Transferability of National Institute for Health and Clinical Excellence recommendations for pharmaceutical therapies in oncology to Central-Eastern European countries.

The health burden of malignancies is greater in Central-Eastern Europe than in Western Europe. Furthermore, these countries have more limited healthcare resources, and therefore transparent decision criteria for innovative cancer therapies, including the assessment of cost-effectiveness, are an absolute necessity. Transferability of good-quality technology assessment reports, especially those prepared by National Institute for Health and Clinical Excellence (NICE) in the UK, could be highly beneficial to prevent duplication of efforts and save resources for local technology assessment. Our objective was to summarise key factors influencing the transferability of NICE recommendations in oncology for policy makers and oncologists in Central-Eastern Europe without personal experience in health technology assessment. In general, NICE recommendations are not transferable without adjustment of the analyses to local data. Even if the recommendation is positive, the conclusion can still be negative in lower-income countries, mainly due to relative price differences and the significance of the local budget impact. Technologies with negative NICE recommendations can still be cost-effective in Central-Eastern Europe due to the worse health status and therefore the greater potential health gain of the targeted population. The appropriateness of reimbursement decisions must be improved in Central-Eastern Europe, but copying NICE recommendations without local adjustment may do more harm than good.

Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons.

Chick ciliary ganglionic neurons require an interaction with their peripheral targets for survival during a critical period of their embryonic development in vivo. It has recently been shown that survival of these neurons in dissociated cell cultures is supported by extract from whole chick embryo. In this study, an assay system based on microwell cultures of ciliary ganglionic neurons was used to demonstrate that a very rich source of trophic factor for them is the intraocular target tissues they innervate. Out of 8000 trophic units present in a 12-day embryo, 2500 were contained in the eye. A subdissection of the eye showed its activity to be localized in a fraction containing the ciliary body and choroid coat, with a specific activity almost 20-fold higher than that of the whole embryo. This selective intraocular distribution at a time when survival or death of ciliary ganglionic neurons is decided in vivo suggests that this soluble factor may be involved in the normal development of the ciliary ganglion.

Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals.

Giant nerve fibre activity in intact, freely moving earthworms.

1. An approach is described for recording and characterizing giant nerve fibre activity in intact, freely moving earthworms. 2. Medial giant fibre (MGF) spikes were conducted in an anterior-posterior direction at a mean rate of 32.2 m/s; lateral giant fibre (LGF) spikes were conducted in a posterior-anterior direction at a mean rate of 12.5 m/s. 3. Rates of giant fibre spike conduction and maximal frequencies of firing (up to 500/s) in intact animals were higher than values previously reported in isolated preparations. 4. MGF spikes were followed 1:1 by presumed giant motor axon spikes and facilitating muscle potentials. 5. Single MGF or LGF spikes evoked by applying tactile stimulation were not accompanied by longitudinal contraction, but a series of two or more MGF spikes or three or more LGF spikes were accompanied by such contractions. 6. MGF and LGF spikes occurred infrequently during locomotory movements in the absence of any experimenter-applied stimulation, suggesting that sensory inputs associated with normal locomotion over an irregular substrate are sufficient to excite giant fibres.

Cholinergic neuronotrophic factors: fractionation properties of an extract from selected chick embryonic eye tissues.

An aqueous extract derived from selected intraocular tissues of 15-day chick embryos contains a soluble macromolecular agent which is capable of ensuring the survival of 8-day chick embryonic ciliary ganglionic neurons in monolayer culture. When this ciliary neuronotrophic factor (CNTF) was concentrated using ultrafiltration and subjected to Sephadex G100 and G200 chromatography, activity was detected in most of the eluted fractions. A peak of the most active fractions was eluted in a region corresponding to a molecular weight of 35-40 X 10(3) and contained about 20-30% of the applied protein. CNTF activity bound readily to DE-52 cellulose resin at neutral pH and was eluted with NaCl in a narrow region containing about 20-40% of the applied protein. Gel electrophoretic staining profiles of the active DE52 fraction indicated considerable (but still only partial) simplification in protein composition. While significant CNTF activity losses were incurred in response to each of the above treatments, an active material could be conveniently generated in one working day in milligram amounts having a specific activity of 60,000 trophic units/mg protein. This trophic activity is in the same range as that of the only other known neuronotrophic factor, Nerve Growth Factor.