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Biomedical subjects

D W Hedley

Publications and source records attributed to D W Hedley.

At least 91 records · Page 5Linked to original sources
PubMed1984

Influence of cellular DNA content on survival in advanced ovarian cancer.

Tumor cellular DNA content was measured by flow cytometry in 91 patients with advanced ovarian cancer, using a new and simple technique which allows archival paraffin-embedded tissue to be studied; 69% of the tumors were aneuploid, and 31% were diploid. Tumor ploidy was shown by multivariate Cox model analysis to be an independent prognostic variable and the major determinant of survival. Patients with diploid tumors survived significantly longer than did those with aneuploid tumors (p much less than 0.0001; X2 = 25.44; d.f. = 1).

DNA, Neoplasm↗
PubMed1983

The influence of age on the DNA ploidy levels of breast tumours.

Primary tumour DNA content and estimates of cell cycle kinetic parameters were analysed by flow cytometry in 114 cases of breast cancer. Tumours were classified as: near-diploid, single aneuploid, tetraploid and greater, and multiploid (defined as having more than one aneuploid tumour cell population). No significant correlations were found between ploidy and histologic type, tumour size, lymph node involvement or receptor (oestrogen and progesterone) status. a highly significant correlation between ploidy and proliferative activity (as assessed by the percentage of cells in S phase) was observed, with near-diploid and diploid tumours being associated with a low (less than or equal to 10%) S phase fraction (P = 0.0001). A marked relationship between ploidy and patient age was also seen, with increased DNA content being associated with older patients (P = 0.025). In contrast, no patients with multiploid tumours were over 60 yr, and their age distribution was significantly different from the population as a whole (P less than 0.05), suggesting that multiploidy might be a phenomenon associated with the menopause.

Adult↗
PubMed1983

Treatment of advanced malignant melanoma with high-dose melphalan and autologous bone marrow transplantation.

Twenty-eight patients with advanced life-threatening metastatic malignant melanoma were treated with high dose (140-260 mgm-2) intravenous melphalan and autologous bone marrow. Cyclophosphamide "priming" 300 mgm-2 i.v. was given to 19 patients one week previously and this resulted in clinical but not histological evidence of amelioration of gastrointestinal toxicity. In 11 patients (43%) there was evidence of tumour response to treatment and in 2 patients complete remissions were observed. However in most patients, responses were short-lived and no patient lived longer than 17 months from start of treatment or 24 months from first recorded evidence of distant metastatic disease.

Adult↗
PubMed1983

Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry.

A method has been developed that allows flow cytometry to be used for measuring the cellular DNA content of paraffin-embedded human tumors. Thick (i.e., 30 micron) sections were cut from tissue blocks using a microtome and dewaxed in xylene. The sections were then rehydrated by sequentially immersing them in 100, 95, 70, and 50% ethanol before finally washing in distilled water. Single cell suspensions were then prepared by incubation in 0.5% pepsin, pH 1.5, at 37 degrees C for 30 min. The cells were counted, washed, and stained with 1 microgram/ml 4',6'-diamidino-2-phenylindole for 30 min, and DNA content was measured using an ICP 22 flow cytometer. There was a good correlation between the DNA histograms produced using this method and those obtained using unfixed tissue from the same tumor stained with ethidium bromide plus mithramycin. This method allows the retrospective study of archival material where the clinical outcome is already known, and it should, therefore, be particularly useful for determining the prognostic significance of abnormal DNA content measured by flow cytometry.

DNA, Neoplasm↗
PubMed1979

Monocytes and macrophages in malignant melanoma IV. Effects of C. parvum on monocyte function.

Assays for the capacity of peripheral-blood monocytes (a) to mature in vitro into macrophages, (b) to reduce nitro-blue tetrazolium (NBT) and (c) to lyse antibody-coated human Group A red cells, were applied to a group of 82 patients with histologically proven malignant melanoma. In patients with micrometastatic disease there was an enhancement of red-cell lysis and NBT reduction, suggesting that their monocytes are in some way "activated", whereas NBT reduction was suppressed in those with overt dissemination. Monocyte maturation in vitro was impaired in all patient groups to an extent which correlated with overall tumour burden. Corynebacterium parvum was administered i.v. to 12 patients with disseminated disease and by the intradermal route to 24 patients with micrometastatic disease. The 3 monocyte functions were significantly enhanced by C. parvum.

Bacterial Vaccines↗
PubMed1979

Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan.

