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Biomedical subjects

B Wilson

Publications and source records attributed to B Wilson.

At least 19 recordsLinked to original sources

Epidemiological survey of central nervous system germ cell tumors in Canadian children.

OBJECTIVES: To determine the incidence and characteristics of pediatric patients with central nervous system (CNS) germ cell tumors (GCT) in Canada. METHOD: A national retrospective review of hospital charts was done on all patients with CNS GCT diagnosed between 1990 and 2004. Patients had to be under age 18 years at the time of diagnosis of a CNS germ cell tumor and be a resident of Canada. Information extracted included age and year of diagnosis, pathological diagnosis, location of tumor, evidence of disseminated disease at time of diagnosis and biological markers. RESULTS: One hundred and twenty-one cases were identified (83 germinoma; 38 non-germinoma germ cell tumor). The mean annual incidence of CNS GCT was 1.06 per million children (0.7 per million for germinoma; 0.3 per million for NGGCT). Though yearly incidences varied, there was no clear trend to increased incidence. Male predominance was noted (2.4:1 for germinoma; 11:1 for NGGCT). The primary locations were the pineal and suprasellar regions. At the time of diagnosis, disseminated disease was not uncommon (22% germinoma; 32% NGGCT). Beta human gonadotrophin was elevated in the serum, cerebrospinal fluid (CSF) or both in 7% of patients with germinoma and 36% of patients with NGGCT. Elevation of alpha-fetoprotein in serum, CSF or both was seen in 34% of patients with NGGCT. CONCLUSION: The incidence of CNS germ cell tumors in Canadian children is similar to that observed in other Western countries.

Adolescent↗

Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes.

Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was recently found to inhibit histone deacetylases (HDAC). Increasing reports demonstrate that VPA has neurotrophic effects in diverse cell types including midbrain dopaminergic (DA) neurons. However, the origin and nature of the mediator of the neurotrophic effects are unclear. We have previously demonstrated that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)-treated neuron-glia cultures through the inhibition of the release of pro-inflammatory factors from microglia. In this study, we report that VPA upregulates the expression of neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) from astrocytes and these effects may play a major role in mediating VPA-induced neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain DA neurons from LPS or 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. Our study identifies astrocyte as a novel target for VPA to induce neurotrophic and neuroprotective actions in rat midbrain and shows a potential new role of cellular interactions between DA neurons and astrocytes. The neurotrophic and neuroprotective effects of VPA also suggest a utility of this drug for treating neurodegenerative disorders including Parkinson's disease. Moreover, the neurotrophic effects of VPA may contribute to the therapeutic action of this drug in treating bipolar mood disorder that involves a loss of neurons and glia in discrete brain areas.

Animals↗

Genetic nurse counsellors can be an acceptable and cost-effective alternative to clinical geneticists for breast cancer risk genetic counselling. Evidence from two parallel randomised controlled equivalence trials.

This study compared genetic nurse counsellors with standard services for breast cancer genetic risk counselling services in two regional genetics centres, in Grampian region, North East Scotland and in Cardiff, Wales. Women referred for genetic counselling were randomised to an initial genetic counselling appointment with either a genetic nurse counsellor (intervention) or a clinical geneticist (current service, control). Participants completed postal questionnaires before, immediately after the counselling episode and 6 months later to assess anxiety, general health status, perceived risk and satisfaction. A parallel economic evaluation explored factors influencing cost-effectiveness. The two concurrent randomised controlled equivalence trials were conducted and analysed separately. In the Grampian trial, 289 patients (193 intervention, 96 control) and in the Wales trial 297 patients (197 intervention and 100 control) returned a baseline questionnaire and attended their appointment. Analysis suggested at least likely equivalence in anxiety (the primary outcome) between the two arms of the trials. The cost per counselling episode was 11.54 UK pounds less for nurse-based care in the Grampian trial and 12.50 UK pounds more for nurse-based care in Cardiff. The costs were sensitive to the grade of doctor (notionally) replaced and the extent of consultant supervision required by the nurse. In conclusion, care based on genetic nurse counsellors was not significantly different from conventional cancer genetic services in both trial locations.

Adolescent↗

Heavy metal dispersion, persistance, and bioccumulation around an ancient copper mine situated in Anglesey, UK.

