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FSPH is based on the foundations of the 45-year-old National School of Public Health Administration (ENSP), located in Rennes (Brittany) on a 22-acre campus. The annual budget is 55 milion euros, which is only partly adequate for FSPH missions and objectives. What is currently needed, in addition to ENSP is a high-level academic establishment. It has been argued that France lacks the research resources and funding necessary to hold a leading international position in public health research and expertise. About 85% of international scientific papers published by French teams in the field of public health are produced by Inserm (the French equivalent of NIH) and university hospitals, which are mainly located in Paris. It is proposed to initially network and reinforce existing forces, in close collaboration with top-level institutions in the French capital. This series of three papers proposes to establish a dynamic in two domains: (i) risk analysis and regulation, and (ii) prevention and screening in public health. FSPH will be grounded on scientific excellence, French-English bilingual training, openness to Europe and North America, worldwide notoriety, and collaboration with top-flight academic and research institutions, hospitals, and the private sector.

The authors introduce the two following papers. A general review of MRI evolution during the ten past years is proposed. Some recent evolutions are emphasized: fast imaging, MR angiography, workstations devoted to 3D reformations and functional imaging are illustrated. The complementary position of CT and MR, and the worldwide machines diffusion are summarized. The authors of following papers are introduced and presented.

The use of prognostic factors to help select breast cancer patients for adjuvant therapy is of considerable concern to the oncology community. This need for selection of prognostically less favorable cases is stimulating investigators to identify new and more powerful prognostic factors. Unfortunately however, this identification process is becoming more confusing because of a lack of guidelines for investigators to use to study new factors and for reviewers and readers to use to evaluate papers on this topic. In this paper, we will describe across our experience the main problems encountered in the study of biological prognostic studies. Considering evaluation criteria to be developed in the future, it appears that only multicentric and multidisciplinary structures are able to define decisional trees based on technically and clinically validated parameters in particular patients subgroups. Such a structure exists at the european level ("Receptor Study Group" of the EORTC) and a similar structure has now been created in France to answer these questions.

The aim of this paper is to discuss the psychological factors involved in the process of learning and especially to conceptualize the impact of cognitive disorders on the emotional.

Light is the major synchronizer of the internal clock located in the suprachiasmatic nuclei of the anterior hypothalamus. Retinal ganglion cells contain melanopsin, a photoreceptor with a peak sensitivity to blue wavelength (460-480 nm). Light signal is transmitted from the eye to the clock, then to the pineal gland which produces melatonin, considered as the hand of the clock. Even a weak intensity of light (LEDs, tablets, mobile phones, computers...) is able to block the secretion of melatonin, the hormone of darkness. Light is also able to phase advance or phase delay the circadian system according to the timing of exposure. This Phase Response Curve (PRC) is used to resynchronize the clock in various situations of circadian desynchronization. Exposure to Light at Night (LAN) results in a disruption of the circadian system which is deleterious to health. In industrialized countries, including France, 75 % of the total workforce is estimated to be involved in atypical hours, far from the classical diurnal hours of work. Of interest, shift work and night work involve 15.4 % of the French workforce. A number of epidemiologic studies, peiformed mainly on nurses, showed an association between sustained night work (3 to 20 years) and an increased risk of breast cancer Health problems faced by flight attendants have also been reported, though other causes like exposure to radiations cannot be ruled out. Other deleterious effects are reported in this paper. The potential mechanisms of the deleterious effects of LAN on health are suppression of melatonin andsleep deprivation. The International Agencyfor Cancer Research (IARC) classified shift work that involves circadian disruption as ( probably carcinogenic to humans". Countermeasures (e.g melatonin, bright light, use of psychotropic drugs) have been proposed as a means to improve adaptation to shift work and night work and to fight " clock pollution " and circadian desynchronization by LAN.

Wound healing defects constitute a major socio-economical problem in developed countries, especially because of the population ageing. Research of new therapeutics strategies able to decrease the duration of the treatments is strongly needed. In this context, a number of recent works demonstrated that extracellular matrix and its macromolecular constituents, or some of their fragments (matrikines), possess a number of modulating activities on the wound healing process. The present paper provides an update on recent data showing the importance of extracellular matrix in wound healing and on the new therapeutic strategies that they open.

