[Fast track surgery. Stake in health service, stake for the patients, stake for PMR?].
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Biomedical subjects
Publications and source records attributed to P Leprince.
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Over the years, mechanical circulatoryassistance has progressively improved with the evolution of the clinical indications and the introduction of new devices. The management of situations of extreme emergency, cardiac arrest, acute myocardial infarction with cardiogenic shock, drug overdose, acute myocarditis, postoperative cardiac failure and post-transplantation right ventricular failure, may be undertaken with relatively simple systems such as the ECMO, in the catheter laboratory or at the bedside in the intensive care unit. These systems enable stabilisation of the circulatory problems in order to pass a difficult situation and then withdraw the assistance when myocardial function has been restored. When this is not possible and there is no contra-indication to cardiac transplantation, patients may benefit from more complex assistance devices as a bridge to transplantation. Many continuous flow pumps have been introduced recently. These small mono, left ventricular, assist devices provide improved patient comfort and suggest wider indications of long duration assist devices.
Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.
Post-myocardial infarction cardiogenic shock still carries a very poor prognosis despite the rapid recourse to effective methods of myocardial revascularisation. Circulatory assistance devices allow restoration of adequate haemodynamics with limitation of myocardial work. In the most severe cases, implantation of intra-thoracic devices is associated with a 70% survival rate in the latest series, providing they are used early. However, in many cases, the essential problem is to stabilise the patient's haemodynamic status, sometimes even before myocardial revascularisation. In these situations, implantation of a peripheral femoro-femoral extra corporeal circulation (ECMO: extra corporeal membrane oxygenation) re-establishes an appropriate cardiac output andprovides time to transfer the patient, to perform coronary revascularisation or to assess neurological status, before deciding on the indications for more complicated assist systems. This "bridge to bridge" concept avoids the risk of implanting complicated assist devices in cerebrally dead patients or in those with multi-organ failure beyond treatment. Conversely, it gives some patients with apparent contraindications to complicated assist systems or who are unable to benefit from these systems for geographical reasons, a chance to survive. In early cardiogenic shock, the ECMO which has a low rate of complications, could safely promote myocardial recovery.
OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. METHODS: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. RESULTS: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg). CONCLUSIONS: The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp.
Thiamine triphosphate (ThTP) is found in small amounts in most organisms from bacteria to mammals, but little is known about its physiological role. In vertebrate tissues, ThTP may act as a phosphate donor for the phosphorylation of certain proteins; this may be part of a new signal transduction pathway. We have recently characterized a highly specific 25-kDa thiamine triphosphatase (ThTPase) that is expressed in most mammalian tissues. The role of this enzyme may be the control of intracellular concentrations of ThTP. As the latter has been considered to be a neuroactive form of thiamine, we have studied the distribution of ThTPase mRNA and protein in rodent brain using in situ hybridization and immunohistochemistry. With both methods, we found the strongest staining in hippocampal pyramidal neurons, as well as cerebellar granule cells and Purkinje cells. Some interneurons were also labeled and many ThTPase mRNA-positive and immunoreactive cells were distributed throughout cerebral cortical gray matter and the thalamus. White matter was not significantly labeled. ThTPase immunoreactivity seems to be located mainly in the cytoplasm of neuronal perikarya. Immunocytochemical data using dissociated cultured cells from hippocampal and cerebellum showed that the staining was more intense in neurons than in astrocytes. The protein was rather uniformly located in the perikarya and dendrites, suggesting that ThTP and ThTPase may play a general role in neuronal metabolism rather than a specific role in excitability. There was no apparent correlation between ThTPase expression and selective vulnerability of certain brain regions to thiamine deficiency.
Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte and adipocyte, but can also differentiate into non-mesenchymal cells, i.e. neural cells under appropriate in vivo experimental conditions (Kopen et al., 1999; Brazelton et al., 2000; Mezey et al., 2000). This neural phenotypic plasticity allows us to consider the utilization of mesenchymal stem cells as cellular material in regenerative medicine. In this study, we demonstrate that cultured adult rat stromal cells can express nestin, an intermediate filament protein predominantly expressed by neural stem cells. Two factors contribute to the regulation of nestin expression by rat stromal cells: serum in the culture medium inhibits nestin expression and a threshold number of passages must be reached below which nestin expression does not occur. Only nestin-positive rat stromal cells are able to form spheres when they are placed in the culture conditions used for neural stem cells. Likewise, only nestin-positive stromal cells are able to differentiate into GFAP (glial fibrillary acidic protein)-positive cells when they are co-cultivated with neural stem cells. We thus demonstrated that adult rat stromal cells in culture express nestin in absence of serum after passaging the cells at least ten times, and we suggest that nestin expression by these cells might be a prerequisite for the acquisition of the capacity to progress towards the neural lineage.
