Transfusion massive et dysfonction hémostatique : physiopathologie et gestion clinique

Purpose. – To identify the causes of coagulopathy in massively transfused adults and previously hemostatically competent patients, and to recommend the most appropriate treatment strategies.Principal findings. – In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. Critically low levels of coagulation factors were seldom reported when whole blood was in common use. With the use of packed red cells, dilution or consumption of coagulation factors is a significant issue requiring specific treatment with primarily, fresh frozen plasma. Maintaining a normal body temperature is a simple and effective strategy to improve hemostasis during massive transfusion. Red cells play an important role and hematocrits as high as 35% may be required to sustain hemostasis. The use of platelets and/or fresh frozen plasma should depend on clinical judgment and results of coagulation testing and should be used mainly to treat a clinical coagulopathy.Conclusions. – Coagulopathy associated with massive transfusion remains an important problem. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding.     

Dysfonction myocardique et sepsis : physiopathologie et perspectives thérapeutiques

In the 40% of patients with sepsis who develop cardiovascular disturbances, mortality increases from 20 to 70–80%. These rates have changed little in recent years despite significant advances in the field of antimicrobial and intensive care therapies. Peripheral circulatory abnormalities usually observed in septic shock lead to difficulties in the demonstration of autonomous cardiac involvement, i.e., independent of loading conditions. Although exact mechanisms leading to myocardial dysfunction in sepsis are multiple and may involve several inflammatory mediators, the reality of this septic myocardial dysfunction is now firmly established on the basis of animal and clinical studies. Nitric oxide seems to play a pivotal role at the cellular level, being implicated in the transmission of different cytosolic signals leading to impaired contractile abnormalities. A better knowledge of the pathophysiology of this syndrome will improve the treatment modalities of septic cardiac dysfunction.     

Intoxication aiguë par les glycols et alcools toxiques : diagnostic et traitement

Acute poisonings with glycols (of which ethylene glycol) and toxic alcohols (of which methanol) are relatively rare but potentially serious. They are responsible for metabolic acidosis, with an elevation of anion gap due to the metabolites produced by alcohol dehydrogenase (ADH). Ethylene glycol may induce acute renal failure, hypocalcemia, central nervous system depression, seizures and cardiopulmonary dysfunction, in relation with tissue precipitation of calcium oxalate crystals. Methanol may trigger severe ocular impairment with irreversible blindness. Inhibition of the enzymatic degradation of alcohols and glycols render them non-toxic by preventing the accumulation of toxic metabolites. 4-methylpyrazole or fomepizole is a potent harmless competitive inhibitor of ADH. It is now strongly recommended in ethylene glycol poisoning, with a recent clear demonstration of its efficacy and safety. Moreover, a limited number of observations seems to suggest a rationale for its use in poisoning by the other toxic alcohols, especially methanol. However, the need for hemodialysis is still being discussed. The objective of management should be to provide rapid and practical methods for laboratory diagnosis and administer quickly the efficient antidote that would dramatically affect the consequences of these poisonings.     

Douleurs neuropathiques et inflammatoires: modèles animaux et rôles fonctionnels des neuropeptides

