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Biomedical subjects

M Doran

Publications and source records attributed to M Doran.

At least 19 recordsLinked to original sources
PubMed2007

Oligonucleotide microarray identification of Bacillus anthracis strains using support vector machines.

The capability of a custom microarray to discriminate between closely related DNA samples is demonstrated using a set of Bacillus anthracis strains. The microarray was developed as a universal fingerprint device consisting of 390 genome-independent 9mer probes. The genomes of B. anthracis strains are monomorphic and therefore, typically difficult to distinguish using conventional molecular biology tools or microarray data clustering techniques. Using support vector machines (SVMs) as a supervised learning technique, we show that a low-density fingerprint microarray contains enough information to discriminate between B. anthracis strains with 90% sensitivity using a reference library constructed from six replicate arrays and three replicates for new isolates.

Algorithms↗
PubMed2006

The R269H mutation in presenilin-1 presenting as late-onset autosomal dominant Alzheimer's disease.

Two siblings fulfilling clinical diagnostic criteria for late-onset Alzheimer's disease (AD) are reported. The family history suggested a total of nine individuals affected with AD in three generations with autosomal dominant disease transmission. Neurogenetic testing of the proband revealed a mutation, R269H, in the presenilin-1 (PS1) gene. Late-onset AD may be associated with deterministic PS1 mutations; these should be sought when the family history suggests autosomal dominant disease transmission.

Age of Onset↗
PubMed2006

Self-reported benefits from successive bilateral cochlear implantation in post-lingually deafened adults: randomised controlled trial.

Adult users of unilateral Nucleus CI24 cochlear implants with the SPEAK processing strategy were randomised either to receive a second identical implant in the contralateral ear immediately, or to wait 12 months while they acted as controls for late-emerging benefits of the first implant. Twenty four subjects, twelve from each group, completed the study. Receipt of a second implant led to improvements in self-reported abilities in spatial hearing, quality of hearing, and hearing for speech, but to generally non-significant changes in measures of quality of life. Multivariate analyses showed that positive changes in quality of life were associated with improvements in hearing, but were offset by negative changes associated with worsening tinnitus. Even in a best-case scenario, in which no worsening of tinnitus was assumed to occur, the gain in quality of life was too small to achieve an acceptable cost-effectiveness ratio. The most promising strategies for improving the cost-effectiveness of bilateral implantation are to increase effectiveness through enhanced signal processing in binaural processors, and to reduce the cost of implant hardware.

Adult↗
PubMed2006

Antisocial behaviour orders: the need to consider underlying neuropsychiatric disease.

Antisocial behaviour orders are legally constituted civil orders which aim to stop undesirable behaviour as part of United Kingdom government plans for crime reduction. They have been increasingly used since their introduction in 1999 and have attracted much media attention. The need to consider neurological illness as a possible cause of behaviour deemed anti-social is illustrated by a patient eventually diagnosed with neuroacanthocytosis.

Adult↗
PubMed2005

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin-1 gene.

It is now 10 years since the first report of mutations in the presenilin genes that were deterministic for familial autosomal dominant Alzheimer's disease. The most common of these mutations occurs in the presenilin-1 gene (PSEN1) located on chromosome 14. In the ensuing decade, more than 100 PSEN1 mutations have been described. The emphasis of these reports has largely been on the novelty of the mutations and their potential pathogenic consequences rather than detailed clinical, neuropsychological, neuroimaging and neuropathological accounts of patients with the mutation. This article reviews the clinical phenotypes of reported PSEN1 mutations, emphasizing their heterogeneity, and suggesting that other factors, both genetic and epigenetic,must contribute to disease phenotype.

Age of Onset↗
PubMed2005

Chitosan adhesive for laser tissue repair: in vitro characterization.

