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Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 127 records · Page 7Linked to original sources
PubMed1988

Hypercalcaemia and breast cancer--an increased humoral component in patients with liver metastases.

One hundred and forty-seven patients with hypercalcaemia and advanced breast cancer have been reviewed. One hundred and twenty-five (85%) had definite bone metastases but in 22 (15%) there was no radiographic evidence of skeletal involvement. Sixty-eight (46%) patients also had liver metastases. These were present in 15/22 (68%) without definite skeletal involvement and 53/125 (42%) with bone metastases (P = less than 0.05). In a series of 498 patients with first relapse in bone after primary treatment hypercalcaemia was more common after the development of liver metastases than in patients with disease remaining confined to the skeleton (31% v 15%; P = less than 0.001). A subsequent prospective biochemical study of 35 patients with hypercalcaemia suggested that a humoral factor was more pronounced in 18 with liver metastases. In this group renal tubular reabsorption of calcium was higher, serum phosphate and tubular reabsorption of phosphate lower, and cyclic AMP excretion was increased. The data suggest that there is an association between the presence of liver metastases and the development of hypercalcaemia in patients with breast cancer. The mechanisms by which liver involvement may contribute to the pathogenesis of hypercalcaemia are not known but could arise from either increased production or decreased clearance of a humoral factor.

Bone Neoplasms↗
PubMed1988

Comparison of 99Tcm-labelled MDP and DMAD bone scanning agents in patients with advanced breast cancer.

The detection of focal pathology on a bone scan is dependent on the contrast between uptake in a lesion compared with the affinity of the scanning agent for the surrounding normal bone. Dimethyl-amino diphosphonate (DMAD) has a relatively low uptake in normal bone compared with methylene diphosphonate (MDP). We have compared the bone scan appearance with MDP and DMAD in 11 patients with multiple bone metastases from breast cancer. The median time between scans was 7 days (range 6 to 14). In two patients additional lesions were identified on the DMAD scan. No additional lesions were visible on the MDP scans. In five patients some lesions were visualized more clearly with DMAD and others with MDP. In six patients no differences were seen. Anatomical resolution was generally less clear with DMAD and precise anatomical localization was sometimes impossible. We have demonstrated superior lesion detection with DMAD. The clinical value of this for the detection of early relapse of disease in the skeleton requires further study.

Bone Neoplasms↗
PubMed1988

Bone scan flare predicts successful systemic therapy for bone metastases.

Changes in osteoblast function, assessed by serial bone scans and serum alkaline phosphatase bone isoenzyme (ALP-Bl) and osteocalcin, have been studied in 53 patients receiving systemic therapy for bone metastases from advanced breast cancer. In 12/16 patients with healing of lytic disease on x-ray a paradoxical deterioration in the bone scan appearances after 3 mo treatment was seen. This was characterized by increased activity in baseline lesions and the appearance of new foci of tracer uptake; changes which are indistinguishable from progressive disease. After 6 mo successful treatment the bone scan improved with reduced tracer uptake and no new lesions since the 3-mo scan. New lesions appearing after 6 mo indicated progressive disease. These changes are attributed to a flare in osteoblast activity induced by successful systemic therapy and confirmed by a transient rise in osteocalcin and ALP-Bl. After 1 mo of treatment 15/16 responders showed a rise in both parameters compared with only 5/23 nonresponders (p = less than 0.001). The flare response is the rule rather than the exception after successful systemic therapy for bone metastases. The appearance of new lesions or increasing activity in known lesions during the first 3 mo is as likely to herald radiological response as disease progression.

Adult↗
PubMed1988

Transcatheter embolisation to control severe bleeding in fungating breast cancer.

Severe and recurrent haemorrhage from ulcerating breast or skin lesions was controlled in seven of nine women with breast cancer. Arterial catheterisation and embolisation with a variety of materials (gelfoam, polyvinyl alcohol, steel coils, 50% dextrose) was used. Local anaesthesia only was needed, allowing very ill patients to be treated. This approach is the treatment of choice for severe haemorrhage in breast cancer.

Adenocarcinoma, Papillary↗
PubMed1988

Reappraisal of the baseline bone scan in breast cancer.

