Biomedical subjects

K Saunders

Publications and source records attributed to K Saunders.

At least 19 recordsLinked to original sources

PubMed2001

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.

Adolescent↗

PubMed2001

Identification of dna components required for induction of cotton leaf curl disease.

Cotton leaf curl disease (CLCuD) is a major constraint to cotton production in Pakistan. Infectious clones of the monopartite begomovirus cotton leaf curl virus (CLCuV), associated with diseased cotton, are unable to induce typical symptoms in host plants. We have identified and isolated a single-stranded DNA molecule approximately 1350 nucleotides in length which, when coinoculated with the begomovirus to cotton, induces symptoms typical of CLCuD, including vein swelling, vein darkening, leaf curling, and enations. This molecule (termed DNA beta) requires the begomovirus for replication and encapsidation. The CLCuV/DNA 1/DNA beta complex, together with a similar complex previously identified in Ageratum conyzoides, represent members of an entirely new type of infectious, disease-causing agents. The implications of this finding to our understanding of the evolution of new disease-causing agents are discussed.

Base Sequence↗

PubMed2001

Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study.

BACKGROUND: There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue. METHODS: We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children. FINDINGS: A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children. INTERPRETATION: This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.

Analysis of Variance↗

PubMed2001

Index matching to improve optical coherence tomography imaging through blood.

BACKGROUND: Most myocardial infarctions are caused by the rupture of small rather than large plaques in the arteries of the heart that are beyond the detection limit of current technologies. METHODS AND RESULTS: Recently, optical coherence tomography (OCT) has demonstrated considerable potential as a method for high-resolution assessment of vulnerable plaque. However, intravascular OCT imaging is complicated by the need to remove blood from the imaging field because blood results in substantial signal attenuation. This work examines index matching as a method for increasing penetration. Index matching is based on the hypothesis that the predominant source of scattering in blood is the difference in refractive index between the cytoplasm of erythrocytes and serum. By increasing the refractive index of serum to a value near that of the cytoplasm, or index matching, scattering can be substantially reduced. The concept was tested with a system that pumped blood in vitro through transparent tubing. The test compounds, dextran and intravenous contrast agent, both led to significant improvements in penetration (69+/-12% and 45+/-4%). No significant effect was seen with the saline control. For dextran, the effect could not be attributed to reductions of red cell number or volume because changes in these parameters were not different from the control. In the case of intravenous contrast, a small but significant relative reduction in red cell volume was seen. CONCLUSIONS: This study demonstrates the feasibility of index matching for improving OCT imaging through blood. Future studies are required to identify compounds for effective index matching in vivo.

Blood↗

PubMed2001

Pathogenicity of a natural recombinant associated with ageratum yellow vein disease: implications for geminivirus evolution and disease aetiology.

Yellow vein disease of Ageratum conyzoides is caused by a viral DNA complex consisting of the genomic component (DNA A) of the monopartite begomovirus Ageratum yellow vein virus (AYVV, family: Geminiviridae) and a small satellite-like DNA beta component. AYVV DNA A is unable to induce symptoms in this host alone but can systemically infect A. conyzoides in which it accumulates to low levels. Here, we demonstrate that the yellow vein phenotype can also be produced by co-inoculating A. conyzoides with AYVV DNA A and recDNA-Abeta17, a naturally occurring recombinant of approximately the same size as DNA beta that contains sequences from both DNA A and DNA beta. Symptoms induced by DNA A and recDNA-Abeta17 in A. conyzoides and Nicotiana glutinosa are qualitatively similar to those associated with DNA A and DNA beta although milder. Recombination between DNA A and DNA beta to produce a chimera resembling recDNA-Abeta17 was observed after whitefly transmission of the disease in A. conyzoides. Hence, such recombination events are likely to occur frequently, implying that recombinants will normally be associated with this type of disease complex in the field. Possible implications of these findings for the evolution of begomoviruses and the aetiology of their diseases are discussed.

