Acute hypoxemia leads to activation of the sympathetic nervous system (SNS), yet adrenergic vasoconstriction does not occur and venous plasma norepinephrine (NE) fails to rise as expected. To examine whether this dissociation between SNS tone and plasma NE is due to altered metabolism of NE, we measured arterial NE kinetics ([3H]NE infusion technique) and sympathetic nervous outflow to muscle (peroneal microneurography) during 25-30 min of hypoxemia (spontaneous breathing, mean O2 saturation 74%) in six healthy young men. During hypoxemia, muscle sympathetic nervous activity (MSNA) rose significantly from 12.2 +/- 3.3 to 18.6 +/- 3.5 bursts/min, and the total amplitude increased from 123 +/- 36 to 255 +/- 50 mm/min. NE spillover, an index of NE release at the sympathetic nerve terminals, rose from 1.66 +/- 0.30 to 2.33 +/- 0.40 nmol.min-1.m-2 (P = 0.014). However, NE clearance increased also from 0.99 +/- 0.05 to 1.19 +/- 0.11 l.min-1.m-2 (P = 0.014), and arterial NE rose from 281 +/- 50 to 339 +/- 64 pg/ml (P = 0.023). Hypoxemia resulted in a significant rise in forearm blood flow and a decrease in forearm vascular resistance. The fact that skin blood flow and vascular resistance did not change implies that forearm vasodilation was localized to skeletal muscle. Our results suggest that during acute hypoxemia in humans the SNS is activated but the rise in plasma NE is attenuated because NE clearance is increased.

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Background Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti–vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. Methods This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated.

The diagnosis of presumed ocular tuberculosis remains a clinical challenge with currently available diagnostic modalities. Although newer interferon-γ release assays can distinguish exposure to M. tuberculosis from the Bacille-Calmette-Guérin vaccine strain, they currently lack the specificity to distinguish between latent tuberculosis infection and active tuberculosis. Continued improvement in the currently available molecular diagnostic techniques including quantitative PCR may be valuable in our ability to establish an earlier etiologic diagnosis and institute appropriate antimycobacterial therapy.