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Biomedical subjects

A B Heath

Publications and source records attributed to A B Heath.

49 records · Page 3Linked to original sources

A collaborative study to establish the second international standard for streptokinase.

An International Standard for Streptokinase--Streptodornase (62/7) has been used to calibrate high purity clinical batches of SK since 1965. An international collaborative study, involving six laboratories, was undertaken to replace this standard with a high purity standard for SK. Two candidate preparations (88/826 and 88/824) were compared by a clot lysis assay with the current standard (62/7). Potencies of 671 i.u. and 461 i.u. were established for preparations A (88/826) and B (88/824), respectively. Either preparation appeared suitable to serve as a standard for SK. However, each ampoule of preparation A (88/826) contains a more appropriate amount of SK activity for potency testing, and is therefore preferred. Accelerated degradation tests indicate that preparation A (88/826) is very stable. The high purity streptokinase preparation, coded 88/826, has been established by the World Health Organisation as the 2nd International Standard for Streptokinase, with an assigned potency of 700 i.u. per ampoule.

Drug Stability↗

Sensitive and direct assays for functionally active plasminogen activators (tissue-type and urokinase-type) in plasma.

A previously described bioimmunoassay for tissue-type plasminogen activator (t-PA) has been modified in terms of antibody concentration and conditions of incubation to achieve a sensitivity range of approximately 5-500 IU/L of t-PA. A similar assay has been developed for urinary-type plasminogen activator (U-PA), also known as urokinase (UK), achieving a sensitivity range of approximately 5-500 X 10(-1) IU/L. The direct sensitive t-PA assay has been demonstrated to be a quantitative alternative to the traditional semiquantitative euglobulin clot lysis time (ECLT) assay, with correlation coefficients of 0.967 and 0.914, depending on the laboratory where the ECLT was carried out. This assay has the added advantages of avoiding loss of t-PA or UK during the formation of the euglobulin fraction and of calibration in terms of International Standards for both t-PA and UK. With both these assays, it has been demonstrated that the enhanced fibrinolytic activity observed after exercise results from increased levels of t-PA while the level of UK in plasma remains unaltered. Free t-PA (10-60 IU/L) has been demonstrated in resting plasma, whereas the level of free UK activity was 50-100 IU/L. Venous occlusion of matched groups of subjects with and without deep venous thrombosis (DVT) showed a wide variation of response in t-PA levels in each group and no change in UK levels. There was no difference between the DVT and non-DVT groups, and this suggests that the notion of the "nonresponder" being more prone to thrombosis needs to be reexamined.

Adult↗

Inflammatory cell infiltration and survival in squamous cell carcinoma of the vulva.

The prognostic significance of tumour infiltration by inflammatory cells in squamous cell carcinoma of the vulva was examined in a cohort of 34 patients surviving without recurrence for at least 5 years after radical surgery, and a comparative cohort of 35 patients who died of their diseases. Overall, heavy inflammatory infiltration correlated with a good prognosis and light infiltration with a poor one, independent of other indices such as differentiation, tumour size and nodal status. IgA-containing cell infiltration also correlated with a good prognosis but the presence of IgA-containing cells did not alone account for all the inflammation in the good prognosis group. An immunological response to the tumour may be influencing prognosis. At a practical level, the extent of inflammation appears, at least in this material, to be as useful a prognostic index as many more conventional ones.

Aged↗

Dopaminergic control of ketogenesis in fasting.

The role of dopamine in starvation ketonaemia was investigated in male Wistar rats by administration of a specific dopamine receptor antagonist, metoclopramide (4 mg . kg-1 . 24h-1), or placebo, intragastrically during a 48-h fast. Starvation alone caused a fall in blood glucose and gluconeogenic precursor concentrations, which was unaffected by metoclopramide administration. Circulating 3-hydroxybutyrate and acetoacetate levels rose with fasting alone but metoclopramide impaired this ketonaemic response. After 48-h starvation, total ketone body concentrations (mean +/- SEM) were 2.28 +/- 0.19 mmol/l with metoclopramide therapy, 3.49 +/- 0.21 mmol/l with placebo, P less than 0.001. Plasma non-esterified fatty acid levels were similar in metoclopramide- and placebo-treated animals, as were circulating concentrations of insulin, glucagon and growth hormone. Metoclopramide thus decreased the ketonaemic response to starvation without an apparent change in lipolysis or circulating hormone levels, suggesting a direct role for dopamine in production of starvation ketonaemia.

Animals↗

Prophylactic oral methotrexate therapy for multiple superficial bladder carcinoma.

Sixteen patients with multiple, frequently recurring Ta/T1 transitional cell carcinoma of the bladder were treated with methotrexate syrup 50 mg orally every week, for 18 months. In 11 patients the frequency, number and size of tumour recurrences decreased markedly. In 3 patients the incidence of tumour recurrence appeared unchanged and in 2 patients the disease progressed and required cystectomy. Overall, the average number of tumours recurring per patient month at risk fell significantly from 2.6 to 1.2 while taking methotrexate. It is suggested that oral methotrexate may provide an effective alternative to intravesical chemotherapy for the prevention of recurrent superficial bladder carcinoma.

Administration, Oral↗

Radiotherapy and cystectomy for T3 bladder carcinoma.

