[From epidemiological transition to health transition]. / De la transition épidémiologique à la transition sanitaire.

The "Epidemiological Transition" concept proposed by Abdel Omran in 1971 was the first theory attempting to explain the extraordinary progess that industrialized countries have achieved in health since the 18th century. Within the broader framework of the demographic transition, an important implication of this concept was that life expectancy in modern societies would converge toward limits determined by the new epidemiological conditions. In the ensuing decades, however the convergence process appears to have stopped as a result of a number of setbacks including the health crisis in Eastern Europe and AIDS in Africa. These setbacks do not fundamentally contradict the theory. A much greater contradiction was the unexpected dramatic decrease in cardiovascular disease that began as early as the 70s and had a major positive impact on life expectancy. Based on the concept of "Health Transition" described by Julio Frenk et al., we propose a complete revision of the health implications of the demographic transition based the idea of successive cycles of divergences/convergences induced by the appearance and generalization of major breakthroughs in health technologies and strategies. Three such cycles can be clearly identified on an international level corresponding to control of infectious then cardiovascular diseases, and perhaps most recently to the initial successes achieved in the field of ageing.

Generation of trangenic Xenopus laevis using the Sleeping Beauty transposon system.

Using the Sleeping Beauty (SB) transposon system, we have developed a simple method for the generation of Xenopus laevis transgenic lines. The transgenesis protocol is based on the co-injection of the SB transposase mRNA and a GFP-reporter transposon into one-cell stage embryos. Transposase-dependent reporter gene expression was observed in cell clones and in hemi-transgenic animals. We determined an optimal ratio of transposase mRNA versus transposon-carrying plasmid DNA that enhanced the proportion of hemi-transgenic tadpoles. The transgene is integrated into the genome and may be transmitted to the F1 offspring depending on the germline mosaicism. Although the transposase is necessary for efficient generation of transgenic Xenopus, the integration of the transgene occurred by an non-canonical transposition process. This was observed for two transgenic lines analysed. The transposon-based technique leads to a high transgenesis rate and is simple to handle. For these reasons, it could present an attractive alternative to the classical Restriction Enzyme Mediated Integration (REMI) procedure.

A hormone-dependent post-translationally regulated mutant for investigating type I cadherin function.

Type I cadherins are Ca2+-dependent cell adhesion molecules. Their function in early Xenopus laevis development has been extensively studied in recent years, by injecting synthetic mRNAs encoding dominant negative mutants with deletions of the extracellular domain into embryos. However, studies at post-gastrula stages have been hampered by the inabilityto progress through post-gastrula development in embryos expressing these mutant proteins. This problem has been partly overcome by injecting into a few targeted blastomeres in stage 6 N.F. embryos, but only restricted studies are possible with this technique. Several studies have made use of the hormone-binding domain (HBD), which is activated by hormones. In this study, we used this method to analyze the activity of dominant negative cadherins. We generated a mutant E-cadherin (AE-Cad, consisting of the cytoplasmic domain and transmembrane domain) fused to the hormone-binding domain of estradiol receptor (HBDER) and we validated this technique with functional analyses. The function of the mutant deltaE-HBDER was strictly dependent on hormone induction. This conditional mutant had the same effects and exerted the same dominant negative function as the corresponding constitutive mutant.

Cloning and characterization of three Xenopus slug promoters reveal direct regulation by Lef/beta-catenin signaling.

In amphibians and birds, one of the first steps of neural crest cell (NCC) determination is expression of the transcription factor Slug. This marker has been used to demonstrate that BMP and Wnt molecules play a major role in NCC induction. However, it is unknown whether Slug expression is directly or indirectly regulated by these signals. We report here the cloning and characterization of three Xenopus Slug promoters: that of the Xenopus tropicalis slug gene and those of two Xenopus laevis Slug pseudoalleles. Although the three genes encode proteins with almost identical amino acid sequences and are expressed with similar spatiotemporal patterns, their 5'-flanking regions are quite different. A striking difference is a deletion in the X. tropicalis gene located precisely at the transcription initiation site that results in the X. tropicalis promoter being inefficient in X. laevis. Additionally, we identified two regions common to the three promoters that are necessary and sufficient to drive specific expression in NCCs. Interestingly, one of the common regulatory regions presents a functional Lef/beta-catenin-binding site necessary for specific expression. As the Lef.beta-catenin complex is a downstream effector of Wnt signaling, these results suggest that Xenopus Slug is a direct target of NCC determination signals.

