Biomedical subjects
Publications and source records attributed to R Swindell.
In a study of 50 long-stay elderly patients, no significant biochemical evidence of protein sub-nutrition was found. Although their protein intake increased to a certain degree on a whole-food supplement, there was no alteration in their biochemical and immunological status during the period of supplementation.
A prospective randomised trial (534 patients, 1969-75) was designed to determine whether radical mastectomy conferred advantages over modified radical mastectomy for breast cancer in terms of total survival, local recurrence, distant metastasis, and disease-free interval. The results showed no significant difference in outcome as regards these variables between the two treatments.
The level of anti-T antibodies directed towards the precursor T antigen of the MN blood group system was measured in the sera of 55 patients with disseminated melanoma, before and during chemoimmunotherapy. The anti-T titer was subnormal in patients before therapy; patients who responded to therapy had significantly higher titers than did nonresponders in sera taken before therapy, at regression/progression of disease, and during the last pulse of treatment. Higher pretreatment titers were associated with a significntly longer survival time. A single infusion of Corynebacterium parvum was given to 14 other melanoma patients and significant elevation of preimmunization titers was observed on days 14, 21, and 28 after infusion; Bacillus Calmette-Guerin, vaccination of 9 patients did not significantly alter the anti-T titer. The expression of the normally cryptic T antigen on melanoma cells would absorb naturally circulating anti-T antibodies. Less dense expression of T antigen on melanoma cells that were responsive to therapy, i.e., less "malignant," would explain the better prognosis for patients with higher titers. The increase in anti-T antibodies following administration of C parvum but not of BCG is of possible clinical relevance when C parvum is used as an immunotherapeutic agent.
An interface between a commercial flow cytometer (Ortho Cytofluorograf 4800) and a Desk Top Computer (H.P. 9845S) is described. Programs for data acquisition and analysis have been developed. These include cell DNA content analysis, 2-parameter (3D) histograms and sophisticated sub-population selection. Although cell sorting is not possible using the facility, the data acquired per cell is optimised and detailed analysis can be carried out. The system represents a flexible, easily controlled and economical method for storing and analysing flow cytometric data.
The Manchester Children's Tumour Registry data for the period 1954-1977 have been analysed. The overall incidence of malignant disease in children aged 0-14 years in the north-west of England is estimated to be 100 per million person-years. The most common disease group is leukaemia, which forms about one third of the total number of cases. Among solid tumours, by far the most common presenting site is the central nervous system, representing nearly a quarter of all neoplasms. Wilms' tumour, neuroblastoma and soft-tissue sarcomas comprise approximately 5%, 6.5% and 6% respectively of the total. The tumours most frequently seen in adults (e.g. carcinoma of colon, lung and breast) are extremely rare in childhood. A significant excess of males was seen in acute lymphoid leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, medulloblastoma and hepatoblastoma. A female excess was found among germ-cell tumours. During the study period significant increases in incidence were seen among acute lymphoid leukaemia and epithelial tumours, and an increase in germ cell tumours approached significance.
The concentration of the common alpha subunit of the glycoprotein hormones was high in the serum of 21/56 (38%) of premenopausal patients and 22/106 (21%) of postmenopausal patients with primary breast cancer, at the time of presentation. 7/59 (12%) of patients with benign disease also had high alpha subunit levels. Tumour cytosol oestrogen and progesterone receptor status was determined in 80% of the patients with cancer, and there was a trend towards higher alpha levels in patients without receptors, but this was not statistically significant. In the premenopausal patients with cancer there was a significant correlation between alpha subunit level and disease stage, R = 0.47, P = 0.0001, but not in the postmenopausal patients. In view of the correlation with disease stage, high levels of alpha subunit in premenopausal patients with breast cancer at presentation with the primary tumour may indicate poor prognosis.
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C. parvum and BCG produced significant changes in NK, K and T cell lymphocytotoxicity using a Chang liver target cell. A consistent temporal pattern over 28 days of early depression, recovery, overshoot and then decline was described. This was particularly marked for C. parvum and 'K' cell activity. Skin test reactivity to recall antigens at 28 days was not appreciably different from the pre-immunization reactivity. The importance of using lymphocyte concentration-cytotoxicity titration curves and the linearization of such curves is discussed. An immunotherapy schedule with 3 weekly immunization intervals is proposed as the optimum schedule in patients receiving C. parvum at a dose of 2.0 mg/m2 i.v.
Increased lymphocyte cytotoxicity, particularly of 'killer' K cell type was recorded with repeated immunizations of either C. parvum or BCG. A 3 week interval between immunizations was capable of maintaining the increase in cytotoxicity. No marked alterations of 'recall' skin hypersensitivity reactions nor of peripheral blood counts were noted. Expression of cytotoxicity results as percentage 51Cr release, lytic units/ml and cytotoxic capacity (after logit transformation of the cytotoxicity-lymphocyte curves) are described. A 3 week immunization schedule is suggested where BCG and C. parvum are used as immunotherapeutic agents, in the doses quoted.