Asteraceae↗

PubMed2001

pH-mediated field-amplified sample stacking of pharmaceutical cations in high-ionic strength samples.

Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations.

Cations↗

PubMed2001

Correlation of collagen organization with polarization sensitive imaging of in vitro cartilage: implications for osteoarthritis.

OBJECTIVE: Optical coherence tomography (OCT), a new method of high resolution imaging, has shown feasibility for assessing articular cartilage to identify early changes in osteoarthritis (OA) and monitor therapy. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than sound. The resolution of this technology is up to 25 times higher than existing methods. We investigated the correlation between changes observed by OCT and the degree of collagen organization in OA cartilage. METHODS: Polarization sensitive OCT (PSOCT) imaging was used to assess changes in cartilage collagen organization in vitro. RESULTS: The presence (or absence) of PSOCT changes correlated with collagen organization (or disorganization) on histology as assessed by picrosirius polarization microscopy (no significant difference). In multiple cases, cartilage was abnormal by both PSOCT and polarization microscopy, but was grossly normal by routine staining, showing cartilage thickness > 2 mm and no fibrillations. CONCLUSION: This in vitro study suggests PSOCT changes in cartilage are due to the state of collagen organization. The combination of high resolution structural imaging and birefringence detection make OCT a potentially powerful technology for early assessment of OA.

Cartilage, Articular↗

PubMed2000

A discotic disguised as a smectic: A hybrid columnar bragg glass

We show that discotics, lying deep in the columnar phase, can exhibit an x-ray scattering pattern which mimics that of a somewhat unusual smectic liquid crystal. This exotic, new glassy phase of columnar liquid crystals, which we call a "hybrid columnar Bragg glass," can be achieved by confining a columnar liquid crystal in an anisotropic random environment of, e.g., strained aerogel. Long-ranged orientational order in this phase makes single-domain x-ray scattering possible, from which a wealth of information could be extracted. We give detailed quantitative predictions for the scattering pattern in addition to exponents characterizing anomalous elasticity of the system.

Journal Article↗

PubMed2000

A unique virus complex causes Ageratum yellow vein disease.

Ageratum conyzoides L., a weed species widely distributed throughout southeast Asia, frequently exhibits striking yellow vein symptoms associated with infection by Ageratum yellow vein virus (AYVV), a member of the Geminiviridae (genus Begomovirus). Most begomoviruses have bipartite genomes (DNAs A and B), but only a DNA A has been identified for AYVV. We demonstrate that yellow vein disease of A. conyzoides results from co-infection by AYVV DNA A (2,741 nt) and a circular DNA that is approximately half its size (1,347 nt) that we designate DNA beta. Apart from the sequence TAATATTAC, common to all geminiviruses and containing the initiation site of rolling circle replication, DNA beta shows negligible sequence homology either to AYVV DNA A or to DNA B associated with bipartite begomoviruses. DNA beta depends on DNA A for replication and is encapsidated by DNA A-encoded coat protein and so has characteristics of a DNA satellite. However, systemic infection of A. conyzoides by DNA A alone is sporadic and asymptomatic, and DNA A accumulation is reduced to 5% or less of its accumulation in the presence of DNA beta. Therefore, DNA A and DNA beta together form a previously unrecognized disease-inducing complex. Our data also demonstrate that the nanovirus-like DNA 1 component associated with infected A. conyzoides plays no essential role in the disease and represents a satellite-like DNA. Furthermore, the satellite DNA previously found associated with tomato leaf curl virus is probably a defective DNA beta homologue.

Base Sequence↗

PubMed2000

High frequency hearing loss correlated with mutations in the GJB2 gene.

