Search PubMed⌕ Search

Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 235 records · Page 13Linked to original sources
PubMed1983

Controlled trial of adjuvant chemotherapy with melphalan for breast cancer.

370 patients who had carcinoma of the breast with involved axillary lymph-nodes were randomised after total mastectomy and axillary clearance to receive either no additional treatment or melphalan 6 mg/m2 daily for 5 days every 6 weeks for sixteen cycles. There was a trend towards longer relapse-free survival (RFS) in patients treated with melphalan, but this was not significant either in the whole series or in sub-groups according to menopausal status or extent of nodal involvement. In patients receiving melphalan RFS was not significantly affected by either the occurrence of amenorrhoea or the dosage of melphalan received. Overall survival did not differ significantly between the two groups. The results of this trial suggest that there is no place for the use of melphalan as adjuvant therapy in the management of early breast cancer.

Adult↗
PubMed1983

Native and inducible levels of natural cytotoxicity in lymph nodes draining mammary carcinoma.

Lymphocytes isolated from axillary nodes draining breast carcinoma possess variable natural cytotoxic capacity. Augmentation of lymph node cell (LNC) cytotoxicity by interferon (IFN) is also variable, with only some populations displaying potentiated lysis following exposure to either IFN-a or gene-cloned IFN-a2. Where present the IFN-induced augmentation of LNC cytotoxicity was invariably weaker than that observed following similar treatment of autochthonous peripheral blood mononuclear cells (PBMC). Irrespective of their responsiveness to IFN the cytotoxic activity of all LNC preparations examined was significantly increased following pre-incubation with either staphylococcal enterotoxin A (SEA) or factors elaborated by lectin-pulsed allogeneic LNC. THe induction or amplification fo LNC-mediated natural cytotoxicity by lymphokines may provide a local potentiation of natural immune function at the host : tumour interface.

Breast Neoplasms↗
PubMed1983

Twenty-four hour combination chemotherapy: a feasibility study with implications for improved adjuvant treatment of breast cancer.

Forty-three patients with metastatic breast cancer were treated with a total of 385 cycles of combination chemotherapy consisting of adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and vincristine sulphate given over 24 hr and followed by a leucovorin 'rescue'. Thirty patients (70%) responded with three complete remissions. Thirteen patients did not respond, including six in whom the progression of disease was apparently arrested. Duration of response ranged from 2 to 24 months. At 20 months, 10 of 30 responding patients were alive compared with 1 of 13 non-responders. Toxicity was minimal apart from nausea and vomiting. This study confirms previous reports that intensive chemotherapy can be given safely over 24 hr without loss of therapeutic effect. This regimen is now being tested as an adjuvant to mastectomy in node-positive operable breast surgery.

Adult↗
PubMed1983

Variation of receptor status in cancer of the breast.

One hundred and nineteen patients with breast cancer had 2 or more lesions removed for oestrogen (REc) or progesterone receptor (RPc) assay, either synchronously (on 38 occasions) or after an interval (on 91 occasions). In all but 7 both receptors were assayed for each lesion. The assays did not agree on the presence or absence of REc alone, RPc alone or the combination of both receptors in 11, 13 and 16% respectively of the synchronous samples, compared with 23, 30 and 43% of the asynchronous samples. The differences between the synchronous and asynchronous samples were significant for the combined receptors (P = 0.007) but not for REc (P = 0.176) or RPc alone (P = 0.077). Variation between asynchronous biopsies was greater when the earlier lesion contained RPc (18/37 disagreed) than when it did not (8/50) disagreed, P = 0.0023). This was not true for oestrogen receptor. In those remaining receptor positive there was only a weak correlation between the first and second values (Spearman rank correlation coefficient, rho = 0.39 for REc, P less than 0.02, and 0.45 for RPc, 0.05 less than P less than 0.1). Receptor levels and receptor status may change with time. Biopsy is most appropriate at the time when systemic treatment is proposed.

Biopsy↗
PubMed1983

Intermediate dose single agent cyclophosphamide chemotherapy of advanced breast cancer.

Twenty-one evaluable patients with metastatic breast cancer received three pulses of intravenous cyclophosphamide, escalating from 1.5 g/m2 to 2.5 g/m2 in the second and third courses. There were eight partial remissions (34.7%), but most were of short duration. All responding patients had soft tissue or nodal disease, but additional sites of response were bone (three cases), liver and lung (one case each). Marked leucopaenia (median WBC 0.7 X 10(9)/L) occurred 10-12 days after the higher doses (2.5 g/m2) and was associated with nine episodes of severe infection in five patients. Marked vomiting and anorexia led to significant weight loss (mean 4.5 kg) in half the patients, and alopecia was universal. In metastatic breast cancer cyclophosphamide seems to have a shallow dose response curve and high intermittent dosage seems to have no advantage over chronic daily administration.

Adult↗
PubMed1982

Assessment of renal function during high-dose cis-platinum therapy in patients with ovarian carcinoma.

Five courses of cis-dichlorodiammine platinum (II) (100 mg/m2) were given to 22 patients with advanced stage III and IV ovarian cancer. Renal function was assessed by measurement of creatinine clearance, urinary osmolality and urinary B2-microglobulin (B2MG) in all patients, and by urinary alanine aminopeptidase (AAP) and N-acetyl-B-glucosaminidase (NAG) excretion in seven patients. Serum creatinine, creatinine clearance, urinary osmolality, and urinary B2-microglobulin were within the reference ranges and did not change significantly after five courses of cis-platinum in any patient. There was a significant increase in the urinary excretion of both enzymes (AAP and NAG) within 2 days of cis-platinum administration (NAG P less than 0.05 and AAP P less than 0.07). There was evidence of a cumulative effect during treatment for AAP (P less than 0.025).

