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Biomedical subjects

B Young

Publications and source records attributed to B Young.

At least 19 recordsLinked to original sources
PubMed2006

MRI volumetric and intensity analysis of the cerebellum in Parkinson's disease patients infused with glial-derived neurotrophic factor (GDNF).

BACKGROUND: A recent human therapeutic trial using intraputaminal infusion of glial cell-derived neurotrophic factor (GDNF) in Parkinson's disease (PD) was abruptly terminated, partly due to safety concerns raised by the finding of cerebellar lesions in monkeys given high-dose GDNF. METHODS: Magnetic resonance images from nine PD patients participating in this trial were analyzed to determine whether subtle volumetric or intensity changes could be detected in the cerebellum or elsewhere following GDNF treatment for over 1 year. Subtraction images were compared to a reference standard deviation map constructed by using identically-processed paired scans from 25 normal adults. In a separate voxel-based group morphometric (VBM) analysis of the same patient images, grey matter intensity was compared between pre and post-GDNF infusion scans using a repeated measures ANOVA with family-wise error threshold of P = 0.10. Two expert readers independently reviewed serial FLAIR images from all patients. RESULTS: (1) There were no significant cerebellar differences in any of the nine individual PD patients (difference image analysis), (2) there were no significant morphometric differences between pre- and post-GDNF scans (VBM), and (3) there were no signal abnormalities in the cerebellum detected on the FLAIR images in PD patients (clinical scan review). CONCLUSIONS: In concert with lack of evidence of cerebellar dysfunction on clinical examination, we find no imaging evidence of cerebellar injury in human subjects undergoing chronic intracerebral GDNF infusion.

Aged↗
PubMed2006

Acute renal cortical necrosis in a series of young men with severe acute pancreatitis.

Diffuse renal cortical necrosis from any cause is rare in the Western World. Over the last 5 decades, there have been isolated case reports of acute cortical necrosis as a consequence of acute pancreatitis, but the long-term outcome of these patients has not previously been reported. Here, we report 3 young men, aged 16-21 years, who have presented over the past 19 years with severe acute pancreatitis associated with oliguric acute renal failure. They were all found to have diffuse renal cortical necrosis and consequently made no renal recovery. Despite the appreciable mortality associated with acute pancreatitis complicated by acute renal failure, they all survived the initial illness and all have successfully undergone renal transplantation. We present a detailed account of each patient including diagnostic strategies and discuss the possible factors contributing to a favorable outcome in these patients.

Acute Disease↗
PubMed2005

Lobar nephronia in a transplanted kidney.

We report a patient who presented with a solid mass in her graft 15 years after renal transplantation. The appearances by ultrasound were consistent with either malignancy or lobar nephronia (focal acute bacterial nephritis). Biopsy confirmed the diagnosis of a lobar nephronia with marked inflammatory infiltrate and frank pus formation. Treatment with antibiotics was associated with resolution of the mass. Lobar nephronia is a diagnosis based upon renal ultrasonography and must be considered in a patient with a solid mass in the kidney.

Acute Disease↗
PubMed2004

Policy implications associated with the socioeconomic and health system impact of telehealth: a case study from Canada.

This research was undertaken to inform future telehealth policy directions regarding the socioeconomic impact of telehealth. Fifty-seven sources were identified and analyzed through a comprehensive literature search of electronic databases, the Internet, journals, conference proceedings, as well as personal communication with consultants in the field. The review revealed a focus on certain socioeconomic indicators such as cost, access, and satisfaction. It also identified areas of opportunity for further research and policy analysis and development (e.g., social isolation, life stress, poverty), along with various barriers and challenges to the advancement of telehealth. These included confidentiality, reimbursement, and legal and ethical considerations. To become fully integrated into the health care system, telehealth must be viewed as more than an add-on service. This paper offers 19 general and 20 subject-specific telehealth recommendations, as well as seven policy strategies.

Alberta↗
PubMed2003

A systematic review of molecular and biological markers in tumours of the Ewing's sarcoma family.