Genetic hearing impairment affects approximately 1/2000 live births. Mutations in one gene, GJB2, coding for connexin 26 cause 10%-20% of all genetic sensorineural hearing loss. Mutation analysis in the GJB2 gene and audiology were performed on 106 families presenting with at least one child with congenital hearing loss. The families were recruited from a hospital-based multidisciplinary clinic, which functions to investigate the aetiology of sensorineural hearing loss in children and which serves an ethnically diverse population. In 74 families (80 children), the aetiology was consistent with non-syndromic recessive hearing loss. Six different connexin 26 mutations, including one novel mutation, were identified. We show that GJB2 mutations cause a range of phenotypes from mild to profound hearing impairment and that loss of hearing in the high frequency range (4000-8000 Hz) is a characteristic feature in children with molecularly diagnosed connexin 26 hearing impairment. We also demonstrate that this type of audiology and high frequency hearing loss is found in a similar-sized group of deaf children in whom a mutation could only be found in one of the connexin 26 alleles, suggesting connexin 26 involvement in the aetiology of hearing loss in these cases. In our study of the M34T mutation, only compound heterozygotes exhibited hearing loss, suggesting autosomal recessive inheritance.

Audiometry↗

PubMed1999

A nanovirus-like DNA component associated with yellow vein disease of Ageratum conyzoides: evidence for interfamilial recombination between plant DNA viruses.

Yellow vein disease of Ageratum conyzoides, a weed species that is widely distributed throughout Asia, has been attributed to infection by the geminivirus Ageratum yellow vein virus (AYVV). In addition to a single AYVV genomic component (DNA A), we have previously demonstrated that infected plants contain chimeric defective viral components, comprising DNA A and nongeminiviral sequences, that act as defective interfering DNAs. A database search has revealed that the nongeminiviral sequences of one such defective component (def19) show significant homology with sequences of nanovirus components that encode replication-associated proteins (Reps). Primers designed to hybridise to the nongeminiviral DNA were used to PCR-amplify a full-length nanovirus-like component, referred to as DNA 1, from an extract of infected A. conyzoides. DNA 1 is unrelated to AYVV DNA A but resembles nanovirus components that encode Reps and is most closely related (73% identity) to a nanovirus-like DNA recently isolated from geminivirus-infected cotton. DNA 1 is dependent on AYVV DNA A for systemic infection of A. conyzoides and Nicotiana benthamiana and can systemically infect N. benthamiana in the presence of the bipartite geminivirus African cassava mosaic virus. A. conyzoides plants coinfected with AYVV DNA A and DNA 1 remain asymptomatic, indicating that additional factors are required to elicit yellow vein disease. Our results provide direct evidence for recombination between distinct families of plant single-stranded DNA viruses and suggest that coinfection by geminivirus and nanovirus-like pathogens may be a widespread phenomenon. The ability of plant DNA viruses to recombine in this way may greatly increase their scope for diversification.

Amino Acid Sequence↗

PubMed1999

Bean yellow dwarf virus RepA, but not rep, binds to maize retinoblastoma protein, and the virus tolerates mutations in the consensus binding motif.

It has previously been reported that complementary-sense gene products of wheat dwarf virus (WDV), a geminivirus of the genus Mastrevirus that infects monocotyledonous plants, bind to human and maize retinoblastoma (Rb) protein. Rb proteins control cell-cycle progression by sequestering transcription factors required for entry into S-phase, suggesting that the virus modifies the cellular environment to produce conditions suitable for viral DNA replication. Using a yeast two-hybrid assay, we have investigated whether the complementary-sense gene products of bean yellow dwarf virus, a mastrevirus that is adapted to dicotyledonous plants, also bind maize Rb protein. We demonstrate that whereas RepA binds to Rb protein, Rep does not, suggesting that RepA alone regulates host gene expression and progression of cells to S-phase. RepA mutants containing L --> I, C --> S, C --> G, and E --> Q mutations within the consensus Rb protein binding motif LXCXE retained the ability to bind to Rb, but with reduced efficiency. Most notably, the E --> Q mutation reduced binding by approximately 95%. Nonetheless, all LXCXE mutants were able to replicate in tobacco protoplasts and to systemically infect Nicotiana benthamiana and bean, in which they produced wild-type symptoms.