Where there are no data: what has happened to life expectancy in Georgia since 1990?

In recent years there has been a considerable increase in understanding of changes in mortality in Russia and some other former Soviet republics. However, the situation in the republics of the Caucasus remains poorly understood. Information on Georgia is especially fragmentary as a fifth of the country remains outside government control, there has been large scale migration since 1991, and the introduction of fees for vital registration has compromised the quality of official statistics. The aim of the study is to produce plausible estimates for life expectancy in Georgia for the period 1990-1998 and thus to assess whether Georgia has undergone changes similar to other former Soviet republics in the post-independence period. Four models were used to construct life tables. Model 1 used officially published statistics on deaths and population. Model 2 applied new estimates of population derived from household surveys to the observed deaths. Model 3 adjusted model 2 for under-registration at extremes of life, with parameter estimates derived from a survey of infant mortality and comparison of observed rates with Coale-Demeny standard life tables. Model 4 arose following inspection of death rates by cause that revealed implausible discontinuities in cancer mortality rates and involved applying the estimates of under-registration that this finding implied to model 3. The four models produce quite different estimates of life expectancy, differing by 7.8 y for men and 6.8 y for women by 1998. In any of the models, however, Georgia does not appear to have experienced the marked deterioration in life expectancy seen in Russia following the transition to independence. Importantly, Georgia had also not experienced a marked improvement in life expectancy during the 1985 Soviet anti-alcohol campaign, again unlike other Soviet republics.Official statistics substantially over-estimate life expectancy at birth in Georgia. Despite undergoing a civil war, life expectancy in Georgia has been less affected by the transition than has Russia and the overall trends in mortality since the mid 1980s suggest that this may be because alcohol has played a smaller role in these changes than it did in Russia.

Cancer mortality in Russia and Ukraine: validity, competing risks and cohort effects.

BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer. METHODS: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care. RESULTS: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia. IMPLICATIONS: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research.

Xenopus cadherin-11 is expressed in different populations of migrating neural crest cells.

We cloned the Xenopus homologue of cadherin-11 and studied its spatiotemporal expression pattern during early development. The messenger RNA is present from the mid-gastrulation through embryo development. It is expressed in different neural crest cell populations, during their migration and differentiation. This pattern, unexpected for an adhesion molecule, reinforces the idea of novel functions for type II cadherins.

Relax promotes ectopic neuronal differentiation in Xenopus embryos.

We previously isolated a novel rat cDNA encoding a basic helix-loop-helix transcription factor named Relax, whose expression in the developing central nervous system is strictly limited to discrete domains containing precursor cells. The timing of Relax expression coincides with neuronal differentiation. To investigate the involvement of Relax in neurogenesis we tested whether Relax activated neural genes in the ectoderm by injecting Relax RNA into Xenopus embryos. We demonstrate that ectopic Relax expression induces a persistent enlargement of the neural plate and converts presumptive epidermal cells into neurons. This indicates that Relax, when overexpressed in Xenopus embryos, has a neuronal fate-determination function. Analyses both of Relax overexpression in the frog and of the distribution of Relax in the rat neural tube strongly suggest that Relax is a neuronal fate-determination gene.

[Crisis and demographic transition in Africa]. / Crise et transition demographique en Afrique.

PIP: The main task of CEPED, the French Center on Population and Development, is to deal with the relations between population and development. The center in this paper questions the nature of the demographic consequences of adjustment policy and reforms in developing countries. There is no doubt that such policies had important social consequences. The dearth of available statistical data, however, makes it difficult and even pointless to try and dissociate the effects of adjustment policies from the economic crises which put them in place. CEPED asked a group of experts to offer their views on to what extent the global economic crisis and the structural adjustment policies effected during the early 1980s affected demographic trends over the long term in sub-Saharan Africa. Whatever effects the economic crisis and the structural adjustment policies had upon the continent will remain to be felt for years to come. Further research is therefore warranted.^ieng

[Twenty one years of hemodialysis in a patient with primary hyperoxaluria]. / Vingt et un ans d'hémodialyse chez un patient atteint d'hyperoxalurie primitive.

