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T Taube

Publications and source records attributed to T Taube.

8 recordsLinked to original sources

Monitoring of multiple myeloma and bone marrow fibrosis with aminoterminal propeptide of type III collagen (PIIINP).

Bone marrow fibrosis is known in myelomatosis and depends on the extent of plasma cell infiltration. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) has previously been reported to reflect fibrogenesis in the marrow in myelofibrosis. Here we followed 15 consecutive patients with newly diagnosed multiple myeloma with repeated PIIINP measurements during treatment with intermittent courses of melphalan and prednisolone. PIIINP was found to change with clinical behaviour of the disease, nonresponders and patients with recurrent disease having elevated values and the values in responders decreasing to the normal level or remaining there. Collagen fibres in plasma cell infiltrates of biopsies from bone marrow or skeletal tumours of these patients stained heavily with antibodies against PIIINP. Our results suggest that PIIINP works as a noninvasive indicator of bone marrow fibrogenesis. In multiple myeloma PIIINP is a sensitive, but not specific marker of disease course.

Adult

Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption.

We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption--as judged by the eroded surface--increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.

Alkaline Phosphatase

Rationale for the use of bisphosphonates in bone metastases.

Neoplasia affecting the skeleton is an important cause of morbidity, which includes hypercalcaemia, bone pain and fracture. In most instances these events are mediated by an increase in the resorption of bone which decreases bone density and disrupts skeletal architecture, either at focal sites or generally throughout the skeleton. Neoplastic activation of bone resorption in heterogeneous, but there is now good evidence that this is due to the increased activation of osteoclasts, the cells which mediate bone resorption in health. Bisphosphonates are specific inhibitors of osteoclast-mediated bone resorption and are capable of inhibiting osteoclastic activation independent of the mechanism of its stimulation. This provides the rationale for the use of bisphosphonates in the hypercalcaemia of malignancy. Despite refinements in the use of endocrine therapy, chemotherapy and radiotherapy these interventions have had relatively little impact on the skeletal morbidity or mortality of common malignancies affecting the skeleton, particularly breast cancer and myelomatosis. In addition, there is good evidence that skeletal disease is progressive in many patients despite the use of chemotherapy and radiotherapy. Since accelerated bone resorption can be inhibited by long-term treatment with bisphosphonates, their use is likely to decrease skeletal complications such as bone pain and fracture. The bisphosphonates, therefore, hold great promise as agents to improve the quality of life of such patients.

Bone Neoplasms

Aminoglutethimide for advanced prostatic cancer resistant to conventional hormonal therapy.

Aminoglutethimide (AG) and hydrocortisone (HC) were given to 20 patients with advanced prostatic cancer resistant to conventional hormonal therapy. Most patients had painful bone metastases and were heavily pretreated. 12 of 16 patients required narcotic analgetics. 8 of 20 were bedridden. AG + HC produced relief of bone pain in 12 patients (75%) and only 4 required narcotics after treatment. The performance status improved in 8 of 20 patients (40%). However, the number of bone metastases seen in bone scans decreased in only 4 patients (22%). The level of serum alkaline phosphatase decreased in 11 of 18 patients and that of acid phosphatase in 8 of 16 patients. The reduction of bone pain lasted approximately 4 months (range 1-15 months). The median lifespan between the start of AG treatment and death was 8 months (range 2-22 months). There was no difference in survival between responders and nonresponders. 3 patients had skin rash, 1 lethargy and 1 thrombocytopenia.

Aged

Clodronate for osteolytic metastases due to breast cancer.

Breast-cancer patients with multiple osteolytic bone metastases were treated with clodronate (Cl2MDP) 1.6 g/day (17 patients) or placebo (17 patients) for 12 months. Bone pain, extension of bone metastases and formation of new osteolytic foci were reduced by Cl2MDP, and development of severe hypercalcaemia was prevented. After withdrawal of treatment, the patients were followed up for at least 12 months. New bone metastases developed in both groups. There were, however, less fractures and less hypercalcaemia in the Cl2MDP than in the placebo group. The survival rate was higher in the Cl2MDP group than in the placebo group. No side-effects were observed in the Cl2MDP group.

Aged