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Biomedical subjects

R A Sutton

Publications and source records attributed to R A Sutton.

At least 19 recordsLinked to original sources

Radiation dose reduction in diagnostic x-ray procedures.

The performance of K-edge filters to modify the x-ray spectrum is investigated experimentally in a variety of clinical situations involving bone/soft tissue imaging, with the aim of improving the optimization between image contrast and patient exposure. The results show that simultaneous improvement of contrast and reduction of exposure is possible for a wide range of patient sizes. For conditions of fixed contrast skin exposure reductions of better than 50% and integrated dose reductions of up to 30% have been achieved with tolerable increases in tube load. Rare earth salt solutions were used as an inexpensive alternative source of K-edge filtration, and their performance was found to be in no way inferior to that of expensive metal foils.

Filtration

Bartter's syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome.

Renal tubular function was examined in 5 adult patients aged 18-30 years with Bartter's syndrome associated with renal magnesium wasting and hypocalciuria. In the 3 patients studied during hypotonic saline diuresis, distal tubular fractional chloride reabsorption was lower than that reported in normal subjects. In response to a single intravenous dose of furosemide (40 mg), the increment in the excretion of sodium, chloride, and magnesium was equal to or greater than in normal subjects, while in 2 patients, in response to intravenous chlorothiazide (500 mg), the increment in sodium excretion was less than in normal subjects. Magnesium chloride infusion was undertaken in 2 patients in order to compare magnesium and calcium excretions at similar plasma magnesium levels in patients and in normal subjects. The patients exhibited magnesium wasting only at normal or low plasma magnesium levels, while calcium excretion was reduced in the patients at normal and elevated plasma magnesium levels. We conclude that in these patients the enhancement of renal magnesium reabsorption by hypomagnesemia is defective, and the hypomagnesemia is not the cause of the hypocalciuria. The tubule defect responsible for these abnormalities of magnesium and calcium excretion may be located beyond the side of action of furosemide, in the thiazide-sensitive segment of the distal convoluted tubule.

Absorption

The effect of calcitriol on atrial natriuretic factor release from isolated atrium.

Previous studies in our laboratory have shown that patients with idiopathic hypercalciuria (IH) have low basal atrial natriuretic factor (ANF) levels in the plasma. These depressed ANF levels are associated with a high plasma calcitriol levels. In this study, we have evaluated the effect of acute calcitriol administration on ANF release in the isolated atrium. There was a gradual reduction of ANF release as the dosage of calcitriol increased from 1 ng to 10 ng. Beyond 10 ng, additional suppression of ANF release by calcitriol was not observed. These results indicate that acute calcitriol administration causes a significant decrease in ANF release. To further determine whether this reduction in ANF release is due to changes in plasma calcium, additional studies were conducted to examine the effect of acute changes in perfusate calcium on ANF release by isolated atria. Acute elevation of perfusate calcium caused an increase in ANF release, whereas a reduction significantly decreased the secretory rate. These observations suggest that calcitriol affects ANF release by a mechanism not dependent on changes in plasma calcium.

Animals

Accelerator mass spectrometry: application to study of aluminum kinetics in the rat.

The advent of accelerator mass spectrometry (AMS) now permits the ultrasensitive detection of extremely long-lived isotopes, including 14C, 26Al, and 41Ca. Until now, tracer studies of aluminum kinetics have not been possible because aluminum has only two isotopes, with half-lives of 6.5 min (29Al) and 7 x 10(5) yr (26Al), neither of which is suitable for conventional studies. In a novel experiment we have employed AMS to study aluminum kinetics in a normal rat and a 5/6-nephrectomized rat over a 3-wk period of intravenous injection of a tracer dose of 26Al. Kinetics were similar in the two animals; approximately 75% of intravenously injected tracer 26Al was excreted in the urine in the first 24 h as was approximately 80% after 3 wk. Renal clearance of 26Al was approximately 0.75 ml.min-1.kg body wt-1 in both rats. The results clearly demonstrate the potential of this technique for isotope tracer studies in animals as well as in humans.

Aluminum

Effect of chronic cisplatin administration on phosphate and glucose transport by the renal brush border membrane.

Cisplatin (CIS-diamine dichloroplatinum) is a highly nephrotoxic antineoplastic agent which may cause acute renal failure and renal tubular dysfunction. In the present study we have examined the effect of chronic cisplatin administration on sodium-dependent 32P-phosphate and 3H glucose transport by the renal brush border membrane vesicles (BBMV). Our results indicate that both transport mechanisms were significantly reduced at the BBMV following cisplatin therapy due to an increased Km (0.13 +/- 0.09 vs. 0.34 +/- 0.09 mM; p = less than 0.01) without significant change in Vmax (56 +/- 18 vs. 44 +/- 17 pM/mg/s). The results of these studies indicate that cisplatin causes a diffuse renal injury in the proximal segment of the nephron altering both transport mechanisms. Possible mechanisms of cisplatin nephrotoxicity are discussed.

Animals

Causes and prevention of calcium-containing renal calculi.

