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Biomedical subjects

T Taube

Publications and source records attributed to T Taube.

15 recordsLinked to original sources
PubMed1997

Concomitant i.v. and oral clodronate in the relief of bone pain--a double-blind placebo-controlled study in patients with prostate cancer.

Fifty-seven patients with advanced prostate cancer resistant to first-line hormonal therapy were treated with estramustine and additionally randomized for treatment with clodronate or placebo. Clodronate treatment was started with 5 days intravenous administration (300 mg day[-1]) and followed by oral treatment (1.6 g day[-1]) for 12 months. Skeletal pain relief was only about 10% better in the clodronate than in the placebo group. The results do not support the superiority of combined intravenous and oral treatment with clodronate compared with oral administration only.

Administration, Oral↗
PubMed1997

Multiplex PCR for simultaneous detection of the most frequent T cell receptor-delta gene rearrangements in childhood ALL.

A rapid and simple multiplex polymerase chain reaction (PCR) is described that is capable of identifying the six most frequent rearrangements of the T cell receptor (TCR)-delta gene segments in childhood acute lymphoblastic leukemia (ALL). The PCR products amplified in a single reaction are of different size for each TCR-delta gene rearrangement. Therefore, they are readily and unambiguously distinguished after agarose gel electrophoresis and assigned to a specific V-D-J gene rearrangement. There is no need for labor-intensive and time-consuming Southern blot hybridization or nested PCR. To evaluate the multiplex assay we chose 45 DNA samples of childhood ALL analyzed beforehand for TCR-delta gene rearrangements by Southern blot and single PCR of which 30 showed TCR-delta gene rearrangements. The multiplex PCR results corresponded to the Southern blot and single PCR analyses. The described multiplex PCR enables the detection of clonal markers in about 50% of patients in order to monitor minimal residual disease (MRD) in prospective studies with a high turnover of samples.

Blotting, Southern↗
PubMed1994

The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study.

57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkaline phosphatase, prostate-specific antigen and creatinine were made at the time of both bone biopsies and at 1 month. Serum intact parathyroid hormone and vitamin D metabolites were measured at admission and at 3 months. Because of several discontinuations, the study groups at final analysis comprised 20 patients taking E + C and 19 patients taking E and placebo. Bone resorption, as judged by eroded surface and osteoclast number, was markedly increased especially in biopsies taken from tumour-involved bone. Treatments with E + C or E both induced a significant decrease in bone resorption, but were associated with the development of hypocalcaemia, secondary hypoparathyroidism, hypophosphataemia and severe impairment of mineralisation of newly formed bone, i.e. osteomalacia. Since the patients were not vitamin D deficient, we conclude that osteomalacia resulted from a relative deficiency of calcium and phosphate. The transiency of pain relief achieved with anti-resorptive agents in the treatment of bone metastases from prostate cancer may be due to the development of osteomalacia.

Aged↗
PubMed1993

Comparative effects of clodronate and calcitonin on bone in metastatic breast cancer: a histomorphometric study.

We studied the effects of long-term treatment with clodronate, calcitonin or placebo on bone in 36 normocalcaemic women with osteolytic metastases due to breast cancer. Clodronate (1.6 g daily given to 12 patients) induced a significant decrease in osteoclast surface and osteoclast number, and a significant fall in serum calcium and urinary excretion of calcium and hydroxyproline, an effect not noted after treatment with calcitonin (100 U in 12 patients) or in 12 placebo-treated patients. Treatment with clodronate did not abnormally suppress bone turnover nor impair mineralisation, as measured by bone formation and mineral apposition rates.

Adult↗
PubMed1993

Evaluation of the effect of oral clodronate on skeletal metastases with type 1 collagen metabolites. A controlled trial of the Finnish Prostate Cancer Group.

Clodronate relieves bone pain in patients with skeletal metastases. Since the pain relieving mechanism of clodronate may be associated with the antiosteoclastic activity, we have investigated whether the drug has simultaneous actions on bone resorption and pain. Although osteosclerotic metastases are characteristic of prostate carcinoma, bone resorption is also accelerated. The resorbing process can be investigated using a specific immunoassay for ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) which allows the measurement of the degradation of type I collagen in serum samples. We have also determined serum concentration of PICP (carboxyterminal propeptide of type I procollagen) which reflects the synthesis of type I collagen (osteoid). Patients who have relapsed after first-line hormonal therapy, were randomised to receive estramustine phosphate (E) with or without clodronate (C) (E + C, n = 50; E, n = 49). The dose of E was 560 mg and that of C 3.2 g for the first month, thereafter 1.6 g. We saw elevated ICTP and PICP levels in the majority of the patients. A transient decrease in ICTP values occurred simultaneously with pain relief. The changes were more accentuated in the E + C than in the E group but the difference was not significant. In each group serum phosphate concentration decreased markedly (P = 0.001) whereas the activity of alkaline phosphatase remained increased, both indicating a development of osteomalacia during E therapy. The short-term antiosteoclastic effect of C may be explained by the dose reduction, hyperosteoidosis and osteomalacia which inhibit the binding of C on the crystal surfaces and by the late phase of disease.

Administration, Oral↗
PubMed1993

Distinction between focally accelerated bone formation and osteomalacia in carcinoma of prostate metastasised to bone.

We studied the histological indices of skeletal turnover in 40 patients with carcinoma of the prostate and skeletal metastases in order to determine the prevalence of osteomalacia. In 20 patients biopsied through uninvolved bone, the histological indices of bone turnover were normal. In particular, osteoid seam width and bone formation rates were consistently normal, indicating the absence of osteomalacia. In biopsies from tumour-laden bone, hyperosteoidosis was present, usually associated with increased amounts of woven collagen and consistently associated with high rates of bone formation and mineralisation. It was concluded that hyperosteoidosis in prostatic cancer is rarely due to osteomalacia.

Adult↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMedDate not supplied

Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer.

We studied bone biopsies from 65 normocalcaemic women with breast cancer and predominantly osteolytic bone metastases in order to examine the pathophysiology of bone destruction in metastatic bone disease. Quantitative histomorphometric measurements were made at sites of tumour involvement, at sites adjacent to tumour tissue and at sites distant from tumour tissue. There were no significant differences in bone volume or in indices of bone resorption or formation between biopsies taken from sites distant from tumour and the controls. Bone resorption, as judged by eroded surface, increased progressively from bone distant from tumour to tumour-laden bone. The number of osteoclasts was significantly increased in bone immediately adjacent to tumour and within metastases. There was no decrease in the ratio of osteoclast to eroded surface in breast cancer compared to controls suggesting that increased resorption in breast cancer was mainly osteoclast mediated and locally activated by the tumour. Two thirds of the biopsies taken from tumour involved regions showed osteosclerosis with woven bone formation. The volume of the pre-existing lamellar trabecular bone was lower than normal in 75% of these biopsies, suggesting that bone resorption must have been increased before the onset of woven bone formation. Since all patients were receiving hormonal treatment or chemotherapy, it is likely that osteosclerosis at sites of previous resorption mainly resulted from the basic cancer treatment as a sign of response to treatment. Osteoclastic bone resorption was, however, not completely inhibited by the active cancer treatment.

Adult↗