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R C Percival

Publications and source records attributed to R C Percival.

At least 19 recordsLinked to original sources

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

Thallium-pertechnetate subtraction scintigraphy: a quantitative comparison between adenomatous and hyperplastic parathyroid glands.

In a prospective study of 201Tl-99mTc subtraction scintigraphy, 61 hyperparathyroid patients were investigated prior to neck exploration. At surgery, 46 adenomatous and 28 hyperplastic parathyroid glands were excised. We examined the relationship between the pathological category of these glands, their mass, uptake of 201Tl thallous chloride, and the frequency of true-positive and false-negative scintigraphic findings. The variation of sensitivity with parathyroid mass was found to be similar for both adenomatous and hyperplastic glands, with a detection threshold that lay in the range 0.3-0.8 g. The higher overall sensitivity for the detection of adenomas (85%) compared with hyperplasias (44%) was due to the smaller mean weight of the latter. When the parathyroid uptake of thallium was quantified scintigraphically, the practical detection limit of subtraction scanning was found to be an uptake of 0.015%. For glands greater than 1.5 g in weight, uptake increased linearly with mass, and specific uptakes were within the range 0.01-0.04%/g. Below lg, certain small glands had much higher specific uptakes, up to 0.2%/g. The range of specific uptakes found was similar for both adenomatous and hyperplastic categories. Multinodular or diffuse goitre was a cause of failure in 10% of investigations. In a further 5%, a solitary thyroid nodule gave rise to a false-positive result.

Adenoma

Skeletal effects of carcinoma of the breast and prostate.

Recent research has led to improved understanding of the pathology of skeletal metastases in carcinoma of the breast and prostate. Several humoral mechanisms have been identified which have both primary and secondary consequences on skeletal metabolism and probably depend on the complex interplay of a number of factors derived from tumour tissues. An improved understanding of these interactions may lead to new approaches in the management of these common disorders.

Bone Neoplasms

Mechanism of malignant hypercalcaemia in carcinoma of the breast.

To investigate the mechanisms of hypercalcaemia in carcinoma of the breast, 22 patients with hypercalcaemia due to metastatic carcinoma were studied and the findings compared with those obtained in normal subjects and patients with benign and malignant breast disease without hypercalcaemia. As expected, patients with metastases of bone showed biochemical evidence of increased bone resorption. Whereas all patients with hypercalcaemia had skeletal metastases, not all patients with skeletal metastases had hypercalcaemia despite considerable degrees of bone resorption. The presence of hypercalcaemia was associated with a significant increase in renal tubular reabsorption of calcium (p less than 0.001) and decreased reabsorption of phosphate (p less than 0.001) despite adequate rehydration of patients. These studies suggest that increased renal tubular reabsorption of calcium, possibly mediated by a humoral factor with activity similar to that of parathyroid hormone, contributes appreciably to the hypercalcaemia of malignant breast disease.

Absorption

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

Treatment of malignant hypercalcaemia with clodronate.

We have assessed the effects of clodronate (dichloromethylene diphosphonate; Cl2MDP 0.8-3.2g daily by mouth for up to 3 months) in 17 episodes of hypercalcaemia and osteolysis due to carcinoma. Clodronate reduced serum calcium in 14 episodes and bone resorption in all patients. These remained suppressed for the duration of treatment, but recurred promptly when treatment was stopped. Clodronate may be a useful measure for controlling hypercalcaemia and osteolysis in patients with carcinoma.

Adult

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

Carcinoma of the prostate: remission of paraparesis with inhibitors of bone resorption.

We describe a patient with metastatic carcinoma of the prostate associated with paraplegia. The patient also had Paget's disease of bone elsewhere. Because the neurological lesion was thought to be due to Paget's disease, the patient was treated with inhibitors of bone resorption. Treatment rapidly induced clinical remission and inhibition of bone resorption, and withdrawal was associated with relapse. This suggests that such agents may be of value in the treatment of bone disease of prostatic carcinoma.

Aged

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

The mechanism of hypocalcaemia following thyroidectomy.

The mechanism of transient hypocalcaemia following thyroidectomy was studied in 29 consecutive patients undergoing thyroid surgery. Eight of 27 (30%) patients who had a partial thyroidectomy developed transient hypocalcaemia. Hypocalcaemia was attributable to a reduction in renal tubular reabsorption of calcium (P less than 0.05), but was not associated with changes in serum values of immunoassayable parathyroid hormone or calcitonin.

Adult