Nonionic contrast media: economic analysis and health policy development.

The replacement of old radiologic contrast media with supposedly safer but more expensive media has created a dilemma for radiologists and hospital administrators. To quantitate the nature of this trade-off we performed a cost-utility analysis using optimistic assumptions that favoured the new media. A complete conversion to the new media would result in an incremental cost of at least $65,000 to gain 1 quality-adjusted life-year (QALY). For a selective strategy in which only high-risk patients would receive the new media the cost would be about $23,000 per QALY gained. However, the incremental cost for low-risk patients is over $220,000 per QALY gained. Conversion to the new contrast media, although not necessarily the most efficient use of scarce resources, has already occurred in Ontario, primarily because of press publicity, pressure from insurers and a political unwillingness of policymakers to decide the fate of identifiable victims. We found that funding of a new intervention associated with a high cost-utility ratio rather than interventions with lower ratios might save some identifiable victims at the expense of a larger number of unidentifiable ones.     

Gene therapy: some results, many problems to solve.

Gene therapy is raising incredible hopes. The prospects of treating numbers of severe pathologies (hereditary, cancerous, degenerative or infectious) are vast. Nevertheless, the technological bolts to lift are still numerous, whether they be bringing the vectors into focus, the systems of expression of transgenes or the neutralization of immune responses of the host against the vector, the product of transgenes, or the knowledge of the considered pathologies of physiopathology. Solving these difficulties entails the gathering of multiple disciplines, from chemistry to medicine, passing through virology and immunology.     

The many states of aging: a meeting and some demographic aspects

With an expectation of life at birth of 27 years in the middle of the 18th century, 21% of males reached their 60th birthday with a remaining expectation of life of 12 years. Under the conditions of mortality of 1950, in France, 70 percent could celebrate their 60th birthday, and they had still 15 years (only) to live on the average. This last figure started increasing after 1950: the expectancy of life at age 60 is now over 20 years, and it will exceed 25 years around 2050 (for women, the mean will be 31 years). Longevity is an individual capacity. It is now increasing fast, and becomes more and more responsible for the ageing of the population (the rise in the proportion of older persons in the population). We now try to forecast the number of centenarians, and even of super-centenarians (aged 110 years and more), and speculate about the maximum life span. We are in fact entering an entirely new era, when three, four, even five generations can survive simultaneously. Are we prepared to it? The French Ministers for Research and for Social affairs set up a Committee of 15 members (chaired by Henri Leridon) to prepare a National Meeting of Researchers on Ageing, in order to review the situation of research in France on this issue and to make proposals for organising and orienting new studies. The life span of human species, as well as the one of individuals, is undoubtedly depending upon genetic factors. But interactions with environmental factors and with behaviour also play a major role. To be able to disentangle these complex associations, it will be necessary to combine the work of biologists, clinicians and social sciences specialists. The main conclusions of the June 2001 meeting are reported here, together with some orientations of demographic research on mortality at oldest ages and the limits of longevity.     

Improvement in radiographic contrast media through the development of colloidal or particulate media: an analysis.

In the field of active and passive transport of substances across epithelial membranes little progress has been made, mostly for technical reasons, towards a comprehensive view of a wealth of isolated laboratory data. The present study is an attempt to advance the use of the method of computer simulation, with application of the “Continuous System Modelling Program” into the field of membrane transport. High speed of operation and great versatility make this procedure uniquely suitable to transport studies on multicompartment biological systems, such as epithelia. Basic prerequisites are, a detailed knowledge of the morphological parameters of the system, and an abundance of often isolated laboratory data against which the function of a model membrane can be checked. The simulation process becomes then a study of finding the constraints on all rate constants involved (a few of which may be known) which lead to results compatible with experimental facts. Whereas computer modelling is no substitute for experimental studies, it is one way of arriving at a comprehensive view of the complex flow patterns in such complex structures as epithelia. The computer simulation technique can lead to new, testable predictions, and it gives the laboratory investigator a critical perspective of potential pitfalls in experimental techniques used in studies on fluxes in structures as small as those encountered in epithelia. The usefulness of computer simulation in the field of membrane transport is exemplified by applying it to the problem of the initial rate of uptake of Na⁺ by frog skin epidermis. It is shown, here, that the computer data are in excellent agreement with experimental data on epidermis. Beyond this, the computer data permit calculations on kinetic parameters, e.g. Na⁺ pool sizes and rates of Na⁺ fluxes between compartments, which, for the present at least, cannot be directly measured.     

Proteoglycans: many forms and many functions.

Proteoglycans are produced by most eukaryotic cells and are versatile components of pericellular and extracellular matrices. They belong to many different protein families. Their functions vary from the physical effects of the proteoglycan aggrecan, which binds with link protein to hyaluronan to form multimolecular aggregates in cartilage; to the intercalated membrane protein CD44 that has a proteoglycan form and is a receptor and a cell-binding site for hyaluronan; to heparan sulfate proteoglycans of the syndecan and other families that provide matrix binding sites and cell-surface receptors for growth factors such as fibroblast growth factor (FGF). One feature that recurs in proteoglycan biology is that their structure is open to extensive modulation during cellular expression. Examples of protein changes are known, but a major source of structural variation is in the glycosaminoglycan chains. The number of chains and their length can vary, as well as their pattern of sulfation. This may result in the switching of different chain types with different properties, e.g., chondroitin sulfate and heparan sulfate, and it may also result in the selective expression of sulfated chain sequences that have specific functions. The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs. Proteoglycan forms of proteins are thus important modifiers of the organization of the pericellular and extracellular matrices and modulators of the processes that occur there.     

Transporters for amino acids in plant cells: some functions and many unknowns

Membrane proteins are essential to move amino acids in or out of plant cells as well as between organelles. While many putative amino acid transporters have been identified, function in nitrogen movement in plants has only been shown for a few proteins. Those studies demonstrate that import systems are fundamental in partitioning of amino acids at cellular and whole plant level. Physiological data further suggest that amino acid transporters are key-regulators in plant metabolism and that their activities affect growth and development. By contrast, knowledge on the molecular mechanisms of cellular export processes as well as on intracellular transport of amino acids is scarce. Similarly, little is known about the regulation of amino acid transporter function and involvement of the transporters in amino acid signaling. Future studies need to identify the missing components to elucidate the importance of amino acid transport processes for whole plant physiology and productivity.