The aims of this study were to perform the first systematic review of molecular and biological tumour markers in tumours of the Ewing's sarcoma family (ESFT), and evaluate the current evidence for their clinical use. A well-defined, reproducible search strategy was used to identify the relevant literature from 1966 to February 2000. Papers were independently assessed for tumour markers used in the screening, diagnosis, prognosis or monitoring of patients with ESFT. Eighty-four papers studying the use of 70 different tumour markers in ESFT's were identified. Low-quality, inconsistent reporting limited meta-analysis to that of prognostic data for 28 markers. Patients with tumours lacking S-100 protein expression have a better overall survival (OS) (hazard ratio (HR)=0.41, 95% confidence interval (CI) 0.19, 0.89) than those with expression; patients with high levels of serum LDH had a worse OS and disease-free survival (DFS) (OS: HR=2.92, CI 2.16, 3.94, DFS: HR=3.38, 95% CI 2.28, 4.99); patients with localised disease and tumours expressing type 1 EWS-FLI1 fusion transcripts had an improved DFS compared with those with other fusion transcript types (HR=0.17, 95% CI 0.079, 0.37). The knowledge base formed should facilitate more informative future research. Improved statistical reporting and large, multicentre prospective studies are advocated.

Biomarkers, Tumor↗
PubMed2003

The socio-economic impact of telehealth: a systematic review.

We reviewed the socio-economic impact of telehealth, focusing on nine main areas: paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care, mental health, radiology, renal dialysis, rural/remote health services and rehabilitation. A systematic search led to the identification of 4646 citations or abstracts; from these, 306 sources were analysed. A central finding was that telehealth studies to date have not used socio-economic indicators consistently. However, specific telehealth applications have been shown to offer significant socio-economic benefit, to patients and families, health-care providers and the health-care system. The main benefits identified were: increased access to health services, cost-effectiveness, enhanced educational opportunities, improved health outcomes, better quality of care, better quality of life and enhanced social support. Although the review found a number of areas of socio-economic benefit, there is the continuing problem of limited generalizability.

Bias↗
PubMed2002

Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides.

BACKGROUND: Data on genome-wide surveys for chromosome aberrations in primary cutaneous T-cell lymphoma (CTCL) are limited. OBJECTIVE: To investigate genetic aberrations in CTCL. METHODS: We analysed 18 cases of Sézary syndrome (SS) and 16 cases of mycosis fungoides (MF) by comparative genomic hybridization (CGH) analysis, and correlated findings with the results of additional conventional cytogenetics, fluorescent in situ hybridization (FISH) and allelotyping studies. RESULTS: CGH analysis showed chromosome imbalances (CIs) in 19 of 34 CTCL cases (56%). The mean +/- SD number of CIs per sample was 1.8 +/- 2.4, with losses (1.2 +/- 2.0) slightly more frequent than gains (0.6 +/- 1.0). The most frequent losses involved chromosomes 1p (38%), 17p (21%), 10q/10 (15%) and 19 (15%), with minimal regions of deletion at 1p31p36 and 10q26. The commonly detected chromosomal gains involved 4/4q (18%), 18 (15%) and 17q/17 (12%). Both SS and late stages of MF showed a similar pattern of CIs, but no chromosomal changes were found in three patients with T1 stage MF. Of the 18 SS cases also analysed by cytogenetics, seven showed clonal chromosome abnormalities (39%). Five cases had structural aberrations affecting chromosomes 10 and 17, four demonstrated rearrangement of 1p and three revealed an abnormality of either 6q or 14q consistent with CGH findings. FISH analysis showed chromosome 1p and 17q rearrangements in five of 15 SS cases, and chromosome 10 abnormalities in four SS cases consistent with both the G-banded karyotype and the CGH results. In addition, allelotyping analysis of 33 MF patients using chromosome 1 markers suggested minimal regions of deletion at D1S228 (1p36), D1S2766 (1p22) and D1S397 (1q25). CONCLUSIONS: These findings provide a comprehensive assessment of genetic abnormalities in CTCL and a rational approach for further studies.

