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Biomedical subjects

P Walsh

Publications and source records attributed to P Walsh.

At least 19 recordsLinked to original sources
PubMed2006

Oceans and human health: Emerging public health risks in the marine environment.

There has been an increasing recognition of the inter-relationship between human health and the oceans. Traditionally, the focus of research and concern has been on the impact of human activities on the oceans, particularly through anthropogenic pollution and the exploitation of marine resources. More recently, there has been recognition of the potential direct impact of the oceans on human health, both detrimental and beneficial. Areas identified include: global change, harmful algal blooms (HABs), microbial and chemical contamination of marine waters and seafood, and marine models and natural products from the seas. It is hoped that through the recognition of the inter-dependence of the health of both humans and the oceans, efforts will be made to restore and preserve the oceans.

Animals↗
PubMed2005

Development of the Safe Tractor Assessment Rating System.

We describe the development of the Safe Tractor Assessment and Rating System (STARS), a design-based tractor safety rating system that can be applied to new or used tractors to provide an objective assessment of their inherent safety features. A predictive rating system model, based on technical inspection, was used. Key principles underlying the system included the potential for design features to reduce the risk of an injury event occurring, and to reduce the risk of injury if such an event did occur. The rating system was based on current standards, research literature, injury and fatality data, and farmer input via focus groups. Development was an iterative process involving field, pilot, and inter-rater reliability tests. The final system was divided into six domains: rollover protection, runover protection, user protection, information and controls, pedestrian protection, and options. Within each domain, optimum design features were described for the common or serious potential injury risks, and a score was assigned for each feature. Scores were translated into a star rating, from zero stars for virtually no inherent safety features to five stars for the highest inherent safety, for each of the six domains. STARS distinguished well between older tractor models known to have few inherent safety features and newer tractor models known to have higher levels of inherent safety. STARS can provide tractor manufacturers, dealers, and users with information critical for managing tractor-associated injury risk. In Australia, it is initially being implemented within the curriculum of the technical education and training sector.

Accidents, Occupational↗
PubMed2004

Introduction to the DAPPLE Air Pollution Project.

The Dispersion of Air Pollution and its Penetration into the Local Environment (DAPPLE) project brings together a multidisciplinary research group that is undertaking field measurements, wind tunnel modelling and computer simulations in order to provide better understanding of the physical processes affecting street and neighbourhood-scale flow of air, traffic and people, and their corresponding interactions with the dispersion of pollutants at street canyon intersections. The street canyon intersection is of interest as it provides the basic case study to demonstrate most of the factors that will apply in a wide range of urban situations. The aims of this paper are to introduce the background of the DAPPLE project, the study design and methodology for data collection, some preliminary results from the first field campaign in central London (28 April-24 May 2003) and the future for this work. Updated information and contact details are available on the web site at http://www.dapple.org.uk.

Air Pollution↗
PubMed2003

Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.

The congenital myopathies are a group of disorders characterised by the predominance of specific histological features observed in biopsied muscle. Central core disease and nemaline myopathy are examples of congenital myopathies that have specific histological characteristics but significantly overlapping clinical pictures. Central core disease is an autosomal dominant disorder with variable penetrance which has been linked principally to the gene for the skeletal muscle calcium release channel (RYR1). Two recent reports have identified the 3' transmembrane domain of this gene as a common site for mutations. Two other studies have reported single families that have features of both central core disease and nemaline myopathy (core/rod disease) caused by mutations in RYR1. Screening of the 3' region (exons 93-105) of the RYR1 gene for mutations in 27 apparently unrelated patients with either central core disease or core/rod disease by single strand conformation polymorphism analysis and DNA sequencing identified three described and nine novel mutations in 15 patients.

DNA Mutational Analysis↗
PubMed2003

Development of new generation rinderpest vaccines.

Veterinary science has benefited much from the advances in biotechnology during the past 20 years. New and improved diagnostic techniques for infectious diseases have been developed and new and highly effective vaccines to prevent such diseases have been introduced and more have been, or are about to be, field-tested. The latest development in negative strand virology, reverse genetics, the ability to rescue live virus from a DNA copy of the RNA genome, is being used to address questions concerning virus pathogenicity at the molecular level and to produce "marker" vaccines, i.e. vaccines that allow serological identification of all vaccinated animals. Such a vaccine would greatly benefit the continuing campaign for the global eradication of rinderpest since it would then be possible, by serological means, to detect wild type virus circulating in local areas or regions where it is still necessary to vaccinate and where the vaccination levels are below those required to eliminate the virus. Here we describe different approaches we have taken to produce such a vaccine using reverse genetics to add a marker to the existing and widely used Plowright rinderpest vaccine.

