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Biomedical subjects

R Swindell

Publications and source records attributed to R Swindell.

At least 109 records · Page 6Linked to original sources
PubMed1985

The Christie Hospital tamoxifen (Nolvadex) adjuvant trial for operable breast carcinoma--7-yr results.

The Christie Hospital Tamoxifen Trial was a randomised trial to assess the efficacy of tamoxifen (Nolvadex) as an adjunct to surgical treatment for operable breast carcinoma. From 1 November 1976 to 1 June 1982 1005 patients were registered, of whom 961 are evaluable. Following surgery, premenopausal women were randomly allocated to either tamoxifen (TAM) 20 mg/day for 1 yr or to have an irradiation menopause. Postmenopausal women had TAM 20 mg/day for 1 yr or no further treatment (controls). The analysis at 7 yr shows that there is no statistically significant difference in the overall survival for premenopausal women between those given TAM and those given ovarian irradiation. Similarly for the postmenopausal women there was no significant difference in overall survival between the TAM and control groups. However, if the series of 961 patients is analysed as a whole and allowance is made for node status then the TAM-treated patients show a significant survival benefit (P = 0.05). There was also a statistically significant delay in first relapse for the TAM-treated patients (P = 0.04); with a particularly marked reduction in distant metastases in postmenopausal patients (P = 0.06). TAM was extremely well tolerated, with very few side-effects.

Adult↗
PubMed1985

The effect of oestrogen and progesterone receptors on recurrence and survival in patients with carcinoma of the breast.

Recurrence and survival rates were studied in 175 women with breast cancer who, until the development of recurrent disease, received no treatment other than a modified radical (Patey) mastectomy, and in whom the oestrogen (REc) and progesterone (RPc) receptor content of the primary tumour was measured. At the time of first relapse most patients received endocrine therapy. At a minimum follow-up of 58 months post menopausal patients who possessed REc had an increased relapse-free survival (RFS) (P = 0.02). When examined by node status patients with 1-3 axillary nodes containing tumour also had an improvement in RFS (P = 0.02). There was no benefit for node-negative or premenopausal patients. In 163 patients in whom RPc was measured, RFS was unaffected by the possession of this receptor regardless of the degree of node involvement or menopausal status. Patients with REc had a significantly longer survival following mastectomy than patients without it (P = 0.006). This was most marked in post-menopausal (P = 0.003) and node-positive (P = 0.03) patients. Survival following mastectomy was also increased in patients possessing RPc (P = 0.04) and again was most marked for post-menopausal patients (P = 0.01), although no difference could be identified within node subgroups. There were significant differences in the post-relapse survival of REc and RPc positive and negative patients (REc P = 0.03, RPc P = 0.001). Patients with both receptors survived approximately 37 months longer than their receptor-negative counterparts. This study failed to confirm that the measurement of REc and RPc can reliably predict early relapse in breast cancer. The greater overall survival of receptor-positive patients is mainly due to an increase in survival following relapse. This may reflect the response of receptor-positive tumours to endocrine therapy given for recurrent disease.

Breast Neoplasms↗
PubMed1985

Combined modality management of local and disseminated adult soft tissue sarcomas: a review of 257 cases seen over 10 years at the Christie Hospital & Holt Radium Institute, Manchester.

Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). The commonest sites were lower limb (33%), visceral (21%), trunk (13%), retroperitoneum (12%) and upper limb (10%). Leiomyosarcoma (27%), liposarcoma (14%) malignant fibrous histiocytoma (10%) and neuro plus fibrosarcomas (15%) were the most frequent histological subtypes. A high proportion of uterine sarcomas (17%) is a point of distinction from many other series. Histological grade was specified in 72% of cases and the distribution (Grade I--27%; II--6%; III--67%) reflected a referral bias towards advanced disease. Local resection of the primary tumour was performed in 76% of cases. In many instances this only amounted to 'shelling out' and true compartmental excisions were rare. Amputation was performed in 31% of patients with limb sarcomas. Ninety-eight patients (38%) had experienced one or more local recurrences prior to referral and the overall local recurrence rate was 56%. Suitable patients (78%) received chemotherapy, 50% entering multicentre trials in collaboration with the EORTC. The commonest regime used in patients with advanced disease was CYVADIC which produced an overall response rate of 37%. Ifosfamide, used as a single agent in 16 patients, induced 3CR and 5PR for an overall response rate of 50%. When used in combination with MTX and VADIC, there was no difference in response rate, but numbers in these pilot studies were small. Seventeen high risk patients received adjuvant chemotherapy with VAC, but the results (11 relapses) were disappointing. An EORTC trial, comparing adjuvant CYVADIC chemotherapy with control has accrued 307 patients, 49 of these from the Christie Hospital. Preliminary results within this centre - 13/25 relapses in the control arm, 5/23 in the chemotherapy arm-suggest an advantage for chemotherapy but the data are statistically not significant. Post-operative radical radiotherapy after resection of the primary tumour or local recurrence was performed in 51 patients, with local control in 65% of cases, although metastases developed in 41%. At the time of analysis (1st April 1984) 98 (38%) were alive, of whom 72 showed no evidence of disease and 52 had never relapsed. Malignant disease was the cause of death in 92%. Overall survival was not influenced by sex, but patients less than 40 years of age fared significantly better (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Activity of JM9 in advanced ovarian cancer: a phase I-II trial.