Chromosome Aberrations↗
PubMed2002

Childhood cancer and users' views: a critical perspective.

The understanding of users' views of childhood cancer services has been hampered by several important problems. First, this area has been dominated by the tradition of psycho-oncology, with its overly narrow focus on the psychopathological sequelae of chronic childhood illness. Second, a set of inappropriate and undertheorized assumptions has prevailed about the nature of childhood and children's experiences of illness and children's ability to articulate and report on these. Third, the roles, responsibilities and experiences of parents of children with cancer have been unhelpfully conceptualized and underinvestigated. Finally, there has been a lack of suitable methods for making progress with empirical research in this area. In this paper, we argue that interpretive perspectives and associated methods can offer much to those seeking more insightful and better-informed approaches to the views of users of childhood cancer services. We offer some specific examples of where such approaches have already demonstrated considerable promise, showing, for example, that the parenting role is distinctive and should not be assumed to be interchangeable, theoretically or practically, with that of a carer. We conclude by identifying areas where both empirical research and theoretical development are needed.

Adaptation, Psychological↗
PubMed2002

Parents' accounts of wheeze and asthma related symptoms: a qualitative study.

AIMS: To examine parents' accounts of how they recognise and judge respiratory symptoms in children, and to investigate their interpretations of respiratory survey questions about wheeze, shortness of breath, and cough. METHODS: Qualitative study using semistructured interviews. Data were analysed using the constant comparative method. Nineteen parents of children aged under 6 years were recruited from a cohort of parents who had responded to an earlier respiratory symptom survey and from one general practice. RESULTS: Parents judged respiratory symptoms using a range of cues, including changes in the sound of breathing and changes in appearance and behaviour. Experiential resources and contextual factors played an important role in parents' judgements. Interpretations of questions about respiratory symptoms were varied, particularly in relation to the terms "attacks of wheeze" and "shortness of breath". Parents' descriptions of wheeze differed from descriptions of the sound of wheeze used in some survey questionnaires. Parents drew fine distinctions between different "types" of cough and identified a distinct "asthma" cough. CONCLUSIONS: Attention needs to be given to the complexity of reporting respiratory symptoms in children and to the importance of contextual factors in parents' judgements. We suggest that questions which require parents to report on children's internal feelings or states be avoided. Consideration should be given to providing parents with explicit direction on what cues to attend to or ignore in reporting symptoms, and to clarifying some questions that are currently used in clinical practice and in surveys.

Asthma↗
PubMed2001

Improving the fit of bivariate smoothing splines when estimating longitudinal immunological and virological markers in HIV patients with individual antiretroviral treatment strategies.

CD4+ lymphocyte count and HIV RNA plasma viral load are longitudinally monitored in patients with HIV infection. Because data collection intervals may be unequally spaced and these markers experience high within-patient variability, they may be smoothed before use in subsequent models. Estimation strategies must be able to accommodate the drastic changes in viral load which may occur when an individual's treatment strategy is updated. Because these treatment changes are not regimented, these dynamics cannot be modelled using standard methods. We propose univariate and bivariate cubic smoothing splines to fit CD4+ count and viral load over time. The method is developed using state space equations, and the Kalman filter is used to calculate the log-likelihood. Non-linear optimization is used to obtain the maximum likelihood estimates. A modification of the Kalman filter allows non-informative or diffuse priors at the initial observation. Since treatment changes are expected to alter the shape of the curve, we further extend the Kalman filter to permit greater flexibility in the smoothing spline at these time points. The method produces smoothed estimates of the viral load and CD4+ count curves over time.

Anti-HIV Agents↗
PubMed2001

Combination of ATP-bioluminescence and PNA probes allows rapid total counts and identification of specific microorganisms in mixed populations.

We have combined ATP-dependent bioluminescence with a novel chemiluminescent in situ hybridization (CISH) method using peroxidase-labeled peptide nucleic acid (PNA) probes targeting species-specific rRNA sequences to provide total counts and subsequent identification of specific microorganisms. Both methods are applied to the same membrane filter following a short incubation time and both methods provide results in the form of spots of light that are captured by the MicroStar detection system. Each spot of light represents individual micro-colonies detected by either ATP bioluminescence or PNA CISH. This new concept is particularly intended for in process and quality control of non-sterile products to rapidly provide total counts as well as presence/absence of specific indicators and/or pathogens in non-sterile, filterable samples.

