Analgesic nephropathy in Canada: clinical syndrome, management, and outcome.
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Biomedical subjects
Publications and source records attributed to D R Wilson.
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In a computer presented examination the ratio of examinees to computer terminals is generally large. This implies that a computer presented test might span an entire day or several days with different groups of examinees taking the examination at different times. In such a situation, examinees who take the examination later on have the opportunity to gather information from their colleagues who took the examination earlier. This report investigates whether information exchanged between groups of examinees taking a computer presented patient management problem test improves the performance of late takers versus early takers. Results indicate that there is no exchange of information between groups of candidates.
The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2-3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.
Na-K-ATPase activity and renal function were compared in rats studied after relief of 24 h of unilateral or bilateral ureteral ligation (UUL or BUL), that is, in the absence or presence of post-obstructive diuresis. Na-K-ATPase activity in the outer medulla of the rat kidney after relief of UUL was not significantly altered immediately but was markedly reduced 1 and 3 days post-obstruction. The decrease in medullary Na-K-ATPase activity was not significantly different from that observed after relief of BUL. These results indicate that decreased Na-K-ATPase activity in the post-obstructive kidney is not responsible for post-obstructive diuresis and is not due to uremia, but is a local phenomenon which is probably secondary to altered renal structure or function. It may be due to decreased filtered sodium load or direct tubular damage, but other data suggests that the decreased medullary solute concentration gradient in the post-obstructive kidney (UUL or BUL) may influence Na-K-ATPase activity which, in turn, contributes to the decreased ability to conserve sodium and water.
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Twenty-eight patients with symptomatic Paget's disease of bone were treated with synthetic salmon calcitonin for periods of 9 to 42 months (average, 23 months). Serum alkaline phosphatase concentration and urinary hydroxyproline excretion, which had been elevated before treatment, were decreased by calcitonin treatment in all patients, and some decrease was sustained in 23 in association with variable decreases in pain, heat and stiffness of major joints. Improvement was sustained further in approximately half of these patients; the other half had partial return of symptoms. Calcium absorption was increased in 9 of 10 patients studied; the increase did not correlate with plasma concentrations of parathyroid hormone. The mean endogenous fecal calcium excretion was decreased significantly but there was no significant change in mean urinary calcium excretion. Mean accretion rate of calcium to bone, studied in 10 patients, was decreased by 35% after 6 months of treatment and by a further 23% 1 year later. There was no consistent effect of calcitonin treatment on bone mineral mass. No serious adverse effects of treatment such as allergic reactions were observed. Calcitonin appears to be effective initially in most patients with Paget's disease of bone, but with long-term treatment resistance may be acquired.
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The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.
Thirty-seven male dialysis patients, from three university hospital centers known to have adequate iron B12, and folate stores, were entered into a controlled trial to study the effects of nandrolone decanoate (200 mg i.m. weekly) on their anemia. An initial six-month stabilization period was followed by a randomized 12-month study, with crossover between treatment and control groups occurring at six months. Patients received parenteral iron therapy plus oral folate throughout the trial. All serious illnesses or major blood losses excluded the patients from analysis. The 24 patients with remnant kidneys showed an increase in hemoglobin and hematocrit of 24% by the end of six months of treatment (P less than 0.005), with a corresponding decrement during the six months of control, but the five anephric patients showed no statistically significant change compared to those patients whose kidneys were in place during the study. Complications of treatment were minimal, with injection site hematoma the only significant local effect and a rise in triglyceride the only significant systemic disturbance. Despite the improvement in anemia, the disadvantages, including the high cost of treatment, the apparent plateauing of benefits by five months, the minimal subjective improvement in life style, the risk of i.m. injection, plus the long term effects of increased lipids, should limit this therapy to patients with remnant kidneys who have severe symptomatic anemia or frequent transfusion requirements.
The aim of this study was to determine the effect of changes in osmolality on the reduced renal medullary Na-K-ATPase (EC 3.6.1.3) activity of the postobstructive kidney. The effect of osmolality on renal medullary Na-K-ATPase activity was studied by incubating tissue slices from sham-operated and bilaterally obstructed rats in media with osmolality varied before enzyme isolation using sodium chloride, choline chloride, or sucrose. Both sham-operated and bilaterally obstructed rat renal medullary enzyme showed a similar increase in activity with increased osmolality due to sodium chloride. Medullary Na-K-ATPase from the postobstructive kidney also showed increased activity with osmotic changes induced by choline chloride or sucrose. It is proposed that the decrease of Na-K-ATPase activity observed after bilateral ureteral obstruction is due, at least in part, to the loss of the solute concentration gradient in the kidney.
