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Biomedical subjects

A C Davis

Publications and source records attributed to A C Davis.

At least 19 recordsLinked to original sources
PubMed2001

Prevalence of permanent childhood hearing impairment in the United Kingdom and implications for universal neonatal hearing screening: questionnaire based ascertainment study.

OBJECTIVE: To estimate the prevalence of confirmed permanent childhood hearing impairment and its profile across age and degree of impairment in the United Kingdom. DESIGN: Retrospective total ascertainment through sources in the health and education sectors by postal questionnaire. SETTING: Hospital based otology and audiology departments, community health clinics, education services for hearing impaired children. PARTICIPANTS: Children born from 1980 to 1995, resident in United Kingdom in 1998, with severe permanent childhood hearing impairment (hearing level in the better ear >40 dB averaged over 0.5, 1, 2, and 4 kHz). MAIN OUTCOME MEASURES: Numbers of cases with date of birth and severity of impairment converted to prevalences for each annual birth cohort (cases/1000 live births) and adjusted for under ascertainment. RESULTS: 26 000 notifications ascertained 17 160 individual children. Prevalence rose from 0.91 (95% confidence interval 0.85 to 0.98) for 3 year olds to 1.65 (1.62 to 1.68) for children aged 9-16 years. Adjustment for under ascertainment increased estimates to 1.07 (1.03 to 1.12) and 2.05 (2.02 to 2.08). Comparison with previous studies showed that prevalence increases with age, rather than declining with year of birth. CONCLUSIONS: Prevalence of confirmed permanent childhood hearing impairment increases until the age of 9 years to a level higher than previously estimated. Relative to current yields of universal neonatal hearing screening in the United Kingdom, which are close to 1/1000 live births, 50-90% more children are diagnosed with permanent childhood hearing impairment by the age of 9 years. Paediatric audiology services must have the capacity to achieve early identification and confirmation of these additional cases.

Adolescent↗
PubMed2001

Hippocampal involvement in the expression of kindling-induced fear in rats.

Kindling dramatically increases fearful behavior in rats. Because kindling-induced fear increases in magnitude as rats receive more stimulations, kindling provides a superb opportunity to study the nature and neural mechanisms of fear sensitization. Interestingly, these changes in behavior are accompanied by increased binding to inhibitory receptors and decreased binding to excitatory receptors in the CA1 and dentate gyrus regions of the hippocampus. This led us to hypothesize that kindling-induced fear may result from an increased inhibitory tone within hippocampal circuits. To test this hypothesis, we investigated FOS protein immunoreactivity in hippocampal and amygdalar regions of kindled rats that were exposed to an unfamiliar open field. We found that FOS immunoreactivity was significantly decreased in the CA1 region, dentate gyrus, and perirhinal cortex of kindled rats compared to sham-stimulated rats. These results support our hypothesis that kindling-induced fear may be produced by inhibition within hippocampal circuits. They also suggest that neural changes within the hippocampus may be important for the sensitization of fear.

Amygdala↗
PubMed2001

Universal neonatal hearing screening: past, present, and future.

After a brief review of the history of newborn hearing screening including the Downs behavioral testing procedure, the Crib-o-gram and similar devices, and the use of auropalpebral reflex and otoacoustic emissions, there is a discussion of key issues that need to be resolved before universal hearing screening is introduced. Included are questions regarding the target population(s) of screening programs, well baby versus NICU screening, dealing with false-positives and the effects on parent-child relationships, and finally, the availability of resources for screening and follow-up. The results of a recent study in the United Kingdom that assessed the current state of audiology services and found there is a difference between existing standards and what is actually being done in practice, are presented and considered in terms of current trends in the United States to move ahead with universal screening without a solid database of information regarding the preparedness of clinical centers to deal with the need for services that will result from the initiation of universal programs. Caution is urged.

Follow-Up Studies↗
PubMed2001

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4(+/-) mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.

Adipocytes↗
PubMed2000

A novel mutation in the mitochondrial tRNA(Ser(UCN)) gene in a family with non-syndromic sensorineural hearing impairment.

We describe a family with non-syndromic sensorineural hearing impairment inherited in a manner consistent with maternal transmission. Affected members were found to have a novel heteroplasmic mtDNA mutation, T7510C, in the tRNA(Ser(UCN)) gene. This mutation was not found in 661 controls, is well conserved between species, and disrupts base pairing in the acceptor stem of the tRNA, making it the probable cause of hearing impairment in this family. Sequencing of the other mitochondrial tRNA genes did not show any other pathogenic mutations. Four other mutations causing hearing impairment have been reported in the tRNA(Ser(UCN)) gene, two having been shown to affect tRNA(Ser(UCN)) levels. With increasing numbers of reports of mtDNA mutations causing hearing impairment, screening for such mutations should be considered in all cases unless mitochondrial inheritance can be excluded for certain.

