RESUMEN
A patient with acute lymphatic leukaemia developed a bilateral fulminating Pseudomonas aeruginosa pneumonia and required controlled ventilation of the lungs. Marked agitation, hypotension and bronchospasm unresponsive to conventional bronchodilators presented a therapeutic challenge. A continuous intravenous infusion of midazolam failed to provide adequate sedation. A continuous intravenous infusion of ketamine resulted in better sedation, an increase in arterial pressure and a diminution of bronchospasm. The clinical improvement was maintained for the 5 days during which ketamine was infused. Plasma concentrations of ketamine and its metabolites are reported.
Asunto(s)
Broncodilatadores , Cardiotónicos , Cuidados Críticos , Hipnóticos y Sedantes , Ketamina/administración & dosificación , Adulto , Presión Sanguínea/efectos de los fármacos , Humanos , Infusiones Intravenosas , Ketamina/sangre , MasculinoRESUMEN
Stimulation of rabbit polymorphonuclear leucocytes with A23187 causes phospholipase C mediated breakdown of polyphosphoinositides, as evidenced by accumulation of [3H]inositol-labelled inositol bisphosphate and inositol trisphosphate. At the same time the polyphosphoinositides and the products of their breakdown, diacylglycerol and phosphatidic acid, label rapidly with radioactive arachidonic acid. Enhancement of polyphosphoinositide labelling is not as great as enhancement of diacylglycerol or phosphatidic acid labelling, suggesting additional early activation of a second independent synthetic pathway to the last named lipids. Experiments using double (3H/14C) labelling, to distinguish pools with different rates of turnover, suggest the major pool of arachidonic acid used for synthesis of lipoxygenase metabolites turns over more slowly than arachidonic acid in diacylglycerol, but at about the same rate as arachidonic acid esterified in phosphatidylcholine or phosphatidylinositol. Further, when cells are prelabelled with [14C]arachidonic acid, then stimulated for 5 min, it is only from phosphatidylcholine, and to a lesser extent phosphatidylinositol, that radiolabel is lost. Release of arachidonic acid is probably via phospholipase A2, since it is blocked by the phospholipase A2 inhibitor manoalide. The absence of accumulated lysophosphatides can be explained by reacylation and, in the case of lysophosphatidylinositol, deacylation. The importance of phospholipase A2 in phosphatidylinositol breakdown contrasts with the major role of phospholipase C in polyphosphoinositide hydrolysis. Measurements of absolute free fatty acid levels, as well as studies showing a correlation between production of radiolabelled hydroxyeicosatetraenoic acids and release of radiolabel from the phospholipid pool, both suggest that hydrolysis of arachidonic acid esterified into phospholipids is the limiting factor regulating formation of lipoxygenase metabolites. By contrast with A23187, fMet-Leu-Phe (a widely used polymorphonuclear leucocyte activator) is a poor stimulant for arachidonic acid release unless a 'second signal' (e.g. cytochalasin B, or a product of A23187-stimulated cells) is also present. In the presence of cytochalasin B, fMet-Leu-Phe, like A23187, stimulates release of radiolabelled arachidonic acid principally from phosphatidylcholine.
Asunto(s)
Ácidos Araquidónicos/sangre , Calcimicina/farmacología , Neutrófilos/metabolismo , Fosfatidilinositoles/sangre , Animales , Ácido Araquidónico , Ácidos Hidroxieicosatetraenoicos/sangre , Técnicas In Vitro , Lípidos/sangre , Masculino , Modelos Biológicos , Neutrófilos/efectos de los fármacos , Fosfatos de Fosfatidilinositol , Fosfolipasas A/farmacología , Fosfolipasas A2 , Quinacrina/farmacología , Conejos , Estimulación QuímicaRESUMEN
The effect of etomidate on the auditory evoked response was examined in a double-blind study carried out before the start of surgery. Fourteen patients were anaesthetized with 70% nitrous oxide and oxygen after induction with thiopentone. Ventilation was controlled. Seven of the patients received a continuous infusion of etomidate, increasing in five equal steps from 0.01 mg kg-1 min-1 to 0.05 mg kg-1 min-1 over a period of 50 min. The other seven received similarly an equivalent volume of saline. The patients given etomidate were easily distinguishable from those given saline, solely on the basis of changes in the early cortical peaks Pa and Nb. In the etomidate group the latencies of these peaks increased and their amplitudes decreased. These changes were linearly related to serum etomidate concentration. There was no effect of etomidate on the brainstem response.