Résumé  Les douleurs chroniques, d’origine inflammatoire ou neuropathique, s’accompagnent de modifications cellulaires responsables d’une sensibilisation persistante et handicapante. L’étude de ces phénomènes de plasticité nécessite de disposer de modèles animaux fiables. De nombreux modèles existent qui ne font chacun que reproduire certains des sympt?mes douloureux. Leur choix dépend donc des pathologies étudiées. L’apparition de modèles génétiquement modifiés avait fait na?tre de grands espoirs mais les phénotypes apparents de ces animaux se révèlent souvent contradictoires, et difficiles à interpréter. Une composante importante de la plasticité associée à la sensibilisation douloureuse concerne le contenu neurochimique des cellules localisées dans les ganglions rachidiens ou la corne dorsale de la moelle épinière. Cette plasticité neurochimique est illustrée par les variations d’expression de deux neuropeptides, la galanine et la cholécystokinine, ainsi que de leurs récepteurs. Au niveau du premier relais sensoriel, la galanine exercerait un effet essentiellement antinociceptif, à fortes doses, en conditions neuropathiques via son récepteur R1. A l’inverse, la cholécystokinine jouerait un r?le pronociceptif dans les neurones spinaux en s’opposant à l’action des opiacés endogènes via le récepteur CCK2. La connaissance des mécanismes d’action des messagers est nécessaire à l’élaboration de traitements thérapeutiques innovants. Parmi les messagers chimiques impliqués dans la transmission douloureuse, les neuropeptides représentent une cible thérapeutique de choix en raison de leur caractère modulateur et de leur forte plasticité d’expression. Néanmoins, le développement d’analgésiques dérivés d’agonistes ou d’antagonistes de ces peptides nécessite encore de parfaire la connaissance de leurs mécanismes d’action et de leurs interactions et ces progrès requièrent l’utilisation de modèles animaux pertinents.

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Summary  Chronic pain is associated with plastic changes responsible from a persitent sensitization in the spinal cords. The studies of these changes have benefit substantially from the development of experimental animal models. If genetically modified animals have carried a lot of new perspective and hopes, their practical use is difficult due to the important phenotypic variability seen amongst them. However, an important aspect of central sensitization is linked with the changes of expression of neuropeptide such as galanin and cholecystokinin and their receptors. In the dorsal horn, galanin has analgesic effects trough its receptor R1. Conversly, cholecystokinin induces pain via an inhibition of endogenous opio?ds through the CCK2 receptor. Future prospect in analgesic drugs requires a good knowledge about the biochemical cascades involved in the transmission of pain. Amongst these, neuropeptides are good candidate targets because they have a strong analgesic potential, and their expression is highly modulated in persistent pain syndromes. The development of this line of research is still pending on the use of appropriate animal models as well as a better knowledge about their mechanisms.

     

Fibromyalgie et lombalgie chronique: ??tude des facteurs invalidants et facteurs facilitateurs ?? la r??insertion et au maintien professionnel

The aim of this research is to explore the invalidating and facilitating factors related to return to work and/or to maintain work perceived by two groups of patients with chronic diseases: fibromyalgia or chronic back pain. Indeed, the current studies generally examined either return to work or maintaining work; their approach is rarely supported by an integrated view. Our study revealed similarities and differences between the two perspectives but also between the two groups of patients. This will help with the development of future initiatives for returning chronic pain patients to employment.     

CIVD et défaillance d’organes : arguments expérimentaux et cliniques

Disseminated intravascular coagulation (DIC) is thought to contribute to multiple organ failure in a variety of underlying conditions for several reasons. First, clinical studies have found that, in patients with severe sepsis or septic shock, those with DIC exhibited more acquired organ failures than those without DIC, and their mortality rate was higher. Second, experimental studies of DIC associated with sepsis or low-grade activation of coagulation have repeatedly indicated that effective inhibition of DIC can indeed reduce organ failures and mortality. The mechanisms by which this role could be effectuated, however, are not clearly understood. The repeatedly demonstrated microvascular fibrin deposition in tissues of patients who have died from an illness with evidence of DIC may deprive downstream cells of oxygen, and cellular hypoxia could be a mechanism by which cells are damaged. In contrast, many investigators currently believe that it is not fibrin formation itself that is harmful, but rather is the generation of serine proteases and their interactions with pro-inflammatory mediators that contributes to organ failure and death. With the emergence of powerful anticoagulant strategies, aspects involving ischemia-reperfusion damage and organ recovery become important to investigate.     

Stress et douleurs viscérales: une revue

Aim

To review the various psychological theories of stress, to better understand how this takes place in the question of visceral pain, in particular, abdominal pain.

Procedure

Systematic review of significant articles on stress and visceral pain, in both the child and the adult.

Results

A great influence of the events suppliers of stress in the visceral pain is demonstrated. However, the link of causality cannot be demonstrated.

