[Back to the Future. Vaccine trials against Ebola in the history of resistance to immunization]. / « Back to the Future ¼. Les essais vaccinaux contre Ebola, au regard de l'histoire des résistances à l'immunisation.

Vaccine trials against Ebola virus have been conceived and organized, in August 2014, after the epidemic started in three countries of West Africa. If the preparedness had been missing, the planners tried to anticipate the resistance to vaccination, in Guinea, Sierra Leone and Liberia. This article offers a retrospective view on the resistances to vaccination throughout its history, from smallpox inoculation to anti-polio vaccine. Resistances have been linked to the political contexts and the rejection of an oppressive power, either local or foreign, as well as mistakes and scientific uncertainties. The analysis of the historical factors of resistance leads to reverse the question: what convinces people to accept a vaccine trial, despite the obscurities of the immunization processes inside the body? The article hypothesizes that Guineans and West Africans face a dilemma similar to their counterparts in the past, whether or not to rally to an experimental immunization, the results of which are still pending. They may appropriate the Western beliefs about the efficacy of vaccines to their own ways of circumventing misfortune. Further field studies will be required to assess the role of the vaccinal trials and the response to the epidemic in the "convalescence" of these societies, being aware that the trials will not allow a complete assessment of the vaccines, because of the end of the epidemic.

[Medical ethics and cultures of the world]. / Ethique médicale et cultures du monde.

We celebrate the anniversary of the Société de Pathologie exotique, founded in 1908. Is the term exotic still appropriate to single out a kind of pathology, in the era of Globalization? And what is the meaning of labeling different sets of ethical values, some of which can be said exotic, with the legitimate purpose of acknowledging, on an equal footing, the irreducible differences among cultures? Further research often reveals behind the so-called pluralism of values the socio-economic inequalities, which explain disparities. "Exotic" indicates a crying need for more in-depth analysis of medical practices in all countries, including Western ones, and an alternating close and remote look at all of them, in order to display "a rainbow of values on an ethical horizon".

[How can social sciences contribute to vaccination in the tropics?]. / Programmes de vaccination en milieu tropical l'apport d'une réflexion en sciences sociales.

In the past, governments were eager to propagate vaccines along generally adopted authoritarian methods. Yet, a retrospective inquiry detects uneven acceptance of vaccines, for reasons which point to differences in cultures and political contexts and involve also the efficacy and reliability of vaccines. After the Alma Ata conference in 1978, vaccines in the Tropics have become part of the core package of primary health care. In the context of political unrest and defiance toward the dominant powers (as illustrated in many countries, from Philippines to Nigeria), it remains more crucial than ever to pay due attention to the needs and demands of the population and listen to the way they wish to receive preventive and curative care. The importance of communicating on science in the making and respecting the individual's bodily integrity and intellectual autonomy is paramount in the Tropics.

A brief history of vaccines and vaccination.

Human vaccinology, with its primary focus on the individual, seems far removed from veterinary medicine, with its concern for the health of the herd. Yet several episodes in the past (smallpox, fowl cholera, anthrax, swine erysipelas, rabies, tuberculosis, etc.) serve to illustrate the proximity between research on veterinary and human vaccines. In some cases the human vaccine was developed first, while in other cases it was the animal vaccine. The history of vaccinology clearly demonstrates the importance of these 'two medicines' working together. Foot and mouth disease (FMD) vaccines were among the first vaccines to be developed, beginning at the end of the 19th Century. Thanks to the discoveries of several researchers, including European researchers such as Vallée (French), Waldmann (German), Frenkel (Dutch) and Capstick (British), FMD vaccines began to be produced on an industrial scale from 1950 onwards, making possible vaccination of millions of animals in Europe and beyond. Vaccination strategies against FMD have always been dependent on the properties of the vaccines being used. At the beginning of the 21st Century FMD vaccines are designed in such a way that serological tests can differentiate infected from vaccinated animals, which has affected OIE regulations on international trade in animals and animal products. The history of vaccination against rinderpest, bovine contagious pleuropneumonia, and Marek's disease will also be dealt with.

