Wall-thickness and midwall-radius variations in ventricular mechanics.

A fluid-fiber-collagen stress tensor is used to describe the rheology of the left ventricle of the heart. Linear theory is used to find the equilibrium solutions for the end-diastolic and end-systolic states of general axisymmetric shapes that are small perturbations of a thick-walled finite cylinder. The general problem can be studied by superposing the effects of variable midwall radius but constant wall thickness with those of variable wall thickness but constant midwall radius. A Fourier series representation is used to describe the midwall radius and thickness functions. Numerical calculations are performed to determine the deformed geometry and spatial distributions of tissue pressure, stresses, and fiber strains. The calculations proved to be highly accurate when compared to an analytical solution obtained for the special case of no fibers. The results show significant longitudinal differences when compared to results for the cylindrical geometry, with more sensitivity to variation in wall thickness than to variation in midwall radius.     

Self-Warming Lidocaine/Tetracaine Patch Effectively and Safely Induces Local Anesthesia during Minor Dermatologic Procedures

BACKGROUND Dermatologic procedures often cause some degree of pain. A self-warming patch containing lidocaine and tetracaine (L/T) was developed to provide topical local anesthesia prior to painful procedures.
OBJECTIVES To evaluate the safety and efficacy of a self-warming L/T patch to provide anesthesia in adult patients undergoing minor dermatologic procedures.
METHODS An active or placebo study drug was placed on adults 30 minutes prior to minor dermatologic surgical procedures in a prospectively randomized, double-blinded manner. Subcutaneous lidocaine injection was available during the procedure as a rescue medication if requested by the subject. Immediately following the procedure, the subjects, the investigator, and an independent observer rated pain intensity and adverse events were recorded.
RESULTS Patient-reported pain intensity was significantly lower in the L/T patch group (   p < .001  ). Investigators and an independent observer rated the pain in the L/T patch group to be less than in the placebo patch group (   p = .004  and   p < .001  , respectively). Forty-nine percent of patients in the placebo group required rescue subcutaneous lidocaine compared with 22% in the L/T patch study group (   p = .008  ). One patient in the L/T patch group reported a transient moderate burning sensation.
CONCLUSION The self-warming L/T patch was effective in providing clinically useful local anesthesia for minor dermatologic procedures in adult patients.
ZARS, INC., PROVIDED SUPPORT VIA A SPONSORED RESEARCH GRANT TO THE UNIVERSITY OF MIAMI.     

A likelihood approach to HLA serology.

A likelihood approach to HLA serology has been developed in which the aim is not to define a recognition set for a serum but to describe the serum's ability to react with each and every antigen in the test cells, this ability being quantified in terms of the probability of a positive reaction. For a given set of probabilities, one for each antigen, it is possible to derive the probability of the observed set of reactions (the likelihood of the set of probabilities). The maximum possible value of the likelihood for any possible combination of the probability set can then be sought, but this requires a maximization of likelihood with respect to 60-100 independent parameters. Theoretical considerations of the shape of the likelihood surface prove that, in this particular case, this is a feasible proposition. This approach allows the recognition of three groups of antigens: those for which there is considerable evidence of a specificity, those for which there is either no specificity or a very weak specificity, and those for which there is insufficient evidence on which to base a conclusion. The existence of a specificity can be tested using a log likelihood ratio as a statistic, but the usual assumption of a chi 2 distribution of this statistic cannot automatically be made in this situation. Therefore, the distribution is estimated by simulation. A serologist using this approach would receive considerably more information as to the serum's reaction patterns and valid statistics for the existence, or not, of a specificity.     

Recombination between HLA-A and C and between HLA-B and complement locus C4 in the same individual

In a French family with 2 parents and 5 children a crossing over was found in the HLA region on both of the parental haplotypes of one of the children. The following markers were studied: HLA-A, B, C,DR, DQ(MB), DP(SB), complement allotypes C4 and Bf and glyoxalase I polymorphism. In the third child, the paternal haplotype had a recombination between HLA-A and HLA-C and the maternal haplotype a recombination between HLA-B and complement locus C4. Mixed lymphocyte cultures confirmed the serological findings and non-HLA markers (blood groups and immunoglobulin allotypes) showed no evidence of extrapaternity. The family also demonstrates a probable duplication of the C4B1 gene in one of the paternal haplotypes.     

Gene polymorphisms and serological markers of patients with active Crohn's disease in a clinical trial of antisense to ICAM-1

Serological profiles for anti-Saccharomyces cerevisiae antibodies (ASCA)/ perinuclear antineutrophil cytoplasmic antibodies (pANCA) and gene polymorphisms in tumour necrosis factor (TNF)-alpha and intercellular adhesion molecule-1 (ICAM-1) are associated with occurrence and/or outcome in Crohn's disease. The aim of the study was to characterize the ASCA/pANCA profile, soluble ICAM-1 expression and single nucleotide gene polymorphisms (SNPs) in TNF-alpha and ICAM-1 genes. Crohn's patients with moderate disease activity were enrolled in a clinical trial of Alicaforsen (ISIS 2302). Peripheral blood samples were collected prospectively for serum studies and for potential analysis of gene polymorphisms. A multivariate analysis was performed to compare treatment effect with the biomarkers studied. Serological testing for ASCA/pANCA was obtained for 257 patients at baseline: 37% were ASCA(+)/pANCA(-) (Crohn's pattern), 9% had both markers, 15% were ASCA(-)/pANCA(+) and 39% had neither marker. When the data were analysed by multiple regression analysis, a trend was found within the Alicaforsen-treated groups for greater rates of remission in the ASCA(+)/pANCA(-) subgroup versus all other serological profiles (25 versus 14%, P = 0.068), but not versus the placebo remission rate (18.8%). Gene polymorphisms were assessed in 64 patients, 21 from the placebo group. ICAM-1 assessment revealed no over-representation. However, three unique TNF-alpha SNPs were identified that correlated significantly with remission; sites 290 (P = 0.0253), -2735 (P = 0.0317) and -3090 (P = 0.0067). Although the overall clinical trial was negative, we have identified a trend towards clinical remission with Alicaforsen therapy in a subgroup of patients with Crohn's disease expressing ASCA(+)/pANCA(-). Furthermore, we have identified three TNF-alpha SNPs that may also predict a positive therapeutic outcome.