Conclusion

The clinical approach of visceral pain is complex. Therefore, it is open toward complementary therapeutic ways, which seem to bring satisfaction in many situations.     

Genre et douleur: rôle du cycle menstruel

Résumé  Depuis quelques années, l’influence du genre sur la perception douloureuse a suscité de nombreuses recherches épidémiologiques, cliniques et expérimentales. On admet actuellement l’existence d’un effet genre, probablement somme de facteurs physiologiques, psychologiques, socio-culturels et individuels. Parmi ces facteurs, le cycle menstruel et les variations hormonales qu’il entra?ne semblent avoir leur importance. Une méta-analyse portant sur les 16 études expérimentales s’attachant à étudier l’influence du cycle menstruel sur les seuils d’apparition et de tolérance à la douleur en réponse à divers stimuli nociceptifs montre que les seuils sont systématiquement plus élevés en phase folliculaire qu’en phase lutéale pour les stimuli thermiques, mécaniques, ischémiques. On obtient par contre le résultat inverse pour les stimuli électriques. Il est cependant à relever des diversités de méthodologie entre différentes études, rendant leur comparaison délicate. Il conviendrait ainsi de confirmer ces résultats dans une étude testant chez les mêmes femmes, pendant un cycle entier, les divers stimuli.      

Adamantiadi-Behçet syndrome: treatment with recombinant leukocytic interferon

AIM: To evaluate efficacy of synthetic leukocytic interferon (SLI) in patients with severe Adamantiadi-Beh?et syndrome (ABS). MATERIALS AND METHODS: The trial enrolled 18 patients (11 men and 7 women aged 25 to 43 years) with severe ABS. The duration of the disease ranged from 1 to 12 years. Subcutaneous ABS injections in a dose 5 x 10(6) U/m2 for 8 weeks followed by 3 x 10(6) for 16 weeks. The results were estimated by standard clinical and biochemical indices. RESULTS: All 18 patients responded to the treatment. After the course of treatment 13 patients were in remission for 4-52 months. The rest of the patients were given one more course of treatment.     

Gastronomie et diététique : les agrumes

Citrus fruits are widely accessible and consumed, and are great sources of micronutrients particularly of vitamin C, although their energy content is low. They are quite convenient and easy to taste and eat without any addition, at anytime of the day. But their flavours permit them to be useful in sweetened or salted recipes.     

Hémofiltration et choc septique : impact hémodynamique

Hemofiltration is a very popular renal replacement modality related to a supposed improved hemodynamic tolerance. If some animal studies found positive haemodynamic effects including myocardial performance improvement, human studies especially in the setting of acute renal failure or severe sepsis failed to demonstrate any convincing conclusion. Moreover, the analysis of inflammatory biomarkers of sepsis (cytokines, complement...) did not allow to better understand the supposed mechanism of haemodynamic improvement due to this renal replacement therapy. It seems that more efficient modalities of middle molecules removal, such as high volume hemofiltration may induce a greater clinical effect. These preliminary studies are hopeful in the era of blood purification in sepsis, even if mechanisms are still poorly understood.     

Le purpura thrombotique thrombocytopénique : physiopathologie et traitement

Introduction: Thrombotic thrombocytopenic purpura is a rare disorder characterized by widespread platelet thrombotic injuries in the microcirculation. The clinical features are microangiopathic hemolytic anemia and thrombocytopenia. This diagnosis is of considerable importance because of the possibly of fulminant clinical course. Some atypical forms may be unrecognizedCurrent knowledge and key points: The pathogenesis has been elucidated recently, by identification of deficiency of von Willebrand factor cleaving protease either due to IgG antibodies in acute thrombotic thrombocytopenic purpura or constitutional deficiency in the familial form.Future prospects: The current established treatment of thrombotic thrombocytopenic purpura is plasma exchange. However, in the light of recent publications, the treatment could be better rationalized either with infusions of concentrates of purified enzyme or more intensive immunosuppressive therapy.