[French specificities in the history of vaccination. The end of an exception?]. / Les particularités françaises de l'histoire de la vaccination. La fin d'une exception?

Five years after the National Health minister launched the vaccination program against hepatitis B in 1994, French public health experts are not satisfied by the coverage rate among young people. Is this stagnation related to the controversial way the program was initially managed and to the debate that has raged on the link between the vaccine and multiple sclerosis? Is the popular reaction of distrust specific to the vaccine or does it reveal a growing concern towards the whole vaccinal enterprise? More generally, is it the end of the almost unconditional French acceptance of vaccines? A historical retrospective on the history of vaccination in the country of Louis Pasteur.

[Pathology and dental care in the context of cardiovascular conditions: myths, beliefs and realities]. / Pathologies et soins dentaires dans le cadre des affections cardiovasculaires: mythes, croyances et réalités.

The knowledge regarding the links between dental and cardiac affections are generally based on empirical concepts and lead to unjustified clinical practices. Infectious endocarditis (IE) is the principal cardiac diseases concerned with dental procedures. Although in France, the incidence of IE is stable, the incidence of oral bacteria at the origin of IE is diminishing. The risk of IE and thus the indication of antibioprophylaxis depend upon the subjacent cardiopathy and dental treatment. Antibioprophylaxis has to be very strict in patients with high or moderate risks of IE but is not necessary in low risk patients. In all cases, a good oral and dental hygiene and a regular dentist follow up are the most effective methods of preventing IE. Coronary artery disease and dental affections are associated because they present similar risk factors (i.e. smoking, excessive sugar consumption) and also because inflammation increases the risk of acute coronary syndrome. Today, dental cares are not contraindicated in patients with recent coronary syndrome if precise protocols are followed. Concerning the hemorrhagic risk during dental care in patients treated by anticoagulants and/or antithrombotics, dental cares and extractions are possible if INR or heparinemy are within the therapeutic limits and local haemostasis is meticulous. In addition, aspirin does not require to be stopped before minor dental treatments. Finally a better collaboration between dentists and cardiologists would allow an optimum management of patients with cardiac disease requiring dental cares.

[Future molecules in heart failure]. / Molécules du futur dans l'insuffisance cardiaque.

TODAY: The management of heart failure (HF) has considerably progressed over the last two decades. Treatment today relies on prevention and treatment of congestion (limited salt intake, diuretics, converting enzyme inhibitors) and limiting neurohormone stimulation (converting enzyme inhibitors +/- aldactone, beta-blockers). IN THE YEARS TO COME: Based on new concepts, several therapeutic strategies are interesting: blocking over vasoconstrictor systems which have not been taking into account; stimulation of vasodilator and natriuretic systems; modulation of cardiac remodelling; modulation of the immune and inflammatory systems; modification in intrinsic contractility; prevention of rhythm disorders. Among these differing strategies and molecules, it is not easy to predict those that will change the HF prognosis. In any event, their efficacy and safety remain to be demonstrated with large cohort randomised studies. THE PRINCIPLES: To reduce the number of drugs administered, two options appear particularly interesting: measurement of hormone levels (BNP) in order to adjust treatment and administration of molecules with greatest efficacy and safety profiles; limit cardiac remodelling by using new imaging techniques to detect it more precisely and select the molecule(s) exerting the required effect. To target the new molecules better, patients should be classified according to their etiology, stage and progressive profile of their disease, cardiac remodelling, expression of principle endocrine systems and pro-inflammatory cytokines, expression of inflammatory and immune systems and inherent genetic characteristics and response to treatment. This would permit the adaptation of treatment to each individual patient with heart failure.

[Living donors for transplantation and bioethics laws. Survey with French transplantation professionals]. / La transplantation avec donneur vivant et les lois de bioéthique. Enquête auprès des professionnels français de la transplantation.

