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Biomedical subjects

A Coates

Publications and source records attributed to A Coates.

At least 73 records · Page 4Linked to original sources
PubMed1992

Cerebral metastases from malignant melanoma.

A retrospective study was undertaken of factors affecting survival in 129 patients with cerebral metastases from malignant melanoma referred to the Department of Radiation Oncology from June 1982 to January 1990. Their ages ranged from 19 to 83 years and the time interval from diagnosis of the primary tumour to development of cerebral metastases ranged from one month to 17 years. Cerebral metastases were apparently solitary in 59 (46%) and multiple in 70 (54%) patients respectively. Craniotomy with resection of tumour was performed in 49 patients, of whom 24 had a solitary cerebral metastasis as the only evidence of disease. Most patients (94%) received a course of radiotherapy. Median survival of the whole group after detection of cerebral metastases was 5 months (range less than 1-87+). Univariate analysis indicated that a solitary cerebral metastasis, absence of extracranial disease and tumour resection predicted improved survival, but only surgical intervention was of independent prognostic significance in a multivariate analysis. The effect of cranial irradiation on survival could not be assessed, but the dose of radiation did not influence survival. Of the 10 patients who survived for more than 2 years, eight had total resection of a solitary cerebral metastasis.

Adult↗
PubMed1992

Quality of life measures for patients receiving adjuvant therapy for breast cancer: an international trial. The International Breast Cancer Study Group.

Serial quality of life (QL) assessments are being obtained every 3 months for 2 years from patients with operable breast cancer in two ongoing International Breast Cancer Study Group (IBCSG) randomised clinical trials of adjuvant treatment. The QL-assessments include patient-derived perceived coping (PACIS, personal adjustment to chronic illness scale), well-being (Bf-S, Befindlichkeitsskala von Zerssen), mood, physical well-being and appetite (LASA, linear analogue self assessments). The first assessment within 6 weeks of surgery was performed by 70% of the patients. The analysis of serial assessments for 265 patients with each of the first four assessments completed showed that all measures improved with increasing time from study entry; that the degrees of improvement for the four major language groups were similar; and that measures were sensitive to treatment difference. In conclusion, measurement of QL related aspects in a multicultural clinical trial is feasible and possibly relevant for the evaluation of treatment results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group.

PURPOSE: We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail. PATIENTS AND METHODS: In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors. RESULTS: Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders. CONCLUSION: These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.

Breast Neoplasms↗
PubMed1991

Chemical synthesis of 10 kDa chaperonin. Biological activity suggests chaperonins do not require other molecular chaperones.

Molecular chaperones are required for the correct folding and assembly of certain other polypeptides. It is not known whether molecular chaperones themselves require other chaperones to become functional. A 97-amino acid chaperone, the chaperonin 10 protein was chemically synthesised so that during synthesis and purification there was no contact of the chaperone with any other protein. The purified, synthetic chaperonin 10 protein formed oligomeric structures spontaneously and was biologically active as a chaperonin. This is the first description of a chemically synthesised chaperonin, and suggests that no other chaperones are required for correct folding, polymerisation and biological activity of this chaperone.

Bacterial Proteins↗
PubMed1991

Measurement of respiratory system resistance by forced oscillation in normal children: a comparison with spirometric values.

In 377 children, the commercially available Siregnost FD-5 was used to measure respiratory system resistance (Rrs) by forced oscillation at 10 Hz. The children were between 3 and 18 years of age and, by a detailed questionnaire and conventional pulmonary function testing in 335, they were shown to be representative of the normal pediatric population. There was a linear relationship between Rrs and height (Rrs = 13.9-0.064 x ht (cm), r = -0.87). Children less than 6 years of age had no trouble with using the forced oscillation technique. The smoking of tobacco in the house, the presence of carpets in the child's bedroom, or an atopic family history, alone or in combination, had no influence on Rrs or on any spirometric measure. Forced oscillation is useful in children too young to be able to cooperate with conventional pulmonary function testing.

Adolescent↗
PubMed1991

On the receiving end. IV: Validation of quality of life indicators.

