode of action in an artificial urine.

The relative potencies of various modifiers of the crystallization of calcium oxalate (CaOx) were determined under "whole urine equivalent" conditions using a batch crystallizer. The system was used to measure changes in the degree of agglomeration of CaOx crystals produced spontaneously at a level of supersaturation within the range found in the urines of recurrent CaOx stone-formers. The modifiers tested included RNA, heparin, chondroitin-4-sulphate, pyrophosphate (at pH 5, 6 and 7), Tamm-Horsfall mucoprotein and a greater than 10,000 dalton fraction of macromolecules obtained from pooled normal urine by dialysis. The effects of these urinary constituents were also measured on the zeta potential produced at the surface of CaOx crystals. In the case of pyrophosphate, there was a clear correlation between the degree of inhibition of agglomeration and the zeta potential observed on the crystal surface indicating that, for this ion, repulsive electrostatic forces dominate the tendency for CaOx crystals to agglomerate. For the other modifiers tested, the tendency to agglomerate appeared to be dependent on the balance between the positive viscous binding ("sticky") forces and the negative electrostatic forces produced by these macromolecules on the CaOx crystal surface.

Calcium Oxalate↗

Calcium oxalate precipitation in a flow system: an attempt to simulate the early stages of stone formation in the renal tubules.

This paper describes in vitro studies on the generation of supersaturation and the early stages of calcium oxalate (CaOx) precipitation using a reverse osmosis hollow-fiber membrane to simulate the precipitation processes occurring in the distal convoluted tubule and the collecting system of the kidney. The article reports on the preliminary results of using a plug-flow configuration to simulate the reabsorption of water and generation of supersaturation during the approximately three-minute biological residence time of the urine in the upper part of the urinary tract. The results suggest that microcrystallization of CaOx . 2H2O in the renal tubules may play a role in stone formation processes. A survey of the effect of various inhibitors of CaOx precipitation indicates that pyrophosphate, magnesium, glutamic acid, heparin and citric acid reduce the tendency of CaOx crystals formed to agglomerate in this system.

Calcium Oxalate↗

Modifiers of calcium oxalate crystallization found in urine. III. Studies on the role of Tamm-Horsfall mucoprotein and of ionic strength.

The effect was measured of incubating crystals of calcium oxalate monohydrate (COM) with 10 per cent normal urine and 10 per cent artificial urine on the surface zeta potential (ZP) produced on the crystals by various inhibitors of the agglomeration of COM. These studies showed that natural urine contains some constituent, not present in the artificial urine, which interferes with the ability of the inhibitors tested to produce a highly negative ZP on the crystal surface. A second series of studies showed that there are two factors in urine which modify the effect of the polyanionic inhibitors, Tamm-Horsfall mucoprotein (THM) and high ionic strength. At concentrations greater than 10(-8) mol./l., THM interfered with the binding of other polyanions to the surface of COM and reduced the maximum negativity of the ZP achievable on the crystals. This effect was very marked over the urinary concentration range (5 X 10(-8) to 6 X 10(-7) mol./l.; four to 48 mg./l.). By increasing the ionic strength of the incubation medium over the urinary range, the electrical double layer around the COM crystals was compressed and the interference caused by THM accentuated. Within most of the urinary range of ionic strength, THM interfered with the binding of other polyanions at concentrations greater than 10(-9) mol./l. In highly concentrated urine, at the top end of the urinary range of ionic strength, THM polymerized readily and to such an extent that it overwhelmed the inhibitors in urine and strongly promoted the agglomeration of COM crystals. The polymerization point of THM was found to be inversely related to the ionic strength of the solution in which it was dissolved.

Calcium Oxalate↗

Modifiers of calcium oxalate crystallization found in urine. I. Studies with a continuous crystallizer using an artificial urine.

