ABSTRACT
BACKGROUND: Early adrenaline administration is associated with return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest (OHCA). Animal data demonstrate a similar rate of ROSC when early intramuscular (IM) adrenaline is given compared to early intravenous (IV) adrenaline. AIM: To evaluate the feasibility of protocolized first-dose IM adrenaline in OHCA and it's effect on time from Public Safety Access Point (PSAP) call receipt to adrenaline administration when compared to IO and IV administration. METHODS: This is a before-and-after feasibility study of adult OHCAs in a single EMS service following adoption of a protocol for first-dose IM adrenaline. Time from PSAP call to administration and outcomes were compared to 674 historical controls (from January 1, 2013-February 8, 2021) who received at least one dose of adrenaline by IV or IO routes. RESULTS: During the study period, first-dose IM adrenaline was administered to 99 patients (December 1, 2019-February 8, 2021). IM adrenaline was given a median of 12.2 min (95% CI 11.4-13.1 min) after the PSAP call receipt compared to 15.3 min for the IV route (95% CI 14.6-16.0 min) and 15.3 min for the IO route (95% CI 14.9-15.7 min) with a time savings of 3 min (95% CI 2-4 min). Rates of survival to hospital discharge appeared similar between groups: 10% for IM, 8% for IV and 7% for IO. However, results related to survival were underpowered for statistical comparison. CONCLUSIONS: Within the limitations of a small sample size and before-and-after design, first-dose IM adrenaline was feasible and reduced the time to adrenaline administration.
ABSTRACT
Prostate-specific antigen (PSA) has been used clinically as a marker for the diagnosis and staging of prostate cancer due to its specific expression in prostate epithelial cells. In addition to its medical importance, its complex hormonal and tissue-specific regulation makes it an attractive model to study gene regulation. Two approaches have been applied to the identification of regulatory regions which confer this specific expression pattern. In vitro analysis of the regulatory regions of the human PSA gene using promoter reporter constructs and tumor cell lines has revealed a number of the DNA sequences involved in the hormone-dependent expression of PSA. We have pursued an alternative in vivo approach using transgenic animal technology, which is the focus of this review. Using this second approach, a transgenic mouse was generated using a 14 kilobase (kb) region of the human PSA gene encompassing the coding region and intervening sequences as well as 6 kb of upstream sequence and 2 kb of downstream sequence. This genomic DNA clone confers a PSA expression pattern in mice which appears to be very similar if not identical to that of humans, allowing us to investigate tissue-specificity and developmental regulation of PSA expression. In addition, these mice, for which PSA is a self-antigen, provide a model to test the feasibility and efficacy of PSA-directed immunotherapy for prostate cancer. The further identification of the PSA regulatory regions important for tissue-specificity may ultimately allow the design of new therapeutics for the treatment of prostate cancer.
