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Biomedical subjects

W G Robertson

Publications and source records attributed to W G Robertson.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties.

Stones are a common complication of the storage of urine in intestinal reservoirs. Previous studies have identified predisposing physical characteristics in the reservoirs. Biochemical and dietary factors have been little investigated. Fifteen patients (6 males and 9 females) who had undergone various enterocystoplasty operations and who had subsequently formed either upper or lower urinary tract stones were investigated. The programme has been previously described and included stone, blood and urine analysis and dietary review. Comparison was made with 15 age- and sex-matched idiopathic stone formers with normal bladders. Stones were infective in origin in 86% of cases, and 14% were sterile. Metabolic screen showed that 80% of enterocystoplasty patients had risk factors for at least three different types of stone. All patients had raised pH (mean 6.93) and hypocitraturia. Five had a raised alkaline phosphatase. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria were found in 33% of patients. Five had a 24-h urine volume below 1.6 l/day. All patients had a high risk index (PSF) for phosphatic stones and 12 also for calcium oxalate stones. Compared to age-and sex-matched idiopathic stone-formers, the urine had a higher pH, sodium and protein excretion and a lower calcium and citrate excretion. Although the patients were already selected as stone-formers, the data show that metabolic and dietary factors are present. They may be as important in the aetiology of the stones, as the already recognised factors of infection and poor reservoir drainage. Investigation should include such factors, the presence of which may be taken into account in a prophylactic regime.

Adolescent↗
PubMed2006

Is prevention of stone recurrence financially worthwhile?

This review shows that the cost of relying solely on minimally-invasive urological procedures for removing stones when patients return with recurrent stones is considerable and is significantly greater that that incurred by screening already proven recurrent stone-formers to identify the risk factors that are causing their stones and then instituting prophylactic measures to prevent stone recurrence. In the UK, at 1998 prices (when the original survey was carried out) for every stone episode prevented, there is a potential saving of almost 2,000 pound to the local Health Authority concerned. In spite of this, many Health Authorities have taken the liberty to discontinue comprehensive stone screening within the past 20 years under the mistaken supposition that minimally-invasive techniques for removing stones have "solved the stone problem". At UCLH in London where such a comprehensive scheme has been in place for the past 8 years, savings of up to 250,000 pound per year can be made by identifying the particular lifestyle as well as the epidemiological, metabolic and nutritional risk factors involved in a given patient and then instituting appropriate measures to prevent further stones.

Calcium↗
PubMed2005

Uric acid and the kidney: urate transport, stone disease and progressive renal failure.

In this brief review and update, we try to cover recent developments in our understanding of uric acid transport by the kidney, the contribution of uric acid to renal stone disease, its potential role in progressive renal failure and, most recently, the novel and as yet unexplained link between the urinary glycoprotein Tamm-Horsfall protein (uromodulin) and hyperuricaemia and two inherited forms of renal disease with chronic renal failure.

Animals↗
PubMed2004

Kidney models of calcium oxalate stone formation.

This review compares and contrasts three mathematical models used to describe the flow of urine through the renal tubule and the composition of tubular fluid throughout the length of the nephron. From these data the relative supersaturation of tubular fluid with respect to calcium oxalate (CaOx) is calculated at various points along the tubule. This shows that glomerular filtrate is well undersaturated with respect to CaOx and is still undersaturated at the end of the proximal tubule. By the end of the descending limb of the loop of Henle, it is highly supersaturated as a result of water reabsorption and CaOx may nucleate in this region, particularly when the tubular concentration of oxalate is increased. Supersaturation falls slightly by the end of the ascending limb and becomes briefly undersaturated again in the short distal tubule. The final water adjustment in the collecting tubules causes the supersaturation to rise to a very high value by the end of the collecting duct and spontaneous CaOx crystalluria is likely to occur. The review also examines the probability of these crystals growing large enough to be trapped at some point in the nephron within the transit time of tubular fluid from glomerular capsule to ducts of Bellini. All three models agree that, under normal conditions, the likelihood of individual crystals growing large enough to be trapped within the measured urine transit time of 3-4 min is very small. It is concluded that either there has to be aggregation of crystals or some other factor that delays the passage of crystals for them to grow large enough to become lodged at some point in the nephron. Three new hydrodynamic factors are introduced that may lead to delay of crystal passage: (a) fluid drag close to the tubule walls; (b) the drag effect of tubular walls on particles travelling close to the tubule walls, and (c) the effect of gravity on particles travelling in upward-draining sections of tubule. When these factors are introduced into the mathematical model of urine flow and tubular concentration, it is shown that any crystals that form at the end of the descending limb of the loop of Henle and which travel close to the tubular walls may be delayed long enough to grow large enough to become trapped further down the nephron, particularly in upward-draining sections of the nephron. This possibility becomes increasingly significant as urinary oxalate concentration increases. Crystals that nucleate in the late collecting duct, however, are readily passed as small crystals and are at no risk of being trapped in the tubular system. These predictions are used to explain data on the effects of oxalate loading on CaOx crystalluria in stone formers and normal controls. The data are interpreted as showing that if the additional hydrodynamic factors are added to the mathematical model of nephron function, then the 'free-particle' model of calcium stone formation is still possible. This possibility will be further enhanced if crystal aggregation also takes place during the period when crystal passage is delayed by these factors.

