Acute hormonal findings after aneurysmal subarachnoid hemorrhage - report from a single center

Purpose: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome. Material and methods: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident. Results: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15-20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33-45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28-26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06-10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22-77.10, p = 0.04). Conclusion: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings.Peer reviewe

Fatal traumatic brain injuries during 13 years of successive alcohol tax increases in Finland - a nationwide population-based registry study

We sought to investigate how increases in alcohol taxation and changes in alcohol consumption were associated with the incidence rate of fatal traumatic brain injuries (TBI) in Finland during the years 2004-2016. Nationwide, mandatory cause of death database covering all deaths in Finland was searched for all deaths related to TBIs (ICD-10: S06.X) in persons >= 16 years of age during 2004-2016. Study period included 28,657,870 person-years and 325,514 deaths of which 12,110 were TBI-related. Occurrence rates were standardized to European 2013 standard population. Data for alcohol consumption were obtained from the National Institute for Health and Welfare and for alcohol taxation from Ministry of Finance, Finland. Standardized incidence rate of TBI-related death was 22.0 (95%Cl 21.61-22.38) per 100,000 person-years. Overall alcohol consumption decreased on average by 1.2% annually. Concurrently, the overall incidence rate of fatal TBIs decreased by 4.1% annually (by 4.3% in men and 2.4% in women). There was an association between overall alcohol consumption and TBI-related mortality rate (p < 0.001). Tax-rate increases of all beverage types were associated with decreased incidence rate of TBI-related death in men (p < 0.001), in women (p < 0.036) and overall (p < 0.001). In this population-based study, we report that during 13 years of successive alcohol tax increases, overall alcohol consumption has decreased in parallel with a reduction in the incidence rate of fatal TBIs in Finland

DNA Topoisomerase I Is a Cofactor for c-Jun in the Regulation of Epidermal Growth Factor Receptor Expression and Cancer Cell Proliferation

DNA topoisomerase I (Topo I) is a molecular target for the anticancer agent topotecan in the treatment of small cell lung cancer and ovarian carcinomas. However, the molecular mechanisms by which topotecan treatment inhibits cancer cell proliferation are unclear. We describe here the identification of Topo I as a novel endogenous interaction partner for transcription factor c-Jun. Reciprocal coimmunoprecipitation analysis showed that Topo I and c-Jun interact in transformed human cells in a manner that is dependent on JNK activity. c-Jun target gene epidermal growth factor receptor (EGFR) was identified as a novel gene whose expression was specifically inhibited by topotecan. Moreover, Topo I overexpression supported c-Jun-mediated reporter gene activation and both genetic and chemical inhibition of c-Jun converted cells resistant to topotecan-elicited EGFR downregulation. Topotecan-elicited suppression of proliferation was rescued by exogenously expressed EGFR. Furthermore, we demonstrate the cooperation of the JNK-c-Jun pathway, Topo I, and EGFR in the positive regulation of HT-1080 cell proliferation. Together, these results have identified transcriptional coactivator Topo I as a first endogenous cofactor for c-Jun in the regulation of cell proliferation. In addition, the results of the present study strongly suggest that inhibition of EGFR expression is a novel mechanism by which topotecan inhibits cell proliferation in cancer therapy