Base Sequence↗
PubMed1999

The epidemiology of hearing impairment in an Australian adult population.

BACKGROUND: This study measured the prevalence of hearing impairment, and major demographic factors that influence the prevalence, in a representative South Australian adult population sample aged > or = 15 years. METHODS: The study group was recruited from representative population surveys of South Australians. Participants in these surveys who reported a hearing disability were then recruited to an audiological study which measured air and bone conduction thresholds. In addition a sample of those people who reported no hearing disability were recruited to the audiological study. RESULTS: The data reported in this study are the first in Australia to assess the prevalence of hearing impairment from a representative population survey using audiological methods. The data show that 16.6% of the South Australian population have a hearing impairment in the better ear at > or = 25 dBHTL and 22.2% in the worse ear at the same level. The results obtained in this representative sample compare well with those obtained in the British Study of Hearing, although some differences were observed. CONCLUSIONS: Overall, there are only a few studies worldwide that have audiologically assessed the impairment of hearing from a representative population sample. The overall prevalence of hearing impairment in Australia is similar to that found in Great Britain, although there are some differences between the estimates of severity of impairment and some sex differences. The corroboration of the two studies reinforces the status of hearing impairment as the most common disability of adulthood. The present study also showed that there are a large number of Australians who may benefit from a more systematic community-based rehabilitation programme including the fitting of hearing aids. Secondly, the study identified the need for health goals and targets for hearing to be based on an epidemiological approach to the problem.

Adolescent↗
PubMed1999

Variations in genetic assessment and recurrence risks quoted for childhood deafness: a survey of clinical geneticists.

We report here the results of a questionnaire survey of consultant clinical geneticists in the United Kingdom to which we had an 81% response rate. In this questionnaire we asked about: (1) the nature of services currently offered to families with hearing impaired children, (2) what recurrence risks they quoted in isolated non-syndromic cases, and (3) what they might suggest for improving the range of genetic services available at present. We noted great variation both in these services and in the recurrence risks quoted in isolated cases. Based on the results of the questionnaire, we have proposed a protocol for the investigation of permanent childhood hearing impairment, which we believe to be both comprehensive and practical in an outpatient clinic setting. It is only by improving existing clinical and social understanding and knowledge of childhood hearing impairment that it will become possible to use recent molecular advances to develop comprehensive and consistent services for these families.

Child↗
PubMed1998

Time and cost for recruiting older adults.

OBJECTIVES: The purpose of this study was to examine the time requirements and costs of recruiting older adults for participation in a medical center-/university-sponsored, home-based nutrition education study. A two-step recruitment strategy consisting of an introductory letter followed by a telephone call was used. DESIGN: A random selection of 1300 individuals aged 60 to 74 years was drawn from a patient database of a large, rural, tertiary care hospital to receive introductory letters and recruitment telephone calls. One week after the mailing, potential subjects were contacted by trained interviewers and asked to participate in a home-based nutrition education study. PARTICIPANTS: Men and women, aged 60 to 74 years, whose names appeared in a rural, tertiary care hospital database. MEASUREMENTS: Recruitment rate, time required for recruitment by telephone, and cost of the combined mailing and telephone recruitment effort. RESULTS: Of the 1300 individuals selected, 1077 (83%) people were contacted by phone and 223 (17%) people were unable to be reached. A total of 2895 calling attempts were required to determine the recruitment status of those identified as potential participants. Of those reached by phone, the recruitment rate was 45%. The total cost (mailing, telephone, and database management) per recruited subject was $8.56. CONCLUSION: This study has helped to establish the costs of recruitment for home-based education interventions using a two-step strategy of an introductory mailing and follow-up telephone interview.

Aged↗
PubMed1997

Field sensitivity of targeted neonatal hearing screening by transient-evoked otoacoustic emissions.

OBJECTIVE: Population ascertainment of children having bilateral moderate to profound hearing impairment was undertaken to find out how many had passed (false negatives) and how many had failed (true negatives) a neonatal screening test based on transient-evoked otoacoustic emissions (TEOAE). DESIGN: Neonatal screening using a purpose-built TEOAE instrument was undertaken in neonates, at eight hospitals in districts distributed around the United Kingdom starting in 1988. Screening was targeted on neonates at risk of hearing impairment. A total of 7500 babies had been tested by the end of 1995. Searching of audiological records in the districts completed at the end of 1995 ascertained 218 children born between January 1988 and December 1993 who had hearing threshold levels in both ears of 50 dB or more, averaged over the speech frequencies 0.5, 1, 2, and 4 kHz. Of those, 47 had completed the neonatal TEOAE screening test. Retrospective examination of their TEOAE records indicated whether they had passed or failed the screening test. RESULTS: Eleven of the 47 had passed the screening test, although two of those had documented acquired hearing impairment occurring after screening. Disregarding those two cases leaves nine false negatives out of 45, giving a sensitivity estimate of 80% (36 divided by 45). In two of the nine cases, there was documented evidence of progression, one of whom had a family history of progressive hearing loss. CONCLUSIONS: Targeted neonatal hearing screening programs based on TEOAE can expect to identify hearing impairment in approximately 80% of babies screened. The cause of false negatives is a matter for conjecture. There may be several reasons: the test may give an incorrect result, there may be a later acquired hearing impairment, or there may be a progressive hearing loss of unknown origin. Passing a neonatal screening test is not a valid reason to forego further surveillance, or to disregard parental suspicion of hearing impairment.