Binding Sites↗

PubMed1999

Costs of health care use by women HMO members with a history of childhood abuse and neglect.

BACKGROUND: Early childhood maltreatment has been associated with adverse adult health outcomes, but little is known about the magnitude of adult health care use and costs that accompany maltreatment. We examined differences in annual health care use and costs in women with and without histories of childhood sexual, emotional, or physical abuse or neglect. METHODS: A random sample of 1225 women members of a health maintenance organization completed a 22-page questionnaire inquiring into childhood maltreatment experiences as measured by the Childhood Trauma Questionnaire. Health care costs and use data were obtained from the automated cost-accounting system of the health maintenance organization, including total costs, outpatient and primary care costs, and emergency department visits. RESULTS: Women who reported any abuse or neglect had median annual health care costs that were $97 (95% confidence interval, $0.47-$188.26) greater than women who did not report maltreatment. Women who reported sexual abuse had median annual health care costs that were $245 (95% confidence interval, $132.32-$381.93) greater than costs among women who did not report abuse. Women with sexual abuse histories had significantly higher primary care and outpatient costs and more frequent emergency department visits than women without these histories. CONCLUSION: Although the absolute cost differences per year per woman were relatively modest, the large number of women in the population with these experiences suggests that the total costs to society are substantial.

Adolescent↗

PubMed1999

Effect of sleep state on the flash visual evoked potential. A case study.

Controversy exists regarding the influence of sleep state on the flash visual evoked potential. This study recorded the visual evoked potential in a new-born infant in four different sleep states; wakefulness. drowsiness, active sleep and quiet sleep over a five hour period. The infant's heart rate, breathing rate and breathing regularity were also recorded. It was clear that when this subject was awake the VEPs recorded differed substantially from those recorded when sleeping. Two of the four main components had shorter peak latencies, one component was prolonged and one of the peak to trough amplitudes was consistently smaller when alert. This study highlights an important and often overlooked aspect of developmental research that the state of the infant may affect developmental measures.

Evoked Potentials, Visual↗

PubMed1999

Headache medication-use among primary care headache patients in a health maintenance organization.

OBJECTIVE: Medication-use among headache patients 2 and 5 years after a primary care headache visit is assessed, and the pattern of medication-use compared before and after the introduction of subcutaneous sumatriptan among migraineurs. SETTING AND PATIENTS: The study was carried out among headache patients visiting a primary care physician at the Group Health Cooperative of Puget Sound in 1989-90. METHODS: We report medication-use patterns 2 and 5 years later for the 530 subjects completing both a 2-year (1991-92) and a 5-year (1994-95) follow-up interview. Medication-use was determined by self-report for the month prior to the interview. Medication-use to control or prevent headache is shown for all headache patients and for those meeting International Headache Society criteria for migraine at the 2-year and the 5-year follow-up. RESULTS: The overall pattern of medication-use was similar at the 2-year and the 5-year follow-up, before and after the introduction of subcutaneous sumatriptan (March, 1993). There was a modest but statistically significant decline in the use of opioid and sedative-hypnotic medications, and in the use of ergotamine. At 5 years, 11% of migraineurs reported use of sumatriptan in the prior month. The large majority of study patients used symptomatic medications, usually non-prescription analgesics, sedative-hypnotics, and opiates. Only one-fifth of the migraineurs reported use of a prophylactic medication for headache. CONCLUSIONS: Continuing use of symptomatic headache medications was characteristic of patients with migraine and other common forms of headache. The introduction of subcutaneous sumatriptan was not associated with notable change in this pattern, although a modest reduction in use of sedative-hypnotics and opiates was observed. Overall, the pattern of use of headache medications was similar before and after the introduction of subcutaneous sumatriptan.

