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Biomedical subjects

A Rodger

Publications and source records attributed to A Rodger.

At least 91 records · Page 5Linked to original sources
PubMed1991

The CD of ligand-DNA systems. I. Poly(dG-dC) B-DNA.

A systematic theoretical study of the CD of double-stranded poly(dG-dC) and its complexes with small molecules is presented. The intrinsic CD of the polymer and the induced CD of a transition belonging to a molecule bound to DNA are calculated using the matrix method. The calculations show considerable differences between pyrimidine-purine and purine-pyrimidine binding sites, and we find that the induced CD of a groove bound molecule is one order of magnitude stronger than that of an intercalated molecule. The results form a sound basis for interpreting the CD of ligand-DNA systems in terms of molecular geometry, interactions, and spectroscopy.

Circular Dichroism↗
PubMed1991

Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity.

The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.

Adult↗
PubMed1991

Sequence selective binding to the DNA major groove: tris(1,10-phenanthroline) metal complexes binding to poly(dG-dC) and poly(dA-dT).

Molecular modelling and energy minimisation calculations that incorporate solvent effects have been used to investigate the complexation of delta and lambda-[Ru(1,10-phenanthroline]2+ to DNA. The most stable binding geometry for both enantiomers is one in which a phenanthroline chelate is positioned in the major groove. The chelate is partially inserted between neighbouring base pairs, but is not intercalated. For delta, though not for lambda, a geometry with two chelates in the major groove is only slightly less favourable. Minor groove binding is shown to be no more favourable than external electrostatic binding. The optimised geometries of the DNA/[Ru(1,10-phenanthroline]2+ complexes enable published linear dichroism spectra to be used to determine the percentage of each enantiomer in the two most favourable major groove sites. For delta 57 +/- 15% and for lambda 82 +/- 7% of bound molecules are in the partially inserted site.

Base Sequence↗
PubMed1991

A binding mode of lambda-[tris(1,10-phenanthroline)ruthenium(II)]2+ exhibiting preference for purine-3',5'-pyrimidine sites of DNA.

Molecular mechanics calculations and molecular dynamics simulations have been used to study the binding of the partially inserted major groove complex of Lambda-[Ru(1,10-phenanthroline)3]2+ with DNA. Energy refinements of this complex showed a clear preference for binding at purine-3',5'-pyrimidine sites over pyrimidine-3',5'-purine sites. The basis for this difference is shown to be a slight change in the binding orientation induced by interchanging the purine and pyrimidine bases. This in turn provides for a better secondary interaction with the helix backbone at a point beyond the immediate binding site. It is this secondary interaction that provides the additional energetic stabilisation for complexes formed at purine-3',5'-pyrimidine sites. Molecular dynamics simulations including explicit representation of solvent support these conclusions and provide an insight into the positional stability of the ligand at a particular site. Repuckering of specific deoxyribose rings to the C3'-endo conformation seems to be an important feature of the DNA/ligand complex.

Base Sequence↗
PubMed1991

A 10-year experience of tamoxifen as primary treatment of breast cancer in 100 elderly and frail patients.

Between 1977 and 1983 100 elderly women (median 76.3 years) with breast cancer were treated with tamoxifen as primary therapy. The median follow-up is 59 months. Sixty-eight responded (40 CR and 28 PR) with median response durations of 47 months and 26 months respectively. Twenty-two patients had disease stabilization for a median of 15.5 months and 10 had progressive disease. The median time to best response was 13.5 weeks for patients achieving CR and 14 weeks for those with PR. Oestrogen receptor values were obtained in 37 patients of which two patients had no ER detectable. Sixty-seven per cent of ER-unknown patients responded compared with 74% of ER-rich. Likelihood of response did not appear to depend upon T-stage or age. Survival was better than that of an unmatched historical group treated with surgery/radiotherapy and compares favourably with recent reports. Although 35% have died of breast cancer, 25% died of other causes and 22% remained free of recurrence at the time of reporting or at death. Only 11% underwent subsequent mastectomy/lumpectomy and the most frequent subsequent treatments were radiotherapy to the breast (32%) and further hormonal therapies (40%). Tamoxifen is a practical primary therapy of breast cancer in elderly and frail women obviating the need for surgery in a high proportion of cases.

Aged↗
PubMed1990

Recruitment to a prospective breast conservation trial: why are so few patients randomised?