Adenosine Triphosphate↗
PubMed2001

Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.

OBJECTIVE: To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. DESIGN: Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. SETTING: Eight clinics specializing in the care of HIV-1 infected patients. PATIENTS: A total of 1077 patients were evaluated for signs of fat maldistribution. INTERVENTIONS: A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. MAIN OUTCOME MEASURES: Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. RESULTS: Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. CONCLUSIONS: HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Parents' accounts of obtaining a diagnosis of childhood cancer.

BACKGROUND: Quick diagnosis and treatment of cancers is a UK government priority. However, the process of arriving at a diagnosis of childhood cancer has been neglected in comparison with the attention given to cancers in adults. We investigated parents' narratives about the period before their child's diagnosis. METHODS: We undertook semistructured interviews with 20 parents whose children (aged 4-18 years) had a confirmed diagnosis of cancer or brain tumour. All interviews were recorded and fully transcribed. Dates of consultations and investigations were noted from children's medical records. Data were analysed by the constant comparison method. FINDINGS: The time before diagnosis is very significant for parents and might affect their adaptation and reaction to their child's diagnosis. Parents were first alerted to their child's illness by a range of signs and symptoms, and by behavioural and affective changes. These early symptoms were often vague, non-specific, and common, and some older children were reluctant to disclose symptoms. Ten families' accounts of this period before diagnosis included a dispute with doctors. Disagreements between parents and doctors about the seriousness of children's symptoms and the need for investigations occurred in both primary and secondary care. Some parents felt that doctors discounted their special knowledge of their child. INTERPRETATION: Parents' accounts offer valuable insights into their experiences of obtaining a diagnosis of childhood cancer and into possible sources of delays in this complex process. If delays are to be avoided or reduced, attention must be given to the different roles of parents, children, general practitioners, hospital specialists, and type of cancer. Our findings have important implications for policy, practice, and research, and for the management of childhood illnesses.

Adolescent↗
PubMed2001

Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos.

The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias. MLL codes for a large multidomain protein and bears homology to the Drosophila developmental control gene trithorax in two small domains in the amino terminal region, the central zinc finger domain and the carboxy SET domain. Like the Drosophila trx, MLL has also been shown to be a positive regulator of Hox gene expression. We have targeted Mll (the murine homologue of MLL) in exon 5 causing expression of three truncated in-frame Mll transcripts. These transcripts retain all or some of the AT hook motifs and the DMT domain. This mutant allele causes early in vivo preimplantation lethality of homozygous embryos prior to the 2-cell stage. Embryos cultured in vitro progress to the 2-cell stage, but further development is arrested. The heterozygotes exhibit mild skeletal defects as well as defects in some neuroectodermal derivatives.

Animals↗
PubMed2001

Bovine Staphylococcus aureus mastitis: strain recognition and dynamics of infection.

Restriction enzyme fragmentation pattern (REFP) analysis was used to recognise Staphylococcus aureus strain variation in naturally occurring bovine subclinical mastitis. Multiple colony REFP analysis identified eight distinct strains of S. aureus in addition to the original strains A and B that were infused via the intramammary route, indicating that individual quarters of the udder may be colonised simultaneously by more than one strain of S. aureus. Examination of multiple colonies per milk sample may benefit bacterial strain recognition as an epidemiological tool in mastitis investigations. The dynamics of intramammary infection were determined using a novel double crossover experimental challenge. Quarters remained persistently infected for several weeks following challenge in all four cows, irrespective of the challenge strain. This indicated that no alteration of the original subclinical infection, including the possible induction of clearance of the quarters infected with S. aureus, or replacement of the original strain by the infused strain was induced by challenge. The persistent subclinical infection in all four animals supports previous reports on the chronicity of S. aureus intramammary infection in dairy cows.

Animals↗