The effects of urinary-tract obstruction on renal function have been clarified using modern physiologic techniques in animal models. These effects are obviously dependent on the severity and duration of obstruction, together with the presence or absence of extrarenal factors, particularly uremia, as exemplified by the differences in renal function between bilateral and unilateral obstruction. The beneficial effects on the unilateral postobstructive kidney of volume expansion (5) and the importance of azotemia in determining POD (20, 21) have possible clinical applications. Further experimental work is required to understand the mechanism responsible for the altered renal hemodynamics and decreased GFR, as well as the abnormalities in medullary function resulting from obstruction. Improvement in the management of this common clinical problem may then be forthcoming.
Body drag, D, and the overall mechanical efficiency of swimming, e, were measured from the relationship between extra oxygen consumption and extra drag loads in 42 male and 22 female competitive swimmers using the front crawl at speeds ranging from 0.4 to 1.2 m/s. D increased from 3.4 (1.9) kg at 0.5 m/s to 8.2 (7.0) kg at 1.2 m/s, with D of women (in brackets) being significantly less (P less than 0.05) than that of men. Mechanical efficiency increased from 2.9% at 0.5 m/s to 7.4% at 1.2 m/s for men, the values for women being somewhat greater than those for men. The ratio, D/e was shown to be identical to the directly measured energy cost of swimming one unit distance, V02/d, and was independent of the velocity up to 1.2 m/s. It averaged 52 and 37 l/km for men and women respectively (P less than 0.05). When corrected for body surface area the values were 27 and 22 l/km-m2 for men and women, respectively (P less than 0.05). The underwater torque, T, a measure of the tendency of the feet to sink, was 1.44 kg-m for men and 0.70 kg-m for women (P less than 0.05). VO2/d increased linearly with T for both men and women of similar competitive experience. However, the proportionality constant delta VO2/d-delta T was significantly less for competitive than noncompetitive swimmers. The analysis of the relationship VO2/d vs. T provides a valuable approach to the understanding of the energetics of swimming.
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Detection of rejection by serial determinations of urine FDP using the latex agglutination slide test proved to be a reliable, simple and inexpensive method. In the absence of infection, clinical and biochemical acute rejection was preceded by a two-titer rise in excretion of urine FDP in 80% of 26 patients studied. It was not useful in predicting rejection in 44 stable long-term allograft recipients, although persistent elevation of urine FDP after anti-rejection therapy in these patients or those in the immediate post-transplant period implies ongoing rejection. Maintenance immunosuppression should be continued in these patients, but repeated high-dose steroid therapy should be limited because of their poor-term prognosis. Persistent increase in urine FDP may allow selection of those patients who would benefit from a trial of anticoagulant or antiplatelet therapy.
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The purpose of this study was to clarify the means by which lithium induced a disorder of urine acidification. Rats infused with hydrochloric acid (1 mEq/kg) developed acute metabolic acidosis (blood Ph = 7.32; bicarbonate, 18 mEq/liter) with a urine pH of approximately 5.85. The addition of lithium chloride (4 mEq/kg i.p) caused an increase in the urine pH (6.38) and a further decrease in blood bicarbonate (11.0 mEq/liter). During bicarbonate loading, lithium caused the urine PCO2 to fall significantly (urine minus blood PCO2 decreased from 25.3 +/-2.8 To 14.4 +/- 2.3 mm Hg) These changes were not seen following equimolar i.p. administration of sodium chloride. Similarly, lithium administration depressed bicarbonate reabsorption by 11.1% (from 30.6 to 27.2muEq/ml of GFR) during alkali infusion, while saline caused only a 5% decrease (30.0 to 28.5muEq/ml of GFR). The combination of an increase in urine PCO2 in alkaline urine indicates that lithium produced a defect in distal nephron hydrogen ion secretion. The fall in bicarbonate reabsorption following lithium administration oculd be due to a mild hydrogen ion secretory defect located in the proximal tubule or a severe defect in the distal nephron.