The vicinity of an ancient abandoned copper mine located on the Isle of Anglesey was assessed for the dispersion of copper, zinc, lead, and cadmium into the surrounding environment. Extraction of soil, lichens, cattle feces, and Calluna vulgaris L. (ling) tissue, using aqua regia, was carried out and together with water samples, these were analyzed using flame atomic absorption spectroscopy. Atmospheric dispersion and dilution was plotted from the workings to the coast and the resultant dilution ascertained. Evidence of bioaccumulation by plants and animals is presented and partitioning within plants highlighted. The results suggest that atmospheric dispersion has ceased but residual metal concentrations in the soil remain persistent and could present health hazards to animals and humans in the past and in the future.

Animals↗

Potent regulation of microglia-derived oxidative stress and dopaminergic neuron survival: substance P vs. dynorphin.

Unregulated microglial activation has been implicated as a pivotal factor contributing to Parkinson's disease. Using mesencephalic neuron-glia cultures, we address the novel possibility that peptides endogenous to the substantia nigra (SN), substance P and dynorphin (10(-13)-10(-14) M), are opposing mediators of microglial activation and consequent DA neurotoxicity. Here, we identify that substance P (10(-13)-10(-14) M) is selectively toxic to DA neurons in a microglia-dependent manner. Mechanistically, substance P (10(-13)-10(-14) M) activated microglial NADPH oxidase to produce extracellular superoxide and intracellular reactive oxygen species (ROS). Neuron-glia cultures from mice lacking a functional NADPH oxidase complex (PHOX-/-) were insensitive to substance P (10(-13)-10(-14) M) -induced loss of DA neuron function. Mixed glia cultures from (PHOX-/-) mice failed to show a significant increase in intracellular ROS in response to substance P compared with control cultures (PHOX+/+). Further, dynorphin (10(-14) M) inhibited substance P (10(-13) M) -induced loss of [3H] DA uptake. Here we demonstrate a tightly regulated mechanism governing microglia-derived oxidative stress, where the neuropeptide balance of dynorphin and substance P is critical to DA neuron survival.

Animals↗

Monitoring emergence from coma following severe brain injury in an octogenarian using behavioural indicators, electrophysiological measures and metabolic studies: a demonstration of the potential for good recovery in older adults.

This case study describes a multi-disciplinary investigation of the emergence from coma of an 80-year old female (KE) following severe traumatic brain injury. The relationship between cognitive/behavioural ability and the integrity of cerebral function was assessed using neuropsychological measures, positron emission tomography, electroencephalography, somatosensory evoked potentials and trans-cranial magnetic stimulation. These investigations were performed as KE was beginning to emerge from coma (4 weeks) and, again, approximately 1 year following brain injury, when she was judged to have achieved her maximum level of recovery. Neuropsychological measures revealed improvement during the first year post-injury in KE's speed of information processing, memory and executive abilities. Electrophysiological and metabolic studies indicated a restoration of functional integrity that was consistent with the gradual recovery in higher brain function documented using behavioural procedures. This case study demonstrates the rehabilitation potential of pre-morbidly healthy older adults following severe traumatic brain injury.

Accidents, Traffic↗

Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers.

The antimicrobial activity of extracts of Curcuma zedoaria and Curcuma malabarica tubers was tested against six bacterial and two fungal strains using the agar well diffusion and broth dilution methods. Petroleum ether, hexane, chloroform, acetone and ethanol extracts exhibited antibacterial as well as antifungal activity. Acetone and hexane extracts of both tubers showed comparable antimicrobial activity as indicated by minimum inhibitory concentration (MIC) values, but other extracts of Curcuma malabarica showed significantly lower activity than those of Curcuma zedoaria. The MIC values for different strains and extracts ranged from 0.01 to 0.15 mg/ml in Curcuma zedoaria and from 0.01 to 0.94 mg/ml in Curcuma malabarica. Staphylococcus aureus (Gram positive) was inhibited by Curcuma malabarica but not by Curcuma zedoaria. This study is the first report of the antimicrobial properties of Curcuma malabarica. The findings also support the use of Curcuma zedoaria tubers in traditional medicine for the treatment of bacterial and fungal infections.

Anti-Infective Agents↗

Accidental head injuries in children under 5 years of age.

