MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

[Contraction-relaxation coupling of skeletal muscle in patients susceptible to malignant hyperthermia]. / Etude du couplage contraction-relaxation du muscle squelettique de patients susceptibles à l'hyperthermie maligne.

OBJECTIVE: To assess whether halothane exposure could influence contraction-relaxation coupling of human skeletal muscle with malignant hyperthermia susceptibility. STUDY DESIGNED: Laboratory investigation. MATERIAL AND METHODS: Muscle biopsies from 14 patients, including six classified as susceptible to MH (MHS) and eight as classified as non-susceptible (MHN) according to criteria of the European MH group. Mechanical parameters of strips were obtained before and after 3 vol% halothane exposure. The contraction and relaxation parameters were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (respectively maxVc and maxVr); peak of the positive (+dP/dtmax) and negative (-dP/dtmax) twitch tension derivative; ratio R1 = maxVc/maxVr and ratio R2 = (+dP/dtmax) (-dp/dtmax). RESULTS: In MHN muscle, halothane markedly increased maxVc and maxVr, so that the ratio R1 was unchanged. Both +dP/dtmax and -dP/dtmax increased such that the ratio R2 did not vary. In MHS muscle, halothane induced a significant decrease in maxVr (p < 0.05) without changes in maxVc, so that the ratio R1 increased significantly. +dP/dtmax remained unchanged whereas -dP/dtmax decreased significantly; the ratio R2 increased (p < 0.05). CONCLUSION: Our results indicated that, in MHN muscle the contractility property is improved with halothane exposure. In MHS muscle, halothane caused an impairment of relaxation. The mechanical abnormalities observed in this study might be related to sarcoplasmic reticulum dysfunction in MH diseases.

Shortening velocity of skeletal muscle from humans with malignant hyperthermia susceptibility: effects of halothane.

The aim of this investigation was to assess the effect of halothane on the velocity of shortening and lengthening of muscle from normal subjects and from patients with malignant hyperthermia susceptibility. Strips were mounted horizontally at optimal length in normal Krebs-Ringer's solution and mechanical parameters were obtained before and after exposure to 3 vol.% halothane. The maximun shortening velocity at zero load (V(max)) was determined by using Hill's characteristic equation. The contraction and relaxation indices were measured under isotonic and isometric conditions: maximum shortening and lengthening velocities (maxV(c) and maxV(r), respectively); isometric peak twitch tension; peak of the positive (+dP/dt(max)) and negative (-dP/dt(max)) twitch tension derivative; ratio R1=maxV(c)/maxV(r) and ratio R2=(+dP/dt(max))/(-dP/dt(max)). In normal muscle, halothane markedly increased V(max), maxV(c) and peak twitch tension by 30+/-10%, 30+/-5% and 40+/-15%, respectively. The maxV(r) values increased concomitantly with the maxV(c) values, such that no change in the ratio R1 was observed. Both +dP/dt(max) and -dP/dt(max) increased such that the ratio R2 did not vary. In malignant hyperthermia susceptibility muscle, halothane induced a significant decrease in V(max) (-30+/-10%) and maxV(r) (-45+/-15%) without changing maxV(c). The decrease in maxV(r) was greater than that of maxV(c), such that the ratio R1 increased significantly. Peak twitch tension and +dP/dt(max) remained unchanged whereas -dP/dt(max) decreased significantly; the ratio R2 increased by 40+/-10%. These results suggest that halothane alters the contractile properties of malignant hyperthermia susceptibility muscle.

[Caffeine skinned fiber tension test: application to the diagnosis of susceptibility to malignant hyperthermia]. / Test à la caféine sur fibres pelées: application au diagnostic de la susceptibilité à l'hyperthermie maligne.

