Relative activities of heparin fractions obtained by gel chromatography.

In order to investigate the reported heterogeneity of commercial heparin injections, lung and mucous preparations were fractionated by gel chromatography according to molecular size. Eluent pools were characterized by measuring electrophoretic mobility, anticoagulant activity using a reactivation assay and an anti-Xa assay, lipolytic activity and the protamine neutralization value. The only biological activity to show a marked relationship with the molecular size of the heparin fraction was the anti-Xa activation activity. This effect was more pronounced with the mucous heparins than with the lung heparin preparation studied.

Measurement of the heparin neutralizing capacity of protamine.

Several methods of estimating the heparin neutralizing capacity of protamine were investigated for their reliability and practicability. The results from two chemical methods were compared with those from two in vitro biological assays, one of which was the method of the British Pharmacopoeia (1973). An in vivo method using mice was used to assess the accuracy of the in vitro test methods. Three standard heparin preparations were tested against the W.H.O. 1st International Reference Preparation for Protamine. Two of the heparin preparations were of mucosal origin, one of which was the 3rd International Standard, and the third heparin preparation was of lung origin (the 2nd International Standard for Heparin). The mean neutralization values (all methods) of heparin by protamine for a House Reference Preparation and the 3rd and 2nd International Standards for Heparin were 95.8, 109.8 and 89.9 units per mg of Protamine, respectively. All methods read the House Reference Preparation to have a lower value than the 3rd International Standard, which had a higher value than the 2nd International Standard for Heparin. There was a constant relationship between the results of any one method and those of another. The chemical and in vitro biological methods gave results of comparable precision although the latter required a greater degree of technical skill and time to perform.

An evaluation of the British Pharmacopoeial assay of heparin: a comparison with other methods.

The potencies of six commercially manufactured heparins have been measured by the British Pharmacopoeial (BP) assay and activated partial thromboplastin time (APTT), protamine sulphate, and anti-Xa assays. The APTT/BP potency ratios were found to vary with the preparation but this was not dependent on the tissue source of heparin. For mucosal heparins, the anti-Xa/BP potency ratios were close to unity, but for heparin of lung origin the anti-Xa potency was approximately one-quarter of the BP potency. Four heparin fractions prepared by column gel chromatography of a commercial heparin were similarly examined by all four assays, and there was a wide divergence between the BP potency estimates and those obtained with the other methods. The degree of divergence was found to depend on the molecular size of the fraction.

Dose-area product measurements in paediatric radiography.

The dose-area product (DAP) could provide a useful quantity for monitoring doses for paediatric radiography, because it is a sensitive parameter, which is simple to record. A study of DAP measurements has been carried out for single radiographic projections for paediatric patients and comparisons made with measurements of entrance dose. The technique has been used to investigate doses for examinations performed with and without a grid. There is a linear relationship between DAP and entrance dose, with a variation of +/- 20% for pelvis, abdomen, spine and skull radiographs, but data for chests are more scattered. Logarithm of the DAP is linearly related to an equivalent patient diameter and reference levels could be set in terms of DAP either by patient age range or size. Effective doses determined from DAPs were 0.1-0.3 mSv for abdomen, pelvis and spine anteroposterior radiographs for 5-15 year olds, and less than 0.03 mSv for 0 and 1 year olds. Doses for examinations performed without a grid were only 20% of those for which a grid was used in the X-ray room studied. Significant reductions in doses for paediatric radiology can be achieved, where the use of grids can be avoided.

An in-vitro test for the duration of action of insulin suspensions.

A method is described which measures the prolongation effects of commercial insulin suspensions by monitoring the rate of solution of an insulin suspension into a phosphate buffer, pH 7.4, at 37 degrees C. The method can rapidly categorize an insulin into the clinical classifications of either fast, intermediate or slow acting. It offers advantages of speed and sensitivity over the British Pharmacopoeial test for prolongation of insulin effect in fasted animals. Large differences between the dissolution rates of commercial samples of isophane insulin were observed which suggested a lack of bioequivalence.

Socio-demographic trends in Northern Ireland, 1971 to 1991.

"Northern Ireland has demographic and socio-economic structures which set it apart from the rest of the United Kingdom and religion impacts on this social demography more than in any other 'developed' society. Peripherality also serves to underpin some of the distinctiveness of the Province. Socio-economic and demographic data from Population Censuses and demographic data from Annual Reports of the Registrar General are analysed. The socio-demographic trends between 1971, 1981 and 1991 are traced and the spatial patterns are described. Many of the spatial patterns have been remarkably persistent over time and the problems that arise from this are unlikely to be addressed fully given the Province's perverse polity."

National control requirements for blood products in Australia.

The regulatory processes for therapeutic goods in Australia will be outlined with particular emphasis on the Federal Government's policy toward marketing of blood and related products and its role in the regulation of these therapeutic goods. Aspects which will also be briefly addressed are viral contamination, the need for a code of good manufacturing practice for blood products, traceability, standards and the reporting of problems.

Cellular toxicity of urinary catheters.

The cellular compatibility of each of several brands of urinary catheters available on the Australian market was measured by means of cell-culture methods, a rabbit intramuscular implant test, and the traditional mouse systemic toxicity test. Good agreement was obtained between the in-vitro tests and the rabbit implant tests (although the cell-culture tests were simpler, more rapid, more sensitive, and quantitative). The mouse systemic toxicity test was insensitive, and detected no toxic samples. The cell-culture and rabbit-implant test results indicated that some urinary catheters can release substances harmful to mammalian cells. Such substances may contribute to the clinical reactions of urethritis and strictures after urethral catheterization.

Stability of oral pancreatin powders.

In-vitro study which duplicated the conditions to which the orally administered pancreatin is exposed in the human stomach showed that the oral administration of pancreatin in uncoated powder form could result in a substantial loss of enzymic activity. Therefore, it may not be an efficacious replacement therapy in pancreatic disorders where pancreatin secretion is reduced.

In vivo validation of a cell culture test for biocompatibility testing of urinary catheters.

Biocompatibility tests have been compared for their suitability as routine safety tests for urinary catheters. Latex catheters from five manufacturers were tested by each of the following four methods: (1) a cell culture cytotoxicity assay of catheter extracts, (2) intracutaneous injection of the extracts into rabbits, (3) intramuscular implant of catheter pieces into rabbits, (4) catheterization of sheep (mucous membrane irritation). The rabbit intracutaneous and intramuscular tests are both current pharmacopoeial methods for ascertaining the suitability of polymers for medical use. The four tests each showed a cell or tissue response ranging from no detectable change to severe damage, according to the catheter batch or brand, and they each identified the same samples as most toxic and least toxic. However, they differed in sensitivity. The sheep test and the cell culture assay discriminated between catheters of intermediate toxicity and ranked as toxic catheters not identified as such by the two pharmacopoeial tests. The sheep test most closely approximates clinical usage, but is impractical for routine use. The cell culture assay is a suitable alternative. It also has the advantages of a clearly defined endpoint, good sensitivity, reproducibility, speed, and reduced animal usage.