AIM: To evaluate the type and nature of head injuries sustained by children under the age of 5 years who present to a busy accident and emergency (A&E) department following an accidental fall. MATERIALS AND METHODS: This study included all children under the age of 5 years, who over an 8-month period were referred to our A&E Department with head injury following an accidental fall. Data were collected regarding the height of the fall, whether or not stairs were involved, the type of surface that the child landed on and the height of the child. This was correlated with any soft-tissue injury or skull fracture. RESULTS: A total of 72 children (aged 4 months to 4.75 years) fulfilled all the criteria for an accidental fall. The heights of the falls ranged from less than 50 cm to over 3 m, with the majority below 1 m. Of the falls, 49 were onto a hard surface and 23 were onto a soft surface. Of the 72 children, 52 had visible evidence of head injury, 35 (71%) of 49 being the result of falls onto hard surfaces and 17 (74%) of 23 onto soft (carpeted) surfaces. There was no significant difference in the type of surface that resulted in a visible head injury. A visible head injury was seen in all children who fell from a height of over 1.5 m and in 95% of children who fell over 1 m. Of the 72 children, 32 (44%) had skull radiographs performed in accordance with established guidelines and 4 (12.5%) were identified as having a fracture. Of the 3 linear parietal fractures 2 were inflicted by falls of just over 1 m (from a work surface) and 1 by a fall of 80 to 90 cm onto the hard-edged surface of a stone fire surround. The 4th was a fracture of the base of skull following a fall from more than 3 m (from a first-storey window). CONCLUSIONS: In the vast majority of domestic accidents children do not suffer significant harm. Skull fractures are rare and probably occur in less than 5% of cases. To cause a skull fracture the fall needs to be from over 1 m or, if from a lesser height, then a small-area impact point should be considered an integral component of the injury.

Accidental Falls↗

Assessment of fiberoptic near-infrared raman spectroscopy for diagnosis of bladder and prostate cancer.

OBJECTIVES: To determine whether a fiberoptic Raman system, suitable for in vivo use, is able to differentiate between benign and malignant bladder and prostate pathologic findings in vitro. Raman spectroscopy is an optical technique that provides a measure of the molecular composition of tissue by analyzing the way that tissue scatters laser light. Laboratory studies have shown that the technique can be used to identify and characterize transitional cell carcinoma and prostate adenocarcinoma in vitro. METHODS: A total of 220 Raman spectra were recorded from 29 snap-frozen bladder samples collected at cystoscopic procedures, and 197 Raman spectra were recorded from 38 snap-frozen prostate samples collected at transurethral resection of the prostate. The spectra were correlated with the histologic features and used to construct separate diagnostic algorithms for the bladder and prostate. These algorithms were tested as to their ability to determine the pathologic finding of a sample from its Raman spectrum. RESULTS: The bladder algorithm was able to differentiate benign samples (normal and cystitis) from malignant samples (transitional cell carcinoma), with an overall accuracy of 84%. The prostate algorithm was able to differentiate benign samples (benign prostatic hyperplasia and prostatitis) from malignant samples (prostate cancer), with an overall accuracy of 86%. CONCLUSIONS: The results of this study have demonstrated that the clinical Raman system can provide an accurate and objective method to diagnose prostate and bladder cancer in vitro. Because the Raman probe is suitable for use during endoscopic, laparoscopic, or open procedures, this work paves the way for in vivo studies.

Adenocarcinoma↗

Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.

The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 microM) (5-50 microg/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX-/-) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX+/+). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult.

Animals↗

Children's perceptions of dangerous substances.

The aim of this research was to examine age differences in children's perceptions of dangerous substances. Children's responses to photographs of child models encountering alcohol, a syringe, medicine, glue, and household bleach were coded for recognition of substance, awareness of potential danger, and understanding of danger or harm. Responses from 59 children (28 girls and 31 boys, who were all children of the required age in an urban primary school) were compared across three age groups (6-7 years, 8-9 years, and 10-11 years). 15 to 18 of 20 children in each of three age groups recognised all the dangerous substances. Significant differences across age groups were found for awareness of the potential harm from alcohol, glue, and medicine, but not for the syringe or bleach. Children reported less serious consequences from ingesting alcohol than other substances, the consequences of sniffing glue tended to be confused with the sticking properties of glue, children's understanding of transmission of germs, disease, and AIDS through syringes was varied, and there was a tendency among the older children to underestimate the potential harm of self-administration of medicines. Findings were discussed in relation to children's concepts of danger and safety education.

