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Biomedical subjects

R L Prince

Publications and source records attributed to R L Prince.

At least 91 records · Page 5Linked to original sources
PubMed1990

Rapid nongenomic inhibition of renal 25-hydroxyvitamin D3 1-hydroxylase by 1,25-dihydroxyvitamin D3.

The physiological role of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in inhibition of its own formation remains obscure. This study utilizes a kidney slice system to study the effect of physiological concentrations of 1,25(OH)2D3 on 25-hydroxyvitamin D3 1-hydroxylase (1-hydroxylase) formation in vitamin D-replete rats fed a normal-phosphate (NP) or low-phosphate (LP) diet. In vitro, 1-hydroxylase activity was assessed by measuring 1,25(OH)2D3 accumulation at 30 or 60 min after addition of 25-hydroxyvitamin D3 substrate. Degradation of 1,25(OH)2D3 was also assessed over 60 min. Rats fed the LP diet had a threefold increase in 1-hydroxylase activity but the same rate of degradation of 1,25(OH)2D3 as those fed the NP diet. The addition of 50 pM 1,25(OH)2D3 caused a proportional inhibition of 1-hydroxylase in NP and LP rats when added before or 10 min after addition of substrate but not at later time points; 150 pM 1,25(OH)2D3 completely inhibited 1-hydroxylase in the NP but not the LP rats. This inhibitory effect was not reversed by actinomycin D or cycloheximide. These results indicate that physiological concentrations of 1,25(OH)2D3 directly and rapidly modulate 1-hydroxylase activity via a nongenomic mechanism in both LP and NP diet rats.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1990

The effects of the menopause on calcitriol and parathyroid hormone: responses to a low dietary calcium stress test.

Calcium, calcitriol and PTH levels were studied in 11 premenopausal women, aged 41 +/- 3 yr (mean +/- SD), and 11 postmenopausal women, aged 42 +/- 3 yr, at baseline and in 9 women from each group during a 4-day low calcium diet. Serum dialyzable calcium and urinary hydroxyproline excretion were higher in the postmenopausal women at baseline and throughout the low calcium diet. Baseline calcitriol levels were significantly lower in the postmenopausal women, but these were associated with lower vitamin D-binding protein levels; the calculated free calcitriol index was not different between the two groups. After the low calcium diet calcitriol levels rose in both groups to similar levels. PTH levels were not different in the two groups at baseline and rose to the same level on the low calcium diet. These data indicate that estrogen deficiency at the menopause is not associated with deficient calcitriol or PTH reserve, although basal calcitriol levels may be reduced secondarily due to lower vitamin D-binding protein levels or relative hypercalcaemia.

Adult↗
PubMed1990

Effects of transdermal estrogen replacement on parathyroid hormone secretion.

The effect of transdermal 17 beta-estradiol replacement on ionized calcium and PTH levels was examined in 15 postmenopausal women. After baseline studies in the fasting state, the effect of a calcium infusion on PTH levels was studied. Estrogen replacement resulted in a fall in fasting resting ionized calcium and a rise in PTH levels. After calcium infusion there was no change in the shape of the relationship between plasma calcium and PTH. The level of nonsuppressible PTH secretion was not altered. Transdermal estrogen did not alter basal vitamin D-binding protein levels, 25-hydroxyvitamin D levels, or calcitriol levels. We conclude that the effect of transdermal estrogen replacement on PTH secretion is completely explained by the lowering of ionized calcium, causing a rise in PTH secretion. Thus, with this route of estrogen replacement, there is no necessity to postulate a direct effect of 17 beta-estradiol on the parathyroid gland.

Administration, Cutaneous↗
PubMed1989

Ultradistal and cortical forearm bone density in the assessment of postmenopausal bone loss and nonaxial fracture risk.

Forearm bone mineral density (BMD) was measured by single-energy photon absorptiometry in 360 healthy females without known axial fractures, 202 of whom were postmenopausal. The three sites addressed included an ultradistal (U) region containing approximately 60% trabecular bone. The other sites, distal (D) and shaft (S), were progressively more cortical. Reproducibility was 1.7-1.9% CV. The earliest evidence of a significant correlation between BMD and years since menopause was seen in trabecular bone in subjects aged 45-55 years. Fractional decrease in BMD, relative to the premenopausal value, was significantly larger at U than at S for the decades 55-65 years and above. Fractional rates of bone loss at all sites were a maximum in the first postmenopausal decade, the rate at U being 0.035, approximately 1.5 times that at D or S. A total of 33 subjects reported 54 previous minimally traumatic nonaxial (MTNA) fractures. When BMD measurements of the entire study were divided into quintiles, the prevalence of MTNA fracture cases in the lowest quintile was eight times that of each of the upper three quintiles. Prevalence of fracture cases ranked by quintiles of BMD were not different for the three scan sites. Therefore, ultradistal measurements confer no advantages over distal or shaft BMD for discriminating past MTNA fracture cases but do show larger fractional rates of loss during the first postmenopausal decade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Plasma calcitonin levels are not lower than normal in osteoporotic women.