Asunto(s)
Etomidato/farmacología , Potenciales Evocados Auditivos/efectos de los fármacos , Imidazoles/farmacología , Adolescente , Adulto , Tronco Encefálico/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Etomidato/sangre , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
gamma-Hexachlorocyclohexane stimulates arachidonic acid release from macrophage phospholipids. It is also a powerful stimulator of leukotriene C4 production, yet (by comparison with zymosan) produces only a small effect on prostaglandin production. This suggests that synthesis of leukotrienes and prostaglandins can be independently regulated. The most likely mechanism of action of gamma-hexachlorocyclohexane is through its effect on phosphatidylinositol metabolism.
Asunto(s)
Hexaclorociclohexano/farmacología , Macrófagos/metabolismo , Fosfolípidos/metabolismo , SRS-A/biosíntesis , Animales , Ácido Araquidónico , Ácidos Araquidónicos/metabolismo , Femenino , Hidrólisis , Técnicas In Vitro , Macrófagos/efectos de los fármacos , RatonesRESUMEN
The nitrous oxide and halothane contamination in the inspired air of anaesthetists and in the atmospheres of operating theatres, anaesthetic induction and recovery rooms, were measured during normal unmodified working sessions in 20 hospitals using integrated personal samplers. The nitrous oxide (and halothane) levels ranged from < 10 to 3000 ppm (< 0.1 to 60 ppm) in the different areas with an average of 388.5 ppm (2.8 ppm) for the inspired air of the anaesthetists during 2 hour sampling periods. There was no correlation between the levels of the anaesthetists' exposures and those in the static air samples and this appeared to be due primarily to a wide variation in work practices and techniques. Thus it is potentially misleading to assess anaesthetists' occupational exposure by collecting ambient air samples in the operating rooms. Comparisons with more prolonged measurements in one hospital indicated that the installation of relatively simple active scavenging devices will be effective in most hospitals.
Asunto(s)
Contaminación del Aire/análisis , Halotano/análisis , Óxido Nitroso/análisis , Quirófanos , Contaminación del Aire/prevención & control , Anestesia por Inhalación/normas , Anestesiología , Exposición a Riesgos Ambientales , Humanos , Quirófanos/normas , Sala de Recuperación/normas , Reino UnidoRESUMEN
1. Adipose tissue samples were obtained by needle biopsy from three subcutaneous sites (thigh, abdomen and upper arm) in twenty-two obese women. The fatty acid composition was determined using gas-liquid chromatography and the results presented relate to eleven component fatty acids. 2. The fatty acid composition of adipose tissue obtained from the arm and abdomen was remarkably similar, with the exception of the levels of lauric acid. 3. The analyses showed that the majority of the saturated fatty acids were present in smaller proportions whilst the majority of unsaturated fatty acids were present in larger proportions in the thigh than in the two other sites. Highly significant inter-site differences were demonstrated for six of the major fatty acids and also for both the total amounts of saturated and unsaturated fatty acids and their ratios. 4. No marked differences in the fatty acid composition of adipose tissue from obese subjects were revealed during this study when compared with previously reported results obtained from 'normal-weight' subjects.
Asunto(s)
Tejido Adiposo/análisis , Ácidos Grasos/análisis , Obesidad/metabolismo , Abdomen , Adolescente , Adulto , Anciano , Brazo , Femenino , Humanos , Ácidos Láuricos/análisis , Persona de Mediana Edad , MusloRESUMEN
An animal model was used to investigate the comparative fetal toxicities of three inhalational anesthetics. Pregnant Sprague-Dawley rats were exposed for eight hours a day throughout the 21 days of gestation to graded concentrations of halothane (0.16-0.32 per cent), or nitrous oxide (1-50 per cent), or a nitrous oxide (10 per cent) and halothane (0.16 per cent) mixture, or methoxyflurane (0.01-0.08 per cent). High subanesthetic concentrations of all the inhalational anesthetics could cause fetal growth retardation (e.g., 3-21 per cent decreases in normal fetal weights), but this was unaccompanied by significant fetal loss (overall rate: 4.8 +/- 1.2 per cent, mean +/- SE, in anesthetic groups) or any evidence of skeletal or gross abnormalities related to treatment. It is concluded that these rodent studies do not implicate any specific inhalational anesthetic agent in fetal toxicity, and that the effects of additional factors, such as stress, must be considered.
Asunto(s)
Feto/efectos de los fármacos , Halotano/toxicidad , Metoxiflurano/toxicidad , Óxido Nitroso/toxicidad , Animales , Exposición a Riesgos Ambientales , Femenino , Masculino , Intercambio Materno-Fetal , Embarazo , RatasRESUMEN
Chronic exposure of pregnant Sprague Dawley rats to a range of halothane concentrations from 50-3200 p.p.m. for 8 hours a day on days 8-12 of gestation failed to demonstrate significant teratogenicity in terms of foetal loss, growth, or skeletal abnormalities. Exposure to 1600 p.p.m. showed significant changes only in foetal weights, which were slightly decreased.