Thirty-nine patients with advanced solid tumors, including 28 with ovarian cancer, were entered in a phase I-II trial of a new platinum analog, JM9. Twenty-three patients had received prior chemotherapy which did not include cisplatin. Based on preliminary information from an ongoing study, our starting dose was 180 mg/m2. The total dose of JM9 was administered in 1 L of saline infused over 1 hour, with no additional hydration or electrolyte supplementation. Courses were repeated at 3-week intervals or after full recovery from thrombocytopenia. One hundred thirty-nine courses (range, one to six per patient) were administered at four dose levels: 180 mg/m2 (13 courses); 240 mg/m2 (64 courses); 300 mg/m2 (45 courses); and 350 mg/m2 (17 courses). The dose-limiting toxic effect was thrombocytopenia, which was dose-related and cumulative. Median platelet count nadirs were 50, 47, 25, and 28 X 10(9)/L for previously treated patients at dose levels of 180, 240, 300, and 350 mg/m2, respectively. For patients who had not received prior chemotherapy, the corresponding values were 403, 61, 44, and 36 X 10(9)/L. The nadir was predictable at Day 14 with recovery by Day 21 in earlier courses, but with delay of recovery to Days 28-42 in later courses and at higher dose levels. Twenty-five courses of chemotherapy in 15 patients were associated with a platelet count nadir of less than 20 X 10(9)/L, but despite this, serious hemorrhage was rare. Leukopenia was dose-related and mild; the median wbc count (X 10(9)/L) was 2.2 (range, 1.0-7.3) at the highest dose level of 350 mg/m2. The leukocyte count nadir was later than that for the platelet count (Days 21-28), and recovery was often not complete by the time of retreatment. All patients showed a progressive rise in mean corpuscular volume in successive courses, often accompanied by a fall in hemoglobin. Transfusions were required in 14 patients, 12 of whom had received prior chemotherapy. Nausea and vomiting, starting within 1 hour of drug administration, occurred in all patients, but appeared to be less severe and prolonged compared to that occurring with cisplatin. Diarrhea occurred in most patients at the two higher dose levels. There was no evidence of significant renal impairment, electrolyte disturbance, hearing loss, or peripheral neuropathy. Two patients had mild allergic reactions shortly after drug infusion and two others developed vasculitic rashes which were self-limiting.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗
PubMed1984

The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas.

As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of the primary tumour from 175 patients with each of two monoclonal antibodies (HMFG-1, HMFG-2), raised against milk fat globule membrane antigens known to be preserved in formalin-fixed tissues. Sections were assessed by light microscopy as to both the overall distribution of antigen expressed and its site in tumour cells. The findings were related to relapse-free survival by life-table analysis. The median duration of follow-up was 36 months. Two patterns of staining with antibody HMFG-1 gave information of prognostic significance but staining with HMFG-2 was without significance. Complete absence of staining with HMFG-1 in 13 patients was associated with an extremely poor prognosis and 10 (77%) of these patients developed metastases within 18 months of follow-up (p less than 0.001). Extracellular staining (ECS) in 22 patients, however, was associated with a favourable prognosis. As assessed by a semi-quantitative method, only one patient (5%) demonstrating a high level of ECS developed metastases (p less than 0,004). These two patterns were analysed for a relationship to other prognostic indicators. Absence of staining was independent of histological grade, tumour size, axillary lymph node status and menopausal status. ECS was associated with low histological grade although this relationship was not absolute. In addition to their use in diagnosis, we conclude that monoclonal antibodies such as HMFG-1 may be useful as prognostic indicators.

