Personality traits of agreeableness and extraversion are associated with ADH4 variation.

BACKGROUND: Personality traits are associated with substance dependence (SD); genetic factors may influence both. Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study. METHODS: We assessed dimensions of the five-factor model of personality in 243 subjects with SD (175 European Americans [EAs] and 68 African Americans [AAs]) and 296 healthy control subjects (256 EAs and 40 AAs). We also genotyped 7 ADH4 markers (spanning the locus) and 38 unlinked ancestry-informative markers in these subjects. The relationships between the diplotypes, alleles, and genotypes at ADH4 and personality traits were examined using multivariate analysis of covariance (MANCOVA), controlling for potential confounders. RESULTS: Generally, SD patients, older individuals, and male subjects scored higher on neuroticism and lower on other personality factors. Personality factors were associated with the diplotypes. The allele A or genotype A/A of single nucleotide polymorphism (SNP)6 (rs1800759 at the gene promoter) was significantly associated with agreeableness scores. There were associations between extraversion and SNP1 (hcv2033010 at the 3' end) and SNP2 (rs1042364 in exon 9) in subjects with higher conscientiousness scores. CONCLUSIONS: The personality traits of agreeableness and extraversion are related to ADH4 polymorphism. Among the ADH4 markers that appear to predispose to certain personality traits, the functional variant rs1800759 (SNP6) in the promoter region is most important. We conclude that personality traits and SD have a partially overlapping genetic basis.     

Reduced virulence of Candida albicans mutants affected in multidrug resistance.

Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.     

Capillary gas chromatographic assay of camphor and m-cresol in dermatological creams

Camphor and m-cresol mixtures are used in antiseptic and anti-itching creams. No compendial method exists for these preparations. This paper reports a capillary gas chromatographic method using FID detection with 2,6-di-tert-butyl-4-methylphenol as internal standard on a 30 m×0.32 mm Supelcowax®-10 column (0.25 μm film) with helium as carrier gas. Ramped temperature programming was applied. The method allows simultaneous quantitation of camphor and m-cresol in the presence of o- and p-cresols, calamine and zinc oxide. Overall percent recoveries (±SD, n=9) of camphor, o-, p- and m-cresol from spiked placebo creams, at a labeled amount of 10 (w/w)% were 96.9±0.6, 98.2±0.6, 99.2±0.5 and 101.0±0.9%, respectively, and at a labeled amount of 1% were 96.7±0.6, 97.8±0.9, 97.8±0.6, and 100.3±1.0%, respectively. The recovery studies were carried out at ±30% of the labeled amounts. Linear peak area or height ratios were obtained (r>0.999) for camphor, o-, p- and m-cresol covering a concentration range of 10–200% of the labeled amount. Linearity (r>0.999) was also obtained for m-cresol when the relative concentration of o- and p-cresol was varied from 5 to 100% of the m-cresol concentration. The resolution between the ‘critical pair’ of p- and m-cresol was ≥1.1. The limit of quantitation was 23 pg for m-cresol and 9.3 pg for camphor using an injection split of 1:50. The repeatability (%RSD) for all compounds were <2% for peak area and <1.4% for peak height ratios. System suitability and robustness of the method were established. The method was successively applied to the assay of available commercial products and allows assay of camphor and the three cresol isomers.     

More-sensitive enzyme-multiplied immunoassay technique for procainamide and N-acetylprocainamide in plasma, serum, and urine

A commercially available (Syva Co.) enzyme-multiplied immunoassay technique (EMIT) for the quantitative determination of procainamide (PA) and N-acetylprocainamide (NAPA) was modified to allow automated quantitative analysis of approximately 100 samples per day, in a working range of 0.1 to 2.0 micrograms/mL. Such a test was needed to evaluate the pharmacokinetic characteristics of controlled-release dosage forms characterized by long half-lives at low plasma concentration. Analytical recovery of PA and NAPA from serum, plasma, and urine was satisfactory, but at extreme ratios for PA:NAPA the accuracy of determining the lower-concentration component became unsatisfactory. In fact, however, we found no such ratios in 5400 clinical samples assayed by this procedure.     

Developing a Peer Review Process for Web-based Curricula

The World Wide Web creates new challenges and opportunities for medical educators. Prominent among these are the lack of consistent standards by which to evaluate web-based educational tools. We present the instrument that was used to review web-based innovations in medical education submissions to the 2003 Society of General Internal Medicine (SGIM) national meeting, and discuss the process used by the SGIM web-based clinical curriculum interest group to develop the instrument. The 5 highest-ranked submissions are summarized with commentary from the reviewers.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

Sparing of perceptual implicit memory despite suppression of the electrophysiological word repetition effect: a study with general anesthetic isoflurane.

OBJECTIVE: Much effort has been devoted to the search for the neurophysiological correlates of implicit memory. A commonly held view is that the early portion (250-500 ms) of the event-related potential (ERP) word repetition effect reflects processes important for perceptual implicit memory whereas the latter portion reflects processes implicated in explicit memory. It is, however, difficult to disentangle with certainty the relative contributions of each form of memory on ERPs since both forms co-exist in normal subjects. To dissociate ERP effect related to implicit and explicit memory, we used isoflurane sedation in normal subjects to suppress explicit remembering while sparing implicit memory. These ERPs were compared with those of non-medicated control subjects. METHODS: Thirteen subjects performed an incidental encoding task for words presented auditorily during the inhalation of a subanesthetic dose of isoflurane. After termination of isoflurane administration, we assessed free recall and recorded ERPs during a syllable completion task (implicit memory) and during a passive listening task (ERP repetition effect). Eleven non-medicated control subjects were tested in a similar manner. RESULTS: The controls showed robust early and late ERP repetition effect. The isoflurane group had implicit memory without free recall and showed no ERP repetition effect. CONCLUSIONS: These findings failed to show an association between any part of the repetition effect and perceptual implicit memory. The results are consistent with the view that processes linked to explicit memory contribute to the ERP repetition effect since there was a marked difference in free recall between the control and isoflurane groups. SIGNIFICANCE: The present study shows that the reversible alterations of memory by general anesthetics can be used to study the neurophysiological correlates of memory processes.