Light is the major synchronizer of the internal clock located in the suprachiasmatic nuclei of the anterior hypothalamus. Retinal ganglion cells contain melanopsin, a photoreceptor with a peak sensitivity to blue wavelength (460-480 nm). Light signal is transmitted from the eye to the clock, then to the pineal gland which produces melatonin, considered as the hand of the clock. Even a weak intensity of light (LEDs, tablets, mobile phones, computers...) is able to block the secretion of melatonin, the hormone of darkness. Light is also able to phase advance or phase delay the circadian system according to the timing of exposure. This Phase Response Curve (PRC) is used to resynchronize the clock in various situations of circadian desynchronization. Exposure to Light at Night (LAN) results in a disruption of the circadian system which is deleterious to health. In industrialized countries, including France, 75 % of the total workforce is estimated to be involved in atypical hours, far from the classical diurnal hours of work. Of interest, shift work and night work involve 15.4 % of the French workforce. A number of epidemiologic studies, peiformed mainly on nurses, showed an association between sustained night work (3 to 20 years) and an increased risk of breast cancer Health problems faced by flight attendants have also been reported, though other causes like exposure to radiations cannot be ruled out. Other deleterious effects are reported in this paper. The potential mechanisms of the deleterious effects of LAN on health are suppression of melatonin andsleep deprivation. The International Agencyfor Cancer Research (IARC) classified shift work that involves circadian disruption as ( probably carcinogenic to humans". Countermeasures (e.g melatonin, bright light, use of psychotropic drugs) have been proposed as a means to improve adaptation to shift work and night work and to fight " clock pollution " and circadian desynchronization by LAN.

Delta-9-tetrahydrocannabinol (THC) is the main psychoactive ingredient of cannabis, a drug which is commonly smoked This paper focuses on the pharmacokinetics of THC. The average THC content in cannabis plant material has risen by a factor offour over the past 20 years, from 4% to 16%. This increase has important implications not only for the pharmacokinetics but also for the pharmacology of THC The mean bioavailability of THC in smoked cannabis is about 25%. In a cigarette containing 3.55% of THC, a peak plasma level of about 160 ng/mL occurs approximately 10 min after inhalation. THC is quickly cleared from plasma in a multiphasic manner and is widely distributed to tissues, leading to its pharmacologic effects. Body fat is a long-term storage site. This particular pharmacokinetic behavior explains the lack of correlation between the THC blood level and clinical effects, contrary to ethanol. The main THC metabolites are 11-OH-THC (the only active metabolite) and THC-COOH, which is eliminated in feces and urine over several weeks. Therefore, abstinence can be established by analyzing THC-COOH in urine, while blood THC analysis is used to confirm recent exposure. Cannabis is the main illicit drug found among vehicle drivers. Various traffic safety studies indicate that recent use of this drug at least doubles the risk of causing an accident, and that simultaneous alcohol consumption multiplies this risk by afactor of 14. Since 2009, synthetic cannabinoids have emerged on the illicit drug market. These substances act on the same CB1 receptors as THC, but with higher afinity. Their pharmacokinetics differs from that of THC, as they are metabolized into multiple derivatives, most of which are more active than THC itself.

Intracerebral hemorrhage (ICH) is one of the most severe forms of stroke, yet several factors continue to undermine effective patient management: (1) Contrary to ischemic stroke, no dedicated ICH classification has so far been established for routine clinical use. (2) The diagnostic workup for patients presenting with acute ICH has not been standardized (3) Specific ICH treatment options remain limited. (4) Major uncertainties exist regarding preventive interventions for unruptured, hemorrhage-prone lesions such as cerebral AVMs, aneurysms, and cavernous malformations. This paper summarizes recent progress in establishing an etiology-based ICH classification, a pragmatic stepwise algorithm for the diagnostic workup of ICH, and novel treatment strategies such as rapid blood pressure-lowering therapy for acute ICH.

Pulmonary involvement in progressive systemic sclerosis can affect either the parenchyma or the vasculature. Both forms are fatal within a few months or years, due to respiratory and/or cardiac failure. Patients must be screened for pulmonary hypertension by ultrasonography, to be confirmed by right heart catheterization if necessary, as early diagnosis and immediate treatment improves the prognosis. The interstitial pulmonary disease progresses slowly, leading to respiratory failure, secondary pulmonary hypertension, and heart failure. Immunosuppressive treatments are disappointing but if prescribed early may prevent or delay the otherwise ineluctable aggravation. Pulmonary involvement threatens the vital and functional prognosis of patients with scleroderma, who may also develop several other complica- tions (especially infections and adverse effects of drugs) that are not dealt with here. This paper focuses on the most significant disease manifestations and current therapeutic options.

Treatments for localized prostate cancer include radical prostatectomy, brachytherapy, conformal external beam irradiation, and focused ultrasound. This paper describes the oncologic and functional results of each approach. The treatment choice depends on the patient's general status and on the results of biopsy and imaging studies. Watchful waiting and hormone therapy are other options for elderly patients.

In the second half of the 20th century, the development of experimental pharmacology led to the discovery of powerful new therapeutic agents, but production has since faltered, particularly in Europe. The purpose of this paper is to review how the gap in the production of novel medicines between Europe and the USA could be filled by proper use of molecular biology data. The European program entitled 'The Innovative Medicines Initiative' could facilitate the translation of information from benchtop to bedside.