It has been suggested that postmenopausal osteoporosis is due to calcitonin deficiency. Interest in this concept has been increased because of the recent availability of nasal calcitonin for the management of osteoporosis. Plasma calcitonin and albumin-adjusted calcium levels were measured in 30 women with postmenopausal osteoporosis and 41 normal women matched for age and sex. Both mean plasma calcitonin and mean albumin-adjusted calcium levels were higher in the postmenopausal osteoporotic women [calcitonin, 21.0 +/- 17.6 (+/- SD) vs. 9.8 +/- 10.2 ng/L (P = 0.003); calcium, 2.33 +/- 0.09 vs. 2.27 +/- 0.07 mmol/L (P = 0.002)]. This result indicates that fasting calcitonin deficiency is not a feature of postmenopausal osteoporosis.

Age Factors↗
PubMed1988

Forearm bone loss in hemiplegia: a model for the study of immobilization osteoporosis.

Hemiplegia is associated with excessive bone loss in the paralyzed arm. The forearm bone mineral content was measured at a proximal cortical site and a distal trabecular site of both the normal and hemiplegic arms in 74 patients with hemiplegia. By comparing the ratios of bone mineral content in the two arms, the effect of immobilization could be quantitated independently of the large population variance in bone mineral content. Bone loss, estimated from this single comparison of bone mineral content in the normal and hemiplegic arms, at the trabecular and cortical sites was positively correlated with the duration of stroke and negatively correlated with reduction in forearm function. At the trabecular site females had a proportionately greater bone loss than males, indicating an interaction between gender and immobilization associated bone loss at this site. The regression line of excess bone loss in the hemiplegic limb against time had a negative slope of 1.3% and 1.5% a year of the starting value for the trabecular and cortical sites, respectively, over the 15 years studied. This study indicates that a reduction in function is associated with significant bone loss occurring over prolonged periods that may account, at least in part, for the significant osteoporosis seen in elderly people and in subjects with conditions resulting in reduced mobility such as arthritis, obstructive airways disease, and neurological disease.

Aged↗
PubMed1988

Calcitriol deficiency with retained synthetic reserve in chronic renal failure.

Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, there was depression of calcitriol levels and an elevation of PTH and nephrogenous cyclic AMP (NcAMP) levels in the MCRF patients. Furthermore, plasma phosphate levels were higher and the renal phosphate threshold was depressed in this patient group. When all subjects were grouped together calcitriol was positively correlated with GFR. When calcitriol levels were factored for GFR, to permit an assessment of calcitriol production per unit functioning renal mass, there was no significant difference between normal and MCRF subjects. To determine whether reserve for calcitriol production existed, six of the MCRF patients and six of the age- and sex-matched normal subjects received a low calcium diet for one week supplemented by cellulose phosphate to bind calcium within the gut. In both groups there was a significant rise in calcitriol, although the absolute levels were much lower in the MCRF patients than the normal subjects. These results suggest that calcitriol deficiency is a major feature of MCRF despite marked hyperparathyroidism. The rise in calcitriol levels in MCRF suggests persistent reserve secretory capacity in this condition. Therefore, the low serum calcitriol concentration may be due not only to structural renal damage, but also to suppression of calcitriol formation perhaps due to altered renal phosphate handling.

Adult↗
PubMed1988

Effects of theophylline and salbutamol on phosphate and calcium metabolism in normal subjects.

The acute effects of oral theophylline and salbutamol were studied in a randomised double-blind crossover study in 12 normal subjects. Theophylline resulted in a significant fall in plasma phosphate and a small rise in urine phosphate excretion which did not, however, account for the fall in plasma phosphate. The increase in urine phosphate excretion was accompanied by a rise in sodium, calcium and water excretion. These changes were not accompanied by a change in renal cyclic AMP production, plasma parathyroid hormone levels or plasma calcitonin levels. Salbutamol had only minor effects on urine calcium and phosphate excretion.

Adult↗
PubMed1987

Comparison of performance of final-year students from three Australian medical schools.