Baseline staging bone scans in 1,267 consecutive women with breast cancer attending a single clinic between 1980 and 1986 were reviewed. 0.3% of patients with T1, 3% with T2, 8% with T3, 13% with T4 tumors and none of those with Stage 1, 3% with Stage 2, 7% with Stage 3, and 47% with Stage 4 disease had a positive scan due to bone metastases. Two hundred eight-nine (23%) had bone scan abnormalities secondary to radiologically confirmed benign bone disease. In 20 patients, no cause for a bone scan abnormality could be found after a median follow-up of 3.50 yr, a false-positive frequency of 1.6%. The false-negative rate was 0.08%. It is concluded that patients with tumors less than 2 cm are most unlikely to have a positive scan. In this instance, scans are not required routinely. However, we recommend a baseline scan in all patients with Stage 2, 3, or 4 disease.

Bone Neoplasms↗
PubMed1987

Characterization and biological relevance of a 29-kDa, oestrogen receptor-related protein.

The properties of a monoclonal antibody (D5) that can immunoprecipitate human oestradiol receptor (ER) under some but not all conditions are described. The antibody recognises a 29-kDa serine phosphoprotein that is qualitatively and quantitatively related to ER but not other steroid receptors or binding proteins. p29 will not complex with untreated cytosol ER but, after ammonium sulphate, KCl, heat or phosphatase treatments, interaction occurs that can be detected by immunoprecipitation with D5; molybdate and GTP inhibit complex formation. In human endometrium, p29 is increased by oestrogen and decreased by progestins. IRMA and histochemical assays for p29 have been developed and applied to a large series of human breast tumours. Most, but not all ER+ tumours are p29+, whilst ER-tumours are rarely p29+ unless they are also PR+. p29 predicts for clinical response to hormone therapy. ER+ p29+ tumours have a higher response rate than the ER+ p29-tumours. We do not know if p29 is a previously undetected component of the oestradiol receptor machinery or whether it is a product of oestrogen action.

Antibodies, Monoclonal↗
PubMed1987

A mathematical model of the development of drug resistance to cancer chemotherapy.

A mathematical model incorporating descriptions of tumour growth kinetics and the effects of cytotoxic chemotherapy on established tumours, is presented. It is shown how models of this kind may be used to investigate the potential of hypothetical chemotherapy strategies, and to identify general principles for successful treatment. The model is intended to be an aid to clinicians designing new chemotherapy programmes for diseases in which progress has been disappointing.

Antineoplastic Agents↗
PubMed1987

Ovarian function and adjuvant chemotherapy for early breast cancer.

The effect of cyclophosphamide, methotrexate and fluorouracil (CMF) on ovarian function has been studied in 74 pre-menopausal patients with operable breast cancer. After median follow-up of 47 months, 50, 70 and 80% of 35 patients receiving CMF became permanently amenorrhoeic within 3, 6 and 12 months respectively; in contrast, only 5 in the no treatment (control) group of 39 patients became permanently amenorrhoeic within 12 months. Younger patients (less than 35 years) were more likely to retain or regain menstrual function while on or after CMF treatment. Estimation of ovarian and pituitary hormones in a subset of these women showed that CMF treatment was associated with a decrease in serum oestradiol and progesterone and an increase in serum follicle stimulating hormone and luteinizing hormone to post-menopausal levels. These hormonal changes are consistent with the induction of amenorrhoea during CMF treatment and the absence of resumption of menstrual function after completion of treatment suggests that CMF causes permanent ovarian ablation in a majority of these patients.

Adult↗
PubMed1987

Acetylator status and its relationship to breast cancer and other diseases of the breast.

The distribution of N-acetylation phenotypes has been investigated in 410 consecutive patients prior to diagnostic excision of a breast lump and compared to that in 337 healthy controls. Contrary to previously published data there was no excess incidence of fast acetylators in patients with malignant breast disease. There was, however, a significant trend for more rapid acetylator ratios to be associated with advanced disease at first presentation. There was a slight but non-significant excess of fast acetylators in patients with benign breast disease as compared to controls, but there were no significant differences in the proportion of the acetylator phenotypes between cystic breast diseases with or without epithelial hyperplasia. There were no significant associations between oestrogen and progestogen receptors and the acetylator phenotype. It is concluded that the acetylation phenotype has no important association with malignant breast disease.

