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Biomedical subjects

D L Douglas

Publications and source records attributed to D L Douglas.

35 records · Page 2Linked to original sources
PubMed1983

Drug treatment of primary hyperparathyroidism: use of clodronate disodium.

Clodronate disodium (dichloromethylene diphosphonate), a specific inhibitor of bone resorption, was given by mouth (1.0-3.2 g daily) to nine patients with primary hyperparathyroidism for two to 32 weeks so that its clinical and metabolic effects could be evaluated. Bone resorption decreased in all patients as judged by a fall in the fasting urinary calcium to creatinine and hydroxyproline to creatinine ratios. Serum calcium concentration was increased in all patients before treatment and fell in response to treatment to values near the upper end of the normal range. Hypercalcaemia and hypercalciuria recurred when treatment was stopped. In three patients treated for longer than 19 weeks clodronate failed to sustain the reduction in serum calcium concentration but the concentration remained below pretreatment values. These results suggest that clodronate may be of use in the medical management of primary hyperparathyroidism, particularly in patients in whom suppression of bone disease is desirable before surgery or in whom surgery is contraindicated.

Aged↗
PubMed1983

The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma.

We have assessed the effects of the diphosphonate, dichloromethylene diphosphonate (Cl2MDP), in 19 patients with hypercalcaemia and increased bone resorption due to myeloma. Cl2MDP (800-3200 mg daily by mouth or 300 mg daily by intravenous infusion) decreased plasma calcium and biochemical indices of increased bone resorption in 16 of 19 patients. This effect persisted for the duration of treatment (up to 14 weeks). Prolonged treatment was associated with a progressive rise in serum alkaline phosphatase and only a transient fall in hydroxyproline suggesting the stimulation of bone repair. Since myeloma is associated with significant morbidity and mortality due to progressive bone loss, these results suggest that long-term treatment of myeloma with Cl2MDP is worthy of further study.

Aged↗
PubMed1982

Ultrastructural features of the osteoclasts from Paget's disease of bone in relation to a viral aetiology.

The ultrastructure of the osteocytes, osteoblasts, osteoclasts, haemopoietic and other connective tissue cells was examined in 27 biopsies from 22 patients with Paget's disease of bone. Electron microscopy showed characteristic nuclear and cytoplasmic inclusions in the osteoclasts of all of the 25 biopsies exhibiting histological evidence of Paget's disease. Such inclusions were absent from all the other types examined. The intranuclear inclusions consisted of stacked rows or complex whorls of tubular filaments with an individual filament diameter of 12-15 nm, often arranged in a paracrystalline array. The frequency of occurrence of inclusions in the osteoclasts and their individual nuclei measured quantitatively in 18 of the biopsies was related to the histological severity of the disease process. The similarity of the observed inclusions to those of paramyxovirus inclusion bodies (particularly measles) support the hypothesis that Paget's disease is a slow virus infection.

Adult↗
PubMed1981

Effects of 24,25-dihydroxy-vitamin D3 on its plasma level in man.

Small doses of 24,25-dihydroxy-vitamin D3 (24,25(OH)2D3; 2 micrograms daily) given by mouth increased plasma levels of 24,25(OH)2D3 several-fold in normal subjects and in patients with metabolic bone disease. When oral treatment was stopped, or following the intravenous administration of 24,25(OH)2D3, plasma disappearance of 24,25(OH)2D3 was slow (t1/2 approx. 16 days). This suggests that the endogenous production rate of 24,25(OH)2D3 is similar to that of 1,25(OH)2D3 (less than 2 micrograms daily) but that its metabolic clearance is much slower. The slow metabolic clearance of 24,25(OH)2D3 may explain why plasma levels of this metabolite are about 100 times higher than those of 1,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Biochemical markers of bone turnover in Paget's disease.

The two most commonly used biochemical markers of bone turnover are the serum alkaline phosphatase and the urinary excretion of peptide-bound hydroxyproline, both of which are increased in Paget's disease. Serum alkaline phosphatase is assumed to be derived from osteoblasts during the process of bone formation, whereas small peptides containing hydroxyproline are excreted in the urine following the degradation of bone collagen. The alkaline phosphatase is probably the more useful measurement for diagnosis and for following response to treatment, whereas hydroxyproline, although very sensitive, presents technical difficulties in collection and measurement. Several other biochemical changes in Paget's disease indicate abnormal bone metabolism. These include increased urinary excretion of hydroxylysine and its glycosides derived from collagen, as well as the release into the circulation and subsequent urinary excretion of fragments of pro-collagen indicative of increased collagen formation. Proteins specific to bone, such as osteocalcin, are increased in serum, bone, such as osteocalcin, are increased in serum, as are various enzymes possibly derived from bone cells, including acid phosphatase and proline imino-peptidase. Treatment of Paget's disease results in a fall in urinary hydroxyproline before alkaline phosphatase. This indicates that drug treatment, whether with diphosphonates, calcitonin or mithramycin, has a primary action to inhibit bone resorption, with a subsequent adaptive reduction in bone formation rate.

Alkaline Phosphatase↗
PubMed1981

Paget's disease: improvement of spinal cord dysfunction with diphosphonates and calcitonin.