Animals↗
PubMed2002

Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.

Although prostate cancer is the most common non-cutaneous malignancy diagnosed in men in the United States, little is known about inherited factors that influence its genetic predisposition. Here we report that germline mutations in the gene encoding 2'-5'-oligoadenylate(2-5A)-dependent RNase L (RNASEL) segregate in prostate cancer families that show linkage to the HPC1 (hereditary prostate cancer 1) region at 1q24-25 (ref. 9). We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway and has been suggested to be a candidate tumor suppressor gene. We found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozyogous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway might provide opportunities for developing therapies for those with prostate cancer.

Adenine Nucleotides↗
PubMed2002

Amygdaloid projections to ventromedial striatal subterritories in the primate.

The ventral striatum is the part of the striatum associated with reward and goal-directed behaviors, which are mediated in part by inputs from the amygdala. The ventral striatum is divided into 'shell' and 'core' subterritories which have different connectional, histochemical and pharmacological properties. Behavioral studies also indicate that subterritories of the ventral striatum are differentially involved in specific goal-directed behaviors. The amygdala is a heterogeneous structure which has multiple nuclei involved in processing emotional information. While the existence of an amygdalostriatal pathway has long been established, the relationship between amygdaloid afferents and specific subterritories of the ventral striatum is not known. In this study we operationally defined the ventromedial striatum as the region receiving cortical inputs primarily from the orbital and medial prefrontal cortex. We placed retrograde tracer injections into subregions of the ventromedial striatum of macaques monkeys to determine the relative contribution of specific amygdaloid inputs to each region. Calbindin-D28k immunostaining was used to further define the shell subterritory of the ventromedial striatum. Based on these definitions, the amygdala innervates the entire ventromedial striatum, and has few to no inputs to the central striatum. The basal and accessory basal nuclei are the major source of input to the ventromedial striatum, innervating both the shell and ventromedial striatum outside the shell. However, a restricted portion of the dorsomedial shell receives few basal nucleus inputs. Afferent inputs from the basal nucleus subdivisions are arranged such that the parvicellular subdivision projects mainly to the ventral shell and core, and the magnocellular subdivision targets the ventral shell and ventromedial putamen. In contrast, the intermediate subdivision of the basal nucleus projects broadly across the ventromedial striatum avoiding only the dorsomedial shell. The shell has a specific set of connections derived from the medial part of the central nucleus and periamygdaloid cortex. Within the shell, the dorsomedial region is distinguished by additional inputs from the medial nucleus. The ventromedial caudate nucleus forms a unique transition zone with the shell, based on inputs from the periamygdaloid cortex. Together, these results indicate that subterritories of the ventromedial striatum are differentially modulated by amygdaloid nuclei which play roles in processing olfactory, visual/gustatory, multimodal sensory, and 'drive'-related stimuli.

Amygdala↗
PubMed2002

VNS therapy in clinical practice in children with refractory epilepsy.

OBJECTIVES: To study the efficacy, tolerability and safety of the vagus nerve stimulation (VNS) therapy in clinical practice, in 16 children and adolescents with refractory epilepsy. METHODOLOGY: We assessed the efficacy of VNS therapy, retrospectively by comparing seizure frequency, duration and severity at the time of most recent follow up (av: 24.9 months) to that in the 4 weeks prior to VNS surgery. Changes in quality of life, sleep and behaviour at last review was compared with that prior to VNS. Adverse effects elicited by specific questioning, spontaneous reporting and clinical examination are described. RESULTS: Vagus nerve stimulation resulted in a >50% reduction in seizure frequency in 62.5% of children with 25% achieving a >90% reduction. Vagus nerve stimulation was well tolerated in all but one of our cohort, with no serious side-effects. CONCLUSION: Our results support its role as one of the options in intractable childhood epilepsy.

Adolescent↗
PubMed2002

Parotid gland surgery: a retrospective review of 108 cases.

One hundred and eight parotidectomies performed by a single consultant were reviewed. Eighty-five patients had primary parotid disease, 23 patients had extra-parotid primaries. Pleomorphic adenoma was the most common histological diagnosis. In patients with primary parotid disease, a post-operative temporary facial nerve palsy was noted in 15 patients, with a further four developing a permanent palsy. Patients with metastatic disease to the parotid had a poor prognosis.

