RESUMEN
OBJECTIVE: To investigate in a prospective randomised study both long term clinical effects and cost effectiveness of percutaneous coronary interventions (PCI) with or without intravascular ultrasound (IVUS) guidance. METHODS: 108 male patients with stable angina referred for PCI of a significant coronary lesion were randomly assigned to IVUS guided PCI or conventional PCI. Individual accumulated costs of the entire follow up period were calculated and compared in the randomisation groups. Effectiveness of treatment was measured by freedom from major adverse cardiac events. RESULTS: Cost effectiveness of IVUS guided PCI that was noted at six months was maintained and even accentuated at long term follow up (median 2.5 years). The cumulated cost level was found to be lower for the IVUS guided group, with a cumulated cost of &163 672 in the IVUS guided group versus &313 706 in the coronary angiography group (p = 0.01). Throughout the study, mean cost per day was lower in the IVUS guided PCI group (&2.7 v & 5.2; p = 0.01). In the IVUS group, 78% were free from major adverse cardiac events versus 59% in the coronary angiography group (p = 0.04) with an odds ratio of 2.5 in favour of IVUS guidance. CONCLUSION: IVUS guidance results in continued improvement of long term clinical outcome and cost effectiveness. The results of this study suggest that IVUS guidance may be used more liberally in PCI.
Asunto(s)
Angina de Pecho/terapia , Angioplastia Coronaria con Balón/métodos , Adulto , Anciano , Angina de Pecho/economía , Angioplastia Coronaria con Balón/economía , Análisis Costo-Beneficio , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Factores de Riesgo , Resultado del TratamientoRESUMEN
Intensive lowering of serum cholesterol in patients with ischaemic heart disease may retard atherosclerotic progression, and may even cause a limited regression in some patients and partly restore endothelial function. Coronary angiography has been the standard method to evaluate coronary anatomy. However, coronary angiography delineates only the vessel lumen as a silhouette, a perspective that is incapable of reflecting the irregular nature of the atherosclerotic vessel wall changes. Three-dimensional intravascular ultrasound provides cross-sectional and longitudinal images of both the vessel lumen and wall and the plaque volume can be measured in entire arterial segments. Three-dimensional intravascular ultrasound is a reliable technique to measure progression and regression of atherosclerosis in coronary arteries.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria , Ecocardiografía Tridimensional , HumanosRESUMEN
The aim of this study was to evaluate the reproducibility of intravascular ultrasound (IVUS) and intracoronary (IC) Doppler flow velocity measurements. The use of IVUS and IC Doppler has been suggested as a means for percutaneous coronary intervention (PCI) guidance in a series of studies. This would require an acceptable level of accuracy and reproducibility of these two methods for lesion evaluation. In this study, the main focus was on the issue of reproducibility. One hundred and eight patients referred for PCI entered into the study. Inter- and intraobserver variability was measured. Catheter difference was assessed. On-line and off-line measurements were compared. MUSIC criteria were assessed off-line, twice. Calculated and measured diameters were compared. After having obtained initial IC Doppler measurements, the Doppler wire was immediately withdrawn and repositioned for reacquisition of Doppler measurements. IVUS measurements are reproducible and reliable off-line and, to a slightly lesser degree, on-line. Area measurements should be performed more than once and the mean used for vessel description. Lumen diameters should be calculated from the mean of the area measurements. A measuring technique consensus should be reached and adhered to. CFR measurements can be used to determine reduced vs. normal flow reserve. In this study, it was found that proximal to distal velocity ratio and diastolic to systolic velocity ratio variability made these parameters unsuitable for PCI guidance.
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Ultrasonografía Doppler , Ultrasonografía Intervencional , Velocidad del Flujo Sanguíneo/fisiología , Cateterismo , Intervalos de Confianza , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/fisiopatología , Humanos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
We have characterized the neutralization of the inhibitory activity of the serpin plasminogen activator inhibitor-1 (PAI-1) by a number of structurally distinct organochemicals, including compounds with environment-sensitive spectroscopic properties. In contrast to latent and reactive center-cleaved PAI-1 and PAI-1 in complex with urokinase-type plasminogen activator (uPA), active PAI-1 strongly increased the fluorescence of the PAI-1-neutralizing compounds 1-anilinonaphthalene-8-sulfonic acid and 4,4'-dianilino-1,1'-bisnaphthyl-5,5'-disulfonic acid. The fluorescence increase could be competed by all tested nonfluorescent neutralizers, indicating that all neutralizers bind to a common hydrophobic area preferentially accessible in active PAI-1. Activity neutralization proceeded through two consecutive steps as follows: first step is conversion to forms displaying substrate behavior toward uPA, and second step is to forms inert to uPA. With some neutralizers, the second step was associated with PAI-1 polymerization. Vitronectin reduced the susceptibility to the neutralizers. Changes in sensitivity to activity neutralization by point mutations were compatible with the various neutralizers having overlapping, but not identical, binding sites in the region around alpha-helices D and E and beta-strand 1A, known to act as a flexible joint when beta-sheet A opens and the reactive center loop inserts as beta-strand 4A during reaction with target proteinases. The defined binding area may be a target for development of compounds for neutralizing PAI-1 in cancer and cardiovascular diseases.
