Biomedical subjects

R W Retallack

Publications and source records attributed to R W Retallack.

At least 37 records · Page 2Linked to original sources

PubMed1991

Intravenous aminobisphosphonate in Paget's disease: clinical, biochemical, histomorphometric and radiological responses.

Intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) was used to treat 26 patients with Paget's disease. Three daily dosages were studied; 20-30 mg/day in 20 patients, 45 mg/day in three patients and 60 mg/day in three patients, by daily 4-hour infusions for 2-10 days. The fasting urinary hydroxyproline excretion (HypE) declined exponentially, reaching 50% of pretreatment values at 1.92 +/- 0.16 (mean +/- SEM) days. This initial rapid decline was complete by 4 days following treatment to a mean of 28.0 +/- 3.4% of pretreatment values. Thereafter, there was no significant decline in HypE. The initial rate of decline of HypE was unchanged by increasing the daily dose of APD. Transient non-symptomatic hypocalcaemia with secondary hyperparathyroidism occurred in all patients. No adverse changes in the renal handling of calcium or phosphate, as seen with high-dose 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP), were seen in any patient on any daily dose. Fever occurred in 73% of patients in the first 2 days of treatment. Overall, there was a significant fall in the lymphocyte count (P less than 0.005 febrile group, n = 19; P less than 0.02 non-febrile group, n = 7) and a fever-dependent rise in the neutrophil count (P less than 0.005 febrile group only). The occurrence of fever was associated with a more rapid decline in HypE, compared to the non-febrile group, so that HypE was significantly lower in the febrile group by day 5 (P less than 0.025). Seventy-two per cent of patients with bone and/or joint pain reported a reduction in pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Human lactation: forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning.

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast-feeding for 6 months (Lac) and in 40 age-matched controls (Con) using fasting urine and blood biochemistry and forearm single-photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P less than 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 +/- 0.12 mumol/liter GF (mean +/- SEM), Con 1.19 +/- 0.04, P less than 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 +/- 2.5 IU/liter, Con 53.5 +/- 2.7, P less than 0.001, and serum osteocalcin, Lac 14.0 +/- 0.7 microgram/liter, Con 7.3 +/- 0.4, P less than 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25-hydroxy- and 1,25-dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Alterations in vitamin D metabolites during treatment of Paget's disease of bone with calcitonin or etidronate.

We report serum 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels. In untreated Paget's patients serum 25-OHD (73 +/- 29 nmol/liter, n = 36, mean +/- SD) and 24,25-(OH)2D (0.3-12.9 nmol/liter, median 2.2, n = 36) levels were significantly lower than in age-matched controls (94 +/- 30 nmol/liter, n = 32, p less than 0.005, and 1.3-16.4 nmol/liter, median 5.3; n = 32, p less than 0.001, respectively). Also, the 24,25-(OH)2D levels correlated with the 25-OHD levels in the untreated Paget's patients (r = 0.56, p less than 0.01) and in the controls (r = 0.39, p less than 0.05). The percentage molar ratio of 24,25-(OH)2D to 25-OHD in Paget's patients had a median value of 3.7% (range 0.4-14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2-18%). There was no difference between the 1,25-(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25-(OH)2D to 25-OHD in untreated Paget's patients (0.157 +/- 0.09%) was not significantly different from controls (0.124 +/- 0.05%) despite lower 25-OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25-OHD levels (r = 0.392, p less than 0.02); however, 24,25-(OH)2D and 1,25-(OH)2D levels were not correlated with AP.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗

PubMed1990

Serum free 1,25-dihydroxyvitamin D and the free 1,25-dihydroxyvitamin D index during a longitudinal study of human pregnancy and lactation.