Between 1984 and 1986, 888 final-year medical students from The Universities of Sydney, Western Australia and Newcastle took part in trial examinations that comprised multiple-choice questions, modified essay questions and a patient management problem. Differences in student performance among the schools were small. In 1984 and 1985, Newcastle students performed less well than did Sydney students on multiple-choice questions that were prepared by The University of Sydney, but there was no difference between the schools in 1986. Sydney students performed better than did Newcastle students on the multiple-choice question paper that was prepared by The University of New South Wales in 1984, but in the last two years no differences have been detected between the schools in performance on this paper. The performance on modified essay questions in 1984 suggested that Newcastle students were stronger in behavioural sciences and weaker in pathological sciences than were Sydney students. Sydney students performed less well than did Newcastle students in the patient management problem in 1985, particularly in the area of the use of clinical investigations. On the one occasion of testing that involved students from The University of Western Australia (in 1985), these students performed best of the three schools in the patient management problem, and roughly equally with students from Sydney and Newcastle in the multiple-choice question papers. Differences among the schools usually amounted to less than 10% and might have been accounted for by differences in familiarity with test instruments. We conclude that medical students are likely to graduate from The University of Sydney, Western Australia and Newcastle with similar levels of knowledge of internal medicine. Possible differences in problem-solving ability require further study, particularly in the clinical setting.

Australia↗
PubMed1986

Hypercalcemia during resolution of acute renal failure associated with rhabdomyolysis: evidence for suppression of parathyroid hormone and calcitriol.

Hypercalcemia during the recovery phase of renal function is a relatively common complication of rhabdomyolysis-associated acute renal failure. The cause is unclear but it has been suggested recently that both hyperparathyroidism and high levels of calcitriol are implicated. We present evidence which does not support these hypotheses.

Acute Kidney Injury↗
PubMed1986

A role for calmodulin in renal production of 1,25-dihydroxyvitamin D3.

The conversion of circulating 25-hydroxyvitamin D3 (25OHD3) to its active metabolite 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the renal tubule mitochondrion by the enzyme 25OHD3-1 alpha-hydroxylase is closely regulated in vivo according to the physiological need for calcium and phosphorus. The mechanism by which this regulation is achieved at the cellular level has not been clarified, although a number of lines of evidence suggest that calcium ions (Ca2+) are involved. This study was designed to determine whether calmodulin, the ubiquitous cell protein that binds and mediates many of the regulatory functions of Ca2+, plays a role in the regulation of renal vitamin D metabolism. The calmodulin antagonists trifluoperazine (TFP), Janssen R24571, and the naphthalene sulfonamides W5 and W7 inhibited conversion of 25OHD3 to 1,25-(OH)2D3 by isolated renal tubules from vitamin D-deficient chicks in a dose-dependent manner (ED50: TFP, 12 mumol/liter; R24571, 10 mumol/liter; W7, 30 mumol/liter; W5, 75 mumol/liter). TFP did not inhibit production of the alternative metabolite 24,25-(OH)2D3 by chick renal tubules. In a similar manner, TFP, W7, and W5 inhibited conversion of 25OHD3 to 1,25-(OH)2D3 by isolated energized chick renal mitochondria, with no detrimental effect on mitochondrial respiratory indices. Bovine brain calmodulin in a concentration of 1 X 10(-7) mol/liter enhanced 1,25-(OH)2D3 production by isolated chick renal mitochondria in Ca2+ -containing medium, but not in the absence of Ca2+. Preincubating mitochondria with anticalmodulin antiserum resulted in decreased conversion of 25OHD3 to 1,25-(OH)2D3, an effect that was prevented by exogenous calmodulin. These data support the notion of a role for calmodulin in the Ca2+ -mediated control of renal 1 alpha-hydroxylase activity.

Animals↗
PubMed1985

Clinical validation of dialysable calcium in relation to other methods of serum calcium measurement.

Dialysable calcium (CaD) values were measured by a simple technique not interfered with by protein bound calcium and validation attempted by comparison with concentrations of ionised calcium (CaI) and clinical categorisation. CaD values were also compared with total calcium (CaT) and albumin adjusted calcium (CaA) concentrations. The normal ranges for CaD, CaT, CaA, and CaI were calculated from the results in healthy blood donors. In 50 normal subjects CaD was more highly correlated with CaI than CaT or CaA. The effects of lying down and of venous stasis in 10 normal subjects showed that CaD was slightly influenced by posture only, whereas CaT was noticeably affected by posture and venous stasis; CaA reduced but did not abolish these effects on CaT. The correlation coefficient of CaD and CaI in patients with chronic renal failure was 0.81. CaD was compared with CaT and CaA values in 293 consecutive hospital patients; discrepant results were obtained in 14.3% and 13.0% of cases respectively and there were some clinical grounds for accepting CaD as correct in 86% and 74% of these cases. Measurement of CaD is a simple, reliable method for estimating accurately the calcium concentration free from biologically inactive protein bound calcium.