Asunto(s)
Inhibidor 1 de Activador Plasminogénico/química , Inhibidor 1 de Activador Plasminogénico/metabolismo , Serpinas/química , Serpinas/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/química , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Secuencia de Aminoácidos , Naftalenosulfonatos de Anilina , Unión Competitiva , Colorantes Fluorescentes , Humanos , Cinética , Ligandos , Sustancias Macromoleculares , Modelos Moleculares , Fragmentos de Péptidos/química , Estructura Secundaria de Proteína , Espectrometría de FluorescenciaRESUMEN
Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS). Inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS and in the prevention of complications after percutaneous coronary interventions (PCI). Several large clinical trials have demonstrated the effectiveness of this class of agents. The first of these agents to show beneficial effects after coronary interventions was the mouse/human chimeric Fab fragment antibody c7E3 abciximab (ReoPro). The purpose of this article is to describe the pharmacology of abciximab and to review the results of the clinical trials carried out with the drug in patients with ACS, treated either with or without acute/elective PCI.
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Enfermedad Coronaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Angioplastia Coronaria con Balón , Ensayos Clínicos Controlados como Asunto , Humanos , Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/química , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/efectos de los fármacos , Factores de RiesgoRESUMEN
Platelet activation plays a major role in the pathophysiology of acute coronary syndromes (ACS), and inhibition of platelet function is the basic pharmacological treatment of ACS. Platelet membrane glycoprotein IIb/IIIa inhibitors, a new class of potent antiplatelet agents, have been used in the treatment of ACS, as well as in the prevention of complications after percutaneous coronary interventions. The aim of this article is to describe the potential possibilities of platelet inhibition and to review the pharmacology of glycoprotein IIb/IIIa inhibitors, the results of the clinical trials with these agents, and their current use in the pharmacological treatment of ACS and in relation to percutaneous coronary intervention.
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Enfermedad Coronaria/tratamiento farmacológico , Glicoproteínas de Membrana/antagonistas & inhibidores , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Complejo GPIb-IX de Glicoproteína Plaquetaria , Glicoproteínas de Membrana Plaquetaria , Receptores de Superficie Celular/antagonistas & inhibidores , Ensayos Clínicos Controlados como Asunto , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Receptores de Superficie Celular/efectos de los fármacosRESUMEN
The accelerated formation of advanced glycation end-products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. The effects of a novel inhibitor of AGE formation, NNC39-0028 (2,3-diaminophenazine), and a breaker of already formed AGE cross-links, N-phenacylthiazolium bromide (PTB), were investigated in streptozotocin-diabetic female Wistar rats. Diabetes for 24 weeks resulted in decreased tail collagen pepsin solubility, reflecting the formation of AGE cross-linking. Collagen solubility was significantly ameliorated by treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin excretion (UAE) in diabetic rats was observed in serial measurements throughout the study period, and was not reduced by any treatment. Vascular dysfunction in the eye, measured as increased clearance of 125I-albumin, was induced by diabetes. NNC39-0028 did not affect this abnormality. This study demonstrated a pharmacological inhibition of collagen solubility alterations in diabetic rats without affecting diabetes-induced pathophysiology such as the increase in UAE or albumin clearance. Treatment with PTB, a specific breaker of AGE cross-links, had no effects in this study.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Fenazinas/farmacología , Tiazoles/farmacología , Albuminuria/orina , Animales , Colágeno/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Angiopatías Diabéticas/sangre , Ingestión de Líquidos/efectos de los fármacos , Ojo/irrigación sanguínea , Femenino , Productos Finales de Glicación Avanzada/biosíntesis , Riñón/anatomía & histología , Riñón/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Radiofármacos , Ratas , Ratas Wistar , Albúmina Sérica/metabolismo , Albúmina Sérica Radioyodada , Solubilidad , Cola (estructura animal) , Tendones/efectos de los fármacos , Tendones/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
