Classical neurotransmitters and neuropeptides involved in generalized epilepsy: a focus on antiepileptic drugs.

We describe the alterations of classical neurotransmitters and neuropeptides in generalized epilepsy. A neuronal network in this disease is developed. Gamma aminobutyric acid (GABA) hypoactivity induces dopamine hyperactivity because dopaminergic neurons are affected by the inhibitory influence of the GABAergic system through GABA(A) receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate (NMDA) receptors, which strongly inhibit serotoninergic neurons, and via postsynaptic ionotropic glutaminergic receptors, which can induce epileptic seizures. A collection of specific subreceptors of classical neurotransmitters and neuropeptides involved in epileptogenesis is reported. The question arises whether agonists/antagonists of neuropeptides (neuropeptide Y, galanin…) could have additional antiepileptic properties. The effect of conventional and newer antiepileptic drugs interfering with these subreceptors is discussed on the basis of the neuronal network suggested. From these data, it is concluded that new antiepileptic drugs interfering with other specific subreceptors (GABA(B) antagonists, metabotropic glutaminergic receptors subtype 5 (mGlu5R) antagonists, mGlu2/3R agonists, 5-serotonin (5-HT(7)) agonists) could further stabilize the neuronal network in generalized epilepsy.

Mortality associated with anaesthesia: a qualitative analysis to identify risk factors.

From a prospectively defined cohort of patients who underwent either general, regional or combined anaesthesia from 1 January 1995 to 1 January 1997 (n = 869 483), all consecutive patients (n = 811) who died within 24 h or remained unintentionally comatose 24 h after anaesthesia were classified to determine a relationship with anaesthesia. These deaths (n = 119; 15%) were further analysed to identify contributing aspects of the anaesthetic management, other factors and the appropriateness of care. The incidence of 24-h peri-operative death per 10 000 anaesthetics was 8.8 (95% CI 8.2-9.5), of peri-operative coma was 0.5 (0.3-0.6) and of anaesthesia-related death 1.4 (1.1-1.6). Of the 119 anaesthesia-related deaths, 62 (52%) were associated with cardiovascular management, 57 (48%) with other anaesthetic management, 12 (10%) with ventilatory management and 12 (10%) with patient monitoring. Inadequate preparation of the patient contributed to 30 (25%) of the anaesthesia-related deaths. During induction of anaesthesia, choice of anaesthetic technique (n = 18 (15%)) and performance of the anaesthesiologist (n = 8 (7%)) were most commonly associated with death. During maintenance, the most common factors were cardiovascular management (n = 43 (36%)), ventilatory management (n = 12 (10%)) and patient monitoring (n = 12 (10%)). In both the recovery and the postoperative phases, patient monitoring was the most common factor (n = 12 (10%) for both). For cardiovascular, ventilatory and other anaesthetic management, human failure contributed to 89 (75%) deaths and organisational factors to 12 (10%). For inadequate patient monitoring, human factors contributed to 71 (60%) deaths and organisational factors to 48 (40%). Other contributing factors were inadequate communication (30 deaths (25%) for all four aspects of the anaesthetic management) and lack of supervision (particularly for ventilatory management). Inadequate care was delivered in 19 (16%) of the anaesthesia-related deaths with respect to cardiovascular management, in 20 (17%) with respect to ventilatory management, in 18 (15%) with respect to patient monitoring and in 23 (19%) with respect to other anaesthetic management.

The CO single breath transfer factor of the lung. A reliable clinical parameter in valvular heart disease.

The CO single breath transfer factor of the lung expressed per unit of alveolar gas volume during breath-holding, Tv, and its component factors Dmv and Vcv have been determined in 46 patients suffering from valvular heart disease. It has been shown that Tv cannot be correctly interpreted, unless the values of Dmv and Vcv are known. The results of measurements of gas transfer using this method offer a reliable guide for establishing the efficacy of the cardiac pump, and for following up the effect of therapy in valvular heart disease.