Biomedical subjects

D Easton

Publications and source records attributed to D Easton.

At least 73 records · Page 4Linked to original sources

PubMed1991

Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis.

We have determined the estrogen receptor, progesterone receptor (PR), and 1,25-dihydroxyvitamin D3 receptor content of 136 breast carcinomas by an immunocytochemical method. The presence of the three receptors was not related to clinical features of presentation such as T-stage or to age or menopausal status. However, each of the three receptors has a different relationship to the course of the disease in these patients. The presence of PR was significantly associated with an improved overall survival (chi 2 = 4.61, P = 0.032). Patients whose tumors contained immunocytochemically detectable 1,25-dihydroxyvitamin D3 receptor had a longer disease-free interval than those patients with negative tumors (chi 2 = 4.01, P = 0.045). The presence of estrogen receptor and PR were found to correlate with an increased survival between relapse and death (P = 0.027 and P = 0.09, respectively). The relationships between estrogen receptor and PR and prognosis are more apparent when the degree of cell staining is considered. Combined receptor analysis improves our ability to predict the course of the disease and may therefore facilitate better management of the patients.

Adult↗

PubMed1991

A quantitative analysis of the accuracy of in vivo pH measurements with 31P NMR spectroscopy: assessment of pH measurement methodology.

31P NMR spectroscopy provides a means of monitoring intracellular pH (pHi). In order to determine the significance of observed pH changes, an assessment of the measurement uncertainty is required. This paper considers the possible sources of error involved, firstly in chemical shift assignment and, secondly, in relating chemical shift to pH. A statistical analysis of these errors is presented and an expression for the accuracy of pH measurements obtained using in vivo 31P NMR spectroscopy is derived. Computer simulations and clinical measurements are considered to determine the likely error in clinical measurements. A comparison of pH measurement methodology using a centre-of-gravity calculation, Gaussian and Lorentzian fitting is also presented and discussed.

Humans↗

PubMed1991

Bone marrow micrometastases in primary breast cancer: prognostic significance after 6 years' follow-up.

Using an antiserum to epithelial membrane antigen we have screened multiple bone marrow aspirates from 350 patients with primary breast cancer taken at the time of initial surgery. 89 (25%) patients were found to have micrometastases and their presence was related to pathological size (P less than 0.01), the presence of peritumoral vascular invasion (P less than 0.001), and positive lymph nodes (P less than 0.005) but not menopausal status. At a median follow-up of 76 months (range 34-108) 107 patients had relapsed with distant metastases. 48% (43 of 89) of these patients had micrometastases initially compared with 25% (64 of 261) who did not (P less than 0.005). The test predicts for relapse in bone (P less than 0.01) and other distant sites excluding bone (P less than 0.001) and is associated with a shorter overall survival (P less than 0.005). We conclude that the detection of micrometastases signals a high likelihood of early relapse and decreased survival in breast cancer.

Adult↗

PubMed1990

Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region.

The frequency of nasopharyngeal carcinoma is nearly 100-fold higher in southern Chinese than in most European populations. Earlier studies have suggested that an increased risk of nasopharyngeal carcinoma is associated with specific haplotypes in the HLA region: relative risks slightly over twofold were found for haplotypes A2, Bw46 and the antigen B17. We now report a linkage study based on affected sib pairs which suggests that a gene closely linked to the HLA locus confers a greatly increased risk of nasopharyngeal carcinoma. The maximum likelihood estimate is of a relative risk of approximately 21. The relationship between this suspected disease susceptibility gene (or genes) and known viral and environmental aetiological factors remains to be elucidated.

China↗

PubMed1990

Models for skin tumour risks in workers exposed to mineral oils.

The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on the scrotum and the 2.4th power for tumours on the hand and forearms. These results accord well with experiments on animals. There was some evidence of an increasing trend in risk with increasing age at first exposure.

Adult↗

PubMed1990

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals↗

PubMed1990

The contribution of inherited predisposition to cancer incidence.

Only a small proportion of cancers, arising in inherited syndromes such as polyposis coli, have an unequivocally inherited basis. Nevertheless, most common cancers show familial clustering, much of which may be due to inherited predisposition. If so, there may be wide variation in genetic susceptibility to common cancers. The precise models of susceptibility are unclear, but for ovarian cancer and breast cancer there is some evidence that a small proportion of cases result from highly penetrant dominant genes. This has been confirmed recently for breast cancer by genetic linkage studies. Clear evidence for genetic susceptibility has been obtained for Hodgkin's disease and nasopharyngeal carcinoma, where the existence of susceptibility genes at the HLA locus has been demonstrated by linkage analysis. These genes could account for the majority of cases of these cancers. Identification of other cancer susceptibility genes should be possible, either directly using linkage analysis, or through identification of constitutional phenotypes related to cancer risk.

Disease Susceptibility↗

PubMed1989

The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation.

Eighty-two patients were randomly allocated to receive intravenous acyclovir 5 mg kg-1 t.d.s. for 23 days followed by oral acyclovir 800 mg 6-hourly for 6 months or matching placebos after allogeneic bone marrow transplantation. Herpes simplex and varicella zoster virus infections were significantly reduced during the period of administration of acyclovir. No reduction in cytomegalovirus infection was demonstrated. The drug was not toxic.