We report a male patient with primary hyperoxaluria from childhood who survived more than 21 years on conventional haemodialysis. Despite the severity of his bone disease, he was married and actively employed up until 2 years before his death. His condition really worsened a few months before his death. He presented with only renal and bone involvement and had hardly any cardiovascular complications, that was probably a reason for his prolonged survival. Such an evolution is very unusual and we speculate that the length of haemodialysis sessions in addition to the large surface of the membrane probably contributed to such an outcome. During the time period on HD, anemia was transiently controlled by recombinant erythropoietin despite oxalate involvement of the marrow. He was refused a liver-kidney transplant and died from malnourishment at 43 years of age. To our knowledge, such an outcome has not yet been reported. It shows that careful prolonged hemodialysis sessions should be helped in admet patients without severe cardiovascular involvement.

Health crisis in Russia. II. Changes in causes of death: a comparison with France and England and Wales (1970 to 1993).

"Trends in Russian mortality appear all the more negative in comparison with the very favourable trends in most Western countries, especially during the last two decades. To highlight the most damaging causes, we compare Russian cause-specific mortality trends with those observed in France and England and Wales, two countries for which we have reconstructed continuous time series of deaths by cause.... It was within the framework of...30 categories [of causes] that we calculated death rates by age group and standardized mortality rates by cause...."

Health crisis in Russia. I. Recent trends in life expectancy and causes of death from 1970 to 1993.

The authors analyze trends in life expectancy and causes of death in Russia from 1970 to 1993, with a focus on reasons for the recent declines in life expectancy. "Before discussing the trends themselves, we shall...look at the possible distortions that changes in data quality may have produced. However, even if it has been exaggerated to some degree, nobody contests the reality of the Soviet health crisis, and we shall attempt to derive some explanation by analysing the age and cause-of-death structures of mortality in Russia."

[Causes of adult mortality in developing and developed countries with low mortality rates]. / Causas de defuncion de adultos en paises en desarrollo y desarrollados con bajas tasas de mortalidad.

"In a certain number of developing countries, life expectancy levels now approach those of the developed world. But, though life expectancies at birth may be similar, the infant mortality rate in developing countries remains higher, but is compensated by a lower rate of mortality for adults. Is it to be expected that as infant mortality rates continue to decline, the developing countries will maintain their advantageous adult mortality rates and that life expectancy will forge ahead of the level achieved in developed countries?... To answer this question, recent trends in adult cause-specific mortality rates in four developing countries (Chile, Hong Kong, Mexico, and Costa Rica) were compared with those in three industrialized countries (France, Germany and Japan). The results were inconclusive. Whilst life expectancies in some of these countries may be expected to forge ahead (Chile, Hong Kong), in others the margin between their life expectancies and those of developed countries have already narrowed." (SUMMARY IN ENG)

[African populations and AIDS]. / Populations africaines et SIDA.

PIP: This work discusses uncertainties in current knowledge of the probable effects of AIDS on African population growth, and describes a new publication of the French Center for Population and Development (CEPED) on the likely social and demographic consequences of AIDS in Africa. Tropical Africa entered into the demographic transition later than most of the developing world, and is still largely at the stage when mortality has declined but fertility remains high. The UN projects that today's African population of 700 million will increase to 2.5 billion by 2050. It is often assumed that Africa is too economically, politically, and ecologically fragile to support such massive growth, and that war, famine, or pestilence will inevitably intervene. It is then suggested that AIDS will fill this role. However, the plagues that afflicted Europe and that serve as a model of possible effects in Africa did so at a time of technological backwardness and of very slow population growth. It is likely that AIDS in Africa will not result in an ultimately smaller population, but rather that it will slow the transition and stabilization, because mortality decline is in effect the main motor of the transition. Population data of all kinds are scarce in Africa, and epidemiologic data are even scarcer. Broad predictions are possible, but the influence of specific phenomena, such as the AIDS epidemic, are much more difficult to discern. The first chapter of the CEPED work, "African Populations and AIDS", summarizes existing knowledge of the biological dynamics of HIV infection and discusses the most common opportunistic infections in Africa. The second chapter describes the evolution of the epidemic in Africa, which is characterized by great contrasts in seroprevalence rates within countries, regions, and subgroups of populations. The optimal foundations for AIDS control programs are identified based on the principal modes of transmission and the important role of cofactors. High-risk sexual behaviors should be reduced, other sexually transmitted diseases should be treated and prevented, the blood supply should be controlled, and existing AIDS-control programs should be reinforced. The third chapter examines demographic aspects of the AIDS epidemic. It demonstrates the effects of the average number of sexual partners and of the average age difference between the partners on the prevalence of infection, and shows that average life expectancy has already been affected in countries with high seroprevalence rates. It also shows that demographic growth persists even with high seroprevalence rates. The final chapter explores the principal economic, social, and ultimately political consequences of AIDS, both those already obvious and those likely to appear in the future.^ieng

[Cairo: a double deception]. / Le Caire: une double deception.

