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Biomedical subjects

M S Dorreen

Publications and source records attributed to M S Dorreen.

9 recordsLinked to original sources
PubMed1992

Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants.

In this study we evaluated the clinical response of 12 patients with malignant melanoma and renal cell carcinoma (RCC) following administration of recombinant human interleukin-2 (rhIL-2) by continuous infusion. Serum samples taken before, during and following sequential courses of IL-2 were assayed for the presence of tumour necrosis factor alpha (TNF-alpha) IL-1 alpha, IL-6 and interferon gamma (IFN-gamma) and the presence or changes in these cytokines were examined with respect to clinical response data: our results did not show any direct correlation between the parameters measured and clinical outcome. In addition, peripheral blood mononuclear cells (PBMC) derived from 3 RCC patients were cultured in a serum-free environment and the resulting supernatants assayed for the production of these cytokines and compared to the corresponding serum levels. During one or more courses of treatment only 1 patient, who had metastatic bone disease, demonstrated detectable serum TNF-alpha; serum IL-6 levels were elevated in a proportion of all patients studied and a sustained IL-6 response occurred in a patient who had complete disease remission; IL-1 alpha was detected in the serum of 3 RCC patients; IFN-gamma could not be detected in any serum sample tested. Cytokine levels in sera and supernatants derived from 3 RCC patients were compared but no correlation was found: TNF-alpha and IL-6 were shown to be present at much higher concentrations in supernatants when compared to sera whereas the levels of IL-1 alpha were almost undetectable. This lack of correlation is probably due to the presence of "interfering" proteins in sera which either depress or enhance the ability to detect cytokines in sera using enzyme immunoassays.

Carcinoma, Renal Cell↗
PubMed1992

Stage I seminoma of the testis: is post-orchidectomy surveillance a safe alternative to routine postoperative radiotherapy?

Experience with the management of 128 patients with Stage I testicular seminoma over a 10-year period, 1980-1989, is presented. Fifty-six patients were treated with post-orchidectomy radiation therapy and 72 patients were put on surveillance. Patients thought to be at higher risk of relapse were generally treated with radiotherapy. There have been no tumour related deaths in this series; 5.4% of the irradiated group and 18% of patients on surveillance have relapsed to date. All relapses have been salvaged with further therapy and are currently in complete remission. In this interim analysis, surveillance appears to be a safe alternative to adjuvant radiation therapy provided regular, prolonged follow-up can be ensured. Surveillance is, however, time consuming and resource demanding, and should be undertaken only as part of a formal clinical study. Adjuvant post-orchidectomy radiotherapy should be considered the treatment of choice until further long-term data are available.

Adult↗
PubMed1991

Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2.

The immunological and haematological effects of continuous infusion of recombinant human interleukin-2 (rhIL-2) in 6 patients with metastatic melanoma and 6 with disseminated renal cell carcinoma are reported. In patients with malignant melanoma dacarbazine was given before IL-2; in renal cell carcinoma IL-2 alone was given. In malignant melanoma, 1 complete (CR) and 1 partial response (PR) were seen; 2 patients had stable disease (SD) and 2 progressive disease (PD). In renal cell carcinoma 4 patients had SD and 2 PD. Toxicity of IL-2 therapy was minimal. All patients showed increased cytotoxicity, that was not major histocompatibility complex restricted, towards target cells sensitive and insensitive to natural killer cells. These activities varied between individual patients and were less marked in cases of renal cell carcinoma. Cellular proliferative responses increased in all patients, being consistently higher following the first course of therapy, as did HLA-DR, CD16 and CD25 activation marker expression. Hypersegmentation of neutrophils and eosinophilia were commonly observed, and in renal cell carcinoma these changes were accompanied by abnormal lymphocyte morphology.

Aged↗
PubMed1988

Results of low-dose methotrexate treatment of persistent gestational trophoblastic disease in Sheffield 1980-1987.

Between January 1980 and October 1987, 115 evaluable patients were treated in Sheffield for persistent gestational trophoblastic disease (GTD) with a low dose methotrexate regimen (LD-MTX). Each course comprised MTX 50 mg given by i.m. injection for 4 doses on alternate days. Courses were repeated every 2 weeks and serum beta-hCG was used to monitor response. Overall, 80/115 (70%) of patients attained durable complete remissions (CR). Twenty-nine patients received the 'AVC' salvage combination of actinomycin-D 0.5 mg i.v. for 5 days, sequenced with cyclophosphamide 500 mg i.v. and vincristine 1 mg i.v., both given for 3 doses on alternate days. Sixteen (55%) patients attained a durable CR but 11 (38%) required further measures, 7 ultimately requiring hysterectomy. Two (7%) died during treatment. With 4 deaths overall (3 from metastatic GTD and 1 from infarction of the bowel), actuarial survival is 94% at over 7.5 years. A new Charing Cross prognostic scale weighted especially for hCG levels, number and sites of metastases, interval between pregnancy and start of treatment (score 0-6 each factor), was applied retrospectively to obtain a total score for each patient. Thus, 21/26 (81%) patients who scored greater than 8, required additional treatment after LD-MTX, compared with 18/89 (20%) of lower scoring patients (p less than 0.001). Because of the frequent morbidity associated with prolonged chemotherapy as well as the development of drug-resistant GTD, it is concluded that the 'high-risk' patients should receive more intensive combination chemotherapy at the outset.

Adult↗
PubMed1988

Primary intracerebral lymphoma: a clinicopathological analysis of 14 patients presenting over a 10-year period in Sheffield.

Intracerebral disease was diagnosed in 14 out of 450 patients who presented with non-Hodgkin's lymphoma between January 1976 and January 1987. Twelve of the 14 presented after June 1980. Age ranged from 31 to 73 years and eight patients were male. Two patients had other tumours, and three had relevant associated immunosuppressive disorders. Radiological assessment of one further patient showed a cavitating bronchial carcinoma. Five patients were untreated, and one died before radiotherapy was complete. Eight patients completed courses of whole-brain irradiation; four of these received higher doses. All entered remission. Three patients are alive, between eight months and seven years after treatment. Of the remaining five, one never recovered intellectual function and died of bronchopneumonia; three died between eight and 30 months after treatment and autopsy showed severe radionecrosis of the brain with no residual tumour. All three had received higher doses of radiation and had undergone burrhole aspiration before treatment. Autopsy was refused on one patient who also appeared to have died from radionecrosis of the brain. Immunohistological examination in eight cases confirms that cerebral non-Hodgkin's lymphoma is a B-cell tumour. As other groups have found, its incidence appears to be rising. Survival rate is poor, and at least some deaths are related to both radiation necrosis and the bulk of residual tumour after diagnostic surgery.

Adult↗
PubMed1987

Angio-immunoblastic lymphadenopathy: a clinical, immunological and molecular study.

Twenty four patients with angio-immunoblastic lymphadenopathy (AILD) presenting between 1974 and 1985 have been reviewed. Clinical features at presentation included rash, fever, lymphadenopathy and hepatosplenomegaly in 75% of patients. Polyclonal hypergammaglobulinaemia was seen in 19/20 patients; 5 had normal immunoglobulin levels. Combination chemotherapy with MVPP was the optimal treatment with 6/7 patients achieving complete remission. Duration of remission ranged from 9 months to 4 years and was significantly longer in patients achieving complete as opposed to partial remission. In 6 patients phenotype studies were performed on single cell suspensions and immunoperoxidase studies on frozen sections of 7 lymph nodes. There was a reversal of the normal T suppressor/helper cell ratio with a predominance of T suppressor cells. Loss of normal B follicles was observed histologically in all except one lymph node. Germline configuration of the beta B-chain of the T cell receptor was observed in lymph nodes of 4 patients with AILD, and a rearranged T cell receptor was observed in 1 patient in whom a second lymph node biopsy had shown alteration of the histological picture to that of T-zone lymphoma. Frozen sera of 15 patients were screened for antibodies to HTLV I and III and were found to be negative.

Adult↗
PubMedDate not supplied

Second primary malignant neoplasms in patients treated for Hodgkin's disease at St Bartholomew's Hospital.

The incidence of second malignant neoplasms (SMN's) was investigated in a group of 529 patients with Hodgkin's Disease (HD) treated at St Bartholomew's Hospital (SBH). SMN's were seen in 27 of these patients giving an incidence rate three and a half times that expected in an age and sex matched normal population (p = much less than 0.001). The incidence rate was higher in those receiving multiple chemotherapy and radiotherapy for relapsed HD compared with those receiving primary radiotherapy, chemotherapy or chemotherapy with adjuvant radiotherapy (p = 0.02). However, the increased incidence rate in those patients treated with chemotherapy on relapse, may reflect in part a delayed effect of their primary therapy, since the incidence rate in the primary treatment group only becomes significantly raised after six years. When allowance was made for this delay the difference between the two groups was no longer significant. The incidence rates for Non-Hodgkin's Lymphoma (NHL) and myelogenous leukaemia were 32 and 57 times those expected, compared with only two and a half times the expected rate for non-haematological SMN's (p = much less than 0.001). The four acute myeloid leukaemias (AML) all occurred within five years of treatment compared to wide-ranging intervals between treatment and occurrence of SMN in the other groups. The increased incidence of NHL may be an alternative expression of lymphoid abnormality rather than a treatment-related occurrence. Multiple SMN's were diagnosed in three patients. This represented a highly significant (p = much less than 0.001) increase over the expected incidence of multiple neoplasia in the general population. Several factors may contribute to the development of SMN's in HD, including an inherent disposition of HD itself. The time-dependent incidence pattern of SMN's with a delay followed by an increased incidence rate, suggests that treatment plays a key role. It is not yet clear whether more intensive, or multiple treatments add to the risk accrued for the initial treatment.

Adult↗
PubMedDate not supplied

Role of biological markers and probes in lung carcinomas.

Bronchial carcinomas are frequently associated with ectopic secretion of hormones which may be responsible for paraneoplastic syndromes. In non small cells carcinomas, serum calcitonin levels may be raised. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (responsible for gynaecomastia) in large cells carcinomas. In small carcinomas, many hormones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embryonic antigen add nothing to the information available with standard staging investigations. More recent studies have identified three protein products: the BB-isoenzyme of creatine kinase, bombesin and neurone-specific enolase. The latter seems a promising marker to follow up the course of the disease.

APUD Cells↗