The survival of 102 patients with category T3 transitional cell carcinoma of the bladder treated by pre-operative radiotherapy and radical cystectomy has been analysed according to the degree of down-staging of tumour as assessed by the depth of infiltration of cancer in the operative specimen. Five-year survival was 60% for patients showing evidence of down-staging compared with 30% when persistent deeply invasive tumour was present at the time of cystectomy. Analysis of available data suggests that survival of patients with category T3 bladder cancer is determined by the response of the tumour to initial radiotherapy rather than the dose of radiotherapy or the addition of cystectomy. Despite radical treatment, the survival of patients with locally advanced bladder cancer is poor; alternative, more effective forms of therapy should be sought.

Carcinoma, Transitional Cell↗

Improvements to assisted distillation cleanup of pesticide residues in animal fats.

The assisted distillation technique, which was developed for the cleanup of pesticide residues from animal fats, has been improved. Nitric acid cleaning of distillation tubes resulted in a significant improvement in the recoveries of hexachlorobenzene (HCB) and lindane (from 76 to 92% and 84 to 89%, respectively). A larger U-tube condenser was developed that condensed 100% of all pesticides studied. With this new condenser, a study of distillation tube flow rates showed that pesticide recoveries at 600 mL nitrogen/min were generally better than those obtained at any other flow rate although recoveries were satisfactory at 400 and 800 mL/min. Recoveries of pesticides at distillation temperatures of 210-240 degrees C were obtained with tubes cleaned with nitric acid, and using the larger U-tube condenser. The distillation temperature of choice was again 230 degrees C because there was little variation from 220 to 240 degrees C.

Adipose Tissue↗

Investigation and simplification of the sweep co-distillation cleanup of pesticide residues in animal fats.

The sweep co-distillation technique of Storherr et al. was investigated and simplified. Six organochlorine pesticides in animal fats were cleaned up under various distillation conditions as follows: No solvent was used, or solvent injection rates were 1 mL/min or 2 mL/3 min. Distillation tubes of 6.7 and 9.0 mm id diameter were compared. Distillation temperatures were varied from 150 to 300 degrees C. The complex condenser of Storherr et al. was compared with a simpler pipet condenser. A U-tube condenser which allows direct introduction onto a Florisil column for secondary cleanup was evaluated. The following modifications to the sweep co-distillation technique resulted: no solvent introduction, distillation temperature 230 degrees C, nitrogen flow rate 600 mL/min, 6.7 mm id distillation tubes with simplified packing, and incorporation of the U-tube condenser. The new technique gave recoveries comparable to those of Storherr et al., but it is faster than most bisolvent partition methods and no large volumes of solvent are required.

Animals↗

Cleft lip and palate in the Oxford area. An examination of the evidence for clustering in space and time.

Children with cleft lip and/or palate born during the period 1965-74 inclusive in the Oxford area were examined for evidence of any tendency for clustering. The methods suggested by Knox (1963), David and Barton (1966), and Smith and Pike (1974) were used. No clustering was evident in space or in time. There was some indication of clustering in space-time for isolated cleft palate during the period 1965-71, but this was not repeated during 1972-74.

Child↗

Calibration and use of an in-house anti-measles IgG standard serum.

For the purpose of research a large quantity of anti-measles IgG working reference serum was needed. A pool of sera from five teenagers was prepared and named Alexandre Herculano (AH). In order to calibrate the AH serum, 18 EIA assays were performed testing in parallel AH and the 2nd International Standard 1990, Anti-Measles Antibody, 66/202 (IS) in a range of dilutions (from 1/50 to 1/25,600). A method which compared parallel lines resulting from the graphic representation of the results of laboratory tests was used to estimate the power of AH relative to IS. A computer programme written by one of the authors was used to analyze the data and make potency estimates. Another method of analysis was used, comparing logistic curves relating serum concentrations with optical density by EIA. For that purpose an existing computer programme (WRANL) was used. The potency of AH relative to IS, by either method, was estimated to be 2.4. As IS has 5000 milli international units (mIU) of anti-measles IgG per millilitre (ml), we concluded that AH has 12,000 mIU/ml.

Adolescent↗

Assisted distillation cleanup of pesticide residues in animal fats: new beadless distillation tube.

A new assisted distillation tube has been developed which contains no glass beads or glass wool. The sample is injected into the top of the tube, and a septum is not required. Large ground-glass joints (10/19) are used at the gas inlet and at the Florisil trap connection for maximum strength. Existing assisted distillation apparatus was easily modified to accept the new tubes. Recoveries of 9 organochlorine pesticides from butter and cattle fat ranged from 87 to 104% at a tube temperature of 230 degrees C and a nitrogen flow rate of 250 mL/min. No significant change occurred in recoveries of 8 of the 9 pesticides after 85 uses of the beadless tube. Only the recovery of HCB from butter decreased, from 95 to 80%, after 51 runs. The new tube was compared with the Unitrex glass bead-packed concentric tube at flow rates of 230, 400, and 600 mL nitrogen/min. Recoveries from the Unitrex tube were similar to those of the beadless tube for all pesticides except DDT which was significantly lower, indicating incomplete distillation at 250 mL/min and possible partial breakdown at 400 and 600 mL/min. A procedure is introduced for pressurized solvent washing of distillation tubes. This procedure is more efficient than vacuum washing.

Animals↗