The effect of selective tachykinin receptor agonists and antagonists on human isolated intralobar pulmonary arterial rings was investigated. Neither Substance P (SP) nor neurokinin A (NKA) contracted the arteries. Both of these agonists, however, were potent and efficacious at relaxing the arteries that were precontracted with phenylephrine. The negative log (M) EC(50) values for SP and NKA were 9.0 and 8.3, respectively. The neurokinin (NK)-3 selective agonist, senktide-analog, and the NK-2 receptor selective agonist, [beta-Ala(8)]NKA(4-10), caused neither contractions nor relaxations of the arteries, whereas the NK-1 receptor agonist Ac-[Arg6, Sar9, Met(O2)11]SP(6-11) (ASM-SP) relaxed the tissue with a potency similar to SP. The relaxations to SP, NKA, and ASM-SP were competitively antagonized by the selective NK-1 receptor antagonist CP 99994, with a pK(b) in the nanomolar range. Antagonism of the ASM-SP-induced relaxations was also noted with FK 888, RP 67580, and L 732,138, although these antagonists were much less potent than CP 99994 in this regard. Another NK-1 receptor selective antagonist, SR 140333, caused an insurmountable antagonism of the SP-induced relaxations. The NK-1 receptor-mediated relaxations could be blocked by removing the endothelium, or by a combination of N-nitro-L-arginine and indomethacin. Measurement of prostanoid generation revealed that in endothelial-intact but not endothelial-denuded tissue, ASM-SP caused a selective increase in the production of 6-keto-PGF1alpha, the stable metabolite of prostacyclin. The results indicate that stimulation of NK-1 receptors leads to relaxation of human intralobar pulmonary arteries, which is mediated largely by nitric oxide and prostacyclin released from the endothelium of these vessels.
Asunto(s)
Arteria Pulmonar/fisiología , Receptores de Neuroquinina-1/fisiología , Receptores de Taquicininas/agonistas , Receptores de Taquicininas/antagonistas & inhibidores , Vasodilatación/fisiología , Adolescente , Adulto , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Endotelio Vascular/fisiología , Epoprostenol/metabolismo , Epoprostenol/fisiología , Femenino , Humanos , Técnicas In Vitro , Pulmón/fisiología , Masculino , Persona de Mediana Edad , Neuroquinina A/farmacología , Óxido Nítrico/fisiología , Fragmentos de Péptidos/farmacología , Fenilefrina/farmacología , Sustancia P/análogos & derivados , Sustancia P/farmacología , Vasoconstricción/efectos de los fármacosRESUMEN
We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.
Asunto(s)
Bronquios/efectos de los fármacos , Neuronas Aferentes/efectos de los fármacos , Solución Salina Hipertónica/farmacología , Tráquea/efectos de los fármacos , Nervio Vago/efectos de los fármacos , Administración por Inhalación , Animales , Bronquios/irrigación sanguínea , Bronquios/inervación , Bronquios/fisiología , Permeabilidad Capilar/efectos de los fármacos , Cobayas , Técnicas In Vitro , Masculino , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/fisiología , Neuronas Aferentes/fisiología , Ganglio Nudoso/efectos de los fármacos , Ganglio Nudoso/fisiología , Receptores de Neuroquinina-1/fisiología , Tráquea/irrigación sanguínea , Tráquea/inervación , Tráquea/fisiología , Nervio Vago/citología , Nervio Vago/fisiologíaRESUMEN
OBJECTIVES: A generalised transient improvement may follow intra-articular administration of glucocorticoids to patients with inflammatory arthropathy. This may represent a systemic anti-inflammatory effect of glucocorticoid released from the joint, mediated through processes such as altered leucocyte trafficking or suppressed release of pro-inflammatory cytokines. Patients, who had received intra-articular injections of glucocorticoids were therefore studied for evidence of these two systemic effects. METHODS: Patients with rheumatoid arthritis were studied. Peripheral blood leucocyte counts, tumour necrosis factor alpha (TNF alpha) release by peripheral blood monocytes, blood cortisol concentrations, and blood methylprednisolone concentration were measured for 96 hours after intra-articular injection of methylprednisolone acetate. RESULTS: Measurable concentrations of methylprednisolone were present in blood for up to 96 hours after injection. Significant suppression of the hypothalamic-pituitary-adrenal axis persisted throughout this time. Altered monocyte and lymphocyte trafficking, as evidenced by peripheral blood monocytopenia and lymphopenia, was apparent by four hours after injection and resolved in concordance with the elimination of methylprednisolone. Granulocytosis was observed at 24 and 48 hours. Release of TNF alpha by endotoxin stimulated peripheral blood monocytes was suppressed at four hours and thereafter. Suppression was maximal at eight hours and was largely reversed by the glucocorticoid antagonist, mifepristone. CONCLUSIONS: After intra-articular injection of methylprednisolone, blood concentrations of glucocorticoid are sufficient to suppress monocyte TNF alpha release for at least four days and to transiently alter leucocyte trafficking. These effects help to explain the transient systemic response to intra-articular glucocorticoids. Suppression of TNF alpha is principally a direct glucocorticoid effect, rather than a consequence of other methylprednisolone induced changes to blood composition.