Attitude↗

Determination of the charge state distribution of a highly ionized coronal Au plasma.

We present the first definitive measurement of the charge state distribution of a highly ionized gold plasma in coronal equilibrium. The experiment utilized the Livermore electron beam ion trap EBIT-II in a novel configuration to create a plasma with a Maxwellian temperature of 2.5 keV. The charge balance in the plasma was inferred from spectral line emission measurements which accounted for charge exchange effects. The measured average ionization state was 46.8+/-0.75. This differs from the predictions of two modeling codes by up to four charge states.

Journal Article↗

The Leeds University Maternity Audit Project.

OBJECTIVES: To measure levels of and changes in compliance with evidence-based recommendations in obstetrics in the UK. To identify barriers to and factors associated with compliance. DESIGN: A quantitative case-note audit for 1988 and 1996, and a qualitative interview study of key staff. SETTING: Twenty maternity units, selected at random from all UK units SUBJECTS: Fifty consecutive cases of pre-term delivery (PTD), Caesarean section (CS), instrumental delivery (ID), and perineal repair (PR) operations in each period in each unit. The lead clinician, midwifery manager, a senior midwife, neonatologist, and middle-grade obstetrician in each unit. MAIN OUTCOME MEASURES: Maternal steroid use in PTD, antibiotic use in CS, use of the ventouse (vacuum extractor) rather than forceps as instrument of first choice for ID, and use of polyglycolic acid (PGA) sutures for PR in each time period. Facilities for implementing, staff attitudes to, and the degree of planning to follow each recommendation. MAIN RESULTS: The median proportion of ventouse as instrument of first choice in each unit was 8% (range 0-32%) in 1988, rising to 64% (range 0-98%) in 1996. PGA use for PR was 0% (range 0-30%) in 1988, and 72% (range 0-100%) in 1996. Steroid use for eligible PTD was median 0% (range 0-23%) in 1988, rising to 82% (range 63-95%) in 1996. Antibiotic use for CS was 7% (range 0-25%) rising to 84% (range 10-100%) in 1996. There was no relationship between unit size, type of unit, facilities, staff attitudes or degree of planning, and compliance with the recommendations, nor was the level of adherence to one standard typically correlated with adherence to the others. However, there was a positive correlation (R = 0.6, P < 0.005) between local availability of the Cochrane database of perinatal trials and unit compliance with the audit standards in the latter time period. CONCLUSIONS: We have documented a massive shift in practice in line with the evidence, although many units still have substantial room for improvement. About 2000 wound infections, 200 deaths due to prematurity, nearly 8000 women in pain from catgut sutures, and 1500 cases of severe perineal trauma from forceps remain preventable. The reasons why units vary remain obscure, although the qualitative interviews often revealed local factors such as key enthusiastic staff. There was no sign of evidence being positively driven into practice by any systematic managerial process. The relationship between Cochrane availability and high-standard care may be simply a marker of commitment to the evidence, but it remains plausible that if senior staff make Cochrane available for their juniors, audit compliance improves.

Adult↗

Neurons reduce glial responses to lipopolysaccharide (LPS) and prevent injury of microglial cells from over-activation by LPS.

The microenvironment of the CNS has been considered to tonically inhibit glial activities. It has been shown that glia become activated where neuronal death occurs in the aging brain. We have previously demonstrated that neurons tonically inhibit glial activities including their responses to the bacterial endotoxin lipopolysaccharide (LPS). It is not clear whether activation of glia, especially microglia in the aging brain, is the consequence of disinhibition due to neuronal death. This study was designed to determine if glia regain their responsiveness to LPS once the neurons have died in aged cultures. When cultured alone, glia from postnatal day one rat mesencephalons stimulated with LPS (0.1-1000 ng/mL) produced both nitric oxide (NO) and tumor necrosis factor alpha (TNFalpha), yielding a sigmoid and a bell-shaped curve, respectively. When neuron-containing cultures were prepared from embryonic day 14/15 mesencephalons, the shape of the dose-response curve for NO was monotonic and the bell-shaped curve for TNFalpha production was shifted to