Germline mutations of the MSR1 gene in prostate cancer families from Germany

The MSR1 gene at 8p22 has been suggested as a candidate gene for hereditary prostate cancer because germline variants have been found to be associated with the disease. Aside from a single nonsense mutation (R293X) that was found repeatedly at low frequencies in several samples, little evidence has been gained by follow-up studies to confirm the gene's relevance for prostate cancer. Prompted by reasonable support for a linkage to 8p22, we sought to determine the mutation spectrum of MSR1 in our family sample. Screening of 139 probands (representing 139 prostate cancer families) revealed 15 novel and a total of 20 sequence variants within the 10 coding exons and their intronic proximities. Aside from the known mutation c.877C>T (R293X) present in two of our families, we identified a second nonsense allele (c.251C>G; S84X) and a splice-site mutation (c.818-1G>A) that results in mRNA instability (each in a single pedigree). The novel missense alleles were c.703C>T (H235Y), c.856C>T (P286S), c.905C>T (P302L), c.1193C>G (A398G), and c.1289A>G (K430R). Of the eight variants that affect the encoded protein (splice site, nonsense, and missense), only R293X as well as the polymorphism c.823C>G (P275A) were additionally present at remarkable frequencies in further samples of sporadic prostate cancer and controls. Of note, carriers of R293X were equally frequent in 367 sporadic prostate cancer cases (1.9%) and in 197 controls (2.0%). To our knowledge, our study is the first to demonstrate further loss of function variants of MSR1 apart from R293X. Nevertheless, the low frequencies of deleterious alleles, in addition to an apparently moderate penetrance, does not support MSR1 as a major susceptibility gene in this family sample.     

Linear and non-linear heart rate variability measures in chronic and acute phase of anorexia nervosa

Previous results on heart rate variability (HRV) analysis in anorexia nervosa (AN) include some apparently conflicting data. In order to find out the reason for different results and to improve understanding of autonomic control in AN we compare HRV in acute and chronic AN. Spectral powers, fractal scaling exponent and sample entropy were computed from 24 h RR series derived from Holter ECG recordings in 17 anorexic patients, nine chronic and eight healthy women. We found that all linear and non-linear HRV measures change in different direction in acute and chronic AN. Acute AN is characterized by decreased HR and increased HRV. In chronic AN, HR is increased, HRV reduced and the difference between awake and sleeping values is high. HRV measures are associated with body mass index only in chronic AN. As HRV measures are significantly different between acute and chronic AN, we propose that HRV analysis might provide additional data in clinical practice.     

Determination of fluorides in pharmaceutical products for oral hygiene

Fluorides are common ingredients in pharmaceutical products for oral hygiene due to their recognized effect in the prevention of tooth decay. In dental products, fluorides can be added in several different forms, such as sodium fluoride, sodium monofluorophosphate, tin fluoride, or in the form of different amines. This work describes potentiometric determination of fluorides in the samples of toothpastes and mouthwash. The method was optimized for the particular analytical purpose; namely, for the analysis of toothpastes and mouthwash by applying different sample preparation protocols depending on the fluoride source. Good recovery (93–103%) confirmed the correctness of the sample preparation procedures. Calculated limit of detection and limit of quantification for the optimized method were 1 × 10^?3 mg/L and 2.8 × 10^?3 mg/L fluoride, respectively. In the minority of the analyzed samples, calculated contents agreed well with the certified values, whereas the samples of mouthwash demonstrated better agreement.     

Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats

Background  

Fructose consumption produces deleterious metabolic effects in animal models. The sites of fructose-induced insulin resistance are documented to be the liver, skeletal muscle, and adipose tissue, but effects of fructose-rich diet on cardiac insulin signaling and action were not investigated.     

High Dose Adenosine Stress Echocardiography for Noninvasive Detection of Coronary Artery Disease

Objectives. The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD).

Background. In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has suboptimal sensitivity for detecting milder forms of CAD.

Methods. Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 μg/kg body weight per min over 3 min followed by 140 μg/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 μg/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as ≥50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients.

Results. The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617).

Conclusions. We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

(J Am Coll Cardiol 1996;28:1689–95)>     

Is hyperlipidemia correlated with longer survival in patients with amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is the most serious form of degenerative motor neuron disease in adults, whose relentless course leads to death within 2-5 years, generally due to respiratory failure. Apart from the age and site of onset, no other factors have consistently demonstrated to be related to the ALS outcome. The aim of the study was to investigate the influence of fasting serum lipid levels (cholesterol and triglycerides) and the body mass index (BMI) at the time of diagnosis on survival in ALS patients. The study included 82 patients with ALS residing in the Belgrade area who were diagnosed with ALS over a time period of 4 years (2006-2009). Survival was assessed by the Kaplan-Meier method. In this retrospective study, 39 (47.56%) patients had normal values of lipids and 43 (52.43%) patients had hyperlipidemia. The mean survival time from the onset of symptoms for patients with normal lipidemia was 4.21 ± 0.5 years, while the mean survival time from the onset of symptoms for patients with hyperlipidemia was 5.0 ± 0.67 years (P = 0.36). We also did not register a significant difference in survival in relation to gender, the site or age of onset, even though we noticed a longer survival in patients with hyperlipidemia in all of the examined groups, especially in the group of younger patients, with the onset of the disease before the age of 45 years. If we take into account the fact that BMI is pathophysiologically associated with cholesterol and triglyceride serum levels, the results in our study complement each other showing that patients with a higher BMI, registered in 28.8% of the cases, do not live longer. Our findings show that hyperlipidemia, which we found in 52.43% of our ALS patients, at the time of diagnosis, is not related to significantly longer survival.