The concept of mitochondrial disease originated in 1962 when Luft and co-workers described a patient with non thyroidal hypermetabolism related to loose coupling of oxidation-phosphorylation in muscle mitochondria. Over the following quarter of century, with the routine use of the Engel-Gomory staining on muscle biopsy revealing ragged-red fibres as a convenient markers for mitochondrial pathology, numerous papers described clinical, biochemical and morphological aspects of mitochondrial encephalomyopathies. With the discovery in 1988 of mutations in mitochondrial DNA, the concept of mitochondrial disease with maternal transmission led to an explosive expansion of research in the field. Throughout the 1990's the rapid identification of multiple mitochondrial gene defects associated with clinically diverse disorders has left practitioners puzzled about diagnosing such heterogeneous and complexes syndromes. The great complexity of the system and the ubiquitous repartition of mitochondria explain the wide variety of clinical phenotypes associated with primary mitochondrial diseases due to mutations in the mitochondrial genome, in the nuclear genome or in the cross-talk between the two genomes and regulations. In the past few years, the pivotal role of mitochondria in drug sensitivity, their key role in aging, apoptosis or neurodegeneration lead to a mitochondial medicine. Here the term of mitochondrial disease is limited to genetic defect in the respiratory chain where advance were recently especially significant for the evolution of the concept and updated classification.

Cognitive remediation is an innovative psychosocial therapy which can provide a substantial benefit, especially for schizophrenic patients. As its name implies, the aim of cognitive remediation is to restore cognitive functions. Most cognitive domains (attention, memory and executive functions) are impaired in schizophrenia. Remediation therapy must be administered by an expert, and is based on cognitive training on the one hand, and on learning of cognitive strategies on the other hand. With these techniques the patient is better able to solve complex cognitive problems and to apply these new skills to everyday situations. Several techniques are available in France, using either computer-based or paper/pencil approaches. The programs are administered over several months, with one or more sessions per week. Cognitive remediation itself provides only a modest cognitive benefit, which must be enhanced by the adjunction of other therapies such as behavioral therapy, learning of social skills, or a vocational program during the first months of employment.

Pulmonary involvement in progressive systemic sclerosis can affect either the parenchyma or the vasculature. Both forms are fatal within a few months or years, due to respiratory and/or cardiac failure. Patients must be screened for pulmonary hypertension by ultrasonography, to be confirmed by right heart catheterization if necessary, as early diagnosis and immediate treatment improves the prognosis. The interstitial pulmonary disease progresses slowly, leading to respiratory failure, secondary pulmonary hypertension, and heart failure. Immunosuppressive treatments are disappointing but if prescribed early may prevent or delay the otherwise ineluctable aggravation. Pulmonary involvement threatens the vital and functional prognosis of patients with scleroderma, who may also develop several other complica- tions (especially infections and adverse effects of drugs) that are not dealt with here. This paper focuses on the most significant disease manifestations and current therapeutic options.

The PubMed database contains about eighty scientific papers on crenobalneotherapy (i.e., medical balneology or spa therapy) published in the last three years, mostly in journals with an impact factor. These studies focus on the actions of thermomineral products (waters, muds, gases, steam) on biological systems (immune system, antioxidant system, cytokine networks, nociception, etc.). Hot mineral waters can have an action on the circulatory system. Ingested mineral water can act on carbohydrate, lipid and mineral metabolism. Dermocosmetologic mineral products have shown real benefits. Medical benefits of thermal treatment have been observed in patients with rheumatic conditions, psoriasis, venous insufficiency, ENT conditions, gynecolgical disorders, and anxiety. Unfortunately, many publications in this area suffer from methodological flaws. Clinical investigations of thermal medicine encounter dificulties of a methodological and financial nature, and problems of patient recruitment. The aim of the French thermal research institute is to provide support and advice for teams wishing to conduct well-designed controlled trials.

Treatments for localized prostate cancer include radical prostatectomy, brachytherapy, conformal external beam irradiation, and focused ultrasound. This paper describes the oncologic and functional results of each approach. The treatment choice depends on the patient's general status and on the results of biopsy and imaging studies. Watchful waiting and hormone therapy are other options for elderly patients.

Babinski made important contributions to both psychiatry and neurology. He disagreed with Charcot's theatrical interpretation of hysteria and made a subtle distinction between Suggestion and Persuasion, thereby differentiating Hysteria from Pithiatism. This paper examines Charcot's concepts and the way in which Babinski refined and honed his master's theories.

In the second half of the 20th century, the development of experimental pharmacology led to the discovery of powerful new therapeutic agents, but production has since faltered, particularly in Europe. The purpose of this paper is to review how the gap in the production of novel medicines between Europe and the USA could be filled by proper use of molecular biology data. The European program entitled 'The Innovative Medicines Initiative' could facilitate the translation of information from benchtop to bedside.

