Melatonin modulates M4-type ganglion-cell photoreceptors.

In the retina, melatonin is secreted at night by rod/cone photoreceptors and serves as a dark-adaptive signal. Melatonin receptors have been found in many retinal neurons including melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting it could modulate the physiology of these inner retinal photoreceptors. Here, we investigated whether melatonin modulates the alpha-like M4-type ipRGCs, which are believed to mediate image-forming vision as well as non-image-forming photoresponses. Applying melatonin during daytime (when endogenous melatonin secretion is low) caused whole-cell-recorded M4 cells' rod/cone-driven depolarizing photoresponses to become broader and larger, whereas the associated elevation in spike rate was reduced. Melanopsin-based light responses were not affected significantly. Nighttime application of the melatonin receptor antagonist luzindole also altered M4 cells' rod/cone-driven light responses but in the opposite ways: the duration and amplitude of the graded depolarization were reduced, whereas the accompanying spiking increase was enhanced. These luzindole-induced changes confirmed that M4 cells are modulated by endogenous melatonin. Melatonin could induce the above effects by acting directly on M4 cells because immunohistochemistry detected MT1 receptors in these cells, although it could also act presynaptically. Interestingly, the daytime and nighttime recordings showed significant differences in resting membrane potential, spontaneous spike rate and rod/cone-driven light responses, suggesting that M4 cells are under circadian control. This is the first report of a circadian variation in ipRGCs' resting properties and synaptic input, and of melatoninergic modulation of ipRGCs.

Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Comparison of dose to the lungs.

The purpose of this study was to compare deposition of aerosol to the lung from a metered-dose inhaler (MDI) and aerosol holding chamber and from a jet nebulizer in ventilator-dependent patients. Twenty-one patients were entered into the study, all receiving assisted ventilation and inhaled bronchodilators because of airflow limitation. The average age was 68 yr; there were 10 men and 11 women. The patients were randomized to receive either 4 puffs (800 micrograms) of radiolabeled fenoterol by MDI of 1.75 ml (1,750 micrograms) of radiolabeled fenoterol solution by nebulizer. Imaging of lung fields was made by a portable scintillation camera at 5-min intervals during the study. Results showed that 20 patients completed the study, 9 receiving fenoterol by MDI, and 11 by jet nebulizer. Four were excluded from analysis because of previous pneumonectomy, two from each group. Lung deposition measured as a percent of given dose from either system was 5.65 +/- 1.09 (mean +/- SEM) for MDI plus extension chamber and 1.22 +/- 0.35 for jet nebulizer (p less than 0.001). Therefore, this trial shows significantly greater efficiency of aerosol deposition to the lung in ventilator-dependent patients when using an MDI plus aerosol holding chamber than when using a jet nebulizer.

Videofluorography and pulsed fluoroscopy using a 512 X 512-pixel digital image system.

The combination of videofluorography and pulsed fluoroscopy using an analog videodisc system has previously been investigated with regard to image quality and potential for dose reduction. The authors found that the system could be improved still further by replacing the analog disc with a 512 X 512-pixel digital image system, thereby increasing fluoroscopic image quality and permitting stored images to be recorded with a multiformat camera. The pulsed method is compared with low-dose-rate fluoroscopy, in which a continuous image is obtained at 1/4 of the normal rate. Whereas image quality using a low dose rate was inadequate for any useful purpose, pulsed fluoroscopy was sufficient for all but the most critical stages of the examination.