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Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 271 records · Page 15Linked to original sources

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↗

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↗

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↗

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↗

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↗

Tumour markers in breast cancer.

The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers.

Breast Neoplasms↗

Birmingham Medical Research Expeditionary Society 1977 Expedition: the diuresis and related changes during a trek to high altitude.

Continuous 24-hr urine collections were made by 17 subjects during a trek to 5400 m. Fluid intake was recorded by diary. Weight and fat folds were measured daily. The results were compared with daily measurements of packed cell volume (PCV) and reticulocyte count. Early fluid retention was matched by a fall in PCV. There was a diuresis with negative fluid balance towards the end of the ascent and again early in descent. There was a slight trend for fluid retention to occur in those most affected by acute mountain sickness but the effect was not marked.

Adult↗

Predictive classification of human breast carcinomas based on lactalbumin synthesis.

The milk protein lactalbumin was found in the cytosol fraction of 20 of 53 human breast carcinomas. Oestrogen receptor (E.R) was detected in 36 of the tumours. The presence of lactalbumin was closely associated with the presence of E.R.; in tumours containing both, there was a positive linear correlation between concentrations of lactalbumin and E.R. Synthesis of lactalbumin by a mammary carcinoma seems to indicate an intact oestrogen receptor mechanism and may therefore be useful in identifying tumours responsive to endocrine therapy.

Breast Neoplasms↗

Increasing growth with raised circulating somatomedin but normal immunoassayable growth hormone.

Two patients are described with elevation of circulating somatomedin A concentration but normal growth hormone levels. One,a young male, appeared clinically acromegalic; the other, a young female, was tall with kyphoscoliosis, and her appearance resembled Marfan's syndrome. In both patients plasma growth hormone concentration was suppressible by hyperglycaemia. It is suggested that their clinical syndromes resulted from excessive somatomedin activity.

Acromegaly↗

Release of colony-stimulating activity from the isolated perfused rat liver.

1. Colony-stimulating activity appeared in the perfusate of the isolated rat liver during perfusions with either whole rat blood, rat plasma or an artificial perfusate of Eagle's medium and albumin. 2. Dialysable inhibitors of colony formation were also released during perfusions. 3. Colony-stimulating activity in artificial perfusate could be enhanced by the addition of rat plasma in vitro. Concentrations of cycloheximide that inhibited albumin synthesis by the liver did not inhibit the release of colony-stimulating activity.

Animals↗

Effect of inhalation anaesthetics on division of bone-marrow cells in vitro.

The effect of halothane or nitrous oxide or both, on division of cultured, murine bone-marrow cells was investigated. Halothane caused a dose-dependent depression of growth rate ranging from a minimal effect at 0.5% to almost total inhibition at 2.0%. Nitrous oxide 75% had an effect similar to 0.5% halothane and the combination of 0.75% halothane with 75% nitrous oxide produced results little different from 1.0% halothane alone. There was good recovery from 1.0% but not from 2.0% halothane. It is concluded that, in vitro, bone-marrow cells show a similar sensitivity to these agents as was found for other mammalian cell lines which have been investigated. The effect of nitrous oxide was no more than proportional to its narcotic potency relative to halothane.

Animals↗

Depression of bone marrow colony formation in gold-induced neutropenia.

Bone marrow culture in semi-solid agar was used to assess the proliferative activity and the response to sodium aurothiomalate of the myeloid precursor cells from patients during and after recovery from neutropenia associated with the use of this drug. Colony formation was reduced during the neutropenia and returned to normal after recovery. The rheumatoid process itself did not impair colony formation even in patients with Felty's syndrome. Sodium aurothiomalate inhibited colony formation by normal marrow in a dose-dependent manner. Bone marrow colonies from patients who had recovered from neutropenia induced by sodium aurothiomalate were not abnormally sensitive to the inhibitory effect of the drug in vitro. The metabolism of gold is probably altered in a small proportion of patients, which causes high local concentrations within the bone marrow leading directly to marrow depression.

Adult↗

The diagnosis of the carrier state for the Lesch--Nyhan syndrome.

Skin biopsies from the mother of a classical case of the Lesch-Nyhan syndrome grew only wild type fibroblasts. This suggested that she is not a heterozygous carrier of the mutant X-linked structural gene which causes the syndrome, and that a fresh mutation caused the disorder in her son. Evidence of mosaicism was sought in skin fibroblasts, hair follicles, jejunal mucosa, cultured bone marrow cells and phytohaemagglutinin (PHA) stimulated lymphocytes from known hemizygotes and heterozygotes for the so-called complete, and partial deficiencies of hypoxanthine guanine phosphoribosyltransferase (HGPRT). These studies were designed to determine the genetic status of the mother of the propositus and to determine if the genetic diagnosis could be improved by the simultaneous study of this wider range of tissues. The results are compatible with the mother of the propositus being a non carrier of a mutant gene causing the Lesch-Nyhan syndrome in her son. Only the study of cultured skin fibroblasts, and of the enzyme levels in hair follicles, contributed diagnostically useful information in this case.

Adult↗