The utility of screening for occult malignancies in very elderly people is controversial. Indeed, the following factors must be taken into account: increasing life expectancy, better efficacy and tolerability of cancer therapies, the cost of screening, and medico-legal issues. The dilemma is between missing a curable cancer and over-diagnosing and over-treating a vulnerable patient. Proper patient information is clearly needed The informed patient's own preference is crucially important. This paper focuses on the most frequent malignancies that can be detected by screening, namely breast, colorectal and prostate cancer.

Despite a good reputation abroad, specialized medical training programs in France fail to attract a sufficient number of high-level foreign students. This report examines ways of improving the situation. If French universities are to increase their international renown, they must always be referred to by the same name in scientific papers. Students following channels of excellence must be distinguished from other students. They must have a level of medical knowledge equivalent to that of a 6th-year French medical student, together with a good knowledge of French and a letter from their dean stating that their training in France is compatible with their career in their country of origin. For full medical specialist training (up to five years) the only access requirement should be the equivalent of entrance examinations for French residents. Thereafter, the theoretical and practical training should be similar to that received by French residents. Complementary specialist training courses (one year) should take place in selected university hospitals. Intensive training courses (six months) should be open to physicians who have already specialized. Diplomas should be delivered after testing knowledge and skills.

Cartilage is a hydrated connective tissue that withstands and distributes mechanical forces within joints. Chondrocytes utilize mechanical signals to maintain cartilaginous tissue homeostasis. They regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix (ECM). Some mechanotransduction mechanisms are known, while many others no doubt remain to be discovered. Various aspects of chondrocyte mechanobiology have been applied to tissue engineering, with the creation of replacement tissue in vitro from bioresorbable or non-bioresorbable scaffolds and harvested cells. The tissues are maintained in a near-physiologic mechanical and biochemical environment. This paper is an overview of both chondrocyte mechanobiology and cartilage tissue engineering

Telemanipulation has been developed for industrial purposes since the 1970s. More recently, telemanipulated arms entered the operating room. This paper briefly describes the history of surgical robotics and discusses the advantages and disadvantages for both patients and surgeons. The authors advocate the development of robotic surgery, as it facilitates the training of young surgeons and can be useful during certain phases of an operation. Thus, robotic surgery is more a promising tool than a simple toy.

As the indoor mold Stachybotrys chartarum (SC) has been linked to serious health disorders, its identification in water-damaged dwellings is of utmost importance. The aim of this work was to compare wall relative humidity (RH) measurements with the results of mold identification studied on 458 samples collected from 100 dwellings. Mold identification was based on direct microscopic examination of wall samples collected by the gummed paper technique. Mean (+/- SD) wall RH (%) was much higher (97.0 +/- 6.1) when SC was identified (30 samples) than when other molds were identified (291 samples, 41.8 +/- 36.9) and when no molds were identified (137 samples, 38.9 +/- 34.8). There was a direct relationship between wall and room-air RH but the scatter of results implies that the latter cannot be used as a surrogate for the former. This study suggests that simple wall RH measurement can serve as a reliable indicator of SC infestation of dwellings.

Coronary artery surgery is now being challenged by percutaneous techniques of coronary revascularization, coronary dilatation and arterial stenting. Improvements are being made in three directions, namely selection of optimal conduits, with the aim of improving long-term graft patency; minimizing complications of cardiopulmonary circulation (or avoiding it altogether), and improving access to coronary vessels. The ultimate goal is robotic keyhole surgery of the beating heart. This paper offers a critical analysis of these developments.

This paper describes antivirals active against Myxovirus influenzae (influenza vaccine excluded), together with their indications in inter-pandemic and pandemic situations. Three kinds of antiviral drug, with different mechanisms of action, are active against Myxovirus influenzae: the adamantanes (amantadine and rimantadine); ribavirin; and neuraminidase inhibitors (zanamivir and oseltamivir). Amantadine is available in France but its indications are limited by its inactivity against influenza B virus, its adverse effects, and rapid onset of resistance. Ribavirin is administered by nebulization, exclusively in hospital, for severe cases. Neuraminidase inhibitors are effective on benign influenza; they are also well tolerated, active against subtypes A and B, and rarely elicit resistant mutants in vivo (exclusively seen with oseltamivir, mainly among children). According to their licensing terms, antivirals may be prescribed during epidemics, within 24-48 hours of typical symptom onset. They must not be used prophylactically in place of influenza vaccine, but may be useful when there is a familial or institutional index case, or during pandemics. Use in this latter situation would raise supply problems and, thus, the question of who should be treated first.