Adolescent↗

PubMed1998

A randomized trial of a lay person-led self-management group intervention for back pain patients in primary care.

STUDY DESIGN: Randomized, controlled trial. OBJECTIVE: To evaluate a four-session self-management group intervention for patients with pain in primary care, led by trained lay persons with back pain. The intervention was designed to reduce patient worries, encourage self-care, and reduce activity limitations. BACKGROUND DATA: Randomized trials of educational interventions suggest that activating interventions may improve back pain outcomes. Expert opinion increasingly regards effective self-management of back pain as important in achieving good outcomes. In this study, an educational intervention designed to activate patients and support effective self-management was evaluated. METHODS: Six to 8 weeks after a primary care visit for back pain, patients were invited to participate in an educational program to improve back pain self-management. Those showing interest by returning a brief questionnaire became eligible for the study. Participants (n = 255) randomly were assigned to either a self-management group intervention or to a usual care control group. The effect of the intervention, relative to usual care, was assessed 3, 6, and 12 months after randomization, controlling for baseline values. The intervention consisted of a four-session group applying problem-solving techniques to back pain self-management, supplemented by educational materials (book and videos) supporting active management of back pain. The groups were led by lay persons trained to implement a fully structured group protocol. The control group received usual care, supplemented by a book on back pain care. RESULTS: Participants randomly assigned to the self-management groups reported significantly less worry about back pain and expressed more confidence in self-care. Roland Disability Questionnaire Scores were significantly lower among participants in the self-management groups relative to the usual care controls at 6 months (P = 0.007), and this difference was sustained at 12 months at borderline significance levels (P = 0.09). Among self-management group participants, 48% showed a 50% or greater reduction in Roland Disability Questionnaire Score at 6 months, compared with 33% among the usual care controls. CONCLUSIONS: Self-management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries, producing positive attitudes toward self-care, and reducing activity limitations among patients with back pain in primary care.

Activities of Daily Living↗

PubMed1998

Assessing the feasibility of using computerized pharmacy refill data to monitor antidepressant treatment on a population basis: a comparison of automated and self-report data.

This article compares self-report and automated data as measures of dose and duration of antidepressant use in order to assess the feasibility of using automated pharmacy data in a disease management context. We used self-report and computerized refill data to identify two treatment failures-premature discontinuation of the medication and sub-optimal dosages-at time points 1 and 4 months after initiation of antidepressant therapy. The sources showed modest agreement regarding identification of current users at 1 month (kappa = .33); agreement was high at 4 months (kappa = .72). Agreement regarding dosage adequacy was also higher later in treatment, with kappas of .52 and .65 at 1 and 4 months, respectively. The two sources showed high agreement on an overall measure of acute phase treatment adequacy (kappa = .80). Data completeness was another outcome, with data on current users and overall treatment adequacy generally available from computerized files, data on dose less so. Automated pharmacy data appear to be a feasible means of monitoring treatment adequacy and quality of care as part of a disease management approach to improving care for populations of patients.

Antidepressive Agents↗

PubMed1997

Novel defective interfering DNAs associated with ageratum yellow vein geminivirus infection of Ageratum conyzoides.

Defective DNA forms of the geminivirus ageratum yellow vein virus (AYVV) have been identified in naturally infected Ageratum conyzoides plants. Several examples of the defective DNA have been cloned from purified virus-specific supercoiled DNA and characterized by sequence analysis. All are approximately half the size of AYVV genomic DNA, and all contain intergenic region sequences and the 5' terminus of gene C1 as well as additional sequences that are unrelated to the viral genomic DNA. The chimeric nature of the defective DNA distinguishes it from previously characterized geminivirus defective and satellite DNAs. The defective DNA ameliorates disease symptoms and causes a significant delay in the accumulation of viral DNA during the early stage of infection when coinoculated with the AYW genomic DNA into Nicotiana benthamiana, suggesting a biological role as a defective interfering DNA.

Base Sequence↗