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Biomedical subjects

I T Boyle

Publications and source records attributed to I T Boyle.

At least 73 records · Page 4Linked to original sources
PubMed1987

Malignancy-associated hypercalcaemia: relationship between mechanisms of hypercalcaemia and response to antihypercalcaemic therapy.

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.

Calcitonin↗
PubMed1986

Treatment of cancer associated hypercalcaemia with combined aminohydroxypropylidene diphosphonate and calcitonin.

Eight patients with cancer associated hypercalcaemia were treated with the combination of aminohydroxypropylidene diphosphonate and salmon calcitonin for six days. Serum calcium concentration fell significantly within 24 hours of starting treatment due to a reduction in bone resorption and renal tubular calcium reabsorption. In the longer term hypercalcaemia was controlled by a further progressive reduction in bone resorption, which persisted for six days after treatment was stopped. Renal tubular calcium reabsorption, however, remained suppressed only during drug treatment. The rapid fall in serum calcium was attributable to the acute renal and skeletal effects of calcitonin, whereas in the longer term control of hypercalcaemia was due to diphosphonate mediated suppression of bone resorption. In view of the rapid effect and lack of toxicity, combined treatment with aminohydroxypropylidene diphosphonate and calcitonin would be of particular value in patients with severe hypercalcaemia in whom a quick but sustained reduction in the serum calcium concentration is desired.

Bone Resorption↗
PubMed1986

Influence of urinary sodium excretion on the clinical assessment of renal tubular calcium reabsorption in hypercalcaemic man.

The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.

Calcium↗
PubMed1986

Humoral hypercalcaemia of malignancy: metabolic and histomorphometric studies during surgical management of the primary tumour.

Several aspects of calcium metabolism were studied in five patients during the surgical exploration of malignant tumours associated with humorally-mediated hypercalcaemia. Before operation in all patients the renal tubular threshold for calcium reabsorption was raised and the threshold for renal tubular phosphate reabsorption depressed. On removal of the primary tumour in three cases, serum calcium returned to normal, renal calcium threshold fell, renal phosphate threshold rose, but urinary hydroxyproline excretion did not change. In two patients where the tumour proved inoperable, serum calcium remained elevated and no changes in renal calcium threshold or phosphate threshold occurred. Histomorphometry carried out on biopsy specimens from four patients showed normal bone resorption in three, and slightly increased resorption in one, without depression of osteoblastic bone formation. It is suggested that hypercalcaemia in these patients resulted mainly from an alteration in renal calcium threshold caused by a humoral substance released by tumour cells. Correction of hypercalcaemia on removal of the primary tumour was achieved rapidly and could be explained principally by a reduction in renal calcium threshold with increased loss of calcium into the urine. These data contrast with those of many previous studies which have emphasised the predominant role of accelerated osteoclastic bone resorption as the principal cause of hypercalcaemia in malignancy and suggest that a renal effect of the putative humoral agent may predominate in some cases.

Adenoma, Bile Duct↗
PubMed1985

Comparison of aminohydroxypropylidene diphosphonate, mithramycin, and corticosteroids/calcitonin in treatment of cancer-associated hypercalcaemia.

Thirty-nine patients with cancer-associated hypercalcaemia were randomly allocated to receive aminohydroxypropylidene diphosphonate (APD), mithramycin, or corticosteroids and salmon calcitonin. Corticosteroids/calcitonin had the fastest calcium-lowering effect, owing mainly to an acute reduction in renal tubular calcium reabsorption; continued therapy over 9 days failed to suppress accelerated bone resorption, however, and most patients remained hypercalcaemic. Mithramycin also substantially reduced serum calcium within 24 h. A further dose on day 2 generally controlled hypercalcaemia until day 6 by reducing both bone resorption and renal tubular calcium reabsorption. By day 9, however, about 50% of the mithramycin-treated patients had started to relapse as bone resorption increased again. With APD serum calcium levels fell more slowly but progressively owing to effective suppression of bone resorption; by day 9 the control of hypercalcaemia was significantly better than in the other treatment groups. Symptoms of hypercalcaemia were greatly relieved, especially by APD.

Calcitonin↗
PubMed1984

Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcaemia in malignancy.

