HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Elimination of Laparoscopic Lens Fogging Using Directional Flow of CO2

Background and Objectives: Surgeons constantly struggle with the formation of condensation on the lens of a. laparoscope, which prolongs procedures and reduces visibility of the abdominal cavity. The goal of this project was to build a device, that would direct a flow of carbon dioxide (CO2) into an open chamber surrounding the lens of a laparoscope, acting to keep moisture away from the lens and eliminate condensation. Methods: The device isolates the lens of the laparoscope from the humid environment of the intraperitoneal cavity by creating a microenvironment of dry CO2. This was accomplished by building a communicating sleeve that created an open chamber around the distal 2 to 3 cm of the scope. Into this cavity, dry cool CO2 was pumped in from an insufflator so that the path of the gas would surround the lens of the scope and escape through a single outlet location through which the scope views the intraperitoneal cavity. This chamber is proposed to isolate the lens with a high percentage of dry CO2 and low humidity. The device was tested in 7 different adverse conditions that were meant to challenge the ability of the device to maintain the viewing field with no perceptible obstruction. Results: In all of the conditions tested 25 trials total he device successfully prevented and/or eliminated laparoscopic lens fogging. Conclusions: The device designed for this project points to the potential of a simple and effective mechanical method for eliminating laparoscopic lens fogging