Acetylation↗
PubMed1987

The clinical course of bone metastases from breast cancer.

All patients with carcinoma of the breast seen in this Unit since 1970 were reviewed to study the incidence, prognosis, morbidity and response to treatment of bone metastases. The biological characteristics of the primary tumour were compared in patients relapsing first in bone or liver. Sixty-nine percent of patients dying with breast cancer had bone metastases and bone was the commonest site of first distant relapse. Bone relapse was more common in receptor positive or well differentiated (grade 1) tumours. The median survival was 24 months in those with disease apparently confined to the skeleton compared with 3 months after first relapse in liver. Ten percent of patients with breast cancer developed hypercalcaemia. All had metastatic disease and 85% had widespread skeletal involvement. Fifteen percent of patients with disease confined to the skeleton developed hypercalcaemia. The response in bone to primary endocrine therapy, and chemotherapy, was apparently less than the overall response achieved. A large proportion had apparently static disease reflecting the insensitivity of the UICC assessment criteria. The duration of survival in these patients was similar to responding patients, suggesting a tumour response may occur in the absence of discernable radiological evidence of healing.

Adult↗
PubMed1987

3(Amino-1,1-hydroxypropylidene) bisphosphonate (APD) for hypercalcaemia of breast cancer.

The effect of a single dose of APD on hypercalcaemia has been studied in advanced breast cancer. Twenty-five patients were rehydrated intravenously for 48 h. Twenty-three remained hypercalcaemic and received 5-15 mg APD as a 2 h infusion. Eighteen patients achieved normocalcaemia, 15 after a dose of less than or equal to 15 mg. One patient died within 24 h from rapidly advancing disease and 4 remained hypercalcaemic. Urinary calcium excretion increased during rehydration as glomerular function improved and tubular reabsorption of calcium fell. After APD, calcium excretion fell to normal in 22/24 patients reflecting inhibition of bone resorption. Hydroxyproline excretion remained high. The effect of a single dose of APD on hypercalcaemia lasted a median of 11 days (range 7-17). Transient fever occurred in 2 patients, but there were no other side effects. The possibility of long-term control of osteolysis using a 2 weekly schedule of APD administration is now being studied.

Adult↗
PubMed1987

A comparison of two doses of adriamycin in the primary chemotherapy of disseminated breast carcinoma.

Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy (minimum follow up 21 months) were randomised to receive either adriamycin 70 mg m-2 i.v. 3-weekly for 8 cycles (Regimen A) or adriamycin 35 mg m-2 i.v. 3-weekly for 16 courses (Regimen B). Objective responses were seen in 14/24 (58%) patients with regimen A (4 complete) and 6/24 (25%) with regimen B (1 complete) (P less than 0.02). The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively (P less than 0.01). The toxicity was similar with each regimen. There was no evidence of deterioration in left ventricular ejection fraction nor congestive heart failure in any patient. It is concluded that when given at 3-weekly intervals adriamycin is a more effective treatment for advanced breast cancer at higher rather than lower dosage.

Adult↗
PubMed1987

Histological grade, elastosis, DNA ploidy and the response to chemotherapy of breast cancer.

The relationships between response to chemotherapy of advanced breast cancer and the histological type, grade, elastosis content and DNA ploidy of the primary tumours were examined using paraffin-embedded tissue derived from 125 patients. Higher response rates were seen amongst tumours with a high elastosis content and those that were diploid. However, selection of patients with advanced breast cancer for chemotherapy will not be assisted significantly by an assessment of these features in the primary tumour.

Aneuploidy↗
PubMed1987

Pericardial effusion complicating breast cancer.

Thirty-five patients with metastatic breast cancer and pericardial effusions are described. They were treated with specific endocrine or chemotherapy. Twenty-two (63%) had presented in cardiac tamponade and were rapidly relieved by pericardiocentesis. Eighteen (82%) of these required no further local treatment, 2 obtained relief from a second aspiration and 2 needed additional treatment (intrapericardial bleomycin instillation and surgical pleuropericardial window). The median survival was 13.2 months. No patient relapsed again in the pericardium, suggesting that their prognosis was that of the underlying disease. Cardiac tamponade should be considered in any breathless patient with malignancy. In breast cancer, periocardiocentesis is lifesaving and systemic treatment can usefully prolong life.

Adult↗