Systemic toxicity of di-2-ethylhexyl terephthalate (DEHT) in rodents following four weeks of intravenous exposure

a b s t r a c t Background: Di-2-ethylhexyl-terephtalate (DEHT) is a general purpose plasticizer and a structural isomer to di-2-ethylhexyl phthalate (DEHP) being known for its toxicity. Despite the fact that DEHT is used in quite a number of synthetics for medical device production including equipment for intravenous administration, toxicity of DEHT has not been assessed after/during intravenous exposure. Hence we report here the results of a toxicity study in male and female rats with continuous intravenous infusion of DEHT over 4 weeks. Methods: The study was done according to OECD guidelines under GLP conditions. The dose was infused per day to male and female rats over a period of 4 weeks with saline (control), middle chain triglycerides (vehicle) as well as with 38.2, 114.5 or 381.6 mg DEHT/kg. Each group (n = 6) was closely monitored regarding survival, body weight development, food and water consumption. Moreover blood and urine samples were taken and a standardized necropsy as wall as a histological analysis was performed after the investigation period. Results: DEHT had no effect on survival, body weight development, food and water consumption in the whole dose range investigated. There were no indications as to hematotoxicity or immunotoxicity. Clinical chemistry and histopathology indicated no exposure related effect on hepatic, thyroidal and reproductive functions or organs. Conclusion: DEHT administered via intravenous infusion was tolerated systemically and locally without adverse effects up to and including 381.6 mg/kg/day (NOAEL = 381.6 mg/kg × day). In particular, there were no effects on reproductive tissues/organs, kidneys, liver hepatocytes and peroxisomes, which are known targets of DEHP-toxicity

Genome-wide Association Study of Postoperative Cognitive Dysfunction in Older Surgical Patients

Postoperative cognitive dysfunction (POCD) is a common neurocognitive disorder after surgery and anesthesia, particularly in elderly patients. Various studies have suggested genetic risk factors for POCD. The study aimed to detect genome-wide associations of POCD in older patients.; In this prospective observational cohort study, participants aged 65 years and above completed a set of neuropsychological tests before, at 1 week, and 3 months after major noncardiac surgery. Test variables were converted into standard scores (z-scores) based on demographic characteristics. POCD was diagnosed if the decline was >1 SD in ≥2 of the 15 variables in the assessment battery. A genome-wide association study (GWAS) was performed to determine potential alleles that are linked to the POCD phenotype. In addition, candidate genes for POCD were identified in a literature search for further analysis.; Sixty-three patients with blood samples were included in the study. POCD was diagnosed in 47.6% of patients at 1 week and in 34.2% of patients at 3 months after surgery. Insufficient sample quality led to exclusion of 26 patients. In the remaining 37 patients, a GWAS was performed, but no association (P<5×10) with POCD was found. The subsequent gene set enrichment analysis of 34 candidate genes did not reveal any significant associations.; In this patient cohort, a GWAS did not reveal an association between specific genetic alleles and POCD at 1 week and 3 months after surgery. Future genetic analysis should focus on specific candidate genes for POCD. What do you want to do ? New mail Copy What do you want to do ? New mail Cop

Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs optimized medical treatment strategy: one-year results of the randomized TIME trial

CONTEXT: The risk-benefit ratio of invasive vs medical management of elderly patients with symptomatic chronic coronary artery disease (CAD) is unclear. The Trial of Invasive versus Medical therapy in Elderly patients (TIME) recently showed early benefits in quality of life from invasive therapy in patients aged 75 years or older, although with a certain excess in mortality. OBJECTIVE: To assess the long-term value of invasive vs medical management of chronic CAD in elderly adults in terms of quality of life and prevention of major adverse cardiac events. DESIGN: One-year follow-up analysis of TIME, a prospective randomized trial with enrollment between February 1996 and November 2000. SETTING AND PARTICIPANTS: A total of 282 patients with Canadian Cardiac Society class 2 or higher angina despite treatment with 2 or more anti-anginal drugs who survived for the first 6 months after enrollment in TIME (mean age, 80 years [range, 75-91 years]; 42% women), enrolled at 14 centers in Switzerland. INTERVENTIONS: Participants were randomly assigned to undergo coronary angiography followed by revascularization (if feasible) (n = 140 surviving 6 months) or to receive optimized medical therapy (n = 142 surviving 6 months). MAIN OUTCOME MEASURES: Quality of life, assessed by standardized questionnaire; major adverse cardiac events (death, nonfatal myocardial infarction, or hospitalization for acute coronary syndrome) after 1 year. RESULTS: After 1 year, improvements in angina and quality of life persisted for both therapies compared with baseline, but the early difference favoring invasive therapy disappeared. Among invasive therapy patients, later hospitalization with revascularization was much less likely (10% vs 46%; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.11-0.32; P&lt;.001). However, 1-year mortality (11.1% for invasive; 8.1% for medical; HR, 1.51; 95% CI, 0.72-3.16; P =.28) and death or nonfatal myocardial infarction rates (17.0% for invasive; 19.6% for medical; HR, 0.90; 95% CI, 0.53-1.53; P =.71) were not significantly different. Overall major adverse cardiac event rates were higher for medical patients after 6 months (49.3% vs 19.0% for invasive; P&lt;.001), a difference which increased to 64.2% vs 25.5% after 12 months (P&lt;.001). CONCLUSIONS: In contrast with differences in early results, 1-year outcomes in elderly patients with chronic angina are similar with regard to symptoms, quality of life, and death or nonfatal infarction with invasive vs optimized medical strategies based on this intention-to-treat analysis. The invasive approach carries an early intervention risk, while medical management poses an almost 50% chance of later hospitalization and revascularization