The last Winter Olympics and recent cycling events have once again called attention to the use by endurance sportsmen and women of a variety of approaches designed to increase the blood hemoglobin concentration and oxygen-carrying capacity. An increased hemoglobin concentration and maximal oxygen uptake can be achieved by training at high altitude or by "living high and training low". It can also be procured by "blood boosting" with erythropoietin or darbepoietin, blood infusion, or misuse of hemoglobin-based oxygen carriers. This paper describes methods of increasing oxygen transport, with the accent on blood infusion, which is again relevant today with the development of a test able to detect recombinant human erythropoietins.

From a cycling standpoint, "circular insanity" (Falret) and "dual-form insanity" (Baillarger), both described in hospital patients in 1854, are at the severe end of the spectrum of what we now call "bipolar disorders". Falret was prescient in suggesting that circular insanity was rare in the community, where depressive cycles are prevalent. These disorders are now respectively referred to as the "hard" (manic-depressive) and "soft" (bipolar spectrum) phenotypes of the disorder. This paper focuses on the latter, more prevalent depressive expressions of the spectrum, which share with the manic and circular forms a lifelong tendency to recur. Their cyclicity may involve putative "clock genes". The genetics of psychotic mania overlaps somewhat with the genetics of schizophrenia. As regards depressive recurrence, putative genetic factors have been identified, including a polymorphism of the serotonin transporter, which significantly increases the subject's vulnerability to stress; a mediating pathogenetic variable appears to be temperamental dysregulation (e.g. neuroticism and cyclothymic lability), which produces hyperemotional reactivity to such stressors. The growing recognition that many depressive recurrences belong to a broad spectrum, affecting 5-10% of the population, represents a new public health challenge. Although the new class of serotoninergic antidepressants offer a practical approach to the management of depressive episodes, further research is needed to determine the point of the spectrum at which mood-stabilizing therapy should be started--and in what combinations--in order to prevent recurrence and suicide.

In this paper we review the recent advances for the diagnosis and the management of renal cell carcinoma. Urine tests, genetics and modification of the TNM system help for the diagnosis. Multifocality and microvascular venous invasion are interesting prognostic factors. Recent prospective studies gave important informations on lymph node dissection and the role of surgery in metastatic disease. New surgical tools are in development and new approaches in medical treatment too.

Rheumatoid arthritis (RA) is a frequent, heterogenous crippling disease. The diagnosis must be made as soon as possible in order to begin quickly the treatment. The improvement of our knowledge in the immunopathology of RA allowed the development of new biotherapies directed against harmful mediators such as TNF alpha and Interleukin 1. With anti-TNF alpha agents excellent clinical and biological results are observed in methotrexate refractory RA patients in 70% of cases. Moreover these drugs are able to stop the X ray evolution of the disease. They can be considered as a very important new step in the treatment of RA. Other targeted drugs such as anti-IL1, anti-IL6 agents, anti-B lymphocytes monoclonal antibody (Rituximab), CTL4 IgG are already used or under study. In this paper the modern treatment of RA is reviewed with a special emphasis on anti-TNF alpha and anti-IL1 biotherapies.

The concept of mitochondrial disease originated in 1962 when Luft and co-workers described a patient with non thyroidal hypermetabolism related to loose coupling of oxidation-phosphorylation in muscle mitochondria. Over the following quarter of century, with the routine use of the Engel-Gomory staining on muscle biopsy revealing ragged-red fibres as a convenient markers for mitochondrial pathology, numerous papers described clinical, biochemical and morphological aspects of mitochondrial encephalomyopathies. With the discovery in 1988 of mutations in mitochondrial DNA, the concept of mitochondrial disease with maternal transmission led to an explosive expansion of research in the field. Throughout the 1990's the rapid identification of multiple mitochondrial gene defects associated with clinically diverse disorders has left practitioners puzzled about diagnosing such heterogeneous and complexes syndromes. The great complexity of the system and the ubiquitous repartition of mitochondria explain the wide variety of clinical phenotypes associated with primary mitochondrial diseases due to mutations in the mitochondrial genome, in the nuclear genome or in the cross-talk between the two genomes and regulations. In the past few years, the pivotal role of mitochondria in drug sensitivity, their key role in aging, apoptosis or neurodegeneration lead to a mitochondial medicine. Here the term of mitochondrial disease is limited to genetic defect in the respiratory chain where advance were recently especially significant for the evolution of the concept and updated classification.