Asunto(s)
Antiinflamatorios/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Quimiotaxis de Leucocito/efectos de los fármacos , Metilprednisolona/análogos & derivados , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Antiinflamatorios/sangre , Antiinflamatorios/uso terapéutico , Artritis Reumatoide/inmunología , Recuento de Células , Células Cultivadas , Depresión Química , Femenino , Antagonistas de Hormonas/farmacología , Humanos , Inyecciones Intraarticulares , Lipopolisacáridos/farmacología , Metilprednisolona/administración & dosificación , Metilprednisolona/sangre , Metilprednisolona/uso terapéutico , Acetato de Metilprednisolona , Persona de Mediana Edad , Mifepristona/farmacología , Monocitos/inmunologíaRESUMEN
Cysteinyl leukotrienes are bioactive lipid mediators known to possess potent proinflammatory actions. Included in these are effects on vascular endothelium to promote surface expression of the adhesion molecule P-selectin. In the present study we were interested in investigating the receptor mechanism(s) involved in cysteinyl leukotriene-induced endothelial P-selectin expression. As such we examined the effect of several potent and selective cysteinyl leukotriene receptor antagonists on this response. Incubation of cultured human umbilical vein endothelial cells (HUVEC) with the cysteinyl leukotrienes leukotriene C4 (LTC4) or leukotriene D4 (LTD4) induced surface expression of P-selectin which was concentration dependent and rapid in onset. Expression of endothelial P-selectin induced by either LTC4 or LTD4 was not blocked however by pretreatment of HUVEC with the selective cysteinyl leukotriene-1 (CysLT1) receptor antagonists SKF 104353, pranlukast or zafirlukast before agonist exposure. In contrast, SKF 104353 effectively antagonized the LTC4-induced contractions in isolated human bronchial smooth muscle preparations, shifting the agonist dose-response curve to the right by some 3 log-fold in this tissue. The present results suggest that cysteinyl leukotrienes induce surface expression of endothelial P-selectin via a mechanism independent of the CysLT1 receptor.
Asunto(s)
Endotelio Vascular/efectos de los fármacos , Leucotrieno C4/fisiología , Leucotrieno D4/fisiología , Selectina-P/metabolismo , Células Cultivadas , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Humanos , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiología , Tráquea/efectos de los fármacos , Tráquea/fisiologíaRESUMEN
Narcotic sedation is commonly accomplished with nitrous oxide (N2O) coadministration. Concerns regarding respiratory morbidity and mortality with drug combinations have been reported in the literature, particularly in patients not receiving supplemental oxygen (O2). The purpose of this investigation was to determine the effect of meperidine alone and in combination with N2O on respiration in laboratory rats by evaluating cardiovascular and arterial blood gas data. Fifty-four Sprague-Dawley rats were assigned to one of six groups (nine per group). Groups were allocated based upon the dosage of meperidine administered (0, 4.0, or 8.0 mg/kg intraperitoneally [i.p.]) and exposure to N2O (50% with oxygen) or O2 (100%). Following meperidine administration, animals were placed into a sealed chamber through which flowed either N2O or O2. Arterial blood was obtained, at baseline and at 15-min intervals, from a femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were determined. Plasma samples were analyzed using a System 1306 pH/blood gas analyzer. Group comparisons demonstrated that: (a) N2O coadministration, in animals pretreated with meperidine, did not result in increased arterial CO2 levels, and (b) as expected, arterial O2 levels in all groups increased significantly from preexposure baseline values (P < 0.05). This investigation demonstrated that the coadministration of N2O to meperidine-sedated animals did not enhance respiratory depression.