Various modifiers of the rate of crystallization of calcium oxalate (CaOx) known to be present in urine were studied in a continuous crystallizer system under conditions approximating those in whole urine. Of the small ions examined, magnesium and citrate were only weak inhibitors of the crystal growth rate and degree of agglomeration of CaOx within the urinary range of concentration of these ions. At and beyond the upper limit of the normal, however, both ions became much more active mainly through their ability to complex oxalate and calcium ions respectively. Pyrophosphate showed similar characteristics although its ability to act as an inhibitor at high concentrations was not due to complexation of calcium ions but to adsorption onto the crystal surface of the freshly generated CaOx crystals. The polyanionic inhibitors, chondroitin-4-sulphate, heparin and ribonucleic acid (RNA), also acted as adsorption inhibitors of growth and agglomeration. Of all the inhibitors tested RNA was the most active within the concentration range found in normal urine. Under the conditions of ionic strength employed, it was not possible to measure the effect of Tamm-Horsfall mucoprotein satisfactorily since it polymerized to form particles sufficiently large to interfere with the true crystal counts of CaOx in the test system.

Calcium Oxalate↗

Pathophysiology of stone formation.

Urinary stone disease is a multifactorial disorder arising essentially from an abnormal combination of a number of urinary risk factors. In the case of calcium urolithiasis the main risk factors are a low urine volume, a high urinary pH, increased excretions of calcium, oxalate and uric acid and a low net level of inhibitory activity against the crystallization of calcium salts. The last mentioned, in turn, is dependent on the balance between the macromolecular inhibitors, including glycosaminoglycans, ribonucleic acid and acidic glycoproteins, and the promoters of crystallization such as Tamm-Horsfall mucoprotein. There is currently some debate as to whether or not an immunological factor might also be involved in the renal tubules, which results in crystals becoming bound to the renal epithelium.

Humans↗

Sodium pentosan polysulphate as a polyanionic inhibitor of calcium oxalate crystallization in vitro and in vivo.

Studies in vitro showed that sodium pentosan polysulphate (SPP) is an active inhibitor of calcium oxalate crystal growth and agglomeration and that it acts by increasing the negative zeta potential on the surface of calcium oxalate crystals. Oral administration to human subjects resulted in an increase in the negative zeta potential, which is consistent with an increase in the polyanionic inhibitory activity of urine. SPP may offer a novel approach to the medical management of recurrent calcium oxalate stone disease.

Adult↗

When should patients with symptomatic urinary stone disease be evaluated metabolically?

To determine the optimal time at which to assess the urinary risk factors for calcium stone formation, we followed 11 patients after an episode of acute renal colic with sequential 24-hour urine collections, first in the hospital and then at regular intervals after they were discharged from the hospital. The changes that occurred in the urinary risk factors were compared to those of a control group in which samples were collected during the same interval. The in-hospital 24-hour urine volumes were high but decreased gradually to approach the relatively constant volume of the control group by 3 months. The opposite trend occurred with respect to the 24-hour urinary excretion of calcium. There were no significant changes in the 24-hour urinary pH or excretions of oxalate, uric acid and alcian blue precipitable polyanions. The over-all effect was to cause a progressive increase in the probability of stones forming in the patients. The accurate assessment of the urinary risk factors of calcium stone disease requires at least a 3-month delay following acute renal colic. This delay usually will provide sufficient time for the stone to pass and for the patient to return to the normal dietary and fluid intake.

Adult↗

Inhibition of calcium oxalate crystallisation by pentosan polysulphate in control subjects and stone formers.

In vitro studies showed that sodium pentosan polysulphate (SPP) is an active inhibitor of calcium oxalate (CaOx) crystal growth and agglomeration and that it acts by increasing the negative zeta potential on the surface of CaOx crystals. Oral administration of SPP to control subjects, recurrent stone formers and patients with primary hyperoxaluria resulted in an overall increase of 8% (P less than 0.01) in the polyanionic inhibition of CaOx crystallisation in urine as measured by the zeta potential. SPP could provide a novel approach to the medical prevention of recurrent CaOx stone disease.

Adult↗