OBJECTIVE: To assess the reactivity of sarcoplasmic reticulum to caffeine, using the skinned muscle fibre tension test and to compare it with the reference in vitro contracture test in the diagnosis of malignant hyperthermia (HM) susceptibility. STUDY DESIGN: Laboratory investigation. MATERIAL: Muscle biopsies from 63 patients, including 29 classified as susceptible to MH (MHS) and 34 classified as non-susceptible (MHN) according to criteria of the European and the North American MH groups. METHOD: The reactivity to caffeine and halothane of skinned muscle fibres was compared, according to the type of fibres, with the data of the in vitro contracture test. The type of fibres (type I: oxidative, slow; type II: glycolytic, fast) were determined with strontium dose-response curves. RESULTS: The reactivity to caffeine was significantly lower in the MHS group, for both type I and type II skinned fibres. However, in comparison with the data of the in vitro contracture tests, using the ROC curve analysis, the best sensitivity-specificity compromise was 90%-71% and 74%-84% for type I and type II skinned fibres respectively. CONCLUSION: The skinned muscle fibre tension test cannot be used instead of the in vitro contracture test for the diagnostic of MHS. However, it may strengthen the data of the latter.

[Anesthesia practice by nurse anesthetists in French speaking Sub-Saharan Africa]. / Pratique de l'anesthésie par les infirmier(e)s en Afrique francophone subsaharienne.

OBJECTIVE: To evaluate the practice of anaesthesia in French-speaking subsaharian countries. TYPE OF STUDY: Prospective survey. PERSONS: Two hundred seventeen nurse anaesthetists, from 11 different countries. METHODS: Anonymous questionnaire. RESULTS: One third of nurses were practising anaesthesia since less than five years and 1/3 since more than 10. Only 39 (18%) were working in the country side. Thirty seven (17%) had been trained outside subsaharian Africa (in Cuba 6%, France 5%, Morocco 5% and Germany 1% respectively). Two hundred thirteen (98%) were performing general anaesthesia and 169 (78%) regional anaesthesia. Hundred sixty eight (97%) used spinal anaesthesia, 57 (33%) epidural, 31 (18%) intravenous regional anaesthesia, 24 (14%) axillary block, 17 (10%) caudal block and 10 (6%) peripheral block respectively. For regional techniques, disposable devices were available in 50% of cases. For general anaesthesia, thiopental was administered by 193 (89%) and ketamine by 156 (72%) nurse anaesthetists respectively. In 50% of cases, these drugs were used alone. An ECG was available in 40%, a pulse oximeter in 14% and a capnographe in less than 2% of cases. A ventilator was present in 66% of the places, but used only in 30% of them because of the lack of maintenance and training. CONCLUSIONS: In this study, 50% of nurse anaesthetists were working alone. However, this rate is probably under-estimated, as the questionnaire did not consider anaesthesia practice in the country side.

[Evolution of the demography of anesthesia practitioners in French speaking Sub-Saharan Africa]. / Evolution de la démographie des praticiens d'anesthésie en Afrique francophone au sud du Sahara.

OBJECTIVE: To assess the course of the demography of anaesthesia providers in French-speaking subsaharian countries. TYPE OF STUDY: Retrospective survey. PERSONS: Doctors trained in anaesthesia and nurse anaesthetists registered in West African medical societies. METHODS: Countries, hospitals, anaesthesia manpower, seniority and place of training were analysed. RESULTS: In the 13 French-speaking subsaharian countries including 97.5-M inhabitants, 122 doctors and 868 nurses were registered as anaesthetists in 1998. Mean ratios were one doctor trained in anaesthesia for 799,180 inhabitants and one nurse anaesthetist for 112,327 inhabitants. From 1980 to 1998, these figures increased by a factor 11 for doctors (+1100%) and by a factor two for nurses (+100%). Most doctors were working in the chief town, in both public and private health care institutions. CONCLUSIONS: In all French-speaking subsaharian countries, a major shortage of doctors trained in anaesthesia is existing.

[Chloroquine poisoning with respiratory distress and fatal outcome]. / Intoxication à la chloroquine avec détresse respiratoire d'évolution fatale.

Chloroquine poisoning can cause life threatening cardiovascular disturbances. We report three cases of suicide with chloroquine causing acute respiratory insufficiency from pulmonary oedema with lethal outcome, despite a treatment with diazepam, epinephrine and mechanical ventilation.

ATX II, a sodium channel toxin, sensitizes skeletal muscle to halothane, caffeine, and ryanodine.