Antibodies, Monoclonal↗
PubMed1984

The effect of vinca alkaloids in enhancing the sensitivity of a methotrexate-resistant (L1210/R7A) line, studied by flow cytometric and chromosome number analysis.

Two L1210 murine lymphoma cell lines sensitive and resistant to methotrexate (L1210 and L1210/ R7A , respectively) and previously shown to exhibit collateral sensitivity to the vinca alkaloids have been studied by flow cytofluorimetric techniques following propidium iodide staining of the DNA. Following treatment with a range of concentrations of vincristine, both cell lines showed a build-up of fluorescence in the 4n position. However, the methotrexate-resistant cell line exhibited this effect at lower doses of vincristine. On an equimolar basis, the vinca alkaloids ranked for intensity of this effect in the order vinblastine greater than vindesine greater than vincristine. DNA fluorescent histograms following various times of continuous exposure to vincristine showed an accumulation of material at the 8n position, which was shown by chromosome analysis to be due to polyploidy. It was concluded that methotrexate-resistant cells (L1210/ R7A ) experience difficulty in traversing mitosis and this difficulty is enhanced by the vinca alkaloids.

Animals↗
PubMed1984

Excess risk of breast cancer in the mothers of children with soft tissue sarcomas.

Information was obtained on the health status or cause of death in the mothers of a population-based series of 143 children with soft tissue sarcomas. Among these mothers there were 6 cases of breast cancer. All 6 women were pre-menopausal and 2 had bilateral disease. This represents a significant 3-fold excess risk of breast cancer. Malignant disease had occurred in 6 other women whose ages at diagnosis ranged from 33 to 58 years. This was not significantly in excess of expectation. The incidence of cancer among mothers of various sub-groups of children was computed. For breast cancer mothers of: boys, children who were less than the median age at diagnosis, and children who had pelvic tumours had a greater excess risk than the group as a whole. Among those sub-groups of mothers the highest excess risk was 13.5. For other cancers, no sub-group showed an incidence which was significantly above the expected. A high proportion of infiltrating lobular carcinoma was found among the breast cancers, and histological type may indicate familial disease. These findings are consistent with the cancer family syndrome described by Li & Fraumeni in 1969, but the present results suggest that a higher proportion of childhood soft tissue sarcoma than was hitherto suspected may have a genetic aetiology. Further pedigree and laboratory studies may help to identify familial cases at the time of the child's diagnosis.

Adult↗
PubMed1983

Serum beta 2-microglobulin in patients with non-Hodgkin's lymphoma.

Eighty-one patients with non-Hodgkin's lymphoma had serum beta 2-microglobulin (beta 2M) estimated at presentation. A significant association was found between beta 2M levels and stage of disease (P less than 0.001), presence of hepatomegaly (P less than 0.001) and bone marrow involvement (P less than 0.05). No association was found between the level of beta 2M and histological group, presence of splenomegaly, lymph-node masses greater than 5 cm in diameter, lymphocyte count or the presence of systemic B symptoms. Pretreatment levels of beta 2M did not help predict response to treatment and achievement of a complete remission, the length of remission obtained or survival.

Adolescent↗
PubMed1983

The association of cytosol oestrogen and progesterone receptors with histological features of breast cancer and early recurrence of disease.

Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen (REc) and progesterone (RPc) receptors. Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade, lymphocytic infiltration and tumour elastosis. There were significant associations between epithelial cellularity, stromal fibrosis and the value of REc in those tumours in which the receptor was present. Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor. By contrast, neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis. The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy. Overall relapse-free survival (RFS) was no different for those patients with receptors compared to those without them (REc P = 0.11, RPc P = 0.7). There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account.

Age Factors↗
PubMed1982

Effects of diphenylhydantoin on killer cell activity and other immunological functions. A sequential study including the interaction of Corynebacterium parvum in melanoma patients.

The effects of a single Phenytoin dose, given to patients with malignant melanoma, upon peripheral blood counts, serum immunoglobulins, lymphocyte subpopulations and lymphocytotoxicity (using Chang target cells) were recorded. Sequential blood samples were taken before and 10, 14, 34, 38 and 58 h after the Phenytoin. Early reductions (P less than 0.05) in lymphocyte count, NK, K and PHA induced cytotoxicity, when compared with initial, pre-Phenytoin values were noted. Immunisation with i.v. C. parvum prevented the reductions occurring after a second dose of Phenytoin. Indeed, significant increases above the values of samples taken immediately before the second dose, were observed in T cells, PHA blastogenesis, NK and K cell Cytotoxicity. The second dose did however cause some immunosuppression; the increase in T cells, NK and PHA induced cytotoxicity above initial values expected from previous investigations were not observed. The immunosuppression, particularly of killer cell function, occurring after phenytoin could have implications for the pathogenesis of malignancy and transplacental carcinogenesis, reported as following Phenytoin exposure.