Calcium Oxalate↗
PubMed2004

Role of dietary intake and intestinal absorption of oxalate in calcium stone formation.

The factors affecting the urinary excretion of oxalate are critical to the risk of forming calcium oxalate stones. This article reviews the role of dietary and intestinal oxalate in determining the level of oxalate excreted in urine. The amount of oxalate available for absorption throughout the intestine is highly dependent on the state of oxalate (a) in the food ingested, and (b) in the intestinal contents at each section of the intestinal tract since only the soluble form of oxalate can be absorbed. In this respect, the solubility of calcium oxalate (CaOx) under the prevailing conditions is paramount in determining the amount of oxalate available for absorption at any particular site. In turn, the main factors that control how much oxalate is in the soluble form are pH and the concentrations of calcium, magnesium and (indirectly) phosphate. Based on these parameters, a model of the intestine has been constructed which brings together the available evidence on the prevailing concentrations of these various factors at different sites in the intestine after allowing for dietary intake and the concentration of the above ions in intestinal secretions. The model then calculates the likely concentration of oxalate that is in the soluble form at each site and therefore available for passive absorption at that site. The model shows that oxalate is likely to be absorbed in the stomach, although it can be also absorbed in the small intestine, particularly at the distal end (after the absorption of calcium), and in the colon, since, on a normal intake of calcium and phosphate, most of the calcium in the large bowel would be anticipated to be precipitated as calcium phosphate under the prevailing alkaline conditions and high concentration of phosphate. The amount of free oxalate in the colon is also controlled by the presence or absence of Oxalobacter formigenes, an anaerobe that has an obligate requirement for oxalate as a source of energy and cellular carbon.

Animals↗
PubMed2003

Risk factor analysis and relative supersaturation as tools for identifying calcium oxalate stone-forming dogs.

Twenty-four hour urine samples were collected from 17 calcium oxalate (CaOx) stone-forming (SF) dogs and 17 normal (N), age-, breed- and sex-matched dogs. Urinary CaOx relative supersaturation (RSS) was calculated and found to be significantly higher in the SF group than the N group. RSS measurement is not readily applicable to veterinary practice; thus, alternatives were explored. Discriminant analysis failed to identify key factors differentiating most SF from N dogs. Urinary calcium, oxalate and uric acid, which differed between the SF and N animals, were combined into a measure of relative probability of CaOx stone formation (PSF) to establish whether this approach could be used to assess the risk of CaOx stone formation in dogs. Although there was good correlation between the techniques, RSS more clearly discriminated between SF and N dogs. These data suggest that neither PSF nor discriminant analysis is preferable to RSS for assessing the risk of CaOx stone formation in dogs.

Animals↗
PubMed2002

Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells.

Crystals of calcium oxalate monohydrate (COM) in the renal tubule form the basis of most kidney stones. Tubular dysfunction resulting from COM-cell interactions occurs by mechanism(s) that are incompletely understood. We examined the production of reactive oxygen intermediates (ROI) by proximal (LLC-PK1) and distal (MDCK) tubular epithelial cells after treatment with COM (25-250 microg/ml) to determine whether ROI, specifically superoxide (O(2)(*-)), production was activated, and whether it was sufficient to induce oxidative stress. Employing inhibitors of cytosolic and mitochondrial systems, the source of ROI production was investigated. In addition, intracellular glutathione (total and oxidized), energy status (ATP), and NADH were measured. COM treatment for 1-24 h increased O(2)(*-) production 3-6-fold as measured by both lucigenin chemiluminescence in permeabilized cells and dihydrorhodamine fluorescence in intact cells. Using selective inhibitors we found no evidence of cytosolic production. The use of mitochondrial probes, substrates, and inhibitors indicated that increased O(2)(*-) production originated from mitochondria. Treatment with COM decreased glutathione (total and redox state), indicating a sustained oxidative insult. An increase in NADH in COM-treated cells suggested this cofactor could be responsible for elevating O(2)(*-) generation. In conclusion, COM increased mitochondrial O(2)(*-) production by epithelial cells, with a subsequent depletion of antioxidant status. These changes may contribute to the reported cellular transformations during the development of renal calculi.