OBJECTIVE: To investigate the rate of recruitment to early breast cancer trials and elucidate the reasons for ineligibility and refusal to participate among patients otherwise suitable for these trials. DESIGN: Prospective study of one year's cohort of patients referred to a breast unit with special reference to the subgroup suitable for conservation management and to the proportion eligible for and (after informed consent) ultimately randomised within the Scottish early breast cancer trials. SETTING: The breast unit, Longmore Hospital, Edinburgh, during 1988. PATIENTS: All 3054 patients referred to the breast unit during the year. 324 Found to have invasive breast cancer and 147 initially thought suitable for conservation management. RESULTS: 63 Patients were treated by mastectomy, 19 of whom requested mastectomy rather than conservation management. 84 Patients were excluded from trials, and of the 63 eligible patients, 40 gave informed consent. Most of the 23 patients who refused the trials requested a specific adjuvant treatment after discussion of their management and the trials. CONCLUSIONS: Recruitment to prospective trials in which informed consent is required before randomisation may be slower than predicted because of a high proportion of exclusions and also refusal by patients. Trials may therefore take longer to complete and give distorted results by virtue of the unpredictable nature of the selection of patients.

Axilla↗
PubMed1990

A phase II trial of mitomycin C and 5-fluorouracil as second-line therapy in advanced breast cancer.

Fifty-five patients who had relapsed or progressed from chemotherapy for advanced disease were treated with mitomycin C and 5-FU on a 6 weekly regimen. After a median of 2 cycles of therapy the overall response rate was 12% with no complete responses. Significant leucopenia but no thrombocytopenia was seen and despite the low overall response rate the regimen was tolerable and did produce responses in patients primarily resistant to Adriamycin combination chemotherapy. Low overall activity indicates the need for more effective second line treatment.

Adult↗
PubMed1990

Adenocarcinoma from an unknown primary presenting in women with an axillary mass.

Adenocarcinoma from an unknown primary is generally associated with a poor prognosis. This is not the case with women who present with disease confined to one axilla, when the primary, despite negative investigations, is often found to lie in the ipsilateral breast. Twenty such patients presented to our department between 1977 and 1989 and were generally treated by radical radiotherapy to the breast and peripheral lymphatics. Local control was achieved in the axilla in 17 of the 20 patients (85%). No primary has appeared in the breast, although one patient has died of a carcinoma of the colon. The 5-year actuarial survival of the group is 66%, similar to stage II breast carcinoma patients. The value of radiological and histopathological investigations is discussed. The cosmetic results are good and in view of the excellent local control achieved by irradiation we feel mastectomy is unnecessary in this rare presentation of breast cancer.

Adenocarcinoma↗
PubMed1990

Acute radiation pneumonitis after postmastectomy irradiation: effect of fraction size.

Prior to 1982 the standard radiation tissue absorbed dose administered to the chest wall following mastectomy was 40.0-42.5 Gy in 10 alternate day fractions over 4 weeks. From 1982 the standard maximum dose was 45.0 Gy administered in 20 daily fractions over 4 weeks. On review of the records of the 770 patients treated between 1979 and 1984, 19 (2.5%) had symptoms of acute radiation pneumonitis, 7/484 (1.4%) treated by the earlier technique and 12/286 (4.2%) by the later technique (X2 = 4.56, P less than 0.05). The mean 4 cm depth doses on the chest wall were 33.98 Gy and 36.84 Gy respectively in the earlier and later populations (t = 5.06, P less than 0.001) and 33.62 Gy and 38.30 Gy in those developing acute pneumonitis. Comparison of these two schedules gives an alpha/beta ratio of 8.5 Gy. It is suggested that the sparing of symptomatic acute reactions in human lung by smaller doses per fraction may be less than currently believed.

Acute Disease↗
PubMed1990

Prognostic factors for survival in soft tissue sarcoma.

Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.

Adolescent↗
PubMed1990

Breast cancer stage, social class and the impact of screening.

Two studies were carried out to examine socio-economic factors in breast cancer: a random sample of all new cases in Edinburgh in 1979 was reviewed, and the control population of the Edinburgh randomized trial of breast screening was used to determine stage and survival in relation to social class. Small area statistics from census data were used as measures of social class, the method being now well accepted. More than one-third of women still present with obviously advanced or metastatic breast cancer, but both studies showed this has no association with socio-economic status. Late stage at presentation is a serious problem, and although mass screening is likely to cause an improvement in those who are screened, it cannot in those who do not attend for screening. As attendance is related to social class, less affluent women are less likely to benefit and will continue to be diagnosed with advanced disease.

