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Biomedical subjects

M Denton

Publications and source records attributed to M Denton.

At least 55 records · Page 3Linked to original sources

Incidence and prevalence of hepatitis C among clients of a Brisbane methadone clinic: factors influencing hepatitis C serostatus.

The objective of this study was to describe the incidence and prevalence of hepatitis C infection among clients of a methadone program in Queensland. The clinical notes of clients receiving methadone for treatment of opiate dependence who first registered at the clinic after 1989 were perused for information about their serological status for hepatitis C and hepatitis B infections during a six-week period in 1994. We followed hepatitis C negative clients until August-September 1995. At study entry, 69 per cent of the clients were recorded as being hepatitis C positive. Of those who were negative, the seroconversion rate was 11 per 100 person-years. The high incidence and prevalence of hepatitis C among methadone clients emphasises the need for effective early intervention strategies to prevent the transmission of hepatitis C among injecting drug users.

Adolescent↗

Role of anti-pseudomonal antibiotics in the emergence of Stenotrophomonas maltophilia in cystic fibrosis patients.

A retrospective case-control study of 12 patients positive for Stenotrophomonas maltophilia and 24 age-sex-matched controls revealed that in the year prior to initial isolation, colonised patients spent more days in hospital and received more days of oral ciprofloxacin, intravenous anti-pseudomonal antibiotics, and nebulised aminoglycosides. They were also more likely to have grown Pseudomonas aeruginosa at some time in the past, despite there being no difference in current chronic infection with this organism. The role of anti-pseudomonal antibiotics in promoting Stenotrophomonas maltophilia colonisation in cystic fibrosis is discussed.

Adolescent↗

A new selective differential medium for isolation of Stenotrophomonas maltophilia.

A new selective differential medium for the isolation of Stenotrophomonas (formerly Xanthomonas) maltophilia was developed. The medium, VIA agar, contained vancomycin, imipenem, and amphotericin B as selective agents and incorporated a mannitol/bromothymol blue indicator system. Compared with Xanthomonas maltophilia Selective Medium (XMSM), VIA agar was less inhibitory to Stenotrophomonas maltophilia and was more selective than XMSM in preventing the growth of unwanted bacteria from contaminated specimens. Although vancomycin-resistant strains of Enterococcus faecium may grow on VIA agar, these can be easily distinguished from Stenotrophomonas maltophilia because of mannitol fermentation.

Amphotericin B↗

Genetic mapping of RP1 on 8q11-q21 in an Australian family with autosomal dominant retinitis pigmentosa reduces the critical region to 4 cM between D8S601 and D8S285.

The locus (RP1) for one form of autosomal dominant retinitis pigmentosa (adRP) was mapped on chromosome 8q11-q22 between D8S589 and D8S285, which are about 8 cM apart, by linkage analysis in an extended family ascertained in the USA. We have studied a multigeneration Australian family with adRP and found close linkage without recombination between the disease locus and D8S591, D8S566, and D8S166 (Zmax = 1.137-4.650 at theta = 0.00), all mapped in the region known to harbor RP1. Assuming that the mutation of the same gene is responsible for the disease in both families, the analysis of multiply informative meioses in the American and Australian families places the adRP locus between D8S601 and D8S285, which reduces the critical region to about 4 cM, corresponding to approximately 4 Mb, which is completely covered by a yeast artificial chromosome contig assembled recently.

Adult↗

Linkage of blepharophimosis syndrome in a large Indian pedigree to chromosome 7p.

Blepharophimosis syndrome (BPES) is an autosomal dominant disorder involving abnormal eyelid development. Cytogenetic and linkage analyses have previously implicated the chromosome 3q23 region in multiple cases of this syndrome. However, in a few cases cytogenetic analyses have implicated other chromosomal regions in this condition. Here we report linkage of BPES in a large Indian pedigree to chromosome 7p13-p21; affected only two-point and multipoint analyses using D7S488, D7S2551 and D7S2562 both showed peak lod scores of 3.61 coincident with D7S2562. Recombinations in affected individuals placed the critical region between D7S488 and D7S629. When both affected and unaffected individuals were considered, a maximum two-point lod score of 3.38 at theta = 0.08 was obtained with D7S2551 while a peak multipoint lod score of 3.64 was obtained between D7S488 and D7S2551. Segregation analysis revealed two unaffected individuals carrying the affected haplotype accounted for the difference in peak, relative to the affected only analysis. The chromosome 7p candidate genes inhibin beta A and epidermal growth factor receptor map outside this region whereas the HOX1 gene cluster may map inside this region. Although BPES is sometimes associated with female infertility due to premature ovarian failure, in the current family affected females were fertile. The current finding together with the previous evidence implicating chromosome 3q2 provides strong evidence that BPES involves locus heterogeneity; this point should be considered when counselling affected families.

Blepharophimosis↗

Dynamic mutation loci: allele distributions in different populations.

To assess the relative contributions of trans-acting factors (replication and repair functions) and cis-acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mutation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of different ethnic origins. Genome wide instability of repeats in a particular population would be evidence of trans-acting factor instigation of the mutation process, whereas instability at a particular locus (perhaps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. The FRA16A locus is highly polymorphic in only the European population. Some other loci exhibit distinct distributions of alleles between different populations. Therefore sequences in the vicinity of the repeat -- the cis component of a particular locus -- appear(s) to be more important in the mutation mechanism than sporadic genome-wide instability induced by trans-acting factors such as the DNA mismatch repair enzymes.