Adenoma, Pleomorphic↗
PubMed2001

Community health councils. Another brick in the wall.

The government's decision to abolish community health councils in England does not appear to be the result of public consultation. A survey of councils for voluntary service in England suggests that most are in favour of strengthening and reforming CHCs. The government's handling of the issue does not bode well for future consultation in the NHS.

Community Participation↗
PubMed2001

Management of primary cutaneous melanoma of the head and neck: The University of Colorado experience and a review of the literature.

BACKGROUND: While elective lymph node dissection (ELND), adjuvant radiation therapy and sentinel lymph node biopsy have all been advocated in the routine management of primary cutaneous melanoma arising in the head and neck, the optimal management has not been defined. METHODS: We have reviewed our experience of 273 patients with primary melanoma of the head and neck entered into a prospective database at the University of Colorado Health Sciences Center (UCHSC) from 1978 through 1998 and contrasted this with other reports in the literature. RESULTS: A total of 168 patients were identified that received their initial management at UCHSC and had no clinical evidence of distant disease. Only nine patients (5%) underwent ELND, and no patients received adjuvant radiation therapy. The local recurrence rate and 5-year melanoma specific survival, according to Breslow thickness, were similar to centers where adjuvant radiation therapy or ELND are routinely performed. Our preliminary experience and a review of the literature suggests that the technique of sentinel lymph node biopsy is an accurate and low risk procedure that provides valuable prognostic information useful in the further management of these patients. CONCLUSIONS: There is no clear indication that either ELND or adjuvant radiation therapy impacts on the outcome of patients with primary melanoma of the head and neck. Sentinel lymph node biopsy, in appropriate cases, is becoming the standard of care.

Adolescent↗
PubMed2001

CUSP/p63 expression in rat and human tissues.

The human homolog of KET, p63, bears strong homology to the tumor suppressor p53 and plays an essential role in epithelial development. CUSP, the most abundant cutaneous product of p63, has been identified as an autoantigen in chronic ulcerative stomatitis (CUS). The original report of KET expression at least partially contradicts p63 expression subsequently reported by many different groups. We have examined p63 expression by Northern analysis of RNA from multiple human tissues and by indirect immunofluorescence of rat tissue with CUS patient sera. Northern analysis reveals p63 RNA in skin, thymus, placenta, skeletal muscle, kidney, and lung, with non-transactivating p63 RNA in skin, thymus, and placenta. Reverse transcriptase polymerase chain reaction (rtPCR) assays show abundant non-transactivating p63 RNA, and little to no transactivating p63 RNA, in human basal cell carcinoma as well as in normal skin adjacent to the tumors. p63 RNA expression was not detected in brain, heart, colon, spleen, liver, or small intestine. Immunofluorescence reveals p63 expression in skin, oral epithelium, tongue, kidney, and trachea, but not in liver, large intestine, testis, skeletal muscle, or heart. Focal p63 expression within tissues, the complex array of isoforms encoded by the gene, and the specificity of the probes and antibodies utilized, may all contribute to contradictory accounts of CUSP/p63 expression.

Animals↗
PubMed2001

A randomized, double-blind placebo-controlled trial of the effects of the 5-hydroxytriptamine(4) agonist cisapride on the female urinary bladder.

OBJECTIVE: Anecdotal reports have proposed the use of the 5-hydroxytriptamine(4) agonist cisapride as a treatment for female voiding dysfunction on the basis of the known prokinetic actions of the medication. The purpose of our study is to assess the effects of this agent on the normal bladder in vivo. STUDY DESIGN: In this randomized, double-blind placebo-controlled trial, patients were randomized to receive either 20 mg cisapride or an identical placebo. They then underwent urodynamic evaluation that included uroflowmetry, multichannel filling cystometry, pressure-flow studies, and a urethral pressure profile. After a washout period of at least 7 days, subjects were then crossed over to the other arm and the tests were repeated. RESULTS: Twenty women without significant urinary incontinence agreed to participate. There was a decrease in the maximum cystometric capacity from 556 mL for placebo to 496 mL for cisapride (P <.001). There was no difference in the detrusor pressure at maximum flow, the maximum detrusor pressure, the flow rate, or the percentage of maximum cystometric capacity voided. CONCLUSIONS: In healthy women, cisapride caused a significant decrease in the maximum cystometric capacity, which could account for the higher reported rates of urinary frequency and urgency with this medicine. There was no evidence that this prokinetic agent improved voiding function.

