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Biomedical subjects

D Baxter

Publications and source records attributed to D Baxter.

At least 55 records · Page 3Linked to original sources
PubMed1988

Racial inequalities in health: a challenge to the British National Health Service.

The existence of racial inequalities in health in the United Kingdom is examined using both indirect and direct data. The evidence strongly supports the view that the health experience of black and other ethnic minority groups is worse than that of the indigenous white population. Ways of improving this situation are outlined; they indicate the need for a coordinated Health service response incorporating planning, training, and equal opportunities in both service provision and employment practices.

Black People↗
PubMed1986

A radioreceptor assay for pharmaceutical preparations of insulin.

A radioreceptor assay has been developed that is suitable for the measurement of the potency of crystalline insulin and pharmaceutical insulin formulations. It utilizes the well characterized and widely available IM-9 human lymphocyte cell line as the source of receptor. Bovine, porcine and human crystalline and formulated insulins have been assayed against the 4th International and European Standards for Insulin and the potencies compared with those obtained by the mouse blood glucose method. Results with bovine insulin were in full correspondence with the in vivo results. Porcine and human insulins were 15-20% more potent by the radioreceptor assay than by the in vivo method when the mixed bovine and porcine insulin 4th International and European Standards were used, but were equivalent when compared with like materials. Average 95% confidence limits for formulated insulins in two assays were +/- 6% of the mean. The coefficient of variation on repeated assay of the same sample was 3.8%. The three dose parallel line radioreceptor assay with appropriate species species standards is a candidate biological test capable of international adoption as an alternative to in vivo animal testing of insulin.

Animals↗
PubMed1986

The reduction of the number of animals used in the biological assay of insulin.

The biological control of insulin is vital as it is administered daily to a large proportion of the population during the major part of their lives. The development of the biological assay of insulin will be described with the progressive evolution of methods eventually to dispense with the need for animals. From the quantal Mouse Convulsion Method using around 600 mice per sample to the quantitative Mouse Blood Glucose method using an average of 120 mice per sample in which the fall in the blood glucose levels is used to estimate the potency of insulin by its hypoglycaemic effect. This was followed by the development of the in vitro Radioreceptor Method which is a procedure based on competition between the binding of insulin and [125I]-insulin to cells of the cultured human IM-9 cell line. The production of highly purified insulin by the Pharmaceutical Industry has made possible the recent introduction of new High Performance Liquid Chromatography technology.

Animal Testing Alternatives↗
PubMed1985

Intensive induction chemotherapy for small cell anaplastic carcinoma of the lung.

The role of intensive induction chemotherapy in small cell cancer of the lung remains unclear. Twenty-eight newly diagnosed patients with small cell lung cancer were randomized to receive either high-dose or standard-dose cyclophosphamide, vincristine, and semustine in a trial where the dose of induction chemotherapy was the sole treatment variable. Complete responses (CR) were achieved in 57% of patients receiving high-dose therapy as compared to 21% of patients receiving standard-dose therapy (P less than 0.05). There was a higher rate of severe toxicity in the high-dose group (P less than 0.01). The overall median survival was not improved (36 weeks for the high-dose group vs 43 weeks for the standard-dose group); however, the median survival in patients achieving CR was prolonged (92 weeks for the high-dose group vs 50 weeks for the standard-dose group). These effects were most pronounced in patients with extensive disease; a CR after induction was achieved in five of nine patients treated with high doses but not in any of those treated with standard doses (P less than 0.05). A small group of patients appear to benefit by achieving a long-term remission with intensive induction chemotherapy, but this effect may be offset by increased morbidity.

Aged↗
PubMed1982

Enzyme regulatory site-directed drugs. MOdulation of thymidine triphosphate inhibition of thymidine kinase by 5'-amino-5'-deoxythymidine.

5'-Amino-5'-deoxythymidine (5'-AdThd) was found to antagonize the feedback inhibition exerted by dTTP on dThd kinase (EC 2.7.1.21). This effect was demonstrable in intact cells, cellular extracts, and purified enzyme preparations. Thus, 5'-AdThd markedly stimulated the uptake of dThd in Hela and Vero cells and reduced the inhibitory effects of dTTP on the dThd kinase activity measured in extracts from both cell types. dThd kinase was purified by affinity column chromatography from Hela and Vero cells, and 5'-AdThd was again shown to reduce the inhibition caused by dTTP. The ability of 5'-AdThd to disrupt the homeostatic mechanisms normally regulating the uptake of dThd was sufficient to convert a noncytotoxic concentration of dThd (30 microM) to one that inhibited Hela cell growth by 40%. Since the activity of regulatory enzymes critically influences the pharmacological response produced by many agents, we propose the design of compounds specifically targeted at enzyme regulatory sites as an approach to drug development.