Acyclovir↗

PubMed1989

Cancer treatment trials--past failures, current progress and future prospects.

Randomized trials are usually too small to provide decisive evidence on the effectiveness of cancer therapy, and most therapeutic developments have been based on studies of tumour response. This approach, together with survival comparisons using historical controls, has led to the development of effective chemotherapy for a few very responsive tumours, but not for most common cancers, where the impact of treatment on survival is quite small. It is difficult to distinguish effective and ineffective innovations in the treatment of such cancers, and consistent progress, in which the more effective treatments are developed and the less effective ones discarded, cannot be achieved without comparisons based on large numbers of randomized patients. The combined evidence on adjuvant therapy for breast cancer and colorectal cancer is reviewed, and a new meta-analysis of published chemotherapy trials in advanced ovarian cancer is presented. The evidence that certain adjuvant regimens can prolong survival is conclusive for breast cancer and quite strong for colorectal cancer, and there is suggestive evidence that cis-platinum prolongs survival in advanced ovarian cancer. Such results illustrate the importance of large randomized trials in evaluating and improving the treatment of common cancers. The major difficulty in achieving large patient entry to randomized studies is the reluctance of many oncologists to participate in collaborative clinical research. The reasons underlying this reluctance, and the way in which such collaboration should be organized to meet these objections, are also discussed.

Clinical Trials as Topic↗

PubMed1988

Prevention of herpes zoster in patients by long-term oral acyclovir after allogeneic bone marrow transplantation.

Following allogeneic bone marrow transplantation for leukemia, herpes zoster infections that are potentially severe with a high risk of dissemination develop in 30 to 50 percent of patients. Intravenous acyclovir is an effective treatment for established zoster in immunocompromised persons. Oral acyclovir has relatively low bioavailability, which has made the value of this route of administration for the treatment or prophylaxis of herpes zoster infections uncertain. In this trial, 82 patients undergoing allogeneic bone marrow transplantation for leukemia were randomly assigned to receive either intravenous acyclovir for 23 days followed by oral acyclovir for six months, or matched placebos; the random groups were well-matched in all clinical characteristics. During the six-month period of acyclovir/placebo administration, no patient receiving acyclovir developed herpes zoster, whereas six patients receiving placebo did so (p = 0.006). During the six-month follow-up, there were six cases of zoster in the treatment arm of the study and two cases in the placebo arm. Herpes zoster was not restricted to those patients who had positive evidence of antibody before transplant. This study shows that oral acyclovir is capable of preventing zoster infection during its period of administration; once the drug treatment is stopped, infections occur. In selected patients, the use of long-term oral acyclovir may be of value in preventing zoster infections during the time of greatest immunosuppression.

Acyclovir↗

PubMed1988

Low dose single fraction radiotherapy in the treatment of metastatic bone pain: a pilot study.

Single fraction radiotherapy can be used effectively to palliate painful bone metastases. The optimal single dose of radiotherapy required for pain relief is unknown. Twenty-six patients have been treated with a single fraction of 4 Gy to the site of the bone pain. Partial pain relief was seen in 9/21 (5%). Response occurred within 3 weeks of radiotherapy. These results question the mechanism of pain relief following radiotherapy and suggest a method of pain control using single repeatable low dose treatments.

Aged↗

PubMed1988

Radiotherapy results in laparotomy-staged Hodgkin's disease.

Between 1970 and 1978, 131 patients with laparotomy-staged, supradiaphragmatic Hodgkin's disease were treated at the Royal Marsden Hospital with mantle radiotherapy, reserving chemotherapy for relapse. Forty-four patients relapsed at a total of 64 sites, the majority of which were infradiaphragmatic. Analysis of the factors predicting relapse showed that bulky mediastinal disease, and three or more sites of involvement at presentation significantly decreased disease-free survival in this group. Age above 60 years, high erythrocyte sedimentation rate (ESR) and adverse histology were of borderline significance. Although the majority (75%) of relapsed patients were salvaged with subsequent chemotherapy, it is suggested that patients with three or more sites of nodal involvement and bulky mediastinal disease would be managed best with initial combined modality therapy.

Adult↗

PubMed1988

The relationship between micrometastases in the bone marrow, histopathologic features of the primary tumor in breast cancer and prognosis.

The pathologic features of the primary tumors in 285 patients with breast cancer at the time of initial presentation, and with no clinical evidence of distant metastases, have been analyzed. The results have been compared with the detection of tumor cells in the bone marrow by use of an immunocytochemical method using antisera raised against the epithelial membrane antigen (EMA). The authors found EMA-positive cells (i.e., tumor cells) in the bone marrow of 77 (27%) patients and a significant association between the presence of such EMA-positive cells in the bone marrow and tumor size (P = 0.006) and peritumoral vascular invasion (P = less than 0.001). A possible relationship with estrogen receptor negativity (P = 0.06) also was noted.

Adult↗

PubMed1987

Presurgical determination of estrogen receptor status using immunocytochemically stained fine needle aspirate smears in patients with breast cancer.