OBJECTIVES: Renewed interest in living donor transplantation in France led us to survey French transplanters to determine their opinion concerning this technique and the ethical issues involved. Their concerns and suggestions about current legislation were examined. METHODS: An anonymous questionnaire was sent to physicians working in the different kidney, liver and lung transplantation units operating in France. RESULTS: French transplanters expressed a wide range of opinions concerning living donor transplantation and possible broadening of the current regulations. Sixty-two percent of the transplanters had a positive opinion on living donor transplantation compared with 22% who expressed a negative opinion. For 23% of the transplanters, it is preferable to transplant with a living donor graft compared with 64% who preferred cadaveric grafts. A living donor transplantation program is under study in 65% of the units. There is some debate concerning the legitimate nature of the emergency donation situation for spouses. About one-half of the transplanters were in favor of controlled extension of potential donors to second degree relatives and to the recipient's spouse or living partner. CONCLUSION: There is no real consensus among French transplanters concerning living donor transplantation due to the complexity of the ethical issues involved. Their opinions reflect medical tradition with background marked by autonomy and paternalism. This leads to a wide range of opinions concerning current bioethics legislation and the usefulness of more flexible laws.

Evaluation, selection, and follow-up of live kidney donors: a review of current practice in French renal transplant centres.

BACKGROUND: A resurgence of interest in the concept of live-donor renal transplantation has prompted a closer look at methods of live donor evaluation, selection, and follow-up. The aim of this study was to describe these methods in all 46 French renal transplant centres. METHODS: Questionnaires were sent to all chief renal physicians. RESULTS: The survey was completed by 78% of centres, which accounted for 95% of all live-donor renal transplants carried out in France in 1995 and 1996. There was a substantial variation in all three steps of live-donor management. For example, we observed variations in the screening for specific short- or long-term risk factors (especially cardiovascular or thrombotic risk factors and diabetes). In addition the exclusion criteria differed, especially the cut-off age for donation, which ranged from 45 to 75 years. The composition of teams evaluating and selecting potential donors and the role of the potential donors in the decision-making process varied greatly among centres. Finally, we observed less variation in the methods of donor follow-up. CONCLUSIONS: The current survey revealed a marked disparity in the management of live donors in France. It raises the question of whether these practices should be codified into a set of guidelines for live-donor transplantation.

[Vaccines outside of Europe. Light and shadow of a victory]. / La vaccine hors d'Europe. Ombres et lumières d'une victoire.

In the beginning of the 19th century, vaccination against smallpox spread rapidly in Europe and out of Europe. Although most statesmen eagerly adopted the vaccine, populations displayed mixed attitudes, ranging from mild enthusiasm to resistance. The article illustrates the social response with examples drawn from Algeria, Tunisia, Egypt and Brazil. This analysis puts in sharp focus the crucial importance of a factor for the managers of public health: the adhesion of populations.

Aortic stenosis with severe left ventricular dysfunction and low transvalvular pressure gradients: risk stratification by low-dose dobutamine echocardiography.

OBJECTIVES: We sought to assess risk stratification by using dobutamine stress echocardiography (DSE) in patients with aortic stenosis (AS) and severe left ventricular (LV) dysfunction. BACKGROUND: Few data are available on risk stratification for valve replacement in patients with AS, LV dysfunction and low transvalvular gradients. METHODS: Low-dose DSE was performed in 45 patients (16 women and 29 men; median [quartile range] age in years: 75 [69 to 79]; left ventricular ejection fraction: 0.29 [0.23 to 0.32]; aortic valve area [cm2]: 0.7 [0.5 to 0.8]; mean transaortic gradient [mm Hg]: 26 [21 to 33]). Patients were classified into two groups: group I (n = 32, LV contractile reserve on DSE) and group II (n = 13, no contractile reserve). Valve replacement was performed in 24 and 6 patients in groups I and II, respectively. RESULTS: Perioperative mortality was 8% in group I and 50% in group II (p = 0.014). Survival at five years after the operation was 88% in group I. Compared with medical therapy, valve surgery was associated with better long-term survival in group I (hazard ratio for death [HR-D] 0.13, 95% confidence interval [CI] 0.002 to 0.49) and reduced survival in group II (HR-D 19.6, 95% CI 2.7 to 142). The effect of valve surgery on survival remained significant in both groups after adjustment for age, diabetes, respiratory disease and hypertension. Medical therapy had the same effect in both groups. CONCLUSIONS: In patients with AS, LV dysfunction and low transvalvular gradients, contractile reserve on DSE is associated with a low operative risk and good long-term prognosis after valve surgery. In contrast, operative mortality remains high in the absence of contractile reserve.