Adult↗
PubMed1989

Arm morbidity within a trial of mastectomy and either nodal sample with selective radiotherapy or axillary clearance.

The aim of this study was to assess upper limb morbidity following treatment for operable breast cancer. Patients were randomized to either mastectomy and axillary clearance (40 women: 12 with axillary nodal metastasis and 28 without axillary metastasis) or mastectomy and axillary sampling (54 women). Adjuvant radiotherapy was delivered to those in whom the sample revealed axillary nodal metastasis (28 women) but not to those with no axillary nodal metastasis (26 women). A subjective assessment of the state of the arm was made using a standard questionnaire. Objective assessment included upper and forearm circumference, should joint mobility and assessment of power in the pectoralis muscle. The mean age was 56.8 years (range 33-77 years) and the mean elapsed time from treatment was 5.72 years (range 4.0-7.5 years). Subjective limb oedema was greatest in those who had axillary lymph node metastasis but there was no objective difference. Subjective joint mobility was reduced in the women who received radiotherapy and this was confirmed by objective assessment (P less than 0.05). The objective reduction in arm mobility was related to the treatment rather than the axillary lymph node status. There was no difference in power. In this study women receiving adjuvant radiotherapy had significantly reduced shoulder mobility. This may have implications for current conservation studies using adjuvant radiotherapy.

Adult↗
PubMed1989

Post-irradiation morphoea.

We present details of nine patients who developed morphoea after radiotherapy. In every patient morphoea began within the irradiated area and in four spread beyond it. We believe the irradiation triggered the morphoea despite the absence of any clear-cut relationship to dosage or severity of the acute reaction. Dermatologists and radiation oncologists should be aware that this condition may lead to the mistaken diagnosis of a local tumour recurrence.

Adult↗
PubMed1988

The efficacy of delayed radiotherapy for locoregionally recurrent postmastectomy breast cancer.

Using the results from a randomized controlled trial of patients with operable breast cancer (aimed at assessing the need for immediate postmastectomy radiotherapy in patients with no histological evidence of nodal involvement on subpectoral node biopsy), it has been possible to study the effectiveness of salvage radiotherapy for recurrences in the group of patients who had not received postoperative radiotherapy. While only 1 of 43 patients (2.3%) showed progressive disease, there was a further in-field relapse in 16 of the remaining 42 patients (38%). Four of these patients were salvaged by systemic therapy. Ultimately, therefore, there was failure of delayed radiotherapy for locoregional control in 30% of patients. (However, the overall locoregional control in both arms of the trial was identical).

Breast Neoplasms↗
PubMed1986

An analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer.

This report is an analysis of the morbidity in the bladder and bowel observed in a randomized trial of d(15)+Be neutrons versus megavoltage photons in the treatment of bladder cancer. Acute reactions in the bladder and bowel were significantly worse after photon therapy. Of the patients treated with photons 45.7% had severe reactions in the bladder compared with 10.6% after neutron therapy (p less than 0.001). Severe acute bowel reactions were observed in 8.5% of the patients after photon therapy compared with 3.8% after neutron therapy (p less than 0.05). Late reactions were significantly worse after neutrons. Severe late reactions in the bladder were seen in 58.5% of patients after neutron therapy and in 40.5% after photon therapy (p less than 0.05). In the bowel they were observed in 53.3% of patients after neutron therapy compared with 8% after photon therapy (p less than 0.0001). The disparity in the degree of early and late complications makes assessment of RBE values difficult. It is estimated that for bladder morbidity the RBE value, for photon dose fractions of 2.75 Gy, is less than 3.3 for early reactions and equal to 3.4 for late effects. The respective RBE values for early and late effects in the bowel are less than 3.4 and 3.8.

Clinical Trials as Topic↗
PubMed1986

Sarcoma of bone following therapeutic irradiation for breast carcinoma.

Four patients with sarcoma arising in bone following therapeutic irradiation for breast carcinoma are presented, along with a review of the 40 patients who have been previously reported in the literature. The majority of these lesions arose in the scapula and the most frequently reported histology is osteosarcoma. The incidence of these lesions has been reported as 0.05% to 0.23% in three previous series. The average latent period between irradiation and the diagnosis of the sarcoma is 10.9 years with a range of 4.5-24 years. The average survival following diagnosis in this series was 2.4 months, which is comparable to other series. However, one patient treated by forequarter amputation and another treated by chemotherapy and radiotherapy survived 4 and 3 years, respectively.

Adult↗