BACKGROUND AND OBJECTIVES: Laser tissue repair usually relies on hemoderivate protein solders, based on serum albumin. These solders have intrinsic limitations that impair their widespread use, such as limited tensile strength of repaired tissue, poor solder solubility, and brittleness prior to laser denaturation. Furthermore, the required activation temperature of albumin solders (between 65 and 70 degrees C) can induce significant thermal damage to tissue. In this study, we report on the design of a new polysaccharide adhesive for tissue repair that overcomes some of the shortcomings of traditional solders. STUDY DESIGN/MATERIALS AND METHODS: Flexible and insoluble strips of chitosan adhesive (elastic modulus approximately 6.8 Mpa, surface area approximately 34 mm2, thickness approximately 20 microm) were bonded onto rectangular sections of sheep intestine using a diode laser (continuous mode, 120 +/- 10 mW, lambda = 808 nm) through a multimode optical fiber with an irradiance of approximately 15 W/cm2. The adhesive was based on chitosan and also included indocyanin green dye (IG). The temperature between tissue and adhesive was measured using a small thermocouple (diameter approximately 0.25 mm) during laser irradiation. The repaired tissue was tested for tensile strength by a calibrated tensiometer. Murine fibroblasts were cultured in extracted media from chitosan adhesive to assess cytotoxicity via cell growth inhibition in a 48 hours period. RESULTS: Chitosan adhesive successfully repaired intestine tissue, achieving a tensile strength of 14.7 +/- 4.7 kPa (mean +/- SD, n = 30) at a temperature of 60-65 degrees C. Media extracted from chitosan adhesive showed negligible toxicity to fibroblast cells under the culture conditions examined here. CONCLUSION: A novel chitosan-based adhesive has been developed, which is insoluble, flexible, and adheres firmly to tissue upon infrared laser activation.

Animals↗
PubMed2005

Single-photon emission computed tomography perfusion imaging in the differential diagnosis of dementia: a retrospective regional audit.

A retrospective audit of (99m)Tc-HMPAO SPECT scans was undertaken to assess the utility of brain perfusion imaging in a cohort of young cognitively impaired patients in whom diagnostic uncertainty remained after standard clinical and neuropsychological assessment and structural brain imaging. SPECT scans were assessed by five raters (two neurologists and three nuclear medicine specialists) on two occasions 6 months apart, first without any clinical data and second with brief pertinent clinical information. SPECT diagnoses were compared with criterion diagnoses subsequently established by the two neurologists with access to all clinical, neuropsychological and neuroimaging data. Despite reasonable intra- and interrater reliability, diagnostic accuracy ranged from 32 to 58%. SPECT scan normality or abnormality in blind and informed viewings gave respective sensitivities of 77 and 71%, specificities of 44 and 38%, positive predictive values of 88 and 87% and negative predictive values of 27 and 18%. Calculating pairwise disease group comparisons, likelihood ratios suggested some diagnostic gain in differentiating AD from 'not AD' and from FTD/focal syndromes. SPECT scanning was of little help in establishing diagnoses in this cohort of patients, a finding which supports the conclusion of the American Academy of Neurology evidence-based review that SPECT imaging cannot be recommended for either the initial or the differential diagnosis of suspected dementia because it has not demonstrated superiority to clinical criteria.

Adult↗
PubMed2004

Disseminated enteropathy-type T-cell lymphoma: cauda equina syndrome complicating coeliac disease.

A patient with coeliac disease developed a progressive cauda equina syndrome in the 2 months prior to his death, for which no cause could be identified. At post-mortem examination this proved to be due to disseminated enteropathy-type T-cell lymphoma. Although rare, disseminated enteropathy-type T-cell lymphoma should enter the differential diagnosis in any patient with coeliac disease developing new neurological signs.

Cauda Equina↗
PubMed2004

Prominent behavioural and psychiatric symptoms in early-onset Alzheimer's disease in a sib pair with the presenilin-1 gene R269G mutation.

Two siblings with the R269G mutation in the presenilin-1 gene causing early-onset Alzheimer's disease are presented, only the second family with this mutation to be reported. Behavioural and psychiatric symptoms were prominent in both cases, as well as cognitive decline. Other reports of presenilin-1 gene mutations associated with behavioural and psychiatric symptoms are reviewed. The distribution of such mutations throughout the presenilin-1 gene argues against specific genotype-phenotype correlations, and suggests a role for other genetic and/or epigenetic factors in the pathogenesis of behavioural and psychiatric features in early-onset Alzheimer's disease associated with presenilin-1 gene mutations.

Alzheimer Disease↗
PubMed2004

EEG findings in dementia with Lewy bodies causing diagnostic confusion with sporadic Creutzfeldt-Jakob disease.