The pace of genome sequencing has been tremendously accelerated during the last few years leading to the determination of dozens of entire bacterial genome sequences in addition to several eukaryotic genome sequences and to the publication in 2000 of a draft of the human one. Nowadays scientists have to face a new challenge that corresponds to the elucidation of the function(s) of the thousands of genes uncovered by sequencing. Obviously this task will necessitate a large panel of methodologies. Since its domestication, dog has been the subject of intense breeding and selection practices that result in the creation of many breeds that differ one from the others by a huge variation in shape, size, coat colour, aptitude. Unfortunately these breeding practices along the selection of specific alleles governing those characters have co-selected various deleterious or morbid alleles and nowadays most of the canine breeds suffers from many different diseases of genetic origin. In addition many breeds have developed susceptibility toward many diseases very often similar to those affecting humans such as cancers, heart diseases, allergies.... In this paper we present arguments in favour of the utilisation of the canine model to sort out through linkage disequilibrium studies the phenotype/genotype relationship as an aid to understand the function(s) of the thousands of genes uncovered by sequencing.

Antibodies have long been recognized for their diagnostic and therapeutic potential. The rapidly increasing number of monoclonal antibodies approved for immunotherapy has paved the way to an even greater demand for antibody molecules. In order to satisfy this growing demand, alternative systems based on transgenic organisms are actively explored to increase the production capacity. In this paper, we will focus on transgenic plants as a promising large scale production and processing system.

Technical progress in cataract surgery has led to the phacoemulsification of the eye lens by ultrasound followed by the intraocular lens implantation. In spite of rigorous preventive hygiene and sterilization measures taken before, during and after the operation, two clinical forms of endophthalmitis seriously threaten vision in the operated eye: externally induced endophthalmitis, specifically with pyocyanic bacillus, which often follows the irregular use of reuseable tubings and internally induced endophthalmitis due to the inevitable penetration during the intraocular operation of conjunctival micro-organisms especially staphylococci. A zero-risk level is non-existent and it would be unjust to hold the ophthalmologist responsible for it, when he has done everything possible to reduce the risk. The question of bacteriological examinations, the problem of antibioprophylaxis, and the danger of the reuseable tubings and of the ambulatory surgery, concerning at-risk patients, are discussed in this paper.

The already substantial body of evidence and growing web of suspicions as to the scale and severity of the cascade effects of endocrine disrupters (related to persistent organic pollutants or POPs) on the health of ecosystems and humans have sparked such concern that in June 1998, representatives of 94 countries meeting in Montreal under the aegis of UNEP signed a draft international agreement to phase out the most harmful POPs. Related to particular persistent organic pollutants--toxic semi-volatile and persistent chemical compounds now found everywhere in the environment, such as BPCs, organochlorine pesticides, dioxins and furans, that build up in the bodies of organisms that consume other contaminated organisms along the food chain--endocrine disrupters are strongly suspected of affecting the health of animals and adversely impacting the health, fertility and even intellectual faculties of humans. For example, very low-level exposure to some POPs is associated with some hormone-dependent cancers, damage to the central and peripheral nervous systems, impaired immune system function, reproductive disorders and developmental disruptions in newborns and infants, who can be affected in utero or through breast-feeding. Considering the extreme complexity of the scientific and socio-economic effects of POP-related endocrine disrupters, there are those who, advocate a wait-and-see approach, claiming that there is not enough formal scientific proof. There are others who use the available evidence to advance the research, press for bans on incriminated substances and look for global, integrated and viable alternatives. And there are other still who, with careless disregard for the Precautionary Principle, are quite prepared to talk about the perverse effects of POPs in order to justify the increased use of artificial means of reproduction or the replacement of chemical pesticides by pest-resistant genetically modified organisms (GMOs), thereby opening the door to "solutions" that are potentially more biologically and ethically dangerous than the problems they purport to remedy. This paper provides an overview of the current understanding of the main sources and suspected effects of POPs on animal life and human health, explores the complexity of the scientific, economic and political issues involved in any international process to do away with the incriminated products, discusses the risks and perverse consequences of some of the proposed alternatives, and stresses the importance, in the light of these risks and consequences, of placing renewed emphasis on public and environmental health approaches based on the Precautionary Principle.

The increase in the incidence of AIDS-related tuberculosis over the last decades has fueled the dissemination of multiple drug resistance tuberculosis (including resistant strains to INH and rifampin). This has now been recognized in a variety of settings including hospitals, prisons and shelters. We have identified a nosocomial epidemic at the Muñiz Hospital in the city of Buenos Aires, Argentina. This has evolved as one of the largest institutional outbreaks yet to be recognized. The purpose of this paper is to characterize the evolution of this outbreak which at the end of 1997 had involved in excess of 500 cases. Among the 3,322 patients discharged at the Muñiz Hospital during the years 1996-1997 with the diagnosis of tuberculosis, 440 (13.24%) were discharged with the diagnosis of multiple drug resistance tuberculosis. The immediate mortality (during the ensuing four months following the bacteriological diagnosis) was of 91.3% of cases in 1995 and decreased progressively to 65.9% in 1996 and 55.9% in 1997. The bacteriological confirmation of the diagnosis was made after the patients death in a decreasing number of cases, going from 72.5% of the cases in 1995 to 28.3% of the cases in 1997. Despite the significant progress achieved with regard to the diagnosis and treatment of multiple drug resistance tuberculosis, the measures undertaken to decrease the spread of the cases have had limited success. This is chiefly attributable to the inability to isolate cases. This has continued to promote nosocomial spread of multiple drug resistance tuberculosis in our environment.