Adenosine Triphosphate↗
PubMed1998

Cutaneous advancement flap closure: alternative method for treatment of complicated anal fistulas.

PURPOSE: A retrospective chart review of 20 consecutive patients with 23 anal fistulas treated with cutaneous advancement flap closure was undertaken to ascertain the efficacy of this previously unreported technique. METHODS: The so-called "diamond" and "house" flaps are commonly used to treat anal stenosis, and mucosal advancement flaps are successfully used to close fistulas. The authors began, in 1994, to close selected fistulas with skin advancement flaps after suture closure of the internal opening and adequate drainage of the external opening. Fourteen patients (4 females; average age, 42 years; a total of 14 fistulas) without inflammatory bowel disease and 6 patients (3 females; average age, 35 years) with inflammatory bowel disease (5 with Crohn's disease; 1 with chronic ulcerative colitis; a total of 8 fistulas) were treated. Indications were low internal opening with transsphincteric fistula in both groups. Mucosal advancement was relatively contraindicated, either because of fear of ectropion or, in the inflammatory bowel disease patients, diseased mucosa. No one in the noninflammatory bowel disease group was diverted or kept without anything by mouth, and all were treated as outpatients or with overnight observation. The inflammatory bowel disease group was either diverted (1 patient) or kept on home total parenteral nutrition (5 patients) for three to six weeks. Cyclosporine, antibiotics, 5-acetylsalicylic acid, and other medications were used judiciously in the inflammatory bowel disease group. RESULTS: In the noninflammatory bowel disease group, complete healing of all wounds occurred in 11 patients in an average of 6.5 weeks (average follow-up, 18 months). Complications included donor site separation in two patients and minor incontinence of flatus in one patient. In the inflammatory bowel disease group, five fistulas healed, two failed, and one patient developed a new fistula during an average follow-up of 16 months. Deep venous thrombosis and catheter sepsis occurred in one patient in this group. There were no fatalities in either group. CONCLUSIONS: Although the numbers, especially in the inflammatory bowel disease group, are very small, the results are encouraging. This technique appears to have a place in the armamentarium of the surgeon repairing anal fistulas.

Adult↗
PubMed1995

Uric acid stone formation in a patient after kidney transplantation--metabolic and therapeutic considerations.

The formation of urinary calculi following renal transplantation is a rare event with a frequency of less than 1% (4). Although 133 cases were described up to 1988, only 5 of these had pure uric acid stones (3). We report a case in which an excessive purine-rich diet probably caused the stone formation. Three modalities of treatment were used, percutaneous nephrolithotripsy, shock wave lithotripsy (ESWL) and chemolysis.

Combined Modality Therapy↗
PubMed1994

Zeta potential distribution on calcium oxalate crystal and Tamm-Horsfall protein surface analyzed with Doppler electrophoretic light scattering.

The zeta potential distribution (ZPD) and particle size of Tamm-Horsfall protein (THP) and of calcium oxalate monohydrate (COM) crystals were measured using a Doppler Electrophoretic Light Scattering Analysis Instrument. The studies showed differences in the ZPD pattern between THP derived from normal subjects (nTHP) and from stone patients (pTHP). Both nTHP and pTHP can shift the zeta potential of calcium oxalate crystals towards more negative values; nTHP is significantly more potent than pTHP. The zeta potential of both nTHP and pTHP becomes less negative with decreasing pH and with increasing calcium concentration or ionic strength. Tamm-Horsfall protein particle size measurements showed that nTHP particles are significantly smaller than pTHP particles. The size of both nTHP and pTHP increases with increasing calcium concentration or increasing ionic strength and with decreasing pH. The differences between nTHP and pTHP in surface charge and particle size may be based on differences in molecular structure and may cause functional differences in their ability to inhibit calcium oxalate crystal aggregation.

Calcium Oxalate↗
PubMed1993

A review of new concepts in renal stone research.

