Mechanisms Underlying Vascular Endothelial Growth Factor Receptor Inhibition-Induced Hypertension: The HYPAZ Trial.

[Figure: see text].

GLP-1 Is a Coronary Artery Vasodilator in Humans.

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.

Long-term visual outcome of penetrating keratoplasty in infants and children with Peters anomaly.

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.

Surgical management of glaucoma in infants and children with Peters' anomaly: long-term structural and functional outcome.

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 (IOP21 mmHg with or without antiglaucoma medication, inoperable retinal detachment, phthisis, or chronic hypotony, defined as an IOP of