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Analgésicos Opioides/farmacología , Anestésicos por Inhalación/farmacología , Meperidina/farmacología , Óxido Nitroso/farmacología , Respiración/efectos de los fármacos , Insuficiencia Respiratoria/inducido químicamente , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoAsunto(s)
Envejecimiento/fisiología , Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo/efectos adversos , Presbiacusia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Audiometría , Ensayos Clínicos como Asunto , Femenino , Pérdida Auditiva de Alta Frecuencia/epidemiología , Pérdida Auditiva de Alta Frecuencia/etiología , Pérdida Auditiva de Alta Frecuencia/patología , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Pérdida Auditiva Provocada por Ruido/patología , Humanos , Masculino , Presbiacusia/epidemiología , Presbiacusia/etiología , Presbiacusia/patología , Factores de Riesgo , Distribución por SexoRESUMEN
1. Airway inflammation is a signal feature of human asthma, as is bronchial obstruction and the resultant airflow limitation. An obligatory accompaniment to airway inflammation is increased airway microvascular permeability, which in turn is causally related to bronchial oedema. In this review, we have attempted to describe the mechanisms of increased airway microvascular permeability and its relationship to oedema, bronchial obstruction and the hyperreactivity to spasmogenic stimuli which are such common features of asthma. 2. It is now clear that bronchial obstruction in chronic asthma can involve bronchial wall oedema and swelling in addition to reversible, elevated airway smooth muscle tone, mucus hypersecretion and airway plugging and potentially permanent structural changes in airway architecture. Inflammatory mediators released in the airway wall in asthma including histamine, platelet-activating factor, leukotrienes and bradykinin are potent inducers of increased bronchial microvascular permeability and are thus promoters of bronchial oedema, airway wall swelling and reduction in luminal calibre. 3. The primary mechanism believed to underlie acute increases in microvascular permeability is contraction of post-capillary venular endothelial cells, resulting in the formation of gaps between otherwise tightly associated cells. Extravasated plasma distributes to the interstitial spaces in the airway wall, resulting in oedema and swelling, but may also traverse the epithelium and collect in the airway lumen. 4. Luminal plasma may compromise epithelial integrity and cilial function and thus reduce mucus clearance. Plasma proteins may also promote the production of viscous mucus and the formation of luminal mucus plugs. Together, these effects can result in or contribute to airway obstruction and hyper-responsiveness. 5. An understanding of such mechanisms can provide insight concerning novel and effective anti-asthma therapies.
Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Asma/complicaciones , Permeabilidad Capilar/fisiología , Obstrucción de las Vías Aéreas/tratamiento farmacológico , Obstrucción de las Vías Aéreas/fisiopatología , Asma/fisiopatología , Bronquios/irrigación sanguínea , Hiperreactividad Bronquial/etiología , Hiperreactividad Bronquial/fisiopatología , Permeabilidad Capilar/efectos de los fármacos , Endotelio Vascular/fisiología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/etiología , Contracción Muscular/fisiología , Músculo Liso/fisiología , Edema Pulmonar/etiología , Edema Pulmonar/fisiopatología , Tráquea/irrigación sanguíneaAsunto(s)
Anquilosis/terapia , Prótesis de Recubrimiento , Enfermedades Dentales/terapia , Anquilosis/complicaciones , Anquilosis/etiología , Preescolar , Dentadura Completa , Displasia Ectodérmica/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Maloclusión/etiología , Maloclusión/terapia , Diente Molar , Enfermedades Dentales/complicaciones , Enfermedades Dentales/etiología , Diente Primario , Dimensión VerticalRESUMEN
Twelve patients, three male and nine female, suffering from hypertrophic obstructive cardiomyopathy were operated during the period 1976 to 1991. Operative methods were myotomy-myectomy (Morrow-procedure), mitral valve implantation or both. During the perioperative period two patients developed conduction disturbances requiring pacemaker implantation, five patients had left bundle branch block, and one died. The NYHA class was significantly reduced postoperatively (p = 0.0002). Five of eleven patients surviving the perioperative period died postoperatively after a mean follow-up of 6.3 years. It is the authors' opinion, that operation should be considered in patients suffering from hypertrophic obstructive cardiomyopathy, who have a left ventricle outflow gradient of 50 mmHg or more, and who despite medical treatment have symptoms placing them in NYHA class III-IV.