In a Phase I study, melphalan 140 mg/m2 was administered to 8 patients with disseminated malignant melanoma. Marrow was removed from the patients immediately before melphalan administration and returned i.v. 8 h later. Studies on marrow culture and melphalan pharmacokinetics predicted that this was a safe time to administer non-cryopreserved marrow. Four patients received lower doses of i.v. melphalan without autologous marrow. In the group receiving autologous marrow the time for recovery of peripheral-blood granulocytes to 800/mm2 or greater was significantly less (P = 0.01) than in those not receiving marrow. In 7 patients the tumour showed evidence of response to the drug and there was 1 complete remission. This treatment deserves investigation in patients with tumours more sensitive to drugs than melanoma.

Adult↗
PubMed1979

High dose melphalan and non-cryopreserved autologous bone marrow treatment of malignant melanoma and neuroblastoma.

Autologous non-cryopreserved bone marrow infused 8 hours after an intravenous injection of melphalan, 140 mg/m2, accelerates bone marrow recovery. This effect is most noticeable in the recovery of peripheral blood granulocytes. Twenty patients with disseminated malignant melanoma were treated with this regimen: there were 12 responses, two of them complete but the toxicity of the treatment was not sufficient to justify using this method of treatment routinely since survival was little influenced by treatment (4-11 months). In 8 patients with disseminated neuroblastoma, high dose melphalan/autograft was used in a program of combined modality treatment. Three of the patients are disease free at 16, 11 and 6 months and in one the disease is 'static', not having grown for 13 months. The treatment for this tumour deserves further exploration, and perhaps similar treatment ought to be explored for other tumours.

Bone Marrow Transplantation↗
PubMed1978

Acceleration of bone-marrow recovery by pre-treatment with cyclophosphamide in patients receiving high-dose melphalan.

7 patients with advanced malignant melanoma who were given cyclophosphamide (500 mg intravenously) 7 days before a high dose of melphalan (140 mg/m2) had a more rapid recovery of the peripheral white-cell count than did 4 patients who received melphalan alone. "Priming" by cyclophosphamide might be a practicable means of offsetting the bone-marrow toxicity of some chemotherapy regimens and it may permit higher doses of drugs to be given safely.

Blood-Brain Barrier↗
PubMed1978

Monocytes and macrophages in malignant melanoma. III. Reduction of nitroblue tetrazolium by peripheral blood monocytes.

Peripheral-blood monocytes from normal individuals and from patients with malignant melanoma reduce nitroblue tetrazolium (NBT). A quantitative assay for dye reduction was applied to 25 healthy donors and 31 patients with malignant melanoma. NBT reduction expressed as dye reduction per monocyte was significantly impaired in patients with disseminated disease, and they responded poorly to a phagocytic stimulus. Monocytes from patients with micrometastatic disease, however, showed normal resting NBT reduction but, following exposure to a suspension of latex-polystyrene, showed significantly greater NBT reduction than those from normal individuals. Since NBT reduction is an indirect measure of intracellular hexose-monophosphate-shunt activity we conclude that the monocytes from patients with minimal disease are in some way activated.

Adolescent↗
PubMed1978

Specific active immunotherapy does not prolong survival in surgically treated patients with stage IIB malignant melanoma and may promote early recurrence.

A prospective trial with concurrent controls was designed to assess the effects of specific active immunotherapy in patients receiving intermittent cytotoxic chemotherapy (DTIC + Vincristine) as an adjuvant to surgery in Stage IIB malignant melanoma. The treated group received monthly irradiated allogeneic melanoma cells and BCG, and the controls BCG only. Sixteen patients in the treatment arm had a median relapse-free interval of 5 months, compared to 8 months in 12 controls given chemotherapy and BCG, and because of this we felt that continuation of the study was unjustified on ethical grounds. Although all the controls who relapsed did so at distant sites, 7/11 patients given specific active immunotherapy relapsed initially within the lymphatic drainage area of the primary tumour. The median intervals from starting treatment to relapse at distant sites, and the median survival were identical in the 2 groups. We conclude that immunotherapy comprising irradiated allogenic melanoma cells as employed in this study does not prolong survival in surgically treated Stage IIB malignant melanoma and may even promote early, local relapse.

Adult↗
PubMed1977

Monocytes and macrophages in malignant melanoma. I. Peripheral blood macrophage precursors.

A micro-assay designed to assess the capacity of peripheral blood mononuclear cells to differentiate in vitro into mature macrophages is described. In patients with "final common pathway" malignant melanoma, there was a highly significant deficiency in macrophage precursors (MPs). By conventional morphological criteria such patients did not show a significant monocytopenia. Serum factors do not seem to contribute to the MP defect in the patients. We conclude that these patients have an intrinsic functional defect in their peripheral blood monocytes, but the mechanisms responsible for this defect are as yet unknown.

Adhesiveness↗