Acetylglucosaminidase↗
PubMed1982

The clinical value of immunohistochemically demonstrable CEA in breast cancer: a possible method of selecting patients for adjuvant chemotherapy.

The production of carcinoembryonic antigen (CEA) by human breast cancer tissue has been studied in relation to the prognosis of patients with breast cancer. All of the patients were in a controlled trial of adjuvant chemotherapy for the treatment of operable breast cancer. CEA was studied in primary tumours and axillary node metastases from these patients using an immunoperoxidase (PAP) method. Sections of 290 primary carcinomas and 217 axillary metastases were examined for CEA. The CEA status of the primary tumours was of no value as a prognostic indicator nor in the selection of patients for chemotherapy. In contrast, patients could be divided into 3 groups on the basis of the CEA results in the axillary nodes. In one group, in which cases were strongly positive for CEA (24% of the total) the prognosis, as reflected by recurrence free survival, was relatively good and chemotherapy produced no further advantage. In another group in which cases were weakly positive for CEA (18% of the total) the prognosis was poor but chemotherapy produced significant improvement. In a third group, in which cases were negative for CEA (58% of the total) the prognosis was poor and was not improved by chemotherapy, at least in the short term. Thus, the CEA status of axillary metastases may be clinically useful.

Breast Neoplasms↗
PubMed1981

Localisation of malignant germ-cell tumours by external scanning after injection of radiolabelled anti-alpha-fetoprotein.

Sheep IgG antibody to alpha-fetoprotein was labelled with 131I and used to identify human germ-cell tumours by emission scanning. Eleven patients were studied after resection of their primary tumours. Ten had malignant teratoma and one an endodermal sinus tumour. All eight patients with raised serum alpha-fetoprotein concentrations had metastases apparent in the antibody scans. Of the remaining three patients with normal serum alpha-fetoprotein concentrations, two had positive scans. Three of the patients with positive results were scanned twice; the second scans were negative after treatment, when the alpha-fetoprotein concentrations had returned to normal. These result suggest that antibody scans are useful in the clinical management of patients with germ-cell tumours.

Adolescent↗
PubMed1980

Intravascular haemolysis and renal impairment after blood transfusion in two patients on long-term 5-fluorouracil and mitomycin-C.

In a multicentre trial of adjuvant chemotherapy in gastric adenocarcinoma, a number of patients developed chronic haemolysis and renal failure following long-term treatment with 5-fluorouracil and mitomycin-C. This was exacerbated by blood transfusion, leading to an acute intravascular haemolytic state accompanied by rapid decline in renal function. One patient investigated extensively was treated with antiplatelet drugs, steroids, and fresh frozen plasma without success. At necropsy this patient and another had renal changes typical of the haemolytic-uraemic syndrome and no evidence of tumour recurrence. Long-term treatment with this drug combination is potentially dangerous, and routine monitoring of renal function is recommended.

Adenocarcinoma↗
PubMed1980

Histological detection of oestrogen receptor in human breast carcinomas.

Histological (immunocytochemical and cytochemical) methods for demonstrating oestrogen receptor within breast-cancer cells gave a positive reaction in 29 (83%) of 35 breast carcinomas. Oestrogen receptor could be demonstrated in cytoplasm and nucleus in 15, cytoplasm only in 10, and nucleus only in 4. 24 (68.5%) of the carcinomas had detectable oestrogen receptor by the dextran-coated charcoal method, and all of these were positive by histological methods. The cytochemical method gave much better results than the immunocytochemical method and showed that carcinomas contain variable proportions of oestrogen-receptor-positive and oestrogen-receptor-negative cells.

Adult↗
PubMed1980

Pharmacokinetics of oral and intravenous fluorouracil in humans.

The pharmacokinetics of fluorouracil were examined after single 250-mg iv doses and 500-mg oral doses to female patients with breast cancer. In five patients who received intravenous fluorouracil, the mean peak plasma level of unchanged drug was 13.4 microgram/ml, the elimination half-life was 6.3 min, and the plasma clearance was 1410 ml/min. The last value is similar to the hepatic blood flow. In six patients who received oral fluorouracil, the mean peak value of unchanged drug in plasma, which occurred within 20 min of dosing, was 8.3 microgram/ml, and the fluorouracil elimination half-life was 7.2 min. The overall bioavailability of oral fluorouracil as unchanged drug was 28%, and the variation in plasma drug levels between individuals was similar following oral and intravenous doses. The data provide additional evidence of saturable hepatic metabolism of fluorouracil during the first pass.

Administration, Oral↗
PubMed1980

Effect of prolactin on lactalbumin production by normal and malignant human breast tissue in organ culture.

To determine whether lactalbumin production by normal and neoplastic human mammary tissue is under the same control, the effect of prolactin treatment was studied in organ culture. Of 9 premenopausal normal breast samples, 6 produced lactalbumin in culture, and all 6 responded to prolactin treatment over 4 days. One biopsy of pregnant breast tested also responded to prolactin treatment, producing 200 times more lactalbumin in culture than did normal breast. Two of 4 normal postmenopausal biopsies produced lactalbumin, and one increased synthesis and release after prolonged exposure to prolactin. Of 10 scirrhous carcinomas, 6 produced lactalbumin, but none responded to prolactin treatment. In 2 premenopausal patients, normal breast tissue responded to different concentrations of prolactin, which were without effect on malignant tissue from the same breast. In summary, lactalbumin production in the samples that we have studied can be stimulated in normal but not in malignant breast tissue. This may indicate an absence or deficiency of prolactin receptors in malignant tissue.

Breast↗