Kidney stones are common, and recurrences are the rule. At least 90% of patients with kidney stones probably have some identifiable metabolic risk factor. Effective prophylaxis is often available, but with the relatively low rate of recurrence, compliance with the treatment may be a problem. Studies are required to determine the cost-effectiveness of metabolic investigation and prophylactic therapy versus the possible need for repeated treatment by means of extracorporeal lithotripsy, especially in patients having a first calcium oxalate stone.

Calcium

Chronic hypomagnesemia caused by cisplatin: effect of calcitriol.

A group of six patients with hypomagnesemia (serum magnesium less than or equal to 0.5 mmol/L), previously given treatment with cisplatin for ovarian or testicular cancer, received calcitriol at a dose of 0.5 to 1.0 microgram/day for a period of 4 weeks to determine whether treatment with this vitamin D metabolite could improve their hypomagnesemia. In response to treatment, the serum magnesium concentration fell progressively in association with a rise in serum and urinary calcium levels and a decrease in parathyroid hormone level. In a single previous report, active vitamin D metabolites markedly improved renal magnesium wasting. However, in the present study, increases in serum and urinary calcium levels and suppression of parathyroid hormone, factors known to decrease magnesium reabsorption, presumably overwhelmed any direct effect calcitriol may have had to enhance magnesium reabsorption, so that the net effect was a marked exacerbation of the renal magnesium wasting.

Calcitriol

The effect of verapamil and thiazide in the prevention of renal stone formation.

The effect of the calcium antagonist verapamil, and of thiazide, a well accepted treatment in the prevention of calcium oxalate renal stones, were examined in an experimental renal stone model. Calcium oxalate stones were induced by the synthetic metabolite of vitamin D3, the alpha-OH-vitamin D3 plus ethylene glycol fed rats. A significant decrease in urinary calcium and oxalate was observed following verapamil treatment. Thiazide significantly decreased urinary calcium, but unlike verapamil, did not decrease urinary oxalate. However, no differences in the radiological findings or in the calcium or magnesium content of the kidneys were observed. Although several animal models have been described for the study of calcium oxalate stones, none has yet been proven useful for the evaluation of stone therapy.

Animals

Atrial natriuretic factor levels in renal stone patients with idiopathic hypercalciuria and in healthy controls: the effect of an oral calcium load.

Ionized calcium is a stimulator for the release of several peptide hormones. Atrial natriuretic factor (ANF) is a peptide hormone released from atrial tissue in response to atrial distension or volume expansion. In the present study, we have examined the effect of an oral calcium load in healthy controls and renal stone patients with idiopathic hypercalciuria. Our results demonstrated that ANF release increased in both groups in response to a calcium load. However, idiopathic hypercalciuric patients presented lower basal ANF levels in the presence of high calcitriol levels. The role of calcitriol on ANF release remains to be evaluated.

Adult

Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males.

Twenty-two adult males participated in a 5 week progressive strength training program. One half the subjects received the amino acids L-arginine and L-ornithine and the other half, a placebo. The study used a double blind protocol so that subjects as well as investigators had no knowledge of which substances were being administered. Dosages amounted to 2 grams or 1 gram each of L-arginine and L-ornithine, and 600 mg of calcium and 1 gram of Vitamin C as placebos. These supplements were taken orally for a total of 25 administrations. Following the short term strength program using progressively high intensities, tests were taken for total strength (TS), lean body mass (LBM) and urinary hydroxyproline (UH). The results from ANOVA showed that subjects who were taking the arginine-ornithine combination scored significantly higher in TS and LBM (p less than .05), and significantly lower in UH (p less than .05), than subjects on placebos. It was concluded that arginine and ornithine taken in prescribed doses can, in conjunction with a high intensity strength training program, increase TS and LBM in a relatively short period of time. Arginine and ornithine also aid in recovery from chronic stress by quelling tissue breakdown as evidenced by lower UH levels.

Adult

Prognostic factors in diffuse proliferative lupus glomerulonephritis.

A number of clinical laboratory and biopsy-derived parameters were assessed for their prognostic significance in the short (24 months), intermediate (60 months) and long terms in 45 patients (43 female, 2 male) with diffuse proliferative lupus glomerulonephritis (DPGN). The factors evaluated were serum creatinine (SCr) and urinary protein at time of biopsy, initial dose of prednisone and immunosuppressive after biopsy, activity index (AI), chronicity index (CI), their individual components, extent of extraglomerular (tubulo-interstitial) immune deposits (EGD) and mean number of intraglomerular monocytes per glomerulus (NSE index). Using proportional hazards analysis to evaluate the parameters, SCr (P = 0.003), AI (P = 0.005) and NSE index (P = 0.038) were shown to be significant predictors of outcome when all variables except the components of AI and CI were considered. When AI and CI were omitted but their components included, SCr (P = 0.0005), NSE index (P = 0.024), extent of karyorrhexis (P = 0.035) and glomerulosclerosis (P = 0.033) were then demonstrated to be significant prognostic factors of DPGN. The results suggest that intraglomerular monocyte infiltration has a protective effect and confirm that AI index is a relatively powerful predictor of outcome. Histologic and nonhistologic biopsy factors contribute significant additional prognostic information to that provided by SCr.