Two patients with pathologically confirmed dementia with Lewy bodies (DLB) had electroencephalogram recordings reported to show periodic discharges suggestive or typical of Creutzfeldt-Jakob disease. These findings caused diagnostic confusion and necessitated appropriate precautions for prion disease at postmortem examination. Periodic sharp wave complexes have occasionally been reported in DLB and should not therefore dissuade one from the diagnosis when other clinical and neuropsychological features are consistent with validated diagnostic criteria.

Aged↗
PubMed2003

Pathological heterogeneity of clinically diagnosed corticobasal degeneration.

Two patients fulfilling suggested clinical diagnostic criteria for corticobasal degeneration (CBD) are presented, who were found at postmortem to have alternative pathological diagnoses not suspected during life, namely, Alzheimer's disease and Pick's disease, respectively. The nosological position of these cases is considered in light of a literature review of previous reports of clinically diagnosed corticobasal degeneration with atypical (not corticobasal degeneration) pathology. Since such phenocopies may be common, we suggest that all clinically diagnosed cases of corticobasal degeneration should initially be labelled as "corticobasal degeneration syndrome" (CBDS) to emphasize that this is a diagnosis based on clinical phenotype, with the term corticobasal degeneration being reserved for the specific neuropathological phenotype, which itself may have a variety of clinical presentations.

Alzheimer Disease↗
PubMed2003

Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy.

BACKGROUND: Invasive fungal infections (IFI), particularly those caused by Aspergillus and other angioinvasive molds, are associated with an excessive mortality despite therapy. METHODS: Voriconazole was prescribed on a compassionate basis to patients with IFI who were intolerant to or who had progressed despite standard therapy. Outcome was determined by protocol-based criteria as established by the consensus definitions (complete response [CR], partial response [PR], stable disease, failure, and intolerance). RESULTS: Forty-five patients were enrolled in a compassionate release program (29 [64%] because of failure of response to standard therapy), between 1998 and 2002. Of the 45 patients enrolled, 35 (78%) had invasive Aspergillus, 3 (7%) had Fusarium, and 2 (4%) had Scedosporium infections. Underlying illnesses were as follows: 13 (29%) solid-organ transplant (SOT), 11 (24%) BMT, and 7 (13%) hematologic malignancy. Site of infection was as follows: 26 (58%) pulmonary, 9 (20%) disseminated, 5 (11%) central nervous system (CNS), and 3 (7%) sinus. Overall response rates were as follows: 9 (20%) CR, 17 (38%) PR, 15 (33%) failure, and 4 (9%) intolerant. Seven of the eight (88%) patients with sinus or CNS disease demonstrated stabilization of the IFI. The median duration of voriconazole therapy was 79 days with 9 (20%) patients receiving over 1 year of therapy. Nine thousand one hundred twenty-eight days of therapy were given with only four serious adverse events in two cases considered possibly or probably drug related. CONCLUSIONS: In this population of severely immunocompromised patients with life-threatening IFI who have failed or were intolerant to standard antifungal therapy, voriconazole demonstrated substantial efficacy and an acceptable level of toxicity.

Adult↗
PubMed2002

UK and USA Clinical Mental Health Nurse Specialists' perceptions of their work.

There is little scholarship to compare the work of mental health nurses in different countries, although this is perhaps understandable given that mental health nursing as a discrete discipline exists only in a few countries worldwide. The small-scale study reported here sought to compare the perceptions of UK and American Clinical Nurse Specialists of various aspects of their work, including latest professional developments, current therapies and interventions, and the major problems confronting nurses today. Prior to the main study being undertaken, a short questionnaire was piloted in both countries. The main questionnaire was distributed to 34 American nurses and completed by 25 (75.5% response rate), and to 28 UK nurses and completed by 24 (86% response rate). Descriptive statistics and content analyses were used to analyse the data which suggested that where UK nurses were concerned with the range and availability of services for clients and their families, American nurses were primarily preoccupied with the quality of those services. The American sample placed greater emphasis on the provision of care that enabled clients to take responsibility for themselves than did their UK counterparts. While acknowledging the limitations of the study, the results would appear to suggest that American nurses tend to favour humanistic care, have a belief in the efficacy of chemotherapy and aim to get people functioning independently. They fear the threat to their relationship with clients that managed care might entail. Concurrently, UK nurses appear to be preoccupied with finding appropriate services for their clients and they appear to believe that the changing nature of their work is designed to accommodate structural changes in the health service, rather than to meet the needs of clients. The implications of these findings are discussed.

Adult↗