Adult↗
PubMed1984

Carcinoma of the breast in a male with hypogonadotropic hypogonadism.

There is an increased risk of development of carcinoma of the breast in males with hypogonadism due to Klinefelter's syndrome. A patient with isolated hypogonadotropic hypogonadism and gynaecomastia developed an intraduct carcinoma of the breast. This is believed to be the first reported case of this association.

Adenocarcinoma, Scirrhous↗
PubMed1983

Opposing effects of cyclic adenosine-3',5'-monophosphate and cyclic guanosine-3',5'-monophosphate on the metabolism of 24-hydroxyvitamin D3 in isolated chick renal tubules.

The conversion of 25-hydroxyvitamin D3 (25 OH D3) to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1,24,25-trihydroxyvitamin D3 (1.24,25-(OH)3D3) was studied in renal tubules prepared from chicks raised on a vitamin D deficient diet with or without vitamin D supplementation. As described previously, in tubules from vitamin D deficient chicks, cyclic AMP caused an increase in the net accumulation of 1,25-(OH)2D3, the major metabolite formed under these circumstances. This stimulation was shown to be due to an increased maximum velocity of the hydroxylation reaction. There was also a significant inhibition of the net accumulation of 24,25-(OH)2D3. Cyclic GMP caused a significant inhibition of 1,25-(OH)2D3 formation and stimulation of the net accumulation of 24,25-(OH)2D3. In chicks supplemented with high doses of vitamin D, 24,25-(OH)2D3 was the major metabolite of 25 OH D3 detected and 1-hydroxylase activity was negligible. Under these circumstances, neither cyclic AMP nor cyclic GMP affected net accumulation of 24,25(OH)2D3. This suggested that the apparent effect of the nucleotides on formation of 24,25-(OH)2D3 may have been due to further metabolism of 24,25-(OH)2D3 when 1-hydroxylase activity was high. It is concluded that cyclic AMp and cyclic GMP have reciprocal effects on renal 25 OH D3-1-hydroxylase activity, and both should be considered potential intracellular regulators of 25 OH D3 metabolism.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

A test of 1,25-dihydroxyvitamin D3 secretory capacity in normal subjects for application in metabolic bone diseases.

The circulating concentration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] varies in man in response to a variety of physiological stimuli. In pathological states, random plasma 1,25-(OH)2D3 levels reflect the sum of the underlying pathological process and the homeostatic corrections to those perturbations. Hence random 1,25-(OH)2D3 levels do not allow differentiation as to whether changes in 1,25-(OH)2D3 production or metabolism are primary or secondary to other changes. Similarly random levels do not provide much insight into the reserve of 1,25-(OH)2D3 secretory capacity. We have developed a single infusion of parathyroid extract (PTE) as a test of 1,25-(OH)2D3 secretory capacity. Normal responses in twelve males and six females consisted of an increase in plasma 1,25-(OH)2D3 levels of 78% over basal in the male and 77% over basal in the female subjects. The peak response occurred 18-22 h after the PTE was administered. This test of 1,25-(OH)2D3 secretory capacity should prove useful in the evaluation of patients with metabolic bone disease. As part of this study, the diurnal plasma 1,25-(OH)2D3 level was examined in six males and seven females. There was no significant diurnal rhythm between 8.00 and 22.00 h.

Adult↗
PubMed1983

Hypercalcaemia in association with renal failure: the role of immobilisation.

Hypercalcaemia occurring after ten weeks of immobilisation was observed in four adult patients all of whom had had prior renal failure sufficient to require renal dialysis. In all patients parathyroid hormone levels were normal or low and in three plasma 1,25(OH)2D3 levels were low. These findings are consistent with immobilisation induced increases in bone calcium resorption. Renal excretion of calcium may have been impaired by renal dysfunction resulting in hypercalcaemia and suppression of plasma PTH and 1,25(OH)2D3 levels. Resolution of the hypercalcaemia was associated with remobilisation. Parathyroidectomy is inappropriate treatment.

Acute Kidney Injury↗