The clinical and radiographic features of spinal cord dysfunction secondary to Paget's disease are described. Long-term medical management with the use of the diphosphonates, calcitonins and mithramycin resulted in marked and rapid clinical improvements in 8 of 10 of our own patients. These results are comparable to those seen in 19 other patients previously described in the literature, and are also similar to those obtained by surgical treatment. The recurrence rate and mortality (approximately 10%) of surgical treatment suggest that drug treatment now has a place in the management of paraparesis, particularly when this is of gradual onset. Medical management may also provide a valuable adjunct in those cases where surgery is required (e.g. sudden onset of paraparesis). In patients with cord dysfunction, but without significant anatomical compression of the spinal cord, it is suggested that paraparesis may be caused by a "vascular steal" syndrome, a notion which is supported by the rapidity with which drug-induced remission occurs.

Adult↗
PubMed1981

Spinal cord dysfunction in Paget's disease of bone. Has medical treatment a vascular basis?

The medical treatment of eight patients with paraparesis associated with Paget's disease of the vertebrae is described. Treatment, for 3 to 87 months, with calcitonin or with diphosphonates produced marked clinical improvement in seven of these patients. From this series and a review of 19 additional case reports it is concluded that favourable clinical response is seen in about 90 per cent of patients, and that this may occur very rapidly. Results are as good or better than those obtained by surgical decompression. It seems possible that paraparesis in some cases may be due to diversion of blood supply from the spinal cord to the highly vascular Pagetic bone giving rise to a vascular "steal" syndrome. It is suggested that medical treatment should be used more widely to avoid or delay the need for operation and reduce the risks of recurrence. These patients, however treated, require lifelong follow-up because relapses are common.

Adult↗
PubMed1980

Effect of dichloromethylene diphosphonate in Paget's disease of bone and in hypercalcaemia due to primary hyperparathyroidism or malignant disease.

30 patients with disorders of calcium metabolism were treated with dichloromethylene diphosphonate (C1(2)MDP, or clodronate disodium), an inhibitor of bone resorption. 13 patients with Paget's disease of bone were given C1(2)MDP by mouth (1.6 g/day). Serum-alkaline-phosphatase and urinary hydroxyproline fell to normal or near-normal within 3-7 months, and there was a clinical improvement in all but 1 patient. C1(2)MDP (0.8-3.2 g/day) also reduced plasma-calcium and urinary calcium in 17 patients with hypercalcaemia due to primary hyperparathyroidism or secondary to malignant disease. C1(2)MDP seems to be an effective oral drug for inhibiting excessive bone resorption in man.

Alkaline Phosphatase↗
PubMed1980

Biochemical and clinical responses to dichloromethylene diphosphonate (Cl2MDP) in Paget's disease of bone.

Dichloromethylene diphosphonate (Cl2MDP, or clodronate disodium) is one of the most potent of the known diphosphonates as an inhibitor of bone resorption and differs from EHDP in that it does not inhibit skeletal mineralization. It is one of the second generation diphosphonates now undergoing clinical evaluation. In the study described here Cl2MDP was given by mouth (800-1600 mg/day for 6 months) to 35 patients with symptomatic Paget's disease of bone. Cl2MDP induced a marked fall in serum alkaline phosphatase and urinary hydroxyproline to normal or near normal values in all patients. This was accompanied by clinical improvement in all but 4 patients. Cl2MDP appears to be another effective oral drug for the treatment of Paget's disease of bone and compares favorably with the calcitonins and EHDP.

Alkaline Phosphatase↗
PubMed1980

Dual primary adenocarcinoma of the duodenum and jejunum in a patient with previous colonic cancers.

Primary adenocarcinoma of the small intestine is an uncommon tumour, the incidence being 40-60 times less frequent than carcinoma of the colon. Multiple primary neoplasia of the small bowel, although not infrequently seen with benign growths, is an extremely rare event with malignant lesions. A patient is described who had an adenocarcinoma of the duodenum and jejunum, with a previous history of colonic carcinomas. The case is discussed together with a brief review of the literature.

Adenocarcinoma↗
PubMed1975

Evaluation of diagnostic ultrasound in gynecology.

The experience with 300 consecutive gynecologic patients undergoing diagnostic ultrasound has been evaluated. Follow-up was obtained by recording the clinical course and/or the operative findings. The ultrasound studies were diagnostic in 21 per cent, confirmatory in 74 per cent, and misleading in 5 per cent of the patients. Certain conditions lend themselves to diagnosis with ultrasound: hydatidiform mole, intrauterine pregnancy, dermoid cyst, ascites, simple ovarian cyst, and lost intrauterine contraceptive devices (IUCD's). The studies in patients with chronic pelvic inflammatory disease or adhesions were occasionally misleading. Diagnostic ultrasound was particularly helpful in the obese patient, in whom adequate pelvic examination was difficult.

Adnexal Diseases↗
PubMedDate not supplied

Spontaneous fractures in a patient treated with low doses of etidronic acid (disodium etidronate).

The recommended regimen of etidronic acid (disodium etidronate) for the treatment of Paget's disease of bone is 5mg/kg/day for a period of less than six months. There have, however, been reports of impaired mineralisation of bone and concern that the risk of fracture is increased with this dosage. We report a patient with Paget's disease in whom fractures occurred through pagetic and non-pagetic bone which appeared to be causally related to treatment with lose doses of etidronic acid. The osteomalacia resolved when etidronic acid was discontinued.

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