Clinical and basic research in the field of urolithiasis has developed rapidly in recent years. Progress in extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PNL) has brought about a revolution in the surgical treatment of urolithiasis and research at the cellular and molecular level is now expanding. In spite of these advances, however, clinical treatment of urolithiasis remains far from satisfactory. Stone recurrence in many patients cannot be predicted and is beyond control of urologists mainly because the mechanisms of stone formation are still not fully understood. It is necessary to study the process of stone-formation more intensely at the cellular and molecular level, and to strengthen the links between basic and clinical research in the field. In this review, the processes involved in the formation of stones are compared with those involved in normal bio-mineralization and a model of urolithiasis is put forward based on modern systems science. Attention is concentrated on: (a) Directions of research based on physico-chemical theories of stone formation; (b) The role of renal tubular defects in urolithiasis; (c) The role of free radical reactions in stone formation; and (d) Macromolecular abnormalities and their correction.

Biological Transport, Active↗
PubMed1993

Importance of mild hyperoxaluria in the pathogenesis of urolithiasis--new evidence from studies in the Arabian peninsula.

The hypothesis that mild hyperoxaluria is more important than hypercalciuria in the pathogenesis of urolithiasis is re-examined in the light of new evidence. Small increments in urinary oxalate in the normal to high-normal range are much more critical than similar rises in urinary calcium for increasing the relative supersaturation of urine with respect to calcium oxalate, the oxalate/calcium ratio in urine, the total volume of calcium oxalate crystals excreted, the proportion of abnormally large crystals and aggregates of calcium oxalate and the severity of the disorder as defined by the recurrence rate of stone-formation. Data from the Arabian Peninsula, where the prevalence of calcium-containing stones is considerably higher than in the West, have shown that this occurs in spite of the almost complete absence of hypercalciuria. On the other hand, there is a strong association between stone-formation and the occurrence of mild hyperoxaluria. The life-time expectancy of stone-formation in men from various countries is strongly correlated with the average daily excretion of oxalate in the urine of the normal men in these countries. This relationship extends to include patients with enteric and hereditary hyperoxaluria. There is no such relationship, however, between the life-time expectancy of stones and urinary calcium excretion in the same populations. Studies on the regulation of urinary oxalate indicate that it is largely controlled by the quantity of "free" dietary oxalate available for absorption in the lower intestine. This can be calculated from the intakes of calcium and oxalate and the urinary excretion of calcium.

Calcium↗
PubMed1992

The effect of two new semi-synthetic glycosaminoglycans (G871, G872) on the zeta potential of calcium oxalate crystals and on growth and agglomeration.

The effects of two new semisynthetic glycosaminoglycans (GAGs), G871 and G872, on the crystal growth and agglomeration of calcium oxalate monohydrate (COM) were studied in artificial urine in vitro. A constant composition crystallization system and a seeded crystal growth system were used to measure the rate of crystal growth and degree of agglomeration. The zeta potential on the crystal surface was measured using a Coulter DELSA 440 doppler electrophoretic light scattering analyzer. The previously reported GAG analogue, sodium pentosan polysulphate (SPP or SP54), was studied as a reference inhibitor of crystallization using the same systems. All three substances had a concentration-dependent effect on the zeta potential and on the rate of crystal growth and agglomeration of COM in artificial urine. G872 had a significantly greater effect than either G871 or SPP on all the measured parameters. It is suggested that semisynthetic GAGs, such as those reported in this paper may be of use in the prevention of the recurrence of calcium oxalate stones.

Calcium Oxalate↗
PubMed1991

Evidence for a renal calcium leak in postmenopausal women.

We have measured calcium, albumin, globulin, bicarbonate, and anion gap in the plasma; and calcium, sodium, and creatinine in the urine, in 115 premenopausal and 140 postmenopausal normal women after an overnight fast, and calculated the calcium fractions in the plasma and the calcium/and sodium/creatinine ratios in the urine. The total ultrafiltrable calcium was significantly higher in the postmenopausal group, mainly due to their higher complexed calcium fraction, due in turn to their higher bicarbonate and anion gap concentrations. Urinary calcium was also significantly higher in the postmenopausal group even after correcting for sodium. After matching for total calcium and each of the calcium fractions in turn, the urinary calcium remained significantly higher in the post- than in the premenopausal sets even after correction for sodium. The implication is that the rise in urinary calcium at the menopause is due to reduced tubular reabsorption of calcium rather than to an increase in filtered load. We suggest that estrogens promote tubular reabsorption of calcium and that the rise in bone resorption at the menopause could be accounted for, at least in part, by the effect of estrogen deficiency on the kidney.

Acid-Base Equilibrium↗