[Hospital mortality in cardiology. Analysis of deaths occurring in the Federation of Cardiology of a university hospital center]. / Mortalité hospitalière en cardiologie. Analyse des décès survenus au sein de la fédération de cardiologie d'un centre hospitalo-universitaire.

The aim of this study was to examine the nature of cardiovascular deaths occurring in a University Hospital. All the hospital files of 1999 of the Federation of Cardiology of Henri Mondor Hospital, Creteil, of patients who died in the department or after transfer to the intensive care unit or cardiac surgery department, were analysed. Myocardial ischaemia was the leading cause of death, occurring either in the acute phase of transmural infarction or in patients with chronic cardiac failure. Deaths occurring during acute myocardial infarction were associated with late treatment and/or non-reperfusion of the culprit artery. The delay of diagnosis seemed to be secondary to late consultation or difficulty in diagnosis. This resulted in severe left ventricular dysfunction and, in a quarter of cases, mechanical complications. They led to the early death of the patients (2.9 +/- 3.5 days after admission). Campaigns of patient information and education of doctors who see these patients would seem to be the most appropriate approach to reduce the delay before hospital admission in order to reduce mortality related to myocardial infarction. Cardiac failure is a common cause of death in cardiology departments. The deaths of patients occurred after a long follow-up and several days after hospital admission (11 +/- 10 days). Optimisation of the treatment of cardiac failure, the investigation of ischaemic heart disease, the search for new therapeutic strategies of acute cardiac failure and information of patients about their disease, seem to be the principal measures to take to improve the poor prognosis of this disease.

Prediction of functional recovery of viable myocardium after delayed revascularization in postinfarction patients: accuracy of dobutamine stress echocardiography and influence of long-term vessel patency.

OBJECTIVES: We sought to evaluate dobutamine stress echocardiography (DSE) for predicting recovery of viable myocardium after revascularization with cineangiography as a gold standard for left ventricular (LV) function. We studied the influence of late vessel reocclusion on regional LV function. BACKGROUND: Dobutamine stress echocardiography is a well established evaluation method for myocardial viability assessment. In previous studies the reference method for assessing LV recovery was echocardiography, long-term vessel patency has not been systematically addressed. METHODS: Sixty-eight patients with a first acute myocardial infarction (AMI) and residual stenosis of the infarct related artery (IRA) underwent DSE (mean +/- standard deviation) 21 +/- 12 days after AMI to evaluate myocardial viability. Revascularization of the IRA was performed in 54 patients by angioplasty (n = 43) or bypass grafting (n = 11). Coronary angiography and LV cineangiography were repeated at four months to assess LV function and IRA patency. RESULTS: Sensitivity and specificity of DSE for predicting myocardial recovery after revascularization were 83% and 82%. In the case of late IRA patency, specificity increased to 95%, whereas sensitivity remained unchanged. In the 16 patients with myocardial viability and late IRA patency, echocardiographic wall motion score index decreased after revascularization from 1.83 +/- 0.15 to 1.36 +/- 0.17 (p = 0.0001), and left ventricular ejection fraction (LVEF) increased from 0.52 +/- 0.06 to 0.57 +/- 0.06 (p = 0.0004), whereas in five patients, reocclusion of the IRA prevented improvement of segmental or global LV function despite initially viable myocardium. CONCLUSIONS: Dobutamine stress echocardiography is reliable to predict recovery of viable myocardium after revascularization in postinfarction patients. Late reocclusion of the IRA may prevent LV recovery and influence the accuracy of DSE.

Quantitative systolic and diastolic transmyocardial velocity gradients assessed by M-mode colour Doppler tissue imaging as reliable indicators of regional left ventricular function after acute myocardial infarction.