We have developed an immunocytochemical staining procedure (ERICA) using a monoclonal antibody to the estrogen receptor (ER) to determine ER status from samples obtained by fine needle aspiration of primary and recurrent breast cancer tissue (cyto-ERICA). ER status was assessable on 214 of 246 smeared aspirates from breast cancer patients. In 143 (66.8%) assessable smears positive nuclear staining was observed but was completely absent in 71 (33.2%) cases. In 107 cases we were able to compare results with those obtained with the quantifiable dextrancoated charcoal (DCC) radioligand binding technique using surgically excised material. We observed qualitative agreement in 53 of 62 (85.5%) of primary specimens and 16 of 16 (100%) recurrent samples compared to the subsequent DCC result on the same sample. Aspirates obtained from new secondary deposits were also assessed and in 16 of 19 (84.2%) cases results agreed with that established previously by DCC on the primary breast tumor. In a further 6 of 10 (60%) cases the cyto-ERICA result obtained from recurrent samples qualitatively agreed with that determined by DCC on a previous recurrent lesion. A comparison of staining of aspirates was also made against frozen tissue sections stained with the monoclonal antibody (tissue-ERICA). Where comparison was made of primary tumor specimens agreement was observed in 40 of 45 (88.9%) of cases while specimens from secondary lesions agreed qualitatively in 14 of 17 (82.3%) of cases. In a small number of samples where tissue-ERICA was performed on an earlier lesion to that aspirated for cyto-ERICA an agreement of 4 of 5 (80%) was observed. This technique shows good sensitivity in demonstrating ER in aspirate specimens, should therefore permit us to determine ER status before surgery for primary breast cancer, and may also mean that surgery for recurrent disease to determine receptor status is no longer necessary.

Antibodies, Monoclonal↗

PubMed1987

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.

Adult↗

PubMed1987

Adjuvant aminoglutethimide therapy for postmenopausal patients with primary breast cancer.

Three hundred and twenty-two postmenopausal patients with primary breast cancer and ipsilateral axillary node involvement were randomized to receive aminoglutethimide and hydrocortisone or placebo for 2 years in a double blind randomized trial between April 1980 and March 1985. Two hundred and eighty-six patients were eligible for the study of whom 145 received active drug and 141 received placebo. At the present time significantly fewer patients have relapsed or died without previous relapse in the treatment arm (P = 0.002); 43 of 145 (30%) patients receiving aminoglutethimide have relapsed or died compared with 63 of 141 (40%) of those receiving placebo. Local recurrence is also significantly reduced (P = 0.002) since only 6 patients receiving active treatment developed local recurrence compared to 21 receiving placebo. Side effects were severe enough to necessitate complete withdrawal or reduction of therapy in 27 of 145 (19%) in the treatment arm of the study compared with 21 of 141 (15%) in the placebo arm. A single treatment-related death occurred, due to agranulocytosis. Aminoglutethimide and hydrocortisone therefore delay relapse after surgery for primary breast cancer in postmenopausal women. It is too early to assess any effect on overall survival.

Aged↗

PubMed1987

Prognostic factors related to survival and groin recurrence following therapeutic lymph node dissection for lower limb malignant melanoma.

A retrospective analysis was carried out of 133 patients undergoing therapeutic lymph node dissection for malignant melanoma of the lower limb. A radical ilio-obturator dissection (RID) was performed in 106 patients and a superficial femoral dissection (SFD) in the remaining 27. On univariate analysis five factors were found to be significant indicators of prognosis. These were: Clark level of the primary (P = 0.02); primary melanoma thickness (P = 0.04); total number of positive nodes (P less than 0.001); number of positive femoral nodes (P less than 0.001); and number of positive ilio-obturator nodes (P less than 0.001). On multiple regression analysis only the number of positive nodes in each compartment remained a significant independent factor (P less than 0.001). The morbidity associated with RID was not significantly greater than after SFD. RID was, however, associated with a reduction in subsequent groin recurrence. Radical nodal clearance is the operation of choice. This technique provides maximum prognostic information, reduces the likelihood of local untreatable disease and possibly improves overall survival rates--especially when only one iliac node is involved.

Adolescent↗

PubMed1987

Increased activity of serum amine oxidases in granuloma annulare, necrobiosis lipoidica and diabetes.

Serum monoamine oxidase, diamine oxidase and lysyl oxidase-like activity were measured in patients with granuloma annulare (GA), necrobiosis lipoidica (NL) and diabetes mellitus. In diabetes, all enzyme measurements were raised by a factor of about 2 X 2, and in NL by a factor of about 1 X 5. The rise in patients with GA was small and only significant in the case of benzylamine monoamine oxidase. "Stiff' collagen would seem to link these three disorders and the present results suggest that these amine oxidases could be useful in monitoring collagen abnormality in diabetes and diabetes-associated disorders, particularly in the absence of chronic liver disease. A negative correlation was found between enzyme activity and blood glucose levels, thus collagen changes in these conditions may occur independently of elevated blood glucose levels. Possible involvement of these enzymes in angiopathy remains to be elucidated.

Adult↗