Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes

Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3.     

Frequency modulation locking in 980 nm strained quantum well lasers

The fundamental and second-harmonic spectral characteristics of frequency modulation locking have been observed in strained-layer InGaAs quantum well Fabry-Perot ridge-waveguide lasers emitting at 980 nm.<>     

Pharmacoeconomics of intravenous antibiotic use in serious infection

A pharmacoeconomic study of 15 antibiotics available in Barbados was performed. The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin. The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects. The costs of adverse effects were not included in this study due to lack of accurate data. The total cost of antibiotic use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73). Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93%. Non-drug costs represented a much greater proportion of total costs of generic compounds. For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels. Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy. However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients.     

An examination of spatial variation in mercury concentrations in otter (Lutra canadensis) in south-central Ontario

Hair samples were collected from otter (Lutra canadensis) trapped in several parts of south-central Ontario, Canada. The concentrations of total Hg in hair were compared with methyl mercury concentrations in liver tissues from the same individuals to determine if hair is a suitable monitoring tissue. Hg in the two tissues was significantly correlated. Hair was used to monitor Hg in 51 individuals from four townships. The concentrations of total Hg in hair ranged from 4 to 20 micrograms/g. No significant variation among the four sample regions existed. Generally the highest concentrations were found in the youngest members of the population. Some possible explanations for the observations are presented.     

The effect of the addition of adrenaline to pethidine for patient-controlled epidural analgesia after caesarean section

We have investigated the addition of adrenaline to pethidine for patient-controlled epidural analgesia after elective Caesarean section. In a randomised, double-blind study, patients received patient-controlled epidural analgesia for 24 h using pethidine 5 mg.ml-1 with adrenaline 5 micrograms.ml-1 (adrenaline group, n = 40) or pethidine 5 mg.ml-1 without adrenaline (plain group, n = 38). Visual analogue scale pain scores at rest and on coughing measured 2 h, 6 h and 24 h after surgery were similar between the two groups. There was a trend towards lower mean total consumption of pethidine in the adrenaline group (231.5 mg; SD 140.5 mg) compared with the plain group (289.5 mg; SD 139.5 mg; p = 0.071). Patients in the adrenaline group had higher visual analogue scale scores for nausea at 2 h and 24 h and higher scores for pruritus at 2 h compared with the plain group. Addition of adrenaline to pethidine for patient-controlled epidural analgesia does not appear to have significant clinical advantages.     

Comparison of the intrinsic kinase activity and substrate specificity of c-Abl and Bcr-Abl

We studied the intrinsic tyrosine kinase activity and substrate specificity of c-Abl and Bcr-Abl protein tyrosine kinases (PTKs) using the peptide substrates discovered from a synthetic combinatorial peptide library. Our data indicate that the phosphorylation of these peptides by Bcr-Abl was consistently stronger than that by c-Abl. Bcr-Abl also showed substrate preference towards those peptides with one or more positive charges.     

Telomere length regulation in mice is linked to a novel chromosome locus

Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5-15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.