Citations

Abstract Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.

Background: Cardiovascular (CV) disease is the leading cause of death in U.S. women. Although women are becoming more aware of CV disease, there remains a dichotomy between awareness and perceived risk. We sought to characterize this dichotomy in women attracted to a CV health–screening event, in order to improve strategies to reduce CV risk. Methods: During CV health events held in Rochester, Minnesota, from 2007 through 2011, 294 women underwent screening for blood chemistry, body mass index, and blood pressure. Participants also completed surveys about knowledge of CV disease, risk factors, and perceived risk. Risk level was determined from the 2011 American Heart Association Effectiveness-Based Guidelines for Women. Results: Among participants (age, mean [standard deviation], 53 [15.3] years; white, 98%), 99% were aware that CV disease is the leading cause of death in women. Almost half (47%) perceived themselves to be at personal risk, although 65% were determined to be “at risk” and 12% to be at “high risk” according to guidelines, while 22% were uncategorized. Of the 228 participants “at risk” or “high risk,” 48% and 21%, respectively, did not perceive themselves to be at any risk. Conclusions : Women attracted to CV health events were aware that CV disease is the leading cause of death for women. However, the magnitude of awareness did not directly translate into perception or understanding of actual personal risk. To decrease the rate of CV disease in women, continued efforts are needed to personalize the importance of, and the methods for reducing, CV risk factors.

BackgroundAlcohol withdrawal accounts for a significant amount of hospital admissions and can quickly progress to the development of delirium tremens (DTs), seizures, and death. Rapid identification and management of alcohol withdrawal syndrome (AWS) is vital and can be managed with a number of different treatment strategies. Diazepam loading is a treatment strategy that utilizes the pharmacokinetics of this agent to achieve a rapid reduction in symptoms followed by sustained benefit over a period of days.ObjectiveThe purpose of this review is to evaluate the role of diazepam loading for AWS.MethodsA literature search of four databases—Pubmed, PsychInfo, Biosis, and Embase—was conducted to identify publications between 1960 and August 2011 that described the use of diazepam loading for the treatment of AWS. Eight trials, both open‐label and controlled trials were identified. Only four randomized controlled‐trials (RCTs) have been published and they are reviewed in this paper.ResultsIncluded trials of hospitalized inpatients found that diazepam loading provided rapid symptom relief as well as reduced the incidence of seizures and duration of DTs. In patients diagnosed with severe DTs, rapidly administered doses of diazepam produced a quick calming effect. While no adverse events resulting from diazepam loading were noted, no formal assessment tool was used to evaluate its safety. Larger randomized controlled‐trials are needed to better evaluate safety outcomes.ConclusionsDiazepam loading is an effective treatment option for hospitalized patients experiencing AWS. Diazepam loading uses the concept of symptom‐triggered therapy, a mainstay of current AWS treatment, while exploiting its prolonged elimination half‐life and eliminating the need for additional pharmacologic therapy. Studies reviewed found diazepam loading significantly improved a number of important outcomes in AWS, including time in DTs, compared to traditional treatment strategies. (Am J Addict 2013;22:113‐118)

Objective— Matrix gla protein (MGP) inhibits arterial and cartilaginous calcification. A threonine to alanine (Thr83Ala) polymorphism (codon 83) in MGP is associated with myocardial infarction and femoral artery calcification. We examined the association of the MGP Thr83Ala polymorphism with quantity and progression of coronary artery calcification (CAC), a noninvasive measure of subclinical coronary atherosclerosis. Methods and Results— In 605 participants of the Epidemiology of Coronary Artery Calcification Study, generalized linear mixed models were fit to determine the association of MGP Thr83Ala with CAC quantity and progression. There was a significant additive relation between MGP Thr83Ala and CAC progression ( P =0.001). In the fully adjusted model, every 1 Ala83 allele increase was associated with an estimated 1.9% (95% confidence interval, 0.7%–3.0%) per year since baseline larger increase in CAC quantity. A proxy single nucleotide polymorphism for MGP Thr83Ala (rs6488724) was similarly associated with CAC progression in an independent cohort from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Conclusion— Increased risk of myocardial infarction associated with MGP ThrAla83 genotype observed elsewhere may be related to faster progression of subclinical coronary atherosclerosis. MGP genotype could be a potential candidate for identifying individuals at increased risk of atherosclerotic disease who would benefit from aggressive primary prevention strategies.

Little is known about the distribution of prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in the canine kidney. To determine the basal and stimulated profiles of PGE2 and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6 x 10(-4) M), bradykinin (9.4 x 10(-6) M), or indomethacin (10(-5) M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGE2 and 6-keto-PGF1 alpha were highest in the innermost zones of the inner medulla (PGE2, 3,328 +/- 549 pg/mg; 6-keto-PGF 1 alpha, 1,611 +/- 129 pg/mg) and decreased exponentially to low levels in the cortex (PGE2, undetectable; 6-keto-PGF1 alpha, 13 +/- 2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGE2 in all zones of the kidney and the production of 6-keto-PGF1 alpha only in zones 3-6.(ABSTRACT TRUNCATED AT 250 WORDS)