Some relations between metastatic bone disease and calcium homoeostasis were determined in a consecutive series of 81 patients with solid malignant tumours attending for radionuclide bone scans. Biochemical evaluation showed that bone resorption from metastatic disease was generally not enough to account for hypercalcaemia. While skeletal metastases were present in about half of the patients who developed hypercalcaemia, biochemical indices of bone resorption in these subjects were greatly increased and disproportionate to the extent of metastatic disease detected by the bone scans. Furthermore, a reduced renal phosphate threshold and increased tubular calcium reabsorption were generally observed in hypercalcaemic patients when compared with their normocalcaemic counterparts. These findings suggest that in most cases malignancy associated hypercalcaemia may be caused by the release of a humoral factor by tumour tissue which exhibits "parathyroid-hormone-like" activity with regard to bone resorption, renal phosphate threshold, and renal calcium handling. It may be postulated that this putative humoral mediator predisposes to hypercalcaemia both by stimulating generalised osteolysis and in most cases also by impairing the renal excretion of the resultant increase in filtered calcium load. While hypercalcaemia may arise as a result of metastatic bone disease alone, these data indicate that this may be the exception rather than the rule. Hence the term "metastatic hypercalcaemia" should probably be reserved for patients with extensive skeletal tumour disease in whom biochemical evaluation fails to yield evidence of an underlying humorally mediated cause.

Bone Neoplasms↗
PubMed1984

Focal osteomalacia due to low-dose diphosphonate therapy in Paget's disease.

Transiliac bone biopsies carried out on 13 patients with Paget's disease to evaluate the effects of low-dose diphosphonate (disodium etidronate) therapy showed focal osteomalacia in the 9 patients in whom post-therapy specimens were taken through pagetic bone. Active bone resorption persisted in 5 of these. A mineralisation defect not amounting to osteomalacia--ie, osteoid of increased thickness but of normal extent--was present in the 4 specimens taken through non-pagetic bone. Although 9 patients experienced symptomatic improvement, 2 suffered fissure fractures in affected lower limbs. In Paget's disease, the combination of osteomalacia and continuing active resorption within a lytic lesion may increase the risk of fracture in a weight-bearing bone. It is suggested that although disodium etidronate often provides effective pain relief it should be administered with caution until the optimum dose and duration of therapy are further evaluated.

Aged↗
PubMed1984

Successful localisation of parathyroid adenomata by thallium-201 and technetium-99m subtraction scintigraphy: description of an improved technique.

An improved method for parathyroid scanning using thallium-201 and technetium-99m subtraction imaging is described. The technique successfully localised ten of eleven parathyroid adenomas confirmed at neck exploration. Two false-positive studies were encountered in patients with no adenoma at operation, probably due to thyroid nodules. The technique was less successful in identifying diffusely hyperplastic parathyroid glands and was negative in a single patient with recurrent, functional parathyroid carcinoma.

Adenoma↗
PubMed1984

Correlation of skeletal uptake of 99mTc-diphosphonate and alkaline phosphatase before and after oral diphosphonate therapy in Paget's disease.

In Paget's disease of bone, quantitation of skeletal uptake of radiolabeled diphosphonate has been proposed as a means of monitoring response to therapy. However, the validity of such techniques has been questioned during oral diphosphonate therapy because of possible interaction between oral and radiolabeled diphosphonate. In the present study 18 patients with Paget's disease received a 6 month course of oral diphosphonate therapy. Measurements of 24 h whole body retention (WBR) of 99mTc-labeled hydroxyethylidene diphosphonate (HEDP), serum alkaline phosphatase (SAP), and urinary hydroxyproline excretion were obtained before, during, and after treatment. WBR correlated well with SAP and urinary hydroxyproline throughout the course of therapy. In addition, the relationship between WBR and SAP was maintained after cessation of oral diphosphonate. It would thus appear that in Paget's disease 24 h WBR of HEDP, a quantitative measure of skeletal uptake of diphosphonate, will reflect disease activity even in the presence of an oral diphosphonate load.

Administration, Oral↗
PubMed1984

Hypercalcaemia of malignancy: evidence for a nonparathyroid humoral agent with an effect on renal tubular handling of calcium.

The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

Adult↗
PubMed1984

Five-year double-blind fluoridated milk study in Scotland.