Adult

Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man.

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P less than 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P less than 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.

Administration, Oral

Effect of cisplatin on proximal straight tubule transport of divalent cations in the rabbit.

Clearance and in vitro microperfusion studies were performed in rabbits to determine the effect of cisplatin on proximal straight tubule transport of calcium and magnesium. Rabbits were injected with cisplatin (2.5 mg/kg i.p. once weekly) for 3 weeks, whereas control rabbits received normal saline solution which served as a diluent for cisplatin. In 5 rabbits, 24-hour clearance studies were performed with the aid of a metabolic cage. Following cisplatin treatment, fractional excretion of magnesium rose significantly (73.3 +/- 11.5 vs. 111.4 +/- 17.5%). Glomerular filtration rate fell with cisplatin treatment (4.05 +/- 0.76 vs. 2.81 +/- 28 ml/min). There was no difference in fractional excretion of calcium (26.3 +/- 9.5 vs. 22.7 +/- 3.2%). The cortical and juxtamedullary proximal straight tubules were perfused in vitro. Net volume absorption was the same in the control and cisplatin-treated rabbits. However, there was a significant reduction in JCa (cortical 0.57 +/- 0.10 vs. -0.10 +/- 0.12 pmol/min/mm; juxtamedullary 0.96 +/- 0.17 vs. 0.31 +/- 0.37 pmol/min/mm) and JMg (cortical 0.43 +/- 0.08 vs. -0.15 +/- 0.07 pmol/min/mm; juxtamedullary 0.40 +/- 0.27 vs. -0.30 +/- 0.28 pmol/min/mm). In contrast to chronic administration, acute addition of cisplatin into the bath had no effect on JCa and JMg in the cortical and juxtamedullary proximal straight tubules. These data indicate that chronic but not acute cisplatin treatment depresses the transport of calcium and magnesium in the cortical and juxtamedullary nephrons of the proximal straight tubule of the rabbit.

Animals

Sodium thiosulfate prevents cisplatin-induced hypomagnesemia.

Clearance studies were performed in four groups of male Wistar rats to assess the protective effect of sodium thiosulfate on cisplatin-induced hypomagnesemia. In group I, sodium thiosulfate (400 mg/kg) was injected intraperitoneally once weekly for 3 consecutive weeks. In group II, only cisplatin (2.5 mg/kg) was administered. In group III, both cisplatin (2.5 mg/kg) and sodium thiosulfate (400 mg/kg) were injected via the intraperitoneal route. When both drugs were administered together, they were injected into different parts of the peritoneal cavity. In group IV cisplatin was administered intraperitoneally and sodium thiosulfate intravenously. Sodium thiosulfate prevented a rise in plasma creatinine. The overall glomerular filtration rates of groups III and IV were the same as in group I. Hypomagnesemia was noted in group II, whereas in groups I, III, and IV the plasma magnesium level remained unchanged. The fractional excretion of magnesium was also higher in group II than in groups I, III, and IV. These differences persisted for the duration of the study. These results suggest that concurrent injections of sodium thiosulfate intraperitoneally or intravenously prevented the hypomagnesemic and the nephrotoxic effects of cisplatin and can be of clinical significance.

Animals

Is lymphocyte magnesium concentration a reflection of intracellular magnesium concentration?

Diuretics are known to cause magnesium depletion, and the aim of the present experiment is to establish the relationship between lymphocyte magnesium concentration and intracellular magnesium concentration during chronic diuretic therapy. Studies were conducted in male Wistar rats that were subjected to daily administration of furosemide (2 mg/kg/day IP) for 19 weeks. Clearance measurements were performed during the baseline week and subsequently during the third, seventh, eleventh, fifteenth, and nineteenth weeks in both furosemide-treated (n = 32) and control rats (n = 32). Lymphocyte magnesium concentration was also measured as a determinant of intracellular magnesium concentration. Magnesium concentrations in kidney, bone, skeletal, and heart muscle tissues were also quantitated at week 11 and at the end of the experiment. After 11 weeks of furosemide administration, furosemide-treated rats developed a lower plasma magnesium concentration (0.95 +/- 0.01 mmol/L) compared with that in the control group (0.99 +/- 0.01 mmol/L). This difference persisted from week 11 to week 19 of the experiment. Fractional excretion of magnesium was modestly elevated in the furosemide-treated group. After 7 weeks of furosemide treatment, lymphocyte magnesium concentration decreased significantly in furosemide-treated rats when compared with that in the control group (1.56 +/- 0.09 micrograms/mg protein vs 1.33 +/- 0.07 micrograms/mg protein). During week 19, the lymphocyte magnesium concentration had fallen to 0.75 +/- 0.04 micrograms/mg protein as compared with 1.45 +/- 0.08 micrograms/mg protein in the control rats. There is a significant correlation between lymphocyte magnesium concentration and plasma magnesium concentration. Our present results indicate that during long-term diuretic therapy, lymphocyte magnesium concentration mirrors the reduction in plasma magnesium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals