Search PubMed⌕ Search

Biomedical subjects

R H Begent

Publications and source records attributed to R H Begent.

At least 145 records · Page 8Linked to original sources
PubMed1984

Analysis of radioimmunodetection of tumors by the subtraction technique.

The subtraction method for radioimmunodetection (RID) of cancer is showing potential as a diagnostic tool. An objective assessment of this technique is needed in order to determine its clinical usefulness. A numerical analysis of the RID scintigrams was developed and applied to 21 RID studies on 20 patients for whom a final diagnosis had been established. The subtraction technique was shown to give rise to artifactual positive regions, which could be avoided by experienced clinicians. When artifact-producing regions were excluded, 97 regions were examined (80 nontumor, 17 tumor-containing). The "background" scintigrams were shown to be good models for nontumor regions of the antibody scintigrams, and tumor and nontumor regions were shown to form statistically distinct groups.

Antibodies↗
PubMed1984

Circulating immune complexes (CIC), carcinoembryonic antigen (CEA) and CIC containing CEA as markers for colorectal cancer.

It has been suggested that circulating immune complexes (CIC) would provide a useful tumour marker system and that carcinoembryonic antigen (CEA) may form an antigen component of CIC found in patients with colorectal cancer. In this study the clinical usefulness of CIC and CIC containing CEA (CEA-IC) was investigated. Concentrations of CIC were measured in 30 patients with colorectal cancer. Fourteen patients were studied sequentially at approximately 1 month intervals after apparent curative resection of the primary tumour. Results were correlated with those obtained from serum CEA and compared to clinical status. CEA-IC were measured using a novel assay and compared with CIC and CEA values in 29 patients. CIC concentrations were elevated in patients with known disease and predicted clinical relapse in four of 14 patients. In two patients CIC remained elevated despite sustained remission. CEA-IC were not detectable in any of the patients studied. CIC estimations may augment CEA measurements as indicators of disease recurrence but lack of specificity makes them of little practical value as tumour markers in colorectal cancer. No evidence was found to support previous reports that CEA was an antigen component of CIC in this disease.

Adult↗
PubMed1983

Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital.

Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty-nine (8.8%) patients had central nervous system (CNS) metastases. Thirty-three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life-table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.

Adult↗
PubMed1983

Further advances in the management of malignant teratomas of the testis and other sites.

Between 1979 and 1982, 69 men with metastatic malignant teratoma completed sequential combination chemotherapy (POMB/ACE). Although two-thirds of these patients initially had advanced and bulky disease, life-table analysis projects a survival of 83%. Multivariate analysis indicates that the strongest predictor of survivals is not the clinical and radiological extent of disease but the initial serum concentration of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP). In patients presenting with HCG levels below 50 000 IU/l and AFP levels below 500 kU/l the survival in 47 patients was 96%. This contrasts with the survival projected at 56% in 22 patients presenting with tumour markers at higher concentrations.

Antineoplastic Agents↗
PubMed1983

Improved radioimmunodetection of tumours using liposome-entrapped antibody.

The discrimination of radioimmunodetection of tumours is reduced by the presence of circulating radiolabelled antibody (primary antibody). We have prepared liposomes containing an antibody to the primary antibody (secondary antibody), with the intention of complexing and delivering to the liver primary antibody which is not associated with the tumour. In mice bearing xenografts of human tumours which secrete the marker carcinoembryonic antigen (CEA), liposomally entrapped secondary antibody was able to reduce the blood levels of 125I-labelled anti-CEA within 2 h, without reducing the amount of anti-CEA bound to the tumour. We therefore suggest that the use of liposomally entrapped secondary antibody would improve the diagnostic potential of radioimmunodetection of tumours and their metastases.

Animals↗
PubMed1983

Effective treatment for malignant mediastinal teratoma.

Primary malignant mediastinal teratoma is a rare tumour previously regarded as inevitably fatal. In a series of eight male patients with a mean age of 24 years five remain alive and well. All patients showed raised serum concentrations of human chorionic gonadotrophin or alpha fetoprotein. The patients were treated with intermittent combination chemotherapy that included cisplatin. Six patients responded to chemotherapy with a fall in human chorionic gonadotrophin or alpha fetoprotein to near normal levels and they then had radical excision of the remaining tumour. Living malignant tumour was found in four of the specimens and these patients received postoperative chemotherapy. One patient died after eight months and the remaining five patients are alive and well 13-136 months after the start of treatment. The two patients who did not undergo surgery died at one month and 15 months. Intermittent combination chemotherapy and carefully timed radical excision of these tumours would appear to have produced better results than have been reported in other series.

Adolescent↗
PubMed1983

Clearance of injected radioactively labelled antibodies to tumour products by liposome-bound second antibodies.

Liposomes containing anti-goat immunoglobulin were injected 24 h after administration of 125I-labelled goat antibody against the carcinoembryonic antigen (anti-CEA) to groups of nude mice bearing human tumour xenografts, and normal mice. Controls in each group received radioactively labelled anti-CEA only. In liposome-treated mice, blood 125I levels were lower than those of controls 30 min to 24 h after liposome administration, with corresponding accumulation of 125I activity in the liver and spleen for the first 2 h after liposome injection. [14C]Cholesterol or 99mTc labels in the bilayer were eliminated rapidly from the blood, with uptake in the liver and spleen. In xenograft-bearing mice, 125I activity detected in the tumours up to 6 h after liposome injection was identical to that detected in the tumours of controls. However, 24 h after liposome injection a reduction in the tumour concentration of 125I-labelled anti-CEA was obtained, but the tumour/blood radioactivity was still increased. In two mice given 27 mumol lipid, the blood radioactivity count after 24 h was only 5% of that in the controls. In rabbits, 2 h after administration of liposomes containing anti-goat second antibody, the circulating 125I activity had dropped by 28-40%. The results suggest that administration of liposome-entrapped second antibody approximately 2 h prior to external scintigraphy may clear circulating radioactively labelled primary antibody by up to 50%.

Animals↗
PubMed1982

Liposomally entrapped second antibody improves tumour imaging with radiolabelled (first) antitumour antibody.

The usefulness of antibodies directed against tumour products for localisation and therapy of cancer is limited by the large proportion of administered antibody which remains non-specifically in the circulation and extravascular space. Liposomally entrapped second antibody (LESA) directed against the first (antitumour) antibody has been used to accelerate clearance of non-tumour-bound first antibody without affecting its clearance from the tumour. Intravenously administered LESA binds the first antibody and LESA is cleared by the reticuloendothelial system. LESA accelerated clearance of radiolabelled antibody directed against carcinoembryonic antigen (CEA) from the circulation in four of five patients with gastrointestinal cancer, enhancing gamma-camera imaging of the tumour in three of them. These results suggest that LESA can improve the sensitivity and specificity of tumour imaging with radiolabelled antitumour antibody. This strategy may also have the potential to improve the therapeutic ratio of some toxic agents linked to antitumour antibody.

Adolescent↗
PubMed1982

The role of abdominal surgery in the treatment of advanced testicular germ cell tumours.

Twenty patients with advanced testicular teratoma and 1 with advanced seminoma have undergone abdominal surgery for the removal of residual disease following treatment by sequential chemotherapy (1). Fourteen out of the 21 patients (66 per cent) have achieved complete remission with a follow-up period of 6--41 months. In 12 patients (57 per cent) the tumour had undergone histological maturation or necrosis following chemotherapy, those patients in whom the tumour remained histologically active having a worse prognosis. Raised preoperative serum levels of the tumour markers human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) indicating active disease, forecast a particularly poor prognosis, 5 out of 9 such patients (55 per cent) having died. Computerized tomography gave false negative results in 3 patients (14 per cent). Postoperative complications were few, and 2 patients (9 per cent) suffered with failure of ejaculation. At present our policy is surgical removal of any residual mass after chemotherapy to determine the histology, and, wherever possible, to achieve complete clinical and biochemical remission. Six patients with an apparently poor prognosis have benefited directly from surgery and remain in long term remission. The selection of patients who benefit most from surgery can only be determined by more experience and longer follow up.

Adolescent↗
PubMed1982

Prophylaxis against hypomagnesaemia induced by cis-platinum combination chemotherapy.

Hypomagnesaemia is recognised as a feature of the renal tubular defect produced by cis-platinum therapy for cancer. It may be sufficiently severe to cause tetany and grand mal fits. Attempts to correct established hypomagnesaemia whilst continuing cis-platinum therapy have not proved satisfactory. We have therefore investigated the prophylactic addition of 3 g magnesium sulphate to the high-dose platinum regimen with which metastatic malignant teratoma is treated in this unit. Serum magnesium levels have been measured in eight patients treated in this way and compared with those recorded for eight matched patients previously treated without routine magnesium supplements. Magnesium levels fell into the range frequently associated with clinical manifestation in five of the eight unsupplemented patients and only one of those given magnesium prophylactically. Mean serum magnesium levels were significantly higher in the supplemented group when compared using the paired t-test (P less than 0.01). Routine supplementation with intravenous magnesium sulphate is a simple and effective way of preventing symptomatic hypomagnesaemia associated with cis-platinum therapy.

Adolescent↗
PubMed1982

Circulating immune complexes as markers of response to chemotherapy in malignant teratomas and gestational trophoblastic tumours.

Concentrations of circulating immune complexes (CIC) were measured serially during chemotherapy of 22 patients with gestational trophoblastic tumours (GTT) and 11 patients with malignant teratoma (MT) by the polyethylene glycol precipitation and CIq solid-phase assays. Results were correlated with tumour response as measured by serum concentrations of human chorionic gonadotrophin (hCG) and alpha-foetoprotein (AFP). CIC concentrations correlated with disease status in the early stages of treatment in 4/22 patients with GTT and 5/11 with MT. CIC assays were less sensitive than hCG and AFP as a monitor of disease, and also less specific, in that 8 patients with GTT and 5 with MT developed raised CIC concentrations during chemotherapy in spite of sustained complete remission. Measurements of CIC concentrations by present methods are neither sufficiently sensitive nor specific to be of clinical value as a tumour marker in GTT and MT, and this casts doubt on their potential value in other malignancies. Attention should be directed to identification of the components of CIC, some of which may be more cancer-specific.

Adolescent↗
PubMed1982

Potential for cure in metastatic ovarian teratomas and dysgerminomas.

Between 1977 and 1981 21 patients with metastatic ovarian germ cell tumours received sequential combination chemotherapy; 18 had malignant teratomas and three dysgerminomas. Thirteen patients with malignant teratoma have had no treatment for up to 45 months (mean 27.5 months) and one patient is still having treatment. Life table estimate of survival on 1 July 1981 projects a survival of 71% in those with malignant ovarian teratomas. Four patients with malignant teratoma have died. Two of these had received extensive treatment before referral and a third achieved complete remission but relapsed and did not subsequently respond fully to further treatment. A fourth patient had an undifferentiated tumour compatible with an embryonal carcinoma which proved refractory to all treatment. The three patients with advanced dysgerminomas are all in remission and have had no treatment for 5, 14 and 33 months respectively. The majority of metastatic germ cell tumours of the ovary now appear to be curable provided that effective treatment is begun early.

Adolescent↗
PubMed1980

Chemotherapy of advanced malignant teratomas.

Between 1977 and November 1979 we have treated 53 patients with malignant teratomas (43 males, 10 females). Thirty (70%) out of the 43 male patients had advanced and bulky disease at the time of presentation. Using different drug combinations in a sequential manner as described below, results are as follows: of the initial 33 male patients, 22 (67%) have discontinued treatment (mean 9.5 months). Nineteen have responded completely and 3 have static computed tomography (CT) nodules. Life-table analysis projects a survival of 66% (analysis at 1 December 1979). Nine out of 10 ovarian teratoma patients are alive. Adverse prognostic factors at the start of treatment were recognized in 9/10 male patients and the 1 female patient who have died. Although the survival of patients with malignant teratomas has improved dramatically, there are still problems with drug resistance in patients with very advanced disease. Patients with these tumours should continue to be treated in centres specializing in managing what has now become a potentially curable disease in most cases.

Adolescent↗