AIMS: The aim of this study was to determine whether myocardial velocity gradients assessed by M-mode colour Doppler tissue imaging could be of clinical relevance and represent reliable indicators of regional left ventricular function after acute myocardial infarction. METHODS AND RESULTS: Among 64 consecutive patients with a first acute myocardial infarction, in 50 who had a marked asynergy in the parasternal short-axis view at the mid-papillary muscle level, myocardial velocities and velocity gradients were assessed in the anteroseptum and posterior wall by M-mode Doppler tissue imaging. Similar measurements were obtained in 11 matched healthy volunteers who served as a control group. In patients with anterior myocardial infarction, the peak myocardial velocity gradient in the anteroseptum was significantly lower when compared with controls (mean +/- [SD] 0.0 +/- 0.5 vs 1.1 +/- 0.7 s-1 during systole, P < 0.01; and 0.3 +/- 0.6 vs 2.0 +/- 0.5 s-1 during diastole, P < 0.01). Conversely, the peak systolic myocardial velocity gradient in the posterior wall was significantly higher than in controls (2.6 +/- 1.2 vs 1.8 +/- 1.2 s-1, P < 0.05). In patients with inferior myocardial infarction, the peak velocity gradient in the posterior wall was significantly lower when compared with healthy subjects (0.9 +/- 0.6 vs 1.8 +/- 1.2 s-1 during systole and 1.4 +/- 1.4 vs 4.9 +/- 1.2 s-1 during diastole, both P < 0.01). The peak systolic tissue velocity gradient in the anteroseptum was significantly higher than in controls (2.1 +/- 1.0 vs 1.1 +/- 0.7 s-1, P < 0.01). CONCLUSION: The present study indicates that myocardial velocity gradients assessed by M-mode Doppler tissue imaging are of clinical relevance for the characterization of ischaemic myocardial dysfunction after infarction and may provide quantitative assessment of segmental left ventricular function in this clinical setting.

[Physiopathological basis of the treatment of heart failure]. / Bases physiopathologiques du traitement de l'insuffisance cardiaque.

Therapeutic advances have changed the mode of presentation of cardiac failure over the last decades: the main cause, nowadays, is myocardial ischaemia. The modern treatment of cardiac failure is based on relatively simple physiopathological mechanisms which take into account the different aspects of cardiac physiology: a pump, a muscle, a coronary circulation supplying oxygen to the myocardium, an automatic contraction. The concept of vasodilatation and the blocking of vasoconstrictive systems introduced during the 70s is the basis of modern treatment of cardiac failure which involves angiotensin converting enzyme inhibitors and, increasingly, betablockers. In the near future, with earlier treatment of cardiac failure, the stimulation of vasodilator systems could become a new therapeutic strategy. Early detection of ischaemia and its complications with the aim of limiting the loss of cardiac myocytes is a priority for slowing the progression of cardiac failure. The prevention of cardiac failure also depends on educating cardiologists to treat rapidly the factors predisposing to or prolonging episodes of even mild cardiac failure.

Comparison of regional myocardial velocities assessed by quantitative 2-dimensional and M-mode color Doppler tissue imaging: influence of the signal-to-noise ratio of color Doppler myocardial images on velocity estimators of the Doppler tissue imaging system.

M-mode color Doppler imaging of the myocardium affords a greater sampling rate and signal-to-noise (S/N) ratio than 2-dimensional (2D) imaging. In this study, we compared myocardial velocities assessed by 2D and M-mode Doppler tissue imaging (DTI) at the same site and evaluated the influence of the S/N ratio on velocity estimates of the currently used DTI systems. In patients with and without impaired regional left ventricular function, myocardial velocities assessed by 2D DTI were lower than those obtained with M-mode DTI. The difference between regional velocities derived from both imaging techniques was positively correlated with the extent of the "black zone," which could be considered as indirectly reflecting the S/N ratio for each frame. Thus in the clinical setting and on currently used echocardiographs, 2D DTI may provide underestimated regional myocardial velocities when compared with M-mode, mainly because of the influence of the lower sampling rate and S/N ratio on velocity estimators of the imaging system.

