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1.
Respir Physiol Neurobiol ; 299: 103858, 2022 05.
Article in English | MEDLINE | ID: mdl-35114370

ABSTRACT

Various in vitro neonatal rodent models have been developed to study the control of breathing, but translation of the information requires a behavioral assay, which has led to the widespread use of plethysmography to measure breathing in awake neonatal rodents. Best practice requires correcting changes in ventilation to the corresponding change in metabolic rate, which is the main driver of pulmonary ventilation. Obtaining measures of both simultaneously is ideal, though technically difficult. Here we describe a simple, inexpensive home-made dual chamber approach for simultaneous measurement of pulmonary ventilation and metabolic rate. We found that the dual chamber provides values for pulmonary ventilation and metabolic rate that compare favorably with existing approaches.


Subject(s)
Pulmonary Ventilation , Rodentia , Animals , Lung , Plethysmography , Respiration
2.
Am J Med ; 134(1): 122-128.e3, 2021 01.
Article in English | MEDLINE | ID: mdl-32628915

ABSTRACT

BACKGROUND: Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular endothelial growth factor (VEGF) induces growth of new blood vessels that leak fluid, accounting for 90% of vision loss in AMD. Dysfunction of the retinal pigment epithelium likely initiates AMD. Retinal pigment epithelial cells express a G protein-coupled receptor, GPR143, which downregulates VEGF in response to levodopa. Anti-VEGF therapy effectively treats nAMD, suggesting that excessive VEGF activity drives the pathology. METHODS: In an open-label pilot study, in patients with newly diagnosed nAMD and naïve to anti-VEGF injections (Cohort-1), the effects of carbidopa-levodopa on vision and anatomic outcomes were evaluated for 4 weeks. Then patients were followed 5 months further with ascending levodopa doses. Patients previously treated with anti-VEGF injection therapy (Cohort-2) were also treated with ascending levodopa doses and evaluated for 6 months. RESULTS: Levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment. Through 6 months the decrease in retinal fluid was sustained, with a mean frequency of 0.38 injections/month. At month 6, mean visual acuity improved by 4.7 letters in Cohort-1 (P = .004, n = 15) and by 4.8 letters in Cohort-2 (P = .02, n = 11). Additionally, there was a 52% reduction in the need for anti-VEGF injections in Cohort-2 (P = .002). CONCLUSIONS: Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies.


Subject(s)
Carbidopa/pharmacology , Levodopa/pharmacology , Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Carbidopa/therapeutic use , Cohort Studies , Dopamine Agents/pharmacology , Dopamine Agents/therapeutic use , Drug Combinations , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Pilot Projects , Treatment Outcome
4.
Asia Pac J Ophthalmol (Phila) ; 9(2): 117-125, 2020.
Article in English | MEDLINE | ID: mdl-31977331

ABSTRACT

PURPOSE: The aim of this study was to determine whether there are significant clinical variations in the Belin/Ambrosio Enhanced Ectasia Display (BAD display) parameters between Chinese and North American eyes and whether any variations are related to differences in corneal diameter. DESIGN: Retrospective observational study. METHODS: Files were generated from patients seeking refractive surgical correction. Patients with previous surgery, evidence of corneal ectasia, or scans representing a non-normal cornea were excluded. Unpaired t tests were performed for all variables. Regression analyses were performed for all variables with respect to corneal diameter, and compared to evaluate the influence of corneal diameter between populations. Data were graphed as standard scores (z scores) to compare different parameters. RESULTS: 127 North American and 49 Chinese patients met study criteria. Statistically significant differences existed for corneal diameter (P < 0.01), anterior elevation at the thinnest point (P < 0.01), and Df (P < 0.01). In both populations, statistically significant correlations existed between corneal diameter and most indices, and most profoundly on pachymetric progression and final D. Regression slopes revealed a statistically significant difference for the influence of corneal diameter on ARTmax (P = 0.04) and was nearly significant for final D (P = 0.06). CONCLUSIONS: Corneal diameter had the greatest influence on pachymetric progression and final D, and more profoundly in the Chinese. This suggests that incorporating corneal diameter as an additional variable may make the BAD display more universally applicable. Also, the differences in anterior elevation parameters suggest that specific ethnic/geographic normative values may be beneficial for the BAD display.


Subject(s)
Asian People/ethnology , Refractive Errors/diagnostic imaging , Refractive Errors/ethnology , Tomography , White People/ethnology , Adolescent , Adult , China/epidemiology , Cornea/pathology , Female , Humans , Male , Middle Aged , North America/epidemiology , Refractive Surgical Procedures , Retrospective Studies , Young Adult
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