Four measures of patient functioning and a mood adjective list currently used in trials of the International Breast Cancer Study Group (IBCSG), and an 8-item Linear Analogue Self Assessment (LASA) instrument measuring specific side effects of cancer and cancer treatment (GLQ-8), were cross-validated against three established measures of quality of life, mood and psychological adjustment to cancer, in a heterogeneous sample of cancer patients. Correlations between new and established measures were high, indicating good convergent and concurrent validity. Compliance on the longer mood measures was relatively poor. Despite the difficulty in developing direct and methodologically sound measures of quality of life, the regular inclusion of practical indicators of aspects of quality of life in clinical trials would allow improved assessment of the cost-benefit ratio of treatment to outcome in cancer patients.

Adaptation, Psychological↗
PubMed1991

The use of L-dopa and carbidopa in metastatic malignant melanoma.

A combination of L-dopa and carbidopa was given orally to 17 patients with metastatic melanoma. Maximum tolerated oral doses were given, up to 4 grams daily. No response was seen in 15 patients evaluable for response. Toxicity was considerable, with seven of 17 patients (41%) stopping treatment because of unacceptable gastrointestinal toxicity or postural hypotension. Contrary to previous anecdotal reports, there was no evidence that L-dopa/carbidopa treatment resulted in accelerated progression of metastatic melanoma. Orally administered L-dopa/carbidopa is ineffective as therapy for advanced melanoma when maximum tolerated doses are used.

Carbidopa↗
PubMed1991

Growth hormone response in very short children.

Growth hormone (GH) response to standardized exercise, L-DOPA/propranolol and a 6-h diurnal GH profile (GHP) were evaluated in twenty-three children with very short stature and abnormal growth velocities. Standardized exercise (Jones Stage I) was performed on a cycle ergometer at 53% of the maximum oxygen consumption (VO2max) for 20 min. VO2max was determined by an incremental progressive workload until exhaustion. The mean +/- SEM peak GH concentration (ng/ml) for each test was: exercise, 8.7 +/- 1.3; L-DOPA/P: 12.8 +/- 1.9 and GHP: 3 +/- 0.7. There was no statistical difference between exercise and L-DOPA/P peaks but both peaks were significantly higher than the peak observed during the profile. During exercise 14 of 23 patients had a GH response greater than 8 ng/ml. Two patients were found to be GH deficient. Therefore 16 of 23 patients (86%) had a result concordant with their final diagnosis. During the L-DOPA/P test 17 of 23 patients had a GH response greater than 8 ng/ml. By contrast only 6 of 23 patients had a positive response during GHP. Standardized exercise is as effective as L-DOPA/P as a stimulation test for growth hormone response in very short children with abnormal growth velocities. Exercise has the advantages of being physiological, having minimal side effects, and requiring fewer blood samples. In this population of children, exercise and L-DOPA/propranolol are significantly better than the 6-h growth hormone profile for assessing GH secretion.

Adolescent↗
PubMed1990

On the receiving end--III. Measurement of quality of life during cancer chemotherapy.

From previous studies of the side effects patients identified as important in cancer chemotherapy we identified eight groups of symptoms. Linear analogue self assessment (LASA) scales for these 8 items form a new instrument (GLQ-8) for measuring aspects of quality of life. Patients completed both GLQ-8 and five previously validated LASA scales, together with a new single global quality of life scale (GLQ uniscale) and the visual analogue version of the Spitzer QL Index. This analysis includes 166 patients, with 47 1-hr test-retest and 29 24-hr test-retest pairs. The new scales showed high reliability, with retest correlation coefficients exceeding 0.8 for all items except GLQ uniscale, appetite and anxiety on 1-hour retest, and all except nausea and numbness on 24-hour retest. Correlations were in general higher for the GLQ-8 items than for the 5 older LASA items, while inter-item correlations were lower. Comparisons of the new scales with established instruments and comparisons of new scale scores between known groups supported the validity of the new scales. We conclude that the GLQ-8 and GLQ uniscale are convenient and reliable instruments measuring aspects of quality of life in patients receiving cancer chemotherapy.

Adolescent↗
PubMed1987

Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies.

Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Monitoring distributional assumptions and early stopping for a prospective clinical trial using Monte Carlo simulation.

