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Biomedical subjects

I T Boyle

Publications and source records attributed to I T Boyle.

At least 55 records · Page 3Linked to original sources
PubMed1990

The loss of circadian rhythm for intact parathyroid hormone and nephrogenous cyclic AMP in patients with primary hyperparathyroidism.

The measurement of serum intact parathyroid hormone (PTH) (1-84) over a 24-h period has shown the existence of a circadian rhythm in normal males which is absent in patients with primary hyperparathyroidism. The physiological significance of this observation is reflected in the presence of parallel changes in nephrogenous cyclic adenosine monophosphate (N-cAMP) in normals which are also absent in primary hyperparathyroidism. Serum calcium, adjusted for variations in albumin concentrations, showed a transient fall in normal subjects prior to the nocturnal rise in PTH (1-84). A similar transient fall in serum adjusted calcium was observed in the hyperparathyroid patients. Serum phosphate showed a circadian rhythm in normal subjects, and an attenuated rhythm persisted in primary hyperparathyroidism. These data suggest that both ionic factors and higher centres play important roles in the fine control of PTH (1-84) secretion.

Adult↗
PubMed1990

Immobilization-related hypercalcaemia--a possible novel mechanism and response to pamidronate.

Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome.

Adult↗
PubMed1990

Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling.

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.

Biomarkers↗
PubMed1990

The influence of calciotrophic hormones on lymphocyte transformation and interleukin-2 production in human mononuclear cells.

Peripheral blood mononuclear cells (PBMC) display receptors for parathyroid hormone (PTH) and calcitonin (CT) and, when activated, express receptors for 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). The role of these receptors in unclear. It is well established that 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) has a significant effect on lymphocyte transformation and interleukin-2 (IL-2) activity in PBMC's. We have proceeded to compare the effects of the calciotrophic hormones, 1,25(OH)2D3, 24,25 dihydroxyvitamin D3 (24,25(OH)2D3), 25 dihydroxyvitamin D3 (25(OH)D3), bovine (1-35)PTH (b(1-35)PTH) and salmon CT on both lymphocyte transformation and IL-2 activity in PBMC's from normal human volunteers. We have also sought an indication as to which subset of cells is responsible for the 1,25(OH)2D3 effect. Unlike the other calciotrophic hormones 1,25(OH)2D3 inhibited the proliferation of phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) stimulated cells. 1,25(OH)2D3 had a significantly greater effect on PHA induced cell proliferation and only inhibited cells with the T-helper/inducer (TH, CD4 + ve) phenotype, this suggested that 1,25(OH)2D3 may act selectively on the cells with CD4 + ve phenotype. In addition, of the calciotrophic hormones, 1,25(OH)2D3 had a greater effect on IL-2 activity. These findings indicate that 1,25(OH)2D3 and not the other calciotrophic hormones has a significant immunomodulatory effect.

24,25-Dihydroxyvitamin D 3↗
PubMed1990

Serial bone scans in Paget's disease: development of new lesions, natural variation in lesion intensity and nature of changes seen after treatment.

Serial radionuclide bone scans (n = 96) of 40 patients with Paget's disease were studied and tracer uptake graded using a four-point subjective scale. In nine patients studied without treatment the serial scan appearance improved in some, remained unchanged in others and deteriorated in yet others. Similarly individual lesions demonstrated increased, decreased or unchanged tracer uptake. One lesion disappeared without treatment but no new lesions developed. After treatment with aminohydroxypropylidene bisphosphonate (APD) or ethanehydroxy bisphosphonate (EHDP) the overall scan appearance improved in the majority of patients treated (n = 34), but individual lesions demonstrated increased (n = 20), unchanged (n = 79) or decreased uptake (n = 86). The mean reduction in tracer was 32% and 20 lesions reverted to normal intensity. The site of the lesion or the initial intensity of tracer uptake did not influence response to therapy. New lesions developed in five patients after therapy. There was variable correspondence between scintigraphic changes and biochemical parameters of response. From our study we conclude that serial bone scans must be used with caution when interpreting the response of Paget's disease to therapy.

Aged↗
PubMed1989

Comparison of three intravenous bisphosphonates in cancer-associated hypercalcaemia.

Three intravenous bisphosphonates were compared in the treatment of cancer-associated hypercalcaemia. 48 patients were randomly allocated to one of three treatment groups (each with 16 subjects)--30 mg pamidronate or 600 mg clodronate, both as single intravenous infusions; or etidronate as three infusions of 7.5 mg/kg per day for three consecutive days. Patients were rehydrated with normal saline before bisphosphonate treatment. All three bisphosphonates lowered serum calcium by inhibiting bone resorption; pamidronate was the most potent in this respect. By comparison with the other groups, more patients in the pamidronate group became normocalcaemic, and the effect on serum calcium was apparent sooner and lasted longer.

Administration, Oral↗
PubMed1989

Contrasting mechanisms of hypercalcemia in patients with early and advanced humoral hypercalcemia of malignancy.

