Structure and Behavior in Hydrophilic Matrix Sustained Release Dosage Forms: 4. Studies of Water Mobility and Diffusion Coefficients in the Gel Layer of HPMC Tablets Using NMR Imaging

Purpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T₂ relaxation times across the gel layer. Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T₂ relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.     

Issues in the cross-national assessment of health technology.

With the growing international literature in economic evaluation and the rapid spread of new health technologies, there is a need to undertake, or at least interpret, economic evaluations on the international level. However, the ways in which cross-national differences affect the cost-effectiveness of health technologies or their evaluations have never been studied. This paper explores these issues by taking advantage of a unique situation in which the same economic evaluation of a new indication for a health technology was conducted simultaneously in four countries using an identical methodology. The study showed that if prior agreement on methods can be reached and local data applied, economic evaluations can be undertaken in a way that facilitates the extrapolation of results from country to country.     

Generation of mice with inactivated Rh or Rhag genes.

Mice carrying inactivated Rh and Rhag genes were generated by insertional targeting. KO animals exhibited normal growth, development and fertility and both types were indistinguishable at a gross phenotypic level from their wild type littermates. Preliminary analysis revealed that red cells from Rh-/- mice lack Rh protein and have a moderate decrease of Rhag protein, whereas those from Rhag-/- mice have a total absence of Rhag and Rh proteins. Studies are in progress to delineate the antigenic, biochemical and functional abnormalities of red cells from these animals as well as the impact on hematological parameters and erythropoiesis.     

Changes in elderly suicides in the USA and the developed world 1974–87: Comparison with current homicide

Between 1974 and 1987 there were increases overall in male suicide rates in the USA, with the greatest increases among elderly men. While female suicide levels overall fell in the USA, elderly female suicide rates failed to show the same improvement. Compared with the rest of the western world, suicide rates for elderly people in the USA were among the worst. Suicide was far more prevalent than homicide, but this is not reflected in the media, where homicide is given a high profile but where there is relative silence surrounding suicide among elderly people.     

ENDOTHELIN RECEPTORS IN RAT ADRENAL GLAND VISUALIZED BY QUANTITATIVE AUTORADIOGRAPHY

1. The radioligand [125I]-endothelin was used to map receptors for endothelin in rat adrenal gland using in vitro autoradiography and computerized densitometry. 2. In the adrenal, a high density of binding was found in the adrenal medulla (binding affinity constant 0.18 +/- 0.11 X 10(9)M-1) and zona glomerulosa (binding affinity constant 0.18 +/- 0.07 X 10(9)M-1). Binding was low to undetectable in the zona fasciculata and zona reticularis. Unrelated peptides did not displace endothelin. 3. These results provide evidence of endothelin receptor distribution in adrenal gland and suggest that endothelin might exert multiple actions in the adrenal gland on catecholamine and aldosterone biosynthesis and secretion.     

Clinical importance,statistical significance and the assessment of economic and quality-of-life outcomes

The assessment of economic and quality-of-life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost-effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality-of-life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.