Problems in the “Evidence” of “Evidence-Based Medicine”

The proposed practice of “evidence-based medicine,” which calls for careful clinical judgment in evaluating the “best available evidence,” should be differentiated from the special collection of data regarded as suitable evidence. Although the proposed practice does not seem new, the new collection of “best available” information has major constraints for the care of individual patients.Derived almost exclusively from randomized trials and meta-analyses, the data do not include many types of treatments or patients seen in clinical practice; and the results show comparative efficacy of treatment for an “average” randomized patient, not for pertinent subgroups formed by such cogent clinical features as severity of symptoms, illness, co-morbidity, and other clinical nuances. The intention-to-treat analyses do not reflect important post-randomization events leading to altered treatment; and the results seldom provide suitable background data when therapy is given prophylactically rather than remedially, or when therapeutic advantages are equivocal. Randomized trial information is also seldom available for issues in etiology, diagnosis, and prognosis, and for clinical decisions that depend on pathophysiologic changes, psychosocial factors and support, personal preferences of patients, and strategies for giving comfort and reassurance.The laudable goal of making clinical decisions based on evidence can be impaired by the restricted quality and scope of what is collected as “best available evidence.” The authoritative aura given to the collection, however, may lead to major abuses that produce inappropriate guidelines or doctrinaire dogmas for clinical practice.     

Use of Contemporary Imaging Techniques for Electrophysiological and Device Implantation Procedures

Recent technological advances in cardiac imaging allow the visualization of anatomic details up to millimeter size in 3-dimensional format. Thus, it is not surprising that electrophysiologists increasingly rely upon cardiac imaging for the diagnosis, treatment, and subsequent management of patients affected by various arrhythmic disorders. Cardiac imaging methods reviewed in the present work involve: 1) the prediction of arrhythmic risk for sudden cardiac death in patients with heart disease; 2) catheter ablation of atrial fibrillation or ventricular tachycardia; and 3) cardiac resynchronization therapy. Future integration of diagnostic and interventional cardiac imaging will further increase the effectiveness of cardiac electrophysiological procedures and will help in delivering patient-specific therapies with ablation and cardiac implantable electronic devices.     

L'asthme est-il déjà « en marche » avant l'atopie ?

Asthma is often considered a step in the natural history of atopy, occurring between atopic dermatitis and allergic rhinitis. However, several lines of reasoning suggest that the development of asthma is an independent phenomenon. The importance of events occurring during the prenatal period is probably underestimated. Atopy probably occurs afterward, the onset of allergic sensitizations consequently exacerbating the asthma. Nevertheless, once developed, the two entities interact in a complex manner, since they probably share common immunologic regulatory mechanisms.     

Artériopathie et hétérogénéité artérielle

More and more clinical observations and trials support the concept of heterogeneity of atheroma according to the arterial bed. In a pilot study named “Étude Comparative des Lésions Athéromateuses” (ECLA), we have shown that carotid and femoral plaques possess different characteristics. Carotid arteries display increased lipid content compared to femoral arteries whereas femoral arteries are more prone to calcify and to develop osteoid metaplasia. These observations should lead the researcher and the clinician to look at the cellular and molecular mechanisms governing the heterogeneity of atheromas. At last, a better understanding of the characteristics of plaques should help us to determine plaque stability, to prevent cardiovascular events and to choose the best medical, endovascular or surgical option.     

Allergie aux protéines du lait et aux hydrolysats de protéines de lait : à propos d'une observation au diagnostic retardé

The authors report the case of an infant with a history of eczema due to cow milk and who later had two bouts of urticaria after drinking milk protein hydrolysate. The particular interest in this case is the disconnection between the onset of the eczema (when an allergy workup was not predictive) and the subsequent finding, one year later, of positive IgE-dependant sensitization tests.     

Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

ObjectivesThis study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.BackgroundCoronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.MethodsWe prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (T_mn) (an inverse correlate to absolute flow) at rest and hyperemia.ResultsAll patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting T_mn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic T_mn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting T_mn.ConclusionsDespite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.     

Allergies croisées : de la théorie à la pratique

The notion of allergic cross-reactions must from now on be regarded by allergists as an indispensable element of the diagnostic and therapeutic approach. Indeed, knowledge of proteins and of mechanisms involved in this type of phenomenon is of interest to physicians not only in with regard to pathophysiology but also as an aid in interpretation of certain clinical history data and the results of skin or biological tests. Moreover, it makes the management of patients more rational, and probably in therapy of the future when recombinant allergens will be more widely used.     