The mechanisms of hypercalcemia were assessed in 15 patients with humoral hypercalcemia of malignancy (HHM) who had tumors at various stages of progression. In patients with early tumors, bone biopsies were generally normal and the hypercalcemia was due to an elevation in renal tubular resorption of calcium. Conversely, osteoclastic resorption was markedly increased in patients with advanced tumors, particularly those in whom the biopsies were obtained postmortem. Osteoclast surface (Oc.S) correlated positively with the stage of tumor progression (r = 0.80, p less than 0.002), degree of immobility (r = 0.87, p less than 0.002), and level of urinary cyclic AMP excretion (r = 0.60, p less than 0.02). When compared with a group of ambulant patients with primary hyperparathyroidism (HPT), osteoblast surface (Ob.S%) in HHM was depressed (median and range): 1.2% (0-11.6%) versus 5.3% (1.1-32.0%) (p less than 0.001). However, a relatively low Ob.S (4%) and raised Oc.S (43.5%) were also seen in an immobilized patient with severe HPT. These data suggest that the PTH-related peptides currently invoked in the pathogenesis of HHM may initially cause hypercalcemia by enhancing renal tubular calcium resorption. The increase in osteoclastic activity and depression of osteoblastic activity that subsequently occurs is probably due to the combined effects of immobilization and higher circulating levels of PTHrP on the skeleton. However, the release of other bone-resorbing factors by the tumor, which have a depressant effect on osteoblastic activity, remains possible.

Adult↗
PubMed1988

Treatment of hypercalcaemia in thyrotoxicosis with aminohydroxypropylidene diphosphonate.

Two patients had symptomatic hypercalcaemia accompanying thyrotoxicosis, despite initial treatment with volume repletion, beta blockade and antithyroid drugs. They were further managed with intravenous infusions of aminohydroxypropylidene diphosphonate resulting in rapid normalization of the serum calcium, with relief of symptoms. Aminohydroxypropylidene diphosphonate effectively suppressed the increased bone resorption of thyrotoxicosis without any undesirable adverse effects.

Adult↗
PubMed1988

Clinical experience with aminohydroxypropylidene bisphosphonate (APD) in the management of cancer-associated hypercalcaemia.

Fifty-five patients with symptoms caused by hypercalcaemia associated with cancer were treated with varying regimens of intravenously-administered aminohydroxypropylidene bisphosphonate after initial rehydration. Of 48 patients where adequate data were available, 32 (66 per cent) were rendered normocalcaemic and 16 (33 per cent) remained mildly hypercalcaemic. In these cases, failure to restore normocalcaemia was attributable to elevated renal tubular reabsorption of calcium in nine (18 per cent) and to inadequate suppression of bone resorption in seven (14 per cent). There was no significant difference in response and duration of effect (median 20 days) between single doses of 15, 25 and 45 mg, or when the 45 mg dose was administered over three, six or 24 h. These single dose regimens were similar in terms of effect on calcium levels and duration of action, to multiple daily doses of 15 mg for a mean of six days. While the effect of 5 mg dose was not significantly different from the higher doses, suppression of serum calcium levels was less marked and the effect on duration of action significantly shorter than with the 45 mg dose. In seven cases, treatment with a second course was less effective even with higher doses because suppression of bone resorption was poorer. These data indicate that there is little difference between the therapeutic effects of multiple 15 mg and single 15-45 mg intravenous infusions of aminohydroxypropylidene bisphosphonate in hypercalcaemia associated with cancer. A single intravenous infusion of a moderate dose (for example 15-30 mg) would be a convenient and effective way of treating most patients.

Diphosphonates↗
PubMed1987

The effect of 1 alpha-hydroxyvitamin D3 on the mineralization defect in disodium etidronate-treated Paget's disease--a double-blind randomized clinical study.

A double-blind randomized study of 29 patients with symptomatic Paget's disease was conducted comparing the clinical, biochemical, and histomorphometric responses to 3-month treatment with placebo (10 patients), low-dose disodium etidronate (EHDP) (5-7 mg/kg/day) (10 patients), and low-dose EHDP plus 1 alpha-hydroxyvitamin D3 (1 alpha D3) 0.5 mcg daily (9 patients). In placebo-treated patients no significant changes were observed in symptoms, biochemistry, or bone histomorphometry. Histologically apparent mineralization defects developed after 3 months of therapy in 90% of patients in the EHDP group, compared with 45% of patients in the EHDP/1 alpha D3 group. In 19% of the patients treated with active medication, the mineralization defects in pagetic bone were accompanied by histological evidence of continued osteoclastic resorption. The development of mineralization defects was not related to serum levels of vitamin D metabolites, alkaline phosphatase, or intestinal calcium absorption but did correlate with the occurrence of hyperphosphatemia during treatment, which was most marked in patients treated with EHDP alone. Although mineralization defects were less frequent in the EHDP/1 alpha D3 group, these patients also responded less well symptomatically, thus limiting the potential usefulness of this drug combination in Paget's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1987

Comparison of intestinal calcium absorption and circulating 1,25-dihydroxyvitamin D levels in malignancy-associated hypercalcaemia and primary hyperparathyroidism.

The relation between circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) levels and intestinal calcium absorption--as determined by an oral calcium load test--was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid-like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid-like features. It is postulated that in the former, the 'inappropriately' detectable or raised 1,25(OH)2D levels may have been due to enhanced renal 1 alpha-hydroxylase activity stimulated by the parathyroid hormone (PTH)-like effect of a non-PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non-humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is 'end organ' resistance to the effects of 1,25(OH)2D due to a generalized malabsorptive process.

Calcium↗