A 5-yr double-blind fluoridated milk study has been completed and, following baseline stratification, 94 children aged 4 1/2/5 1/2 yr were allocated to the test group and 93 to the control. Each subject received 200 ml school milk daily, identification between the test and control plastic packs being by colour-coding alone with the former containing 1.5 mgF- giving a potential topical benefit of approximately 7 ppmF- per school day. After 5 yr, 50 of the test children remained and 56 of the controls. While the mean DMFT incremental data relating to permanent teeth was always in favour of the test group, it was not until the fourth year that a significant difference was obtained (P less than 0.01) between the fluoridated group (mean, 1.65) and the non-fluoridated group (mean, 2.56). For permanent teeth which were unerupted at baseline, the mean DMFS differences increased to 39.6% at the same time and to 48.0% by the fifth year. No benefit was noted for previously erupted primary teeth. Cavitation was less in the test group throughout the study. When the third, fourth and fifth year DMFT reductions obtained were compared with previously published artificial water fluoridated data where children were of comparable age at the onset of water adjustment, similar caries inhibition data were noted.

Animals↗
PubMed1984

Circulating vitamin D metabolites and hypercalcaemia of malignancy.

Plasma concentrations of 1.25 dihydroxycholecalciferol were measured in 44 patients with malignancy associated hypercalcaemia and related to other hormonal regulators of calcium metabolism. Immunoreactive PTH concentrations were suppressed in all but 2 patients and, as a group, patients with hypercalcaemia of malignancy had lower 1.25 dihydroxycholecalciferol concentrations than normocalcaemic cancer patients. 1.25 dihydroxycholecalciferol concentrations were clearly detectable in a significant proportion (43%) of hypercalcaemia cases however, suggesting that in these patients the active vitamin D metabolite may contribute to the pathogenesis and maintenance of the hypercalcaemia by stimulating bone resorption, and/or by increasing absorption of calcium from the intestine. Measurement of plasma 1.25 dihydroxycholecalciferol concentration does not provide a wholly reliable method for distinguishing the hypercalcaemia of malignancy from primary hyperparathyroidism.

Calcifediol↗
PubMed1983

Pre-operative localisation of parathyroid tumours using neck vein catheterisation and radioimmunoassay for parathyroid hormone: the Glasgow experience.

Reliable pre-operative localisation of parathyroid tumours can be of value in surgery for primary hyperparathyroidism, and particularly so where re-exploration of the neck is required. Neck vein catheterisation and parathyroid hormone radioimmunoassay have been suggested as a sensitive means of tumour localisation, and we report our experience of the technique over the last five years. A total of 46 patients with primary hyperparathyroidism had 50 studies performed with positive localisation and a pre-operative prediction made on 38 occasions (76%). Forty-two operations were carried out and a parathyroid tumour confirmed in 39 cases for a localisation efficiency of 69 per cent. No negative neck exploration followed a positive localisation. Twelve studies were performed in patients with renal osteodystrophy and localisation to a single site was achieved on only three occasions. It is concluded that neck vein catheterisation and parathyroid hormone assay can correctly localise parathyroid tumours in most cases of primary hyperparathyroidism, but it is suggested that its use be restricted to selected cases such as those subjects with previous negative neck exploration or patients for whom prolonged or repeated surgery may be a particular hazard.

Adenoma↗
PubMed1983

The localisation of parathyroid tumours--a comparison of computed tomography with cervical vein hormone assay.

Computed tomography has been employed for the localisation of parathyroid tissue in 26 patients with primary hyperparathyroidism. In 14 of these selective venous catheter studies with parathyroid hormone assay were also undertaken. Computed tomography proved unreliable, identifying only 39 per cent whereas the cervical venous hormone assay studies localised 69 per cent of lesions correctly--a figure which is in agreement with several other groups. On balance our results suggest that neither technique should be routinely employed pre-operatively but that, following unsuccessful parathyroid surgery, the most useful localisation technique remains venous hormone assay.

Adenoma↗
PubMed1983

PTH and vitamin D responses during treatment of hypomagnesaemic hypoparathyroidism.

The response of calcium regulating hormones in a patient with hypomagnesaemic hypoparathyroidism was assessed during magnesium infusion. Magnesium repletion was accompanied by prompt restoration of PTH secretion which subsequently stimulated 1,25-diOHD3 production, thus correcting hypocalcaemia. Further, failure of the patient to respond to previous 1 alpha-OHD3 therapy suggests that severe magnesium depletion may also result in a state of acquired resistance to the active metabolites of vitamin D.

Calcifediol↗