The recent advances in medical imaging, the avaibility of methods for image analysis and computer graphics, the technological resources provided by microdevices and the design of minimal access surgical procedures have open the road to new concepts. Virtual endoscopy represents one of these emerging areas and points out the applicative potential of three dimensional (3D) imaging. It leads to less invasive diagnosis and therapeutic achievements and provides important cues for education and interventional planning. Image segmentation, visualization, tissue modeling and interactions with surgical instruments are the fundamental components to build clinical applications. They are examined in this paper through 3D navigation systems, surgical simulations and image guided interventions.

The evaluation of the results of organ allografts for each type of organ and for each center is one of the prioritary missions of the Etablissement français des Greffes (EfG). The objectives, the methodology and the results of this evaluation have been defined and discussed with all the organ transplantation teams, after a preliminary work of the Conseil Médical et Scientifique of the Etablissement. This paper describes the evaluation experiment conducted by the EfG between 1995 and 1998. The main objectives of this first phase of the evaluation project are the identification of centers with outside of the norm results and the study of the relationship between the number of transplants performed by each center and the quality of their results. The chosen quality indicators are the excess in the patients mortality rate, computed one year after the first transplantation, for vital organs, and in the one year kidney graft loss rate for kidney transplantation. The excess of mortality is defined as the difference between observed and expected mortality rates. The expected mortality rate is estimated, for each program, by a statistical model based on a set of patient specific risk factors. All the vital organ transplantation teams who have performed more than 10 transplants between 1991 and 1995, and all the kidney transplantation teams who have performed more than 15 transplants between 1991 and 1996 have been included in the study. The main results of this evaluation experiment are the following ones: even if the intercenter variability of the results was statistically significant, it remained of low magnitude, particularly for heart, liver and kidney transplantation. None of the evaluated centers presented results outside of the norm. The results were positively correlated to the number of transplants for liver and lung transplantation. This was not the case for heart and kidney transplantation; this relationship is difficult to analyze for heart-lung transplantation, due to the small number of centers included. Thanks to the data base constituted since 1959 by all the organ transplantation teams, and in spite of the partially retrospective nature of this study, which explains its limits, this evaluation experiment, opens a perspective of extension to other domains of public health. In the future, however, this kind of evaluation should be prospective; a project aimed to developing the evaluation of the results of organ transplant actions in real time was defined and is currently on-going.

Infection on foreign body: bacterial colonization of ureteric stents. The most frequent cause of the early removal of ureteric endoprostheses (double J) is generally due to bacterial colonization. In order to prevent or to restrict the prosthesis colonization, it is necessary to understand the major steps and the factors influencing the colonization. This is the reason why we aimed to extract the most relevant parameters influencing the bacterial colonization from the observations made in vivo thanks to in vitro analyses. We have studied in vivo the relationship between the bacterial colonization of the endoprostheses, the urinary infections and the antibiotherapy. In vitro, we have defined the conditions promoting the primary adhesion of the most frequently isolated bacteria on endoprostheses. Surface properties of bacteria and materials have been compared to:--the bacterial count of infected double J samples with respect to bacterial species,--the bacterial count of the infected samples with respect to pH and Ca2+, Mg2+ concentration. The results show a great variability of the biomaterial surface properties which could be optimized, the fact that the urinary medium acidification could lower the bacterial adhesion and the ambiguous role of Ca2+ and Mg2+ ions which is discussed in this paper. In the case of in vivo analyses, the conflicting results between leukocyturia and bacteriuria lead to the detection of the bacterial colonization under antibiotic treatment. The characterized urinary infection must warn the risk of pyelonephritis.

Procalcitonin (PCT) is a new marker connected to systemic bacterial infection. Blood values are parallel to the severity of the disease. In the present Knowledge on PCT, the usefulness is focused on acute pediatric pathology, ICU, and the follow up of grafts and surgery. This paper dwells on the interest in the differential diagnosis for meningitis (viral versus bacterial). At the opposite of CRP and IL6, a very clear cut off for all the cases has been found. The cut off in this study is about 2-3 micrograms/l. PCT, at the difference of cytokines is a very stable molecule in the blood sample. Also a very small quantity of serum (or plasma) 20 microliters is sufficient for one assay. In the future, a point of care assay will be available and should be very interesting in the emergency wards (pediatric or adult ICU). The origin of PCT seems to be--but perhaps not exclusively--mononuclear cells. The absence of an animal model (except monkeys) is actually a difficulty to progress.

