Departments of Emergency Medicine and Anesthesiology, Centre de Santé et de Services Sociaux Alphonse-Desjardins-Centre Hospitalier Affilié Universitaire de Lévis, Lévis, QC, Canada. email@example.com
Etomidate is frequently used to intubate traumatic brain injury (TBI) victims, even though it has been linked to adrenal insufficiency (AI) in some populations. Few studies have explored the risk of prolonged etomidate-induced AI among TBI victims.
To determine the risk and the length of AI induced by etomidate in patients intubated for moderate and severe TBI.
Participants in this observational study were moderate to severe intubated TBI victims aged = 16 years. The anesthetic used (etomidate versus others) was determined solely by the treating emergency physician. Adrenocorticotropic hormone (ACTH) stimulation tests (250 µg) were performed 24, 48, and 168 hours after intubation. AI was defined as an increase in serum cortisol 1 hour post-ACTH test (delta cortisol) of less than 248.4 nmol/L.
Forty subjects (participation 42.6%) underwent ACTH testing. Fifteen received etomidate, and 25 received another anesthetic. There were no statistically significant differences between groups as to the cumulative incidence of AI at any measurement time. However, at 24 hours, exploratory post hoc analyses showed a significant decrease in delta cortisol (adjusted means: etomidate group: 305.1 nmol/L, 95% CI 214.7-384.8 versus other anesthetics: 500.5 nmol/L, 95% CI 441.8-565.7). This decrease was not present at 48 and 168 hours.
In TBI victims, although a single dose of etomidate does not increase the cumulative incidence of AI as defined, it seems to decrease the adrenal response to an ACTH test for 24 hours. The clinical impacts of this finding remain to be determined.
Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.
A combination of the inhaled corticosteroid budesonide and the long-acting ?2-agonist formoterol has been formulated in a novel dry powder inhaler, Spiromax(?). The objective was to compare lower leg growth in children with asthma treated with inhaled budesonide+formoterol (BF) delivered from the Spiromax inhaler with BF from the Symbicort Turbohaler(?).
Prepubescent children with persistent asthma (n=75, aged 6-11 years) were included in a randomized, double-blind, double-dummy, placebo-controlled, three-way crossover study with active treatment and placebo periods of 2 weeks duration. Lower leg length was measured every second week. As a secondary outcome parameter, 24-hr urine was collected for assessment of free cortisol. Interventions were dry powder BF 160+9??g twice daily (b.i.d.; delivered dose) from the Spiromax inhaler and dry powder BF 200+12??g b.i.d. (metered dose) from the Symbicort Turbohaler.
The least squares mean difference in lower leg growth rates (LLGR) between BF Spiromax and Symbicort Turbohaler was -0.086?mm/week [95% confidence interval (CI) -0.203, 0.032]. The pre-specified non-inferiority margin was -0.200?mm/week, so the lower limit of the 95% CI was just outside this margin. The difference between BF Spiromax and placebo was -0.20?mm/week (95% CI: -0.322, 0.086); p
Blood pressure in 6-month hypertensive NISAG rats daily treated with enalapril in the early postnatal period was lower than in control rats. Enalapril produced significant morphological alterations only in the zona glomerulosa of the adrenal cortex. The volumes of this area and the corresponding endocrine cells were lower than in the control. Enalapril produced a delayed modifying effect on the structure of the adrenal zona glomerulosa by moderating hyperplasic alterations, which are characteristic of intact mature NISAG rats.
Neonatal injection of sodium glutamate before injection of diethylnitrosamine decreased the number of tumor nodes in the liver of male mice, decreased the weight of the testes and adrenals and blood level of testosterone (but increased blood level of corticosterone), impaired recovery of diethylnitrosamine-disturbed sexual motivation in half of males. Anticarcinogenic effect of sodium glutamate is explained by feminization of males under its effect.
To compare the effects of two progestogen-only pills, containing either desogestrel or levonorgestrel, on carbohydrate metabolism, and adrenal and thyroid function.
In a double-blind, randomized, multicenter study in Finland, 84 healthy female volunteers received either desogestrel 75 microg/day or levonorgestrel 30 microg/day for seven treatment periods of 28 days. The following laboratory parameters were measured at screening, and at treatment periods 3 and 7: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin (HbA1C)), adrenal function (total cortisol, cortisol binding globulin (CBG), dehydroepiandrosterone sulfate (DHEAS)), thyroid function (thyroid stimulating hormone, free thyroxine).
Overall, the effect on carbohydrate metabolism was minimal with both study medications. There was a trend for higher glucose and insulin values for the levonorgestrel group at both treatment periods 3 and 7. None of the changes were thought to be clinically relevant. Both preparations had similar small effects on HbA1C values, indicating that carbohydrate metabolism was not affected. No effects were found on thyroid function parameters or DHEAS in either treatment group; however, total cortisol and CBG were slightly higher with desogestrel than with levonorgestrel. These changes were not considered to be clinically relevant. Both treatments were well tolerated.
The effects of both progestogen-only pills on carbohydrate metabolism were minimal and considered to be clinically insignificant. With regard to adrenal and thyroid function, the effects of desogestrel were not significantly different from those of levonorgestrel.