BACKGROUND: At our institution, the total artificial heart (TAH) Jarvik-7 (CardioWest) has been used since 1986 as a bridge to transplantation for the most severely ill patients with terminal congestive heart failure. METHODS: Between 1986 and 2001, 127 patients (108 males, mean age 38 +/- 13) were bridged to transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure despite high-dose inotropic support. Nine patients had a body surface area (BSA) of <1.6 m(2). In Group I patients (78%), the etiology of cardiac failure was dilated cardiomyopathy, either idiopathic (n = 60) or ischemic (n = 38). The other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our experience with regard to 3 time periods: 1986 to 1992 (n = 63); 1993 to 1997 (n = 36); and 1998 to 2001 (n = 33). RESULTS: Although Group II patients represented 30% of indications before 1992, they comprised only 15% during the 2 subsequent periods. Duration of support for transplant patients increased dramatically after 1997, reaching 2 months for the most recent period (5 to 271 days). In Group I, the percentage of transplanted patients increased from 43% before 1993 to 55% between 1993 and 1997, and reached 74% thereafter. The major cause of death was multiorgan failure (67%). The clinical thromboembolic event rate was particularly low with no instance of cerebrovascular accident and 2 transient ischemic attacks. Total bleeding complication rate was 26%, including 2 deaths related to intractable hemorrhage and 2 others related to atrial tamponade. The cumulative experience was 3,606 total implant days with only 1 instance of mechanical dysfunction. CONCLUSIONS: TAH is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation.
OBJECTIVE: Study of the medium term results of aortic and mitral valve replacement with the Bicarbon' prosthesis. METHOD: From 1990 to 1996, 109 valves were implanted (70 in aortic position, 31 in mitral position and 4 double replacements). The average age was 61 years and 75% were male. According to the NYHA, 59% of patients were stage III or IV. The average pre-operative ejection fraction was 59.6%. There was re-intervention in 21.1% of patients and 35.3% had an associated procedure during the intervention. RESULTS: The average follow up was 5.4 +/- 1.98 years in 98 patients (that is 522 patient years). One patient died post-operatively and 19 died later. The overall survival at 7 years was 69.4 +/- 6.3%. Complications, expressed in patient years, were 1.15% for thrombo-embolic complications, 2.1% for haemorrhagic complications. 0.38% for endocarditis, 1.72% for non-infectious peri-prosthetic leaks, and 0.76% for re-interventions. At 7 years, the absence of thrombo-embolic, haemorrhagic, endocarditis, and re-intervention complications was 91.8 +/- 4.2%, 85.3 +/- 4.8%, 95.8 +/- 3.2%, 93.8 +/- 3.5% respectively. According to the NYHA, 95% of patients were in stage 1 or II (p < 0.001). CONCLUSION: Valvular replacement in the aortic or mitral position with the Bicarbon' valve is satisfactory as much in terms of survival as of clinical complications.
The fully implantable complete electric artificial heart "AbioCor" is the ultimate stage in the 3rd generation assistance systems. It has been authorized for clinical use since last year by the Food and Drug Administration (F.D.A.). It is an electrohydraulic heart developed by Abiomed. It consists of implanted internal components: the cardiac pump, an internal lithium battery, a controller and an internal coil allowing electrical energy transfer across the skin, and external components: an external coil and external batteries. The one-piece heart includes two ventricular chambers: right and left. All of the surfaces in contact with blood as well as the four three-leaved valves are made of polyurethane. An electro-hydraulic energy converter powers the ventricles. A stroke volume of 60 to 65 ml allows an output of between 4 and 10 L.min-1. Between 2 July 2002 and 4 November 2002, seven males, aged between 51 and 70 years, underwent implantation. They were suffering from ischaemic cardiopathy (6 cases) or idiopathic dilated cardiopathy (1 case). Among the late complications, 3 severe embolic cerebrovascular accidents occurred. Four late deaths occurred.
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A 28-year-old male patient diagnosed with Becker muscular dystrophy (BMD)-associated cardiomyopathy was successfully bridged to transplantation with the Cardiowest total artificial heart. Dramatic improvement of muscular functional status occurred following transplantation.
1. In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra) may involve modulation of inhibitory neurotransmission. 2. GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3. LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4. These minor direct effects contrasted with a potent ability of LEV (EC(50)=1 - 10 microM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5. Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6. LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7. The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV.
The clinical expression of acute myocarditis is variable from paucisymptomatic to fulminating forms which are usually lethal within days. The latter presentation takes the form of very acute cardiac failure. During this phase, the severity of myocardial dysfunction may be such that death ensues. However, if the patient survives, paradoxically, these forms have a better long-term prognosis with complete recovery of myocardial function being possible after the acute phase. The authors report a typical case of fulminating myocarditis with electromechanical dissociation, which recovered completely after a period of circulatory assistance. This case illustrates the rapidity of deterioration of the haemodynamic status and the importance of organ dysfunction despite early management. In a review of the literature, the authors found about 150 reported cases of acute myocarditis treated with circulatory assistance. In the best series, about half the patients were weaned off the circulatory assistance without having to undergo cardiac transplantation. However, the potential recovery of myocardial function is difficult to predict.
Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.
During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages whose proliferation, survival and cell-fate choice are controlled by environmental and cellular regulatory molecules. Neurotransmitters belong to the chemical microenvironment of neural cells, even at the earliest stages of brain development. It is now established that specific neurotransmitter receptors are present on progenitor cells of the developing central nervous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotransmitters and their corresponding ligand-gated ion channel receptors in immature cells, including neural stem cells of specific embryonic and neonatal brain regions. We summarize in vitro and in vivo data arguing that neurotransmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and survival of neural precursor cells. The understanding of neurotransmitter function during early neural maturation could lead to the development of pharmacological tools aimed at improving adult brain repair strategies.
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