An ELISA-based method for measurement of food-specific IgE antibody in mouse serum: an alternative to the passive cutaneous anaphylaxis assay

Passive cutaneous anaphylaxis (PCA) assay has been a gold standard method to measure allergen-specific IgE antibody (ASIgE Ab) levels in allergy mouse models. Many factors including stringent guidelines for laboratory animal use make PCA a difficult choice. Therefore, alternative methods are needed that can be readily applied for measurement of specific IgE antibody levels in mouse serum. Herein we describe a novel ELISA-based method that is more sensitive in comparison to PCA, IgE isotype-specific (because it has little cross-reactivity with IgG1 or IgG2a isotype) and highly reproducible (<10% inter- or intra-assay variation). Furthermore, we demonstrate the utility of this assay to measure specific IgE Ab against a variety of food extracts including chicken egg, peanut, almond, filbert/hazelnut and sweet potato. These findings are of particular interest to those who are seeking (i) to measure food-extract-specific IgE antibody in animal models and (ii) an alternative to the animal-based PCA method to measure mouse IgE antibodies.     

DFNB74, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 12q14.2-q15

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species.     

Poliomyelitis eradication.

Since the poliomyelitis eradication program began in 1988, the number of poliovirus infected continents and countries have decreased from five to two and from greater than 100 to 53, respectively. A nearly 90% reduction in the incidence of polio has been achieved with a corresponding decrease in virus genomic heterogeneity. Major challenges to eradication remain in south Asia and Africa in those areas with hot and humid climates, high population density, and high birth rates. Of particular concern are countries with ongoing social unrest and poor health infrastructure. With the approaching eradication of polio, post-eradication issues are now being addressed. The World Health Organization (WHO) draft plan for containment of wild polioviruses has been published for comment. Commissions and committees for certification of eradication have been established. Still under discussion is the question of the appropriate strategy for stopping oral polio vaccine (OPV) immunization. Studies are underway to determine whether vaccine-derived polioviruses will continue to circulate after OPV cessation and the potential disease consequences of that circulation.     

A comparison of subtalar joint motion during anticipated medial cutting turns and level walking using a multi-segment foot model

The weight-bearing in-vivo kinematics and kinetics of the talocrural joint, subtalar joint and joints of the foot were quantified using optical motion analysis. Twelve healthy subjects were studied during level walking and anticipated medial turns at self-selected pace. A multi-segment model of the foot using skin-mounted marker triads tracked four foot segments: the hindfoot, midfoot, lateral and medial forefoot. The lower leg and thigh were also tracked. Motion between each of the segments could occur in three degrees of rotational freedom, but only six inter-segmental motions were reported in this study: (1) talocrural dorsi-plantar-flexion, (2) subtalar inversion–eversion, (3) frontal plane hindfoot motion, (4) transverse plane hindfoot motion, (5) forefoot supination–pronation twisting and (6) the height-to-length ratio of the medial longitudinal arch.The motion at the subtalar joint during stance phase of walking (eversion then inversion) was reversed during a turning task (inversion then eversion). The external subtalar joint moment was also changed from a moderate eversion moment during walking to a larger inversion moment during the turn. The kinematics of the talocrural joint and the joints of the foot were similar between these two tasks.During a medial turn, the subtalar joint may act to maintain the motions in the foot and talocrural joint that occur during level walking. This is occurring despite the conspicuously different trajectory of the centre of mass of the body. This may allow the foot complex to maintain its function of energy absorption followed by energy return during stance phase that is best suited to level walking.     

Initial and subsequent dosing of rectal acetaminophen in children: a 24-hour pharmacokinetic study of new dose recommendations

BACKGROUND: Recent studies have determined that an initial rectal acetaminophen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent doses after a 40-mg/kg dose has not been clarified for this route of administration. Based on the authors' previous pharmacokinetic data, they examined whether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals maintain serum concentrations within the target range of 10-20 microg/ml, without evidence of accumulation. METHODS: Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood samples were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic parameters predicted the acetaminophen concentrations in the present study. They also assessed their dosing regimen by determining the fraction of time each individual maintained the target concentration. RESULTS: All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, the target range was maintained 60 +/- 29% of the time. The highest serum concentration with initial or subsequent dosing was 38.6 microg/ml. Pharmacokinetic parameters from the earlier study predicted the serum concentrations observed for both initial and subsequent doses. CONCLUSIONS: A rectal acetaminophen loading dose of 40 mg/kg followed by 20-mg/kg doses every 6 h results in serum concentrations centered at the target range of 10-20 microg/ml. There was large interindividual variability in pharmacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.