The hypothesis discussed in this paper states that defence and survival strategies of cancer cells against therapeutic approaches are similar in their mechanisms and homologous in several genes to the SOS program known in bacteria and induced by several assaults. The almost ineluctable malignant progression and its acceleration in response to various therapies should then be considered as an inducible system inherited from prokaryotes and repressed in multicellular organisms through the anti-oncogene system. The later, weakened in case of some inherited mutations yields even in sporadic cases to repeated assaults and to the decrease with time of internal defences, including antioxidant mechanisms. This theory which presents in a new perspective the biological status of cancer in the frame of Darwinian evolution and hence the strategies able to control its progression, leads itself to some predictions and testable assertions: absence of any anti-oncogene homologues in unicellular organisms, built-in weaknesses in anti-oncogenes, existence of a common repressor and a common derepressor mechanism for several distinct genes involved in cancer and in response to an environmental assault, and finally a possible transfer of drug resistance genes in malignant cells as it is the case for bacteria submitted to stress conditions.

Since the discovery of the antipsychotic effects of chlorpromazine by the french psychiatrists Delay and Deniker in 1952, preclinical pharmacologists have proposed several laboratory tests, that have been used to demonstrate the potential activity of drugs in the treatment of mental disorders including schizophrenia, depressive illness and anxiety. Tests are divided into behavioural tests and neurochemical tests. Electrophysiology tests are not considered in this paper. Concerning schizophrenia, in spite that there is no valid model, behavioural tests presently used are: antagonism against various responses induced by dopamine receptor agonists, inhibition of conditioned behaviours, latent inhibition, startle reaction, models related to the neurodevelopmental hypothesis. For antidepressant activity, models are based on antagonism of various effects of reserpine. More anthropomorphic models involve helplessness behaviours, social isolation, changes induced by limbic system lesions. Biochemical investigations mainly involve in vitro and in vivo tests: study of changes in the metabolism of neurotransmitters using microdialysis and other procedures, interaction with receptor subtypes. As a result of advances in molecular biology, other tools are now emerging, but classical tests remain useful.

(Sub) urban air pollution (AP) is one of the most common and important forms of AP. This paper shortly gives some informations about the main sources of AP (mainly car traffic), the essential determinants of AP (emissions, meteorology, ..), the complexity of effluents and emissions (leading to the choice of AP indicators), the notion of exposition, and the recent evolution of environmental concentrations of air pollutants. Important progress were made towards emissions of industrial and heating sources, with a substantial decrease of SO2 and particulates air concentrations; but despite a marked improvement of fuels quality and of unitary vehicles emissions (and a correlated decrease in Pb and CO emissions) car pollution remains important in terms of photo-oxidant air pollution (CO, NOx, COV, O3); the good use of car in urban area must be reconsidered.

The Codex Alimentarius in its General Principles committee proposes the definitions of risk assessment and risk management linked to ingestion of food additives and food contaminants. Moreover, three European directives imply for all member states an evaluation of food additives intakes by general population and by possible "at risk groups of consumers". This work is conducted in the general case of European Scientific Cooperation and is coordinated by United-Kingdom. This paper describes the French approach, using a step-by-step procedure to evaluate food additives consumption. It emphasizes the importance of scientific works in this field of research to obtain french datas about french consumptions.

The observation in 1995 and 1996 of 12 cases of a new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K. suggested a possible relation between this human cases and bovine spongiform encephalopathy (BSE). Recent papers about this topic are reviewed: BSE transmission to macaques, transmission of scrapie with embryo transfer, incidence of maternal transmission, PrP protein released by platelets, diagnostic test by detection of PrP protein in tissues of sheep, epidemiology of BSE, french regulations, identification of cattle in U.K.

Epithelial structures lining the proximal tubule and the yolk sac are characterized by a high rate of internalization followed by degradation of the proteins exposed to their apical pole. This function implies the expression by these epithelia of specialized proteins which have the ability to bind numerous ligands and/or lysosomal targeting properties. An improved knowledge of these molecules is needed since their expression in a limited number of epithelia may account for the specificity of some pathologies induced in particular by toxins. This paper deals with two such "candidate" proteins, gp330/megalin and gp280 which have been expressed in all species studied. gp280 is the target of teratogenic antibodies and is identified here as the receptor for intrinsic factor-cobalamin complexes but in all likelihood also binds other ligands. Antibodies to gp280 markedly stimulate the fusion of renal endosomes suggesting that it may play a role in targeting processes. gp330/megalin has been recently identified as the ligand of polybasic compounds such as gentamicin and is a key component in the internalization of the drug by tubular cells leading to renal toxicity. gp330/megalin also intervenes in endosomal fusion and some of its toxic properties may be mediated by this route.