Acoustic Stimulation↗
PubMed1997

Changing performance of the Health Visitor Distraction Test when targeted neonatal screening is introduced into a health district.

The change in the performance of the HVDT as targeted neonatal hearing screening has been introduced has been examined for the Nottingham district. The records for all children born in the period 1984-1993 within the district and having a permanent hearing loss of > or = 50 dB in the better ear have been examined. The referral route leading to ascertainment of the hearing loss as well as the result of any screening tests were noted. The data shows an increase in the number referred prior to the HVDT, mainly as a result of neonatal screen failure. At the same time there has been a reduction in the sensitivity of the HVDT from 78% in the first half of the decade to 38% for the second half. There are also some indications of an increase in the coverage and the failure rate over the time. Possible reasons for these changes are discussed.

Evoked Potentials, Auditory, Brain Stem↗
PubMed1997

Behavioural and autonomic responses to sound in pre-term and full-term babies.

The pattern of motor (body movement) and autonomic (heart rate and respiration) responses to no sound and sound trials were compared in 20 pre-term and 22 full-term neonates. Sound levels were calibrated using neonatal ear-sized couplers to produce, in the neonatal ear, sound levels of 80, 90 and 100 dB SPL. Accelerations in heart rate (> or = beats per minute for pre-terms; > or = 7 beats per minute for full-terms) were found to be the best criterion for establishing a possible response using bandpass noise at 80, 90 or 100 dB SPL. Respiration rate decreased in response to sound stimuli, this being significant for the pre-term group for the 100 dB SPL stimulus when comparing the 5 s period post-stimulus with the stimulus period. The number of movements detected during the sound trials was higher than for the control trials, being statistically significant for the pre-term group. These changes were elicited in response to stimuli presented at levels some 20-40 dB lower than for other studies and for behavioural screening because sounds were calibrated in an appropriately sized coupler. It is concluded that the response to sound is different in the pre-term group compared with the full-term group.

Acoustic Stimulation↗
PubMed1996

IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination.

Studies have implicated defective Ig class switch in the pathogenesis of IgA deficiency. To understand better the molecular events that regulate IgA class switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in murine embryonic stem cells. The I alpha exon-deficient mice derived from these embryonic stem cells had normal IgA levels in serum and secretions and normal numbers of IgA B cells in Peyer's patches and spleen. Further, I alpha exon-deficient B cells efficiently underwent IgA class switch in vitro, despite the absence of I alpha exon-containing germline transcripts. Notably, I alpha exon-deficient B cells did not require TGF-beta for IgA class switch since stimulation with LPS alone led to IgA expression. Nonetheless, whereas I alpha exon-deficient B cells constitutively expressed human hypoxanthine phosphoribosyltransferase transcripts, they did not produce IgA in the absence of LPS stimulation. These results demonstrate that the I alpha exon or transcripts containing the I alpha exon are not required for IgA class switch. Further, the effects of TGF-beta on I alpha locus transcription can be supplanted by expression of a heterologous minigene at that locus, but a second signal is required for the induction of IgA class switch.

Animals↗
PubMed1993

A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice.

To directly assess c-myc function in cellular proliferation, differentiation, and embryogenesis, we have used homologous recombination in embryonic stem cells to generate both heterozygous and homozygous c-myc mutant ES cell lines. The mutation is a null allele at the protein level. Mouse chimeras from seven heterozygous cell lines transmitted the mutant allele to their offspring. The analysis of embryos from two clones has shown that the mutation is lethal in homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally smaller and retarded in development compared with their littermates. Pathologic abnormalities include the heart, pericardium, neural tube, and delay or failure in turning of the embryo. Heterozygous females have reduced fertility owing to embryonic resorption before 9.5 days of gestation in 14% of implanted embryos. c-Myc protein is necessary for embryonic survival beyond 10.5 days of gestation; however, it appears to be dispensable for cell division both in ES cell lines and in the embryo before that time.

Alleles↗