Alteration of left ventricular diastolic function during coronary angioplasty-induced ischemia: a color M-mode Doppler study.

OBJECTIVES: The aim of this study was to assess the effects of ischemia on diastolic function by analyzing flow propagation velocity with color M-mode Doppler echocardigraphy. BACKGROUND: Color M-mode Doppler echocardiography has been proposed as a method of assessing left ventricular filling. METHODS: Color M-mode Doppler echocardiography and measurement of hemodynamic data were performed simultaneously at baseline and during angioplasty-induced ischemia. Tau was compared with flow propagation velocity. Late diastolic indexes, left ventricular pressure and flow cessation time were also investigated. RESULTS: During ischemia, left ventricular relaxation rate (tau) increased, whereas flow propagation velocity decreased, from (mean +/- SD) 46.8 +/- 10 ms to 72.6 +/- 18.3 ms and from 59.8 +/- 15.8 cm/s to 30 +/- 8 cm/s, respectively (all p < 0.0001). The maximal slowing of flow propagation velocity was observed 20 to 30 s after the beginning of the inflation, coexisting with a notch on the ascending limb of the negative rate of rise of the left ventricular pressure (dP/dt) curve. Flow propagation velocity was correlated with tau both at baseline (r = 0.53, p < 0.05) and during inflation (r = 0.53, p < 0.03). Left ventricular end-diastolic pressure increased during ischemia from 13.5 +/- 8 mm Hg at baseline to 27.5 +/- 7 mm Hg, while a premature cessation of the entering flow occurred -13.8 +/- 23 ms before the next Q wave onset, compared with 4.5 +/- 19.6 ms after the Q wave onset at baseline (all p < 0.0001). CONCLUSIONS: The analysis of flow propagation velocity showed that early filling is highly dependent on left ventricular relaxation rate, particularly through the phenomenon of asynchrony. During ischemia, the premature cessation of late filling is associated with increased diastolic pressures.

[French expatriates in the tropics. One hundred years of health history]. / Expatriés français sous les tropiques. Cent ans d'histoire de la santé.

It is difficult to synthesize, for the 20th century, the evolution of mortality among travellers, since they make up a heterogenous and elusive category. Data for soldiers sent abroad are the most easily available and suggest two rates in the decline of mortality: one before and one after the Pasteurian revolution. There is no direct link between demographic curves and optimistic or pessimistic biological theories which have alternatively sought to interpret the phenomenon of being "transplanted" in the tropics. Today, the debate remains open as to the respective roles of genetic, behavioural, and ecological factors in the adaptation of the individual and the group. Although traumatology comes first among risks associated with voyaging, infectious disease still occupies an important place in how travel is perceived, perhaps because it symbolizes coming into contact with "strangers".

[Current aspects of infectious diseases in industrialized countries: development or history?]. / L'actualité des maladies infectieuses dans les pays industrialisés: évolution ou histoire?

Man's conception of nature is a historically dated phenomenon. Thus the recent development of infectious diseases in industrialized countries could either be a real phenomenon or simply an artifact related to our current conception of medical progress and research. Is the return of infectious disease a natural process or has modern civilization been less prudent than its predecessors? What are the characteristic features of modern pathogenesis? Are these "changes" the result of some natural dynamics or an evolution in our means of investigation? Modern civilization has not invented technological deviation or diseases of civilization, phenomena well know in the past, but what is new is the fact that science today, with an ever growing amount of information on molecular epidemiology, is still raising questions about infection, recognized new unsuspected forms of the living world which do not fit into our well-knitted outline of infectious agents. We have applied our simplistic and mechanistic schemas designed for the timespan of human life to the evolutionary processes. The effects of evolution and history are thus combined today in a novel way composing a new future for infectious diseases. This new way of looking at infectious diseases is not totally natural nor totally historical. It is perhaps an epistemological revolution going on within epidemiology. The return of infections disease would appear to have a direct effect on magnifying the knowledge and the delinquency of our culture.