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Cardiomiopatía Hipertrófica/cirugía , Adulto , Anciano , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Intraoperatorias/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Estudios RetrospectivosRESUMEN
We have measured the capacity of the sodium-potassium pump, as assessed by 86rubidium uptake and the number of [3H]-ouabain binding sites on white blood cells, in children aged 9-11 years, partly cross-sectionally and partly longitudinally after a physical training programme. Children from a hypertensive subgroup comprising the upper 5% of the blood pressure distribution and children from a randomly selected normotensive subgroup were eligible for the study. In the cross-sectional study 40 children from the hypertensive subgroup and 40 children from the normotensive subgroup were evaluated. A significant increase in 86rubidium uptake was present in boys as compared to girls. After adjustment for differences in sexual maturation the observed significant difference disappeared. Important correlates of pump activity were height, plasma glucose, and physical fitness. In the training study 10 boys from the hypertensive subgroup and 10 boys from the normotensive subgroup were also evaluated after eight months of physical training. A significant fall in 86rubidium uptake was observed. No control group was examined and probably the changes reflect some effects of sexual maturation on cation handling of cells. These results indicate a significant effect of sexual maturation in capacity of sodium-potassium pump in children.
Asunto(s)
Hipertensión/sangre , Leucocitos/metabolismo , Educación y Entrenamiento Físico , ATPasa Intercambiadora de Sodio-Potasio/fisiología , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Ensayo de Unión Radioligante , Factores de RiesgoRESUMEN
1. We have used 125I-labelled fibrinogen (I-FN) in experiments monitoring plasma extravasation from vessels within guinea-pig trachea and peripheral lung tissue in response to platelet activating factor (PAF) and bradykinin (BK). Retained tissue radioactivity derived from I-FN was detected by direct measurement and by autoradiography. 2. Both PAF and BK caused concentration-dependent increases in radioactivity in trachea and peripheral lung, with PAF being approximately 1000 times more potent than BK at both sites. On a wet weight basis, mean tracheal leakage responses to PAF and BK were approximately 6 times and 2 times greater respectively than those in peripheral lung. Furthermore, in trachea, the maximal response to PAF was nearly twice that to BK, although they were approximately equiactive in peripheral lung. The dipeptidyl carboxypeptidase inhibitor, enalapril (1 mg kg-1, i.v.), increased the potency of BK by approximately 40 fold. 3. In trachea, PAF (50 ng kg-1, i.v.)-induced leakage was selectively inhibited by the PAF receptor antagonist, WEB 2086 (5-50 micrograms kg-1), while responses to BK (50 micrograms kg-1, i.v.) were selectively inhibited by the BK2 receptor antagonist NPC 349 (0.5-1 mg kg-1). Neither PAF nor BK-induced leakage were significantly altered by pretreatment with the histamine H1-receptor antagonists mepyramine (10 micrograms kg-1) or ketotifen (50 micrograms kg-1) or the leukotriene receptor antagonist SKF 104353. These data indicate that both agonists caused direct, specific receptor operated increases in tracheal vascular permeability to plasma macromolecules.The alpha/beta1-adrenoceptor agonist adrenaline (100 pgkg-1) caused modest inhibition of leakage induced by BK, but not of the leakage response to PAF.4. Peripheral airway leakage responses to both PAF and BK were also detected by light microscopic autoradiography in paraffin-embedded tissue sections. This was possible since a significant amount of extravasated I-FN was apparently precipitated and fixed in the extravascular space as 125-labelled fibrin. Autoradiograms showed that both agonists caused increases in peripheral bronchial circulation microvascular permeability to I-FN. No evidence for leakage in alveolar wall capillaries or in pulmonary blood vessels was observed. Quantitation of such autoradiographic data will allow a comprehensive evaluation of the effects of putative asthma mediators on microvascular permeability throughout the respiratory tree.
Asunto(s)
Bradiquinina/farmacología , Permeabilidad Capilar/efectos de los fármacos , Fibrinógeno/metabolismo , Factor de Activación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria , Receptores Acoplados a Proteínas G , Animales , Autorradiografía , Azepinas/farmacología , Cobayas , Radioisótopos de Yodo , Pulmón/anatomía & histología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Adhesión en Parafina , Factor de Activación Plaquetaria/antagonistas & inhibidores , Circulación Pulmonar/efectos de los fármacos , Receptores de Superficie Celular/antagonistas & inhibidores , Tráquea/anatomía & histología , Tráquea/efectos de los fármacos , Tráquea/metabolismo , Triazoles/farmacologíaRESUMEN
The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol.l-1) and a mean serum renin of 217 mU-l-1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol.l-1, which rose to 3.4 mmol.l-1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol.l-1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.