Animals↗
PubMed1981

Noninvasive evaluation of mediastinal metastases in bronchogenic carcinoma: a prospective comparison of chest radiography and gallium-67 scanning.

Evaluation of regional node involvement in patients with bronchogenic carcinoma is a crucial step in determining therapy and prognosis. Mediastinoscopy has been recommended for staging all potentially operable cases, but technical limitations and the need for anesthesia make this impractical. Gallium-67 scanning and chest radiography were prospectively compared as noninvasive means of evaluating spread to regional nodes in 75 patients with bronchogenic carcinoma in whom histologic evaluation of hilar and mediastinal nodes was performed. Gallium scanning was more accurate than chest radiography in assessing regional nodes (overall accuracy 85.3% vs. 56%, P less than 0.05). When positive, both procedures correctly indicate malignant involvement of regional nodes (85% vs. 87.3%). A negative gallium scan, however, was significantly more accurate in predicting the absence of such involvement (80% vs. 40%, P less than 0.01). Gallium scanning appears to be a reliable, noninvasive means of assessing mediastinal spread of bronchogenic carcinoma and when used in conjunction with radiographic findings, allows selection of appropriate patients for surgical staging procedures.

False Negative Reactions↗
PubMed1978

The relation between insulin and adipocyte insulin receptors during treatment of human obesity.

Seventeen obese patients were submitted to 1 week's severe then 3 months moderate dietary restriction. The glycaemic and insulinaemic response to oral glucose was measured at baseline, after 1 week and at 3 months, and the results related to adipocyte insulin receptors estimated from fat biopsies taken on each occasion and to the weight lost. Adipocyte insulin binding was found to be significantly inversely correlated with the insulinaemic response to oral glucose (r = -0.54, P less than 0.05), an inverse relationship maintained even after weight loss had been achieved and displayed within as well as between subjects. Variation of 125I-insulin binding to adipocytes was related to receptor number and not to receptor affinity and could not be accounted for by differences in 125I-insulin degradation. Adipose cell size did not correlate significantly either with the insulinaemic response or with cell surface receptor density. The findings suggest: (1) that a significant proportion of obese subjects are not hyperinsulinaemic and that their metabolic response to weight reduction may differ from that of those who are hyperinsulinaemic; (2) that reduced insulin binding to adipocytes in the obese reflects hyperinsulinaemia, when present, and not adiposity as such; (3) that the degree of insulinaemia is a major determinant of the cell surface receptor density.

Adipose Tissue↗
PubMed1977

Effects of abdominal surgery on the development of radiation enteropathy.

A controlled, retrospective study was undertaken to ascertain whether or not abdominal surgery at any time before radiation therapy might result in an increased incidence of radiation enteropathy. One hundred and five patients in three groups were studied; 24 had radiation enteropathy which developed an average of 12.5 months after radiation therapy, and 28 were matched controls without this complication. The records of a further group of 53 unmatched controls, who survived more than 2 years after irradiation were also examined. In the group with radiation enteropathy, 18 (75%) had a history of prior surgery, whereas only 3 (10.7%) of the matched controls had been operated before irradiation (chi2 = 3.52, P less than .005). The incidence of prior surgery in the unmatched control group was 13.2%. These data indicate that abdominal surgery before radiotherapy does increase the risk of subsequent development of radiation enteropathy.

Abdomen↗
PubMed1975

Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).

The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy.

Adult↗
PubMed1975

The control of insulin receptors in the New Zealand obese mouse.

Insulin receptor concentrations in liver plasma membranes of New Zealand Obese (NZO) mice have been studied. When NZO mice were implanted with normal islets of Langerhans their blood glucose and plasma insulin declined. When the implanted islets were removed these changes were reversed and the mice reverted to their insulin resistant state. Changes were observed in the binding of 125I-insulin to liver plasma membranes of implanted NZO mice. Binding increased when the plasma insulin was decreased and conversely insulin binding decreased when the plasma insulin levels became elevated. The increased insulin binding was not accompanied by any changes in the affinity of NZO liver receptors for insulin.

Animals↗