The changes in three different indices of 1,25-dihydroxyvitamin D (1,25(OH)2D) biological activity were studied longitudinally in 35 women during late pregnancy and lactation and in 26 control women. Measurements were made of maternal serum total 1,25(OH)2D and free 1,25(OH)2D concentration (by centrifugal ultrafiltration) and the free 1,25(OH)2D index (the molar ratio of total 1,25(OH)2D and vitamin D binding protein (DBP]. During late pregnancy total 1,25(OH)2D concentrations were significantly elevated when compared to controls, as were free 1,25(OH)2D and DBP concentrations and the free 1,25(OH)2D index. Serum total 1,25(OH)2D, free 1,25(OH)2D and DBP concentrations all fell dramatically during the first 2 weeks of lactation with total 1,25(OH)2D and free 1,25(OH)2D concentrations falling to levels below those of controls. During the course of lactation both total 1,25(OH)2D and free 1,25(OH)2D levels rose significantly although they were not different from controls at 18 weeks of lactation. In contrast, the free 1,25(OH)2D index fell during the first 2 weeks of lactation, but remained at this level, significantly lower than controls. Neither urinary calcium excretion nor dietary calcium intake correlated with total or free 1,25(OH)2D, DBP, or the free 1,25(OH)2D index. The disagreement in the results of free 1,25(OH)2D concentration and free 1,25(OH)2D index demonstrates that these two approaches to measuring biologically active 1,25(OH)2D are not equivalent. In attempting to account for the increased calcium requirements of human reproduction we conclude that in pregnancy any of the 1,25(OH)2D measurements may be appropriate. In lactation, however, either 1,25(OH)2D is not a major factor or 1,25(OH)2D biological activity is inadequately represented by any of the currently available methods.

Adult↗

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↗

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↗

PubMed1988

Tritium isotope effect in high-pressure liquid chromatography of vitamin D metabolites.

A significant chromatographic isotope effect is reported for 1,25-dihydroxyvitamin D3 in a wide variety of HPLC separation systems. The effect is also observed for 24,25-dihydroxyvitamin D3. Retention times differ from less than 1% up to 4% depending on the separation system and the degree and position of tritium substitution. Such an effect must be corrected for whenever both labeled and unlabeled vitamin D metabolites are used in HPLC cochromatography or assay recovery studies.

24,25-Dihydroxyvitamin D 3↗

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↗

PubMed1985

Parathyroid hormone radioimmunoassay: the clinical evaluation of assays using commercially available reagents.

This paper reports on the diagnostic usefulness of two commercial PTH assay kits and four "in-house" assays using commercially available reagents, studying the same samples from normal controls and different patient groups. The ability of such assays to discriminate proven primary hyperparathyroid (1 degree HPT) patients from normals varied significantly but without any apparent correlation with assay components. For all assays, performance declined markedly in 1 degree HPT patient groups with lower serum calcium levels. Patients with PTH secondary to chronic renal disease were well discriminated from normal by all assays. Although immunoassays are useful in many cases of 1 degree HPT, it is difficult to develop C-terminal or mid-region PTH assays that are uniformly diagnostically useful in the clinical situation where they are of greatest potential use i.e. in cases of mildly hypercalcaemic 1 degree HPT.

Antibody Specificity↗

PubMed1985

Estimation of 1,25 dihydroxyvitamin D by cytoreceptor and competitive protein binding assays without high pressure liquid chromatography.

Using two different cultured rat osteosarcoma cell lines (UMR 106 and ROS 17/2.8) we have investigated the recently described cytoreceptor assay for 1,25-dihydroxyvitamin D (1,25-(OH)2D). The assay method is relatively simple and sensitive to 2.4 fmole per tube. Using either cell line, assay of serum samples, whose only preparation consisted of extraction and purification on a disposable diatomaceous earth column, produced variable values for serum 1,25-(OH)2D. Additional purification, using a disposable silicic acid minicolumn to remove other vitamin D metabolites resulted in consistent values and additional HPLC resulted in no further decrease in the values obtained. Our results show that a single two stage non-HPLC column can purify serum samples for assay in the cytoreceptor assay. The method is also applicable to the competitive protein binding assay employing calf thymus cytosol and the correlation between values obtained by both methods is highly significant. It is a sensitive, simple, and accurate method with technical advantages which allow greater sample throughput than other 1,25-(OH)2D assays.

Animals↗

PubMed1981

Serum and milk alkaline phosphatase in human lactation.

Serum and milk alkaline phosphatase (AP) values are reported for the first 16 weeks of lactation. Serum levels at all stages are elevates above normal-pregnant controls. Sequential milk AP values are reported for the first time. Heat inactivation and phenylalanine inhibition studies would suggest that serum AP in lactation is composed of bone and liver isoenzymes, but it shows an increase in the rate at which enzymatic activity is lost when frozen, indicating that lactation serum AP is largely a different isoenzyme. Electrophoresis demonstrates several AP "slow" bands of unknown origin in lactation serum.

Alkaline Phosphatase↗

PubMed1981