The effects of a single immunization of melanoma patients with BCG or C. parvum on the blood counts, serum immunoglobulin levels and lymphoid subpopulations were followed by multiple assays over 28 days. C. parvum produced a decrease in the white cell count, lymphocyte count and lymphoid T and sIg+ cell numbers, which recovered within 1 week; BCG did not produce such a marked depression. Both agents were associated with increases in T cell numbers and lymphocyte PHA blastogenesis after the first week; these declined to pre-immunization values by 3-4 weeks. The sIg-bearing cell subpopulation also increased after BCG. Different methods of expression the results were compared and the difficulties of immunological monitoring are discussed.
Two groups, each of eight patients, with metastatic melanoma were immunized with either C. parvum or BCG at 3-weekly intervals. The serum IgG, IgA, IgM levels, E-rosettes, EA-rosetts, sIg-bearing cells, 'null cells' and lymphocyte blastogenesis at four PHA concentrations were assayed, before immunization and weekly thereafter for 8 weeks. The pre-immunization E-rosette values were significantly reduced, with a significant increase in 'null cell' values and EA-rosette percentages, when compared with healthy controls. Following C. parvum immunization, significant increases occurred in E-rosette percentages with decreases in EA-rosette and 'null cell' counts. A significant reduction in 'null cell' values also occurred with BCG. Other parameters including PHA blastogenesis did not exhibit statistically significant changes. Different methods of expressing the results (particularly of blastogenesis data) were compared, as were the similarities between the present investigation and a study of the effects of a single immunization. The relationship between the subpopulation changes and lymphocyte cytotoxicity described in an earlier article (Thatcher, Swindell & Crowther, 1979a) is discussed.
Thirty-eight patients with metastatic melanoma were evaluated immunologically prior to chemoimmunotherapy. The assays used included recall antigen skin hypersensitivity; lymphocyte count; nonspecific T, non-T, and K cell lymphocytotoxicity; and T and B cell rosette enumeration. Survival curves were computed for each of four ranges of values of a given immunologic test. The higher ranges of positive skin tests, lymphocyte count, cytotoxicity, and T and B subpopulation numbers were consistently associated with the longer survivals. The differences reached statistical significance for non-T cell cytotoxicity and B and T cell peripheral blood counts. Pretreatment immune reactivity, particularly that involvingg non-T cell function, appears related to length of survival.
In a detailed nutritional study of 50 long-stay elderly patients, intakes of vitamins C and D and nicotinic acid were found to be sub-optimal compared to D.H.S.S. recommendations. Whole-food supplementation did not increase calorie, fat or carbohydrate intake, although it did increase protein, vitamins and minerals. However, it did not correct the intake of vitamins C and D and of nicotinic acid to those recommended by D.H.S.S. Supplementation affected neither serum albumin nor transferrin. No positive correlation could be established between physical disabilities and total dietary intake among these patients. However, the appearance of the skin improved and skin thickness increased in the supplemented patients and the blood urea diminished in them also.
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Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.
The objective of this study was to assess treatment outcomes in a large case series of cervical cancer patients undergoing postoperative radiotherapy in a single center. Case notes of women referred to the Christie Hospital during 1985-1997 for postoperative adjuvant radiotherapy for cervical cancer were reviewed. Of 478 women eligible for analysis, 282 (58.9%) underwent radical hysterectomy and 196 (41.1%) had nonradical hysterectomy. The disease-specific 5-year survival for the study population is 70.1%, with a 5-year risk of developing any recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%. Survival was significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and recurrence was significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the group of women who had adjuvant radiotherapy following a nonradical hysterectomy compared with radical surgery. Thirty percent of women having "radical" surgery had positive resection margins and required postoperative adjuvant pelvic radiotherapy. Women with node-positive disease, who received adjuvant radiotherapy, had a high rate of distant metastases. These women would receive chemoradiotherapy now as primary treatment because of the risk of developing distant metastases. If, despite staging investigations, surgery reveals node-positive disease, then these women should receive adjuvant chemoradiotherapy. Survival was better in women who had nonradical surgery due to smaller volume disease when cancers were unsuspected and hence will have been cured by surgery alone. Multidisciplinary team working, as recommended by national guidelines from 1999, should allow better patient selection for treatment.
Venous plasma amino acids have been measured before, during, and after surgical operation in 17 patients. There were no statistically significant changes in plasma amino acid levels during the operation itself, but in the 3 days following operation the concentration of many of the amino acids were altered compared with the preoperative levels. Because some of the changes resemble those seen in early starvation, further studies are necessary to determine whether trauma or starvation is the prime stimulus to the changes observed.