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Biomedical subjects

G H Urwin

Publications and source records attributed to G H Urwin.

15 recordsLinked to original sources

Effects of intravenous etidronate disodium on skeletal and calcium metabolism.

The induction of hypercalcemia in malignant disease is almost invariably associated with increased bone resorption. However, tumor-induced changes in bone formation and renal tubular resorption of calcium are also important factors that induce hypercalcemia in some patients. In addition, alterations in calcium fluxes to and from the extracellular fluid secondary to hypercalcemia are important in maintaining or aggravating the hypercalcemic effects of increased bone resorption. These factors significantly affect the responses to treatment of hypercalcemia with inhibitors of bone resorption. This study examined the relative importance of these factors and the effects of intravenous etidronate disodium (etidronate) in neoplastic bone disease with and without hypercalcemia and in Paget's disease of bone. It is concluded that intravenous etidronate is an effective inhibitor of bone resorption, which accounts in large measure for its effects on serum calcium concentrations. These studies of etidronate in hypercalcemia suggest the response is sustained for several weeks.

Aged

Aminohexane diphosphonate in the treatment of Paget's disease of bone.

We studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long-term control of Paget's disease.

Administration, Oral

Treatment of the hypercalcaemia of malignancy with intravenous clodronate.

We studied the effects of intravenous clodronate (100-300 mg daily for 3-10 days) in 27 episodes of hypercalcaemia due to malignancy. Comparisons were also made between responses in patients with haematological malignancies and those with solid tumours. Following extracellular volume expansion, clodronate induced a significant decrease in serum calcium within 2 days of the start of treatment which was maximal at 7 days. This was associated with a decrease in bone resorption as judged by decreases in urinary excretion of hydroxyproline and calcium. Hypercalcaemia recurred 5-7 days after stopping treatment. Patients with solid tumours had higher pretreatment serum calcium values than those with haematological malignancies despite comparable values for fasting urinary excretion of calcium suggesting that renal tubular reabsorption of calcium was more markedly increased in patients with solid tumours. No difference was observed in the final calcium values between patients with solid tumours and haematological malignancies except in those patients in whom renal tubular reabsorption of calcium was markedly increased before treatment. We conclude that intravenous clodronate provides a safe and effective treatment of hypercalcaemia due to a wide range of tumour types provided that increased bone resorption contributes significantly to the hypercalcaemia. When increased renal reabsorption of calcium is the predominant mechanism for the maintenance of hypercalcaemia, the response to clodronate is incomplete.

Adult

Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption.

We have investigated the hypothesis that carcinoma of the prostate with skeletal metastases is associated with increased bone resorption. In 54 affected patients a close correlation was observed between serum activity of alkaline phosphatase and urinary excretion of hydroxyproline (r = +0.818; P less than 0.001), comparable to that seen in Paget's disease of bone. The administration of synthetic salmon calcitonin (100 U subcutaneously) induced a significant fall in serum calcium and urinary excretion of hydroxyproline, proportional to the prevailing rate of bone turnover, as assessed by serum alkaline phosphatase or hydroxyprolinuria. Administration of the diphosphonate, etidronate, also decreased hydroxyprolinuria, suggesting that urinary hydroxyproline reflected increased rates of bone resorption in this disorder. Histology of bone in sites adjacent to and distant from skeletal metastases showed increased histological indices of bone resorption. These results suggest that the skeletal disease associated with prostatic carcinoma is characterized by generalized increases in bone resorption as well as focal increases in bone formation.

Aged

Intravenous clodronate in the treatment and retreatment of Paget's disease of bone.

The effects of short courses (5 days) of intravenous clodronate 300 mg daily were studied in 31 patients with active Paget's disease of bone. The diphosphonate induced a striking reduction in biochemical indices of disease activity, which was sustained for at least 6 months after withdrawal of treatment. Apparent resistance to further treatment in patients previously treated for Paget's disease was an artefact due to incomplete relapse before retreatment. There was no significant difference in the degree of suppression of alkaline phosphatase activity between patients given intravenous clodronate and 45 patients given clodronate 1.6 g daily by mouth for 6 months. Short-term intravenous clodronate provides a useful alternative strategy for the treatment of patients with Paget's disease.

Administration, Oral

Thallium-technetium subtraction scintigraphy as an aid to parathyroid surgery.

We describe the application of thallium-technetium subtraction scintigraphy in nine patients with failed previous parathyroid surgery or with tertiary hyperparathyroidism due to chronic renal failure. The technique successfully located all adenomas, but only 45% of hyperplastic glands. The series included three abnormal glands located retrosternally. The technique appeared to be more useful in patients with primary hyperparathyroidism than in tertiary hyperparathyroidism, possibly related to differences in gland mass. We conclude that this method of scintigraphy is a valuable adjunct to the management of patients with parathyroid disorders, particularly those requiring revision surgery.

Adenoma

Biochemical markers and skeletal metabolism in carcinoma of the prostate. Use of decision matrix theory and ROC analysis.

The discriminative ability of several skeletal and tumour markers was assessed in 102 patients with prostatic disease. These comprised serum acid and alkaline phosphatase, serum albumin and osteocalcin, urinary excretion of calcium, hydroxyproline and 6-oxo prostaglandin F1 alpha. None of the tests was of value in distinguishing patients with benign prostatic disease from those with tumour not involving the skeleton. Values of serum osteocalcin, urinary excretion of calcium and urinary 6-oxo prostaglandin F1 alpha failed to discriminate significantly between patients with or without metastases. The remaining four markers were compared by decision matrix analysis and receiver operating characteristic (ROC) curves. Serum alkaline phosphatase provided the most sensitive marker of skeletal metastases (80.5%), followed by serum acid phosphatase (80%), hydroxyproline (68%) and albumin (30%). ROC analysis suggested that alkaline phosphatase conformed most closely to the "ideal marker" with highest specificity and sensitivity.

6-Ketoprostaglandin F1 alpha

Generalised increase in bone resorption in carcinoma of the prostate.

Several indirect biochemical indices of bone resorption are increased in patients with carcinoma of the prostate and skeletal metastases. We have examined histological indices of bone resorption in biopsies from affected patients. Bone-forming surfaces and active osteoblast numbers were increased in skeletal sites adjacent to tumour tissue and indices of bone resorption were significantly increased at sites adjacent to tumour. Contrary to expectation, indices of bone resorption were also increased in bone distant from skeletal metastases. These findings suggest that prostatic cancer induces generalised loss of trabecular bone which may minimise disturbances in plasma calcium homeostasis but could contribute to morbidity.

Bone Neoplasms

Assessment of thallium-pertechnetate subtraction scintigraphy in hyperparathyroidism.

Reliable techniques for detecting and localising abnormal parathyroid tissue have been a persistent problem. We have evaluated thallium-pertechnetate subtraction scintigraphy in a prospective study of 40 patients with clinical and biochemical evidence of hyperparathyroidism prior to parathyroid surgery. Four patients were excluded as they were shown to have goitre, making subtraction scanning non-diagnostic. 89% of parathyroid adenomas (totalling 27 glands in 26 patients) and 41% of hyperplastic glands (17 glands in 6 patients) were accurately localised prior to surgery. These included three retrosternal glands, four patients with renal failure and tertiary hyperparathyroidism and five patients who had previously undergone neck exploration. The apparent discrepancy between detecting hyperplastic and adenomatous glands was associated with the smaller size of the former. For both types of gland, scintigraphy successfully located parathyroids 0.6 g or more in weight. These results suggest that this simple and non-invasive method is a useful technique for locating parathyroid tissue before parathyroid surgery.

Adenoma