We have applied the technique of Monte Carlo simulation to the determination of sample size for a partially completed clinical trial of chemotherapy for breast cancer. Simulations based on results observed after the entry of 243 patients in 2 years indicated a power greater than that predicted by the calculations made before the protocol was activated, and allowed a recommendation for an eventual trial closure earlier than would have been permitted by traditional methods. Both estimative and predictive approaches to the simulation of expected survival times for censored patients are presented. The use of simulation is recommended as an aid in reassessing the exact nature of the underlying survival distributions (as these affect the sample size calculations) and in optimizing stopping rules relating to patient accrual to a clinical trial in progress.

Breast Neoplasms↗
PubMed1987

Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma. Treatment of stage II melanoma with viral lysates.

A total of 80 patients with melanoma metastases in regional lymph nodes were treated by i.d. injections with a vaccine prepared from a vaccinia virus-infected allogeneic melanoma cell line; 39 patients have been followed for a 2-year period. Interim results from comparison of the treated group with 151 historical controls treated without the vaccine from September 1978 to December 1981 at the same institution and 56 non-randomized concurrent controls suggest that survival was significantly prolonged in the vaccinated group. At the 2-year period overall survival was 75% in the treated compared to 57% in the historical control group. Subset analysis showed a greater apparent benefit of vaccine therapy among patients who had metastases detected at the time of treatment of the primary melanoma (synchronous metastases), while therapy appeared less effective in patients with metastases detected at some time after treatment of the primary (delayed metastases). In the latter only those with one lymph node appeared to benefit from the treatment whereas in patients with synchronous metastases patients with three or more nodes as well as one node appeared to have improved survival. The survival rates at 2 years for treated patients with synchronous metastases in one, two, three or more lymph nodes was 100%, 83% and 79% respectively compared with that of 82%, 86% and 47% respectively in the equivalent control groups. Survival rates in treated patients with delayed metastases in one, two, three or more lymph nodes was 70%, 70% and 65% compared with 47%, 42% and 35% in the equivalent control groups. Treatment and control groups appeared well matched for a number of known prognostic features, including number and size of involved nodes, sex and thickness of primary tumor. Multivariate analysis indicated the effect of treatment was independent of these factors. Despite the empiricism of this approach the present results suggest that this form of therapy warrants further evaluation in a randomized controlled trial.

Adolescent↗
PubMed1987

Chemotherapy of advanced colorectal cancer. A randomized trial of sequential methotrexate and 5-fluorouracil.

Fifty-five patients with advanced colorectal cancer were entered into a randomized controlled clinical trial to evaluate order of administration and sequential methotrexate (MTX) and 5-fluorouracil (5-FU) therapy. Patients were randomized to receive either MTX, 250 mg/m2, followed 1 h later by 5-FU, 600 mg/m2, or 5-FU followed 1 h later by MTX in the same doses. Fifty-four patients were evaluable for response, of whom 15 (28%) achieved objective partial tumor response. There were no significant differences between the two sequences in response rate, time to treatment failure, or survival duration. The results of this study do not indicate a clinically significant difference between the two sequences tested, in which MTX preceded or followed 5-FU by 1 h. Determination of the value of these drugs given sequentially at longer intervals must await appropriate controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Aminoglutethimide in advanced prostatic carcinoma.

We have treated 34 patients with advanced prostate cancer, resistant to orchiectomy or oestrogen therapy, with aminoglutethimide. Seven patients (21%) showed improvement in pain and performance status for prolonged periods. By NPCP criteria six patients had stable disease and one had partial tumour response. Six of these patients remained on oestrogen therapy. Suppressed gonadotrophin levels (FSH and LH), despite orchiectomy, correlated strongly with benefit from aminoglutethimide. No relationships between response to treatment and changes in serum testosterone, dehydroepiandrosterone, oestradiol or prolactin were found. Six patients had side effects requiring cessation of therapy. A further 27 patients developed less severe toxicity. Despite its toxicity, these results show that aminoglutethimide has a role in the management of advanced prostatic cancer resistant to primary hormonal manipulation.

Aged↗