Bacterial Vaccines↗
PubMed1982

Pre-natal factors in the origin of germ cell tumours of childhood.

The Manchester (England) Children's Tumour Registry is population-based with a high level of ascertainment. Pathologic review ensured diagnostic accuracy. Routine monitoring of annual incidence revealed a significant increase in germ cell tumours from approximately 1 per million person years to approximately 4. Analysis of the children's case records and their mothers' obstetric records showed an association between germ cell tumours and congenital malformations, particularly of the central nervous system, in the children themselves and in their stillborn sibs. An association between infections in pregnancy and early onset of tumours in the offspring was demonstrated. Other factors such as chronic illness in the mothers and drug-taking during pregnancy may be important, but further work is required to establish any definite associations.

Adolescent↗
PubMed1982

The spatial organization of the hierarchical proliferative cells of the crypts of the small intestine into clusters of 'synchronized' cells.

A statistical analysis of the distribution of [3H]TdR-labelled cells in longitudinal and transverse sections of crypts from the ileum of the mouse, indicated that there was a strong tendency for labelled or unlabelled cells to be associated in short vertical runs and lateral clumps, suggesting the presence of clusters of labelled cells on the sides of the crypts. A model is discussed for the cellular spatial organization of the crypt that proposes a vertical alignment of the cells within branches of the proliferative cell lineage. The model would predict vertical alignment of partially synchronized cells as well as some lateral clumping. In the present studies mitoses were not observed at higher levels in the crypt than labelled (S phase) cells. This observation would be predicted by the non-random spatial organization suggested by the model. The model would also make certain predictions concerning cell migration. These are discussed in relation to cell migration studies which include evidence that migration continues in the absence of mitotic activity.

Animals↗
PubMed1981

Effects of Corynebacterium parvum on cellular immunity of cancer patients, assayed sequentially over 63 days.

The immunologic effects of Corynebacterium parvum (2 mg/M2) infused at three-week intervals were determined by 19 sequential assays in each of nine patients with metastatic malignancy. Peripheral blood immunologic profiles were followed for 63 days. No statistical significant changes (P greater than 0.05) occurred in total white cell, lymphocyte, or monocyte counts. Subpopulation assays demonstrated significant increases in E rosetting cells but not in sIg-bearing cells; there was a corresponding significant decrease in null-cell proportions. Killer cell lymphocytotoxicity was measured by 51Cr release from Chang target cells. Significant increases were observed one week after immunization and were maintained on subsequent immunizations. NK- and K-cell cytotoxicity were particularly augmented; T-cell cytotoxicity expressed as lytic units/ml was significantly increased on fewer assay occasions. Killer cell function has a possible in vivo antitumor role and methods of boosting and maintaining the activity deserve consideration. A three-week immunization schedule with C. parvum is supported by the current work and is the basis of a randomized adjuvant immunotherapy study of patients with malignant melanoma.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

The prognosis of breast carcinoma in women aged less than 40 years.

A retrospective analysis has been carried out on 803 patients with breast carcinoma and aged less than 40 years. All the patients were followed up at the Christie Hospital for a maximum for 15 years. The survival for the whole group was 52% at five years, 40% at 10 years and 33% at 15 years. In this study for worsened with decreasing age. When the axillary nodes were involved, the five-year survival for patients aged 30 years and younger was only 34% compared to 51% in the 31-35 year group and 57% in the 36-39 year group. At 15 years the comparable figures were 18, 28 and 38% (P = 0.0001).

Adult↗
PubMed1981

Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children's Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.

Adolescent↗
PubMed1981

Germ cell tumours of childhood: a review of 137 cases.

One hundred and thirty-seven germ cell tumours occurring in 134 children included in the Manchester University Children's Tumour Registry over a 25-year period have been studied. The incidence and sites of these tumours as seen in a comprehensive population-based registry are presented and the relation between the primary site and histological type is assessed. There were 48 deaths in this series of which 34 were directly due to the tumour. The cause of death in the other 14 cases is given. The behaviour of the germ cell tumours was closely related to the presence of yolk sac elements.

Adolescent↗