Detecting SNP-expression associations: a comparison of mutual information and median test with standard statistical approaches.

Single nucleotide polymorphism-gene expression associations have received increasing interest. The aim of these studies is discovering a difference in the location parameters of gene expressions given genotype. Because gene expressions often are highly skewed, heavy-tailed or data of different genotypes vary in dispersion, the median is the most appropriate measure of location. In this case, model assumptions of standard statistical methods for comparing locations such as the analysis of variance (ANOVA) or the Kruskal-Wallis (KW) test are violated. Alternatives that might be more appropriate are the median test (MED) and tests based on mutual information (MI). In simulation studies these approaches and a novel MI test are compared with ANOVA and KW. Location, dispersion and skewness parameters of the gene expression distributions given genotypes are varied as well as genotype frequencies. The MED test and the novel MI-based method keep the nominal significance levels for comparing medians if gene expression data are non-normally distributed. ANOVA and KW have substantially inflated type I errors. They are, however, optimal if standard model assumptions are fulfilled. The MED test generally has larger power than MI and is therefore recommended if model assumptions of standard procedures are violated. A 300 kb region on chromosome 9p21.3, which is associated with coronary artery disease, was analyzed using the HapMap data. Only the alternative approaches were able to identify three genes (ADM, FCGR3B and ADORA1) as promising candidates to clarify the molecular mechanism of the genetic association.

Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646,000 for goats and between 17,000 and 267,000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between -106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

Propofol concentration in exhaled air and arterial plasma in mechanically ventilated patients undergoing cardiac surgery.

BACKGROUND: Measuring propofol concentration in plasma (c(P)PL) and in exhaled alveolar gas (c(P)G) during constant infusion provides information about their respective time courses. In the present study, we compared these time courses in patients undergoing cardiac surgery from the beginning of propofol anaesthesia until eye opening upon awakening. METHODS: The c(P)G was measured before, during, and after continuous infusion of propofol for general anaesthesia in 12 patients at two randomly allocated doses (3 or 6 mg kg(-1) h(-1)). Gas samples were collected on Tenax tubes. After thermodesorption, c(P)G was measured by gas chromatography mass spectrometry. Simultaneously with exhaled gas, arterial blood was sampled for measuring c(P)PL by reversed-phase high-performance liquid chromatography with fluorescence detection. In order to compare the time courses of c(P)PL and c(P)G as dimensionless values directly, each gas and plasma value was normalized by relating it to the corresponding value at the end of the initial infusion after 40 min. RESULTS: The c(P)G ranged between 2.8 and 22.5 ppb, whereas the corresponding c(P)PL varied between 0.3 and 3.3 microg ml(-1). Normalized concentration values showed a delayed increase in c(P)G compared with c(P)PL under constant propofol infusion before the onset of cardiopulmonary bypass, and a delayed decrease after stopping the propofol at the end of anaesthesia. CONCLUSIONS: Propofol can be measured in exhaled gas from the beginning until the end of propofol anaesthesia. The different time courses of c(P)PL and c(P)G have to be considered when interpreting c(P)G.