Alleles↗

Molecular basis of p(CCG)n repeat instability at the FRA16A fragile site locus.

Rare, folate-sensitive fragile sites are the result of the unstable expansion of trinucleotide p(CCG)n repeats, which are normally polymorphic in copy number. Differences in the number and frequency of alleles of the fragile site FRA16A p(CCG)n repeat were observed between different ethnic populations suggesting that certain alleles might be predisposed to instability. Sequence analysis demonstrated that the longer and more variable alleles were associated with loss of repeat interruption. Perfect repeat configuration therefore appears to be a necessary precondition for the instability associated with fragile site genesis.

Alleles↗

Co-existent cross-infection with Streptococcus pneumoniae and group B streptococci on an adult oncology unit.

An outbreak of respiratory infection in an adult oncology unit is described where there was evidence of co-existent cross-infection with Streptococcus pneumoniae serotype 14 and Lancefield group B streptococcus type Ia. The presumed route of transmission was droplet spread from patient to patient. No further cases arose after the ward had been closed to new admissions and all symptomatic patients were treated with erythromycin. We suggest that patients with pneumococcal pneumonia on units housing elderly debilitated patients should be isolated. Infection control teams should be aware of the ability of Lancefield group B streptococci to spread by cross-infection among adult patients.

Adult↗

The use of continuous quality improvement methods in the development and dissemination of medical practice guidelines.

The federal government is currently supporting the development and dissemination of clinical practice guidelines. Physicians fear that payers who promote guidelines are more interested in reducing variation to control their behavior and contain health care spending than in improving quality of care. There is also apprehension that guidelines will shift the responsibility for quality to parties external to the physician-patient relationship and the local professional community. Continuous quality improvement (CQI) methods provide an avenue for physician responsibility and participation in guideline development which can alleviate these concerns. This article describes the efforts of one health maintenance organization (HMO) to use CQI techniques to mobilize plan physicians to develop, disseminate, and implement practice guidelines in a manner that satisfies the needs of physicians, patients, and the HMO.

Anti-Ulcer Agents↗

Gene of type II autosomal dominant retinitis pigmentosa maps on the long arm of chromosome 3.

Linkage analysis has been performed on a large Australian family segregating for the autosomal dominant form of retinitis pigmentosa (ADRP). The majority of patients had no subjective symptoms of night blindness until their second decade and good visual acuity until late in life. The disease in this family has been classified as Type II ADRP according to the subdivisions provided by both Massof and Finkelstein and Fishman and colleagues. Linkage (Omax:0.08 at Zmax:4.78) is here demonstrated between the disease locus and D3S47 (a marker locus on the long arm of chromosome 3), which showed in an earlier study very close linkage without recombination to the disease locus in an Irish pedigree with a clinically more severe and early onset (Type I) ADRP.

Chromosome Aberrations↗

The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.

About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the "reading frame" hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the "reading frame" theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many "in-frame" deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.

Adolescent↗

Linkage heterogeneity between X-linked retinitis pigmentosa and a map of 10 RFLP loci.

In nine families in which X-linked retinitis pigmentosa (XLRP) is segregating, the lod scores of XLRP in a map of 10 RFLP loci were obtained by multipoint linkage analysis. The XLRP locus was located telomeric to DXS7 in seven of the families and centromeric to DXS7 in two of the families. Under the hypothesis of two XLRP loci, a heterogeneity (admixture) test was performed, providing significant evidence of heterogeneity in XLRP (P less than .01). No correlation was detected between the clinical manifestations of XLRP and the two different disease loci.

Chromosome Mapping↗

Localization of the X-linked retinitis pigmentosa locus between DXS7 and DXS84 in a family showing tapetal reflex in heterozygotes.

The linkage relationships between the X-linked retinitis pigmentosa (XLRP) locus and seven Xp loci: DXS14, DXS7, OTC, DXS141, DXS148, DXS84 and DXS206 were analysed in one large family in which the heterozygotes exhibited the tapetal reflex. Evidence drawn from two-point and multipoint linkage analysis and a number of triply informative crossovers suggests that the XLRP locus in this family is between DXS7 and DXS84. The putative order of loci on the short arm of the X chromosome is: centromere - DXS14 - DXS7 - OTC - XLRP/DXS141 - DXS148 - DXS84 - DXS206 - telemere.

Child↗

Determination of cell number in monolayer cultures.

Determining the cytostatic or cytotoxic effects of various conditions on monolayer cells requires techniques that are rapid, reproducible, and able to monitor these effects as a function of time. Methods currently used to monitor cytostasis or cytotoxicity are either static or indirect; that is, they are designed to test effects of various treatments either at single time points or on associated cellular processes, such as membrane integrity. Because of these limitations in extant techniques, we undertook this study to improve methods for the rapid determination of cell number in monolayer cultures. We have arrived at conditions of staining cell nuclei with crystal violet under fixed regimens which allow rapid and reproducible quantification of cell number in cultures grown in 24-well miniwells. Quantification is possible by solubilizing the adsorbed dye into a solution of Triton X-100 and determining optical density (O.D.) using spectrophotometry. The present communication documents that O.D. is linearly related to cell number with a sensitivity of ca. 500 cells and that the technique is applicable to study agents which affect cell proliferation.

Animals↗