BACKGROUND: The function or expression of subtypes of the sodium ion (Na+) channel is altered in biopsies or cultures of skeletal muscle from many persons who are susceptible to malignant hyperthermia (MH). ATX II, a specific Na+ channel toxin from a sea anemone, causes delayed inactivation of the channel similar to that seen in cell cultures of MH muscle. ATX II was added to skeletal muscle to determine whether altered Na+ channel function could increase the sensitivity of normal skeletal muscle to agents (halothane, caffeine, ryanodine) to which MH muscle is hypersensitive. METHODS: Studies were performed of fiber bundles from the vastus lateralis muscle of persons who were deemed not MH susceptible (MH-) or MH susceptible (MH+) according to the MH diagnostic test and of strips of diaphragm muscle from rats. Preparations in a tissue bath containing Krebs solution were connected to a force transducer. ATX II was introduced 5 min before halothane, caffeine, or ryanodine. RESULTS: ATX II increased the magnitude of contracture to halothane in preparations from most MH-, but not MH+, human participants. After ATX II treatment, preparations from 9 of 24 MH- participants generated contractures to halothane, 3%, that were of the same magnitude as those from MH+ participants. Preparations from four of six ATX II-treated healthy participants also gave responses of the same magnitude as those of MH-susceptible participants to a graded halothane challenge (0.5-3%). The contractures to bolus doses of halothane in specimens from male participants were more than three times larger than the contractures in specimens from female participants. In rat muscle, ATX II increased the magnitude of contracture to caffeine (2 mM) and decreased the time to produce a 1-g contracture to ryanodine (1 microM). CONCLUSIONS: ATX II, which causes delayed inactivation of the Na+ channel in cell cultures similar to that reported in cultures of MH+ skeletal muscle, increased the sensitivity of normal muscle to three agents to which MH+ muscle is hypersensitive. The increased sensitivity to halothane, 3%, occurred in most (79%), but not all, MH- participants, and this effect was most evident in male participants. Therefore, abnormal function of the Na+ channel, even if it is a secondary event in MH, may contribute to a positive contracture test result for MH.

Halothane induces calcium release from human skinned masseter muscle fibers.

BACKGROUND: An increase in masseter muscle tone in response to halothane or succinylcholine anesthesia (or both) can be observed in healthy persons. Thus the authors compared the fiber-type halothane and succinylcholine sensitivities in human masseter and vastus lateralis muscles. METHODS: Masseter and vastus lateralis muscle segments were obtained from 13 and 9 healthy persons, respectively. After chemical skinning of a single fiber and loading the sarcoplasmic reticulum with Ca++ 0.16 microM solution, halothane (0.5-4 vol% bubbled in the incubating solution), succinylcholine (0.1 microM to 10 mM), or both sensitivities were defined as the concentration inducing more than 10% of the maximum tension obtained by application of 16 microM Ca++ solution. The myofilament response to Ca++ was studied with and without halothane by observing the isometric tension of skinned masseter fibers challenged with increasing concentrations of Ca++. Muscle fiber type was determined by the difference in strontium-induced tension measurements. RESULTS: A significant difference in halothane sensitivity was found between type 1 masseter fibers (0.6+/-0.2 vol%; mean +/- SD) versus type 1 (2.7+/-0.6 vol%) and type 2 vastus lateralis muscle (2.5+/-0.4 vol%). Succinylcholine did not induce Ca++ release by the sarcoplasmic reticulum. In the masseter muscle, 0.75 vol% halothane decreased the maximal activated tension by 40% but did not change the Ca++ concentration that yields 50% of the maximal tension. CONCLUSIONS: The very low halothane threshold for Ca++ release from the masseter muscle usually could be counteracted by a direct negative inotropic effect on contractile proteins. However, halothane may increase the sensitivity of the sarcoplasmic reticulum Ca++ release to succinylcholine-induced depolarization, leading to an increase in masseter muscle tone.

Malignant hyperthermia: advances in diagnostics and management.

Real-time monitoring of end-tidal carbon dioxide during anaesthesia aids in the early detection of malignant hyperthermia and the occurrence of a rapid increase in end-tidal carbon dioxide, associated with unexplained persistent tachycardia, well before the core temperature begins to rise. Should malignant hyperthermia occur, however, dantrolene permits the dependable reversal of skeletal muscle hypermetabolism.

