RESUMEN
[Figure: see text].
Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Endotelio Vascular/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertensión/inducido químicamente , Indazoles/efectos adversos , Pirimidinas/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Sulfonamidas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Gasto Cardíaco/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertensión/fisiopatología , Indazoles/administración & dosificación , Indazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Pirimidinas/administración & dosificación , Pirimidinas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Resistencia Vascular/efectos de los fármacos , Rigidez Vascular/efectos de los fármacosRESUMEN
Background The mechanism underlying the beneficial cardiovascular effects of the incretin GLP-1 (glucagon-like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP -1. Methods and Results Ten stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post-percutaneous coronary intervention coronary blood flow measurement using a pressure-flow wire before and after peripheral GLP -1 administration. Coronary sinus and artery bloods were sampled for GLP -1 levels. A further 11 control patients received saline rather than GLP -1 in the coronary blood flow protocol. GLP -1 receptor (GLP-1R) expression was assessed by immunohistochemistry using a specific GLP -1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP -1 on absolute forearm blood flow or forearm blood flow ratio after GLP -1, systemic hemodynamics were not affected, and no binding of GLP -1R monoclonal antibody was detected in vascular tissue. GLP -1 reduced resting coronary transit time (mean [ SD ], 0.87 [0.39] versus 0.63 [0.27] seconds; P=0.02) and basal microcirculatory resistance (mean [ SD ], 76.3 [37.9] versus 55.4 [30.4] mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean [SD], 0.48 [0.24] versus 0.83 [0.41] seconds; P<0.001) and basal microcirculatory resistance (mean [SD], 45.9 [34.7] versus 66.7 [37.2] mm Hg/s; P=0.02). GLP -1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP -1 extraction was observed. Conclusions GLP -1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP -1R immunohistochemistry suggests that GLP -1 coronary vasodilatation is indirectly mediated by ventricular-coronary cross talk.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Péptido 1 Similar al Glucagón/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Anciano , Femenino , Humanos , Masculino , Microvasos/efectos de los fármacos , Persona de Mediana Edad , PletismografíaRESUMEN
PURPOSE: To determine the long-term visual outcome of penetrating keratoplasty for Peters anomaly and to identify prognostic factors affecting final vision. METHODS: The records of children 12 years of age or younger who underwent penetrating keratoplasty for Peters anomaly between January 1, 1971 and December 31, 1992 at Emory University were reviewed. Characteristics of the recipient, eye, donor, and surgical procedure were examined with the use of multivariate analyses. RESULTS: One hundred forty-four keratoplasties in 72 eyes of 47 children who were followed for a minimum of 3 years from the date of first keratoplasty (median, 11.1 years) were reviewed. Visual acuities ranged from 20/25 to no light perception. Twenty-nine percent of eyes achieved 20/400 or better visual acuities, whereas 38% had light perception or no light perception. Stromal vessels (p < 0.001) and larger donor corneas (p < 0.001) were independent predictors of poor outcome. Postoperative complications included graft failure (n = 44), cataract (n = 15), glaucoma (n = 14), retinal detachment (n = 16), and phthisis (n = 22). More than half of the eyes (n = 18) without graft failure, retinal detachment and/or phthisis saw 20/400 or better. CONCLUSIONS: Less than one-third of eyes with Peters anomaly undergoing keratoplasty achieved a visual acuity of 20/400 or better. Stromal vessels and large corneal grafts (>or=8 mm) were the only independent predictors of a poor visual outcome.
Asunto(s)
Cámara Anterior/anomalías , Anomalías del Ojo/epidemiología , Anomalías del Ojo/cirugía , Queratoplastia Penetrante/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Análisis Multivariante , Complicaciones Posoperatorias/epidemiología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual , Adulto JovenRESUMEN
OBJECTIVE: To determine the long-term outcome of surgery for congenital glaucoma in infants and children with Peters' anomaly. DESIGN: Retrospective review of a consecutive interventional case series. SETTING: An urban academic tertiary referral institution. PARTICIPANTS: Thirty-four eyes of 19 children are subjects of this report. Included are all children 12 years of age or younger with Peters' anomaly who underwent surgery for primary congenital glaucoma between January 1971 and December 1992 and completed a minimum of 3 years of follow-up from the date of the first glaucoma surgery. INTERVENTION: The surgical procedures performed were trabeculectomy, trabeculotomy, goniotomy, Molteno shunt implantation, cyclodialysis, and cyclocryotherapy. MAIN OUTCOME MEASURES: Primary outcome measures were intraocular pressure (IOP) control and final postoperative visual acuity. Intraocular pressure control was defined as complete success (IOP=21 mmHg without antiglaucoma medication), qualified success (IOP=21 mmHg with antiglaucoma mediation), or failure (IOP>21 mmHg with or without antiglaucoma medication, inoperable retinal detachment, phthisis, or chronic hypotony, defined as an IOP of =6 mmHg). RESULTS: A total of 126 glaucoma procedures were performed on 34 eyes of 19 patients. The median age at time of first glaucoma surgery was 2.1 months (range, 2 days to 8.5 years). The median follow-up was 11.0 years (range, 3.2 to 22.8 years) from the time of first glaucoma surgery. Intraocular pressure control with or without antiglaucoma medication was achieved in 11 eyes (32%) after 1 or more surgical procedures. Major postoperative complications included graft failure in 26 eyes (76%), cataract in 6 eyes (18%), inoperable retinal detachment with phthisis in 12 eyes (35%), and phthisis alone in 6 eyes (18%). Final vision was 20/200 or better in 3 eyes (9%), 20/400 to hand motion in 12 eyes (35%), light perception in 7 eyes (21%), and no light perception in 12 eyes (35%). CONCLUSIONS: Glaucoma surgery, combined with medical therapy, may result in adequate, long-term IOP control in 32% of eyes with glaucoma associated with Peters' anomaly. Visual results are poor due to uncontrolled glaucoma, amblyopia, neurologic impairment, and other anterior and posterior segment anomalies that may accompany Peters' anomaly. Postoperative complications, including graft failure, cataract, inoperable retinal detachment, and phthisis, also contribute to decreased visual acuity.