Sensibilisation parentérale du lapin aux protéines du lait de vache : effets sur la perméabilité intestinale

Objectives

Study of the cow's milk protein intolerance mechanisms in order to knowledge, in which could proportions spread the permeability of intestinal to the β-lactoglobulin and α-lactalbumin at the rabbits sensitized to these two proteins.

Methods

The rabbits were sensitized to these proteins by subcutaneous way and their degree of immunization established by Elisa dosage of the specific IgG. For the study of the transepithelial exchanges, the interaction of the proteins (marked to the ¹⁴C-formol), with the mucous intestinal of sensitized and some control rabbits were follow-up in vitro on fragments of ileums mounted in Ussing chamber. Their transepithelial fluxes were measured, after stimulation by the proteins deposed in the mucous compartment from a sampling made from serosa side.

Results

The animals sensitized present some titers in IgG anti β-lactoglobulin and anti α-lactalbumin, as well as some transepithelial fluxes, significantly more increased than control animals.

Conclusion

These results suggests that at the immunized animals, the interaction of the sensitizing protein with intestinal mucous caused some anomalies of hydroelectrolytic transport.     

Mise au point d'un dosage automatisé des IgE spécifiques des allergènes des pollens de cyprès et de genévrier par VIDAS Stallergy

Study objective

Cypress pollen is a significant cause of allergies in the Mediterranean area. In order to improve the in vitro diagnosis to cypress sensitization, we used a Juniperus ashei extract to develop a new semi-quantitative test for the measurement of IgE specific to juniper and cypress pollen allergens based on the VIDAS automated system.

Methods

The VIDAS Stallergy^® assay combines a two-step enzyme immunoassay sandwich method with a final fluorescence detection. The reagent comprises the Solid Phase Receptacle (SPR) coated with a J. ashei extract, which serves as a solid phase as well as a pipetting device during the assay and a strip that contains all the ready-to-use reagents.

Results

The precision study shows coefficients of variation lower than 1.7% for intra-assay variability and between 1.6 and 9.5 for inter assays variability. Correlation with the CAP system^® method shows an 80.7% agreement to the nearest class (N = 57). For 65% of sera class results are similar with the two techniques, and for 33% of sera, class results are higher with the VIDAS method. Test specificity is confirmed by VIDAS inhibition experiments. A sensitivity study performed using 82 clinically recognized cypress allergic patients shows that 97.6% of the patients are detected with the VIDAS Stallergy^® Juniper reagent.

Conclusion

The Juniper Stallergy^® test allows to measure specific IgEs to cypress pollen, with a sensitivity of detection at least similar to the CAP system^® method.     

L'allergie au tournesol et à son huile : rôles du contact,de l'ingestion et de l'inhalation

We report the case of a 5-years old girl with food allergy to sunflower oil. Sensitivity to sunflower oil and seeds was demonstrated by skin tests whereas assays of serum for sunflower-specific IgE were negative. An oral challenge test with 54 ml of sunflower oil was positive. The patient also reacted to cutaneous contact and inhalation of sunflower seeds. Depending on the route of contact –– skin contact, ingestion or inhalation –– sunflower oil and seeds can trigger symptoms such as urticaria, erythema, vomiting, dyspnea or fatigue.     

Pustulose exanthématique aiguë généralisée liée à l’hydroxychloroquine : à propos d’une observation

We report a 45-year-old woman who presented an acute generalized exanthematic pustulosis induced by hydroxychloroquine. Acute generalized exanthematic pustulosis is a severe eruption that is usually drug related. This side effect should be known as new therapeutic challenge would induce more severe clinical features.     

Tolérance ou réactivité aux allergènes

The default response to allergens is peripheral tolerance, often partial, mainly through immune deviation or suppression by adaptive regulatory T cells. Functional plasticity of dendritic cells and T cells on contact with antigens plus the modulating effects of infection may lead to a failure to acquire or a rupture of immunological tolerance to allergens in genetically predisposed individuals. Specific immunotherapy can restore tolerance by switching allergen-specific responses to less polarized lymphocytes and/or by activating regulatory T cells and IL-10 production.