PIP: The 3rd International Conference on Population and Development, held in Cairo in September 1994, was attended by 180 delegations of UN members and 15,000 participants in both the official conference and a vast forum of nongovernmental organizations. The nearly universal national representation, despite absence of Saudi Arabia, Sudan, and some other Islamic countries, was a great achievement for the conference organizers and the host country. Each delegation expressed its views in an official declaration to the plenary session, while representatives to the main committee debated the program of action drafted in a long series of meetings in preparation for the conference. None of the preparations or addresses to the conference were able to prevent an unrewarding seven-day debate in the main committee over abortion. More disappointing was the failure to engage in a deep debate over development issues. A number of recommendations touched on education, health, and improving the status of women, but only as factors in fertility decline. The issue of development should have been discussed as it relates to the satisfaction of the needs of the five billion living inhabitants of the planet and the ten billion projected for the next century. The second great disappointment of the conference was that some of the progressive contents of the preliminary document submitted to the conference were greatly watered down. The preliminary document offered real progress in achieving a more lucid and ideology-free approach to questions that have long remained taboo because they touch on the freedoms of men and women in their most profoundly intimate aspects. The text clarified aspects of the rights of individuals in relation to social institutions: the right to health and education in sexuality and reproduction, recognition of the existence of different types of unions and families, and the right to family regrouping. Most of the innovative articles provoked controversy in the preparatory meetings. During the conference, the articles dealing especially with abortion, personal autonomy, and family regrouping were amended and changed to such a degree that they often lost their original meaning.^ieng

Mortality by cause in the USSR in 1970-1987: the reconstruction of time series.

"This paper is the first step in an exploration of Soviet cause-of-death statistics which became accessible after 1986. Its main aim is the reconstruction of consistent annual series for the period 1970-1987 in spite of changes in cause-of-death classification caused by the 1980 revision of the Soviet nosological system. In a second part, the series thus reconstructed are analysed to describe the main features of the evolution of mortality during these two decades, using first standardized mortality rates for several very important specific causes and, second, using a method of decomposition of life expectancy changes. For the first time, trends in causes of death are thus shown for the crucial period where life expectancy has grown again after two decades of regression." (SUMMARY IN FRE)

Adjacent neuropathic hyperalgesia in rats: a model for sympathetic independent pain.

Following sciatic nerve section in rats a saphenous nerve mediated adjacent neuropathic hyperalgesia (ANH) develops in response to pressure. This study demonstrates that a similar ANH to heat stimuli develops over the medial dorsum of the hindpaw (MDH) following sciatic section. A similar neuropathic hyperalgesia, with an associated pain syndrome, is seen in man following peripheral nerve section. When chronic bilateral ANH rats were unilaterally injected intradermally over the MDH with noradrenaline (NA), and with vehicle over the contralateral MDH, no side to side pressure or heat withdrawal threshold differences were observed. Likewise, no changes in pressure or heat withdrawal thresholds occurred in chronic ANH rats following chemical sympathectomy with 6-hydroxydopamine (6-OHDA). A similar pattern was seen in control rats treated with NA and 6-OHDA. The pressure and heat ANH seen in the rat was not dependent on sympathetic outflow, and thus provides an animal model for sympathetic independent pain (SIP). Sympathetic modulation was also ineffective on control rat nociceptive thresholds, which is in agreement with prior behavioral findings (Nature, 323 (1986) 158-160).

Reconstitution of annual life tables for nineteenth-century France.

"The nineteenth century was not one of runaway health progress, but it marked a deep transformation of mortality conditions [in France]. The reconstitution of mortality tables by single years of age and calendar years makes it possible to study this transformation in detail, and to distinguish between period fluctuations and structural changes. In the present article, we have given preference to graphic representation, and purposely limited the statistics.... We have also given preference to the period approach." Consideration is given to annual mortality trends, life expectancy, age-specific probability of dying, the war-related crisis years of 1813, 1871, and 1915, and differentials in mortality by sex. Data generally concern the period 1806-1898.