Prevalence and nature of connexin 26 mutations in children with non-syndromic deafness.

OBJECTIVE: To determine (1) the prevalence and nature of connexin 26 mutations in a cohort of Australian children with non-syndromic hearing loss, and (2) the carrier frequency of the common connexin 26 mutation (35delG) in the general population. DESIGN: A cohort, case-finding study. Mutation analysis was performed on DNA extracted from white blood cells, buccal cells, or Guthrie blood spots. SETTING: A hearing loss investigation clinic and a deafness centre in two Australian capital cities, 1 January 1998 to 31 October 2000. PARTICIPANTS: (1) 243 children (age range, 4 weeks to 16 years; median, 4 years), attending hearing loss clinics in Sydney and Melbourne; (2) 1000 blood samples obtained from anonymous Guthrie card blood spots collected in 1984 [corrected] by the Victorian Clinical Genetics Service as part of the newborn screening program. MAIN OUTCOME MEASURES: (1) The prevalence and types of connexin 26 mutations in a cohort of children with prelingual deafness; (2) the carrier frequency of the common connexin 26 mutation, 35delG, in the general population. RESULTS: Connexin 26 mutations were identified and characterised in 52 (21%) of the 243 children; 14 different mutations, including four previously unreported mutations (135S, C53R, T123N and R127C), were identified. The common 35delG mutation was found in 56 of the 104 alleles (ie, 86 of the connexin 26 alleles in which a mutation was positively identified). The mutations V371 and M34T were also relatively common. The carrier frequency of connexin 26 mutations and of the common 35delG connexin 26 mutation in the Victorian population was estimated to be 1 in 54 and 1 in 100, respectively. CONCLUSIONS: Mutations in the connexin 26 gene (especially the 35delG mutation) are a common cause of prelingual hearing loss in Australia.

When the diagnosis of deafness is wrong.

OBJECTIVE: To describe three children in whom there had been major errors in the diagnosis of hearing loss. CLINICAL FEATURES: In three children (two developmentally delayed, one not developmentally delayed) hearing thresholds obtained by behavioural testing were later proven wrong. This resulted in significant family distress and inappropriate educational approaches. INTERVENTION AND OUTCOME: Electrocochleography and brainstem audiometry were performed, demonstrating normal cochlear function. Simultaneous microinspection of the ears gave information about current or old middle ear disease and the likelihood of past conductive hearing loss. In each case hearing aids could be discarded, enabling parents and teachers to concentrate on one rather than multiple problems. CONCLUSION: Electrocochleography and brainstem audiometry should be used more frequently to check the diagnosis of hearing loss in children who are developmentally delayed, hyperactive or autistic and who do not give consistent responses to behavioural testing. It should also be considered if parents are firmly convinced that the diagnosis of deafness is wrong.

Oxytocin infusion during second stage of labour in primiparous women using epidural analgesia: a randomised double blind placebo controlled trial.

OBJECTIVE: To determine whether the high rate of forceps delivery associated with the use of epidural analgesia could be reduced through giving an intravenous infusion of oxytocin during the second stage of labour. DESIGN: A randomised, double blind, placebo controlled trial. SETTING: Delivery suites in three hospitals. SUBJECTS: 226 Primiparous women with adequate epidural analgesia in whom full dilatation of the cervix had been achieved without prior stimulation with oxytocin. INTERVENTION: An infusion of oxytocin or placebo starting at the diagnosis of full cervical dilatation at an initial dose rate of 2 mU/min increasing to a maximum of 16 mU/min. MAIN OUTCOME MEASURES: The outcome of labour was assessed in terms of the duration of the second stage, mode of delivery, fetal condition at birth, postpartum blood loss, and the incidence of perineal trauma. RESULTS: Treatment with oxytocin was associated with a shorter second stage (p = 0.01), a reduction in the number of non-rotational forceps deliveries (p = 0.03), and less perineal trauma (p = 0.03) but was not associated with any reduction in the number of rotational forceps deliveries performed for malposition of the occiput. No adverse effects on fetal condition at birth or in the early puerperium were seen in association with the use of oxytocin. CONCLUSIONS: The use of an oxytocin infusion may reduce the high rate of operative delivery associated with epidural analgesia provided that the fetal occiput is in an anterior position at the onset of the second stage of labour but within the dose range studied does not seem to correct malposition of the fetal occiput.

Galactose metabolism in relation to cataract formation in marsupials.

Erythrocytic galactokinase and/or galactose-1-phosphate uridyl transferase activity were low in many species of marsupials. However, cataract formation was observed only in pouch-young members of these species when reared on cow's milk. The galactose tolerance of young kangaroos was found to be greatly impaired, but improved rapidly and markedly at the stage of which the definitive structure of the ruminant type of stomach as in adults is formed. The combination of high absorption of galactose and low levels of galactokinase and/or transferase thus appears to determine the predisposition of pouch-young marsupials to galactose cataractogenesis.