PubMed Health⌕ Search

Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 253 records · Page 14Linked to original sources
PubMed1984

The value of serial bone scanning in operable breast cancer.

The value of initial and serial isotope bone scans was assessed in 685 patients with operable primary breast cancer. Nineteen (2.8 per cent) patients had a positive initial scan and negative skeletal radiographs; only nine of these developed other evidence of metastatic disease after a mean follow up of 21 months. Five hundred and ten patients had serial scans up to five years after simple mastectomy; 51 (10 per cent) had scan conversion, of whom 37 developed clinical or radiological confirmation of recurrent disease at a mean follow-up of 13 months. Compared with clinical or radiological methods for the detection of first metastases serial bone scans gave a mean lead time of five months in 15 patients and no lead time in the remaining 22 patients. Twelve of forty-five patients with radiologically proven bone metastases had negative scans. Neither initial or serial bone scanning is clinically useful or economically viable as a routine screening or follow-up procedure for patients with operable breast cancer.

Adult↗
PubMed1984

A phase I toxicity study of human rDNA interferon in patients with solid tumours.

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.

Blood↗
PubMed1984

Dibromodulcitol, mitomycin C and vinblastine (DMV) chemotherapy in advanced breast cancer.

A combination of dibromodulcitol 500 mg orally, mitomycin C 10 mg i.v. and vinblastine 10 mg i.v. all given on day 1 and repeated every 4 weeks was given to 40 patients with advanced breast cancer. All but one had received previous endocrine therapy. The response rate (CR + PR) in 24 previously untreated patients was 66% and was 37% in 16 previously treated patients. The survival of responders was significantly longer than non-responders. Thirty-two per cent of patients experienced nausea and vomiting. There was little myelosuppression or thrombocytopenia on the day of starting a new course of therapy but the haemoglobin dropped by 2 g/dl in 32% of patients during therapy. Thus DMV is a relatively non-toxic active regimen for patients with advanced breast cancer.

Adult↗
PubMed1984

A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast.

The metastatic sites of infiltrating duct (IDC) and infiltrating lobular carcinoma (ILC) have been compared using both clinical and autopsy data. The following statistically significant differences were found: Lung parenchymal metastases were more common in IDC. Bone trephine biopsies were more likely to be positive in ILC. Carcinomatous meningitis was associated almost exclusively with ILC. Peritoneal/retroperitoneal metastases of distinctive pattern occurred in ILC. There was often associated linitis plastica-like involvement of the stomach wall and diffuse infiltration of the uterus. Hydronephrosis was a common secondary phenomenon.

Adult↗
PubMed1984

A comparison of three assays used for the in vitro chemosensitivity testing of human tumours.

In this study cell lines have been used to determine the level of correlation between three assays which are in use for in vitro prediction of human tumour chemosensitivity. The methods which were compared included a clonogenic assay, a monolayer assay and a short-term biochemical assay. The results indicated that the monolayer and clonogenic assays were either directly comparable or could be made comparable by reducing the drug exposure time in the monolayer assay. The biochemical assay also gave comparable results for 3 of the 5 drugs tested. It was concluded that although the 3 assays did not produce identical dose-response curves, the assays were equally valid when used for predictive testing because selection of cut-off points which were based on retrospective correlations between in vitro sensitivity data and response data, as established by other authors, compensated for differences in sensitivity between the assays.

Animals↗
PubMed1983

Treatment of advanced prostatic cancer with LHRH analogue ICI 118630: clinical response and hormonal mechanisms.

9 of 12 patients with advanced metastatic carcinoma of the prostate treated with luteinising-hormone-releasing-hormone (LHRH) analogue ICI 118630 for a mean period of 6 months showed objective evidence of response to treatment. Of 8 patients with bone pain, 7 obtained relief. After 6 weeks of treatment testosterone concentrations were reduced to castrate levels (range less than 2 to 5.5 nmol/l) from a pretreatment mean value of 15.7 nmol/l (range 10.3-24 nmol/l). Basal gonadotropin levels and gonadotropin responses to acute LHRH stimulation were suppressed within 2 weeks of treatment. However, the testosterone response to stimulation with human chorionic gonadotropin was unimpaired 4 weeks after the start of treatment. Therefore suppression of the basal testosterone concentration by ICI 118630 was due to inhibition of pituitary luteinising-hormone secretion rather than direct inhibition of testicular Leydig-cell function. ICI 118630 offers an alternative treatment to orchidectomy and oestrogen therapy.

Acid Phosphatase↗
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↗