-Secondary cerebral stress of systemic origin in children with severe craniocerebral injuries-. / Agressions cérébrales secondaires d'origine systémique chez les enfants traumatisés craniocérébraux graves.

OBJECTIVE: To assess incidence of secondary brain insults of systemic origin (SBISOs) such as arterial hypotension, hypoxaemia, hypercarbia, and anaemia in severely head injured children; to assess their impact on mortality and morbidity in the short- and long-term. STUDY DESIGN: Prospective, open study covering a 24-month period. PATIENTS: Seventy-one children, under 15 years of age, admitted to a trauma centre for severe brain injury. METHOD: Analysis of SBISOs and outcome. RESULTS: Twenty-five children were admitted with SBISOs. The mortality rate was 37%. After hospitalization, 84% of the children with SBISOs vs 46% without SBISOs had severe disability (Glasgow outcome score = 1, 2 and 3). After 1 year, 20 out of the 45 children still alive were contacted. One of the four with SBISOs communicated a bad recovery. Fifteen children without SBISOs presented good recovery: GOS = 4-5, paediatric overall performance category (POPC scale) = 1-2. CONCLUSION: Hypotension was associated with significant increase in mortality (x 3.6) in children with severe head injury. The consequences were worse when anaemia was associated.

[Brachial plexus anesthesia via an axillary route for emergency surgery: comparison of three approach methods]. / Anesthésie du plexus brachial par voie axillaire pour chirurgie urgente: comparaison de trois méthodes d'approche.

OBJECTIVES: To compare three techniques of brachial plexus blockade for emergency surgery of the upper limb. STUDY DESIGN: Prospective, randomised study. PATIENTS: One hundred eleven patients admitted to an emergency surgical service, randomly assigned to three groups. METHODS: The patients were given 2% lidocaine with epinephrine 20 mL and 0.5% bupivacaine 20 mL. The three groups were as follows: brachial plexus block using a peripheral nerve stimulator (group St, n = 38); transarterial brachial plexus blockade with injection of 2/3 of the anaesthetic in back of and 1/3 in front of the artery (group TAP, n = 36); transarterial brachial plexus blockade with one single injection in back of the artery (group TP, n = 37). The success rate, time required to perform the technique, latency of analgesia, quality of motor blockade, and adverse effects were compared between the three groups. Analysis of variance was used to compare quantitative data and chi 2 test were used for qualitative data. RESULTS: Rates of success varied between 65 and 75%. Success rates, latency of analgesia and quality of motor blockade were not significantly different between groups. Time to perform the technique was longer when using a nerve stimulator. CONCLUSION: As these three techniques for brachial plexus block in emergency surgery are comparable, no one can be recommended instead of the others.

Myofilament calcium sensitivity is decreased in skinned cardiac fibres of endotoxin-treated rabbits.

OBJECTIVE: The aim was to determine whether myofilament Ca2+ sensitivity is altered in skinned cardiac fibres from endotoxin-treated rabbits. METHODS: Endotoxin was injected i.v. in conscious New-Zealand White rabbits at a dose of 0.5 mg/kg (groups I, II, and III) or 1 mg/kg (group IV). A fifth group was used as control. Hearts were excised 4 h (groups I and IV), 24 h (group II), or 5 days (Group III) after injection. Skinned fibres were obtained with chemical (EGTA + Brij 58) treatment of bundles isolated from papillary muscles. RESULTS: The maximal Ca(2+)-activated force (F0) of skinned cardiac fibres was not different between groups. However, [Ca2+] required to evoke 50% of F0 (Ca50) was higher in the fibres from group I than in controls (1.78 +/- 0.05 vs. 1.53 +/- 0.03 microM; P < 0.05). This effect was dose-dependent (group IV: Ca50 = 2.08 +/- 0.12 microM; P < 0.05 vs. group I), larger after 24 h (group II: Ca50 = 2.12 +/- 0.05 microM; P < 0.05 vs. group I). By 5 days, myofilament Ca2+ sensitivity had returned to normal (group III: Ca50 = 1.54 +/- 0.05 microM). CONCLUSION: Myofilament Ca2+ sensitivity is decreased in skinned fibres taken from rabbit myocardium after i.v. endotoxin injection. This effect is dose- and time-dependent, and reversible with time.