Adult↗
PubMed2001

High uterosacral vaginal vault suspension with fascial reconstruction for vaginal repair of enterocele and vaginal vault prolapse.

OBJECTIVE: The purpose of this study was to review retrospectively the functional and anatomic outcomes of women who underwent vaginal repair of enterocele and vault prolapse with the use of an intraperitoneal suspension of the vaginal vault to the uterosacral ligaments in conjunction with fascial reconstruction of the anterior and posterior vaginal wall. STUDY DESIGN: Two hundred two women with advanced symptomatic uterovaginal prolapse or posthysterectomy vault prolapse underwent a standard transvaginal procedure to correct their prolapse between January 1997 and June 2000. Anatomic results were assessed by standardized examination from 6 months to 3 years after the operation. Functional results were assessed subjectively and with standard quality of life questionnaires. The average age of the women was 60.3 years. Follow-up data were available for 168 of the 202 women. Fifty-three percent of the women had their uterus in place and underwent a vaginal hysterectomy. The prolapse repair was a primary procedure in 45.2% of the women and was performed for a recurrence or persistence in 54.8% of the women. Sixty percent and 78.6% of women underwent anterior and posterior repair, respectively. Thirty-five percent of the women underwent an anti-incontinence procedure. RESULTS: Eighty-nine percent of the women expressed satisfaction with the results of the procedure. Ten women (5.5%) underwent a repeat operation (by the authors) for recurrence of prolapse in one or more segments of the pelvic floor. Quality of life assessment revealed a significant reduction in all aspects of daily living, when the short forms of the incontinence impact questionnaire and urogenital distress inventory were evaluated before and after the operation. Major intraoperative complications included 5 cases (2.4%) of ureteral injury, 1 case of a small bowel injury, and 1 case of a pelvic abscess that required abdominal exploratory operation and diversion of the colon. CONCLUSION: High uterosacral ligament vaginal vault suspension with fascial reconstruction would seem to provide a durable anatomic repair with good functional improvement in patients with significant complex uterine or vaginal vault prolapse.

Adult↗
PubMed2001

Use of V4R in patients who sustain blunt chest trauma.

OBJECTIVE: In blunt chest trauma, the right ventricle is more vulnerable than the left. The purpose of this study was to determine whether recording V4R in patients with blunt chest trauma would provide additional useful information to that already obtained from the standard 12-lead electrocardiogram (ECG). METHODS: Forty-five patients with blunt chest trauma and 40 unmatched control subjects without blunt chest trauma had standard 12-lead ECG and right precordial leads recorded. The ECGs were read blindly by three physicians. RESULTS: Patients with chest trauma were distinguishable from controls on the basis of the left-sided ECGs (odds ratio, 2.9; 95% confidence interval, 1.71-4.90). This was not the case using V4R (odds ratio, 1.23; 95% confidence interval, 0.59-2.0). CONCLUSION: Patients with a significant mechanism and physical findings of blunt chest trauma were more likely than controls to have an abnormal ECG. They were not more likely to have abnormalities in V4R. We recommend that a 12-lead ECG, but not V4R, be routinely obtained on these patients.

Adolescent↗
PubMed2001

Reversible resistance to apoptosis in cutaneous T cell lymphoma.

Mycosis fungoides and its leukemic variant, Sézary syndrome, represent the most common forms of cutaneous T cell lymphomas (CTCL). These disorders are clonal neoplasms characterized by the progressive accumulation of cells that resemble activated/memory CD4+ T cells. Unlike their normal counterparts, these malignant lymphocytes have prolonged life spans and are resistant to dying following treatment with most chemotherapeutic agents. This suggests that CTCL undergo abnormal programmed cell death; however, data regarding apoptotic defects in CTCL are limited. Regulation of apoptosis in lymphocytes that regularly undergo clonal expansion is necessarily complex and will be reviewed here. Clonally expanded lymphocytes rely primarily on Fas-mediated pathways to initiate apoptosis. Factors leading to the resistance of apoptosis in CTCL and new therapeutic approaches for reversing this resistance will be discussed, including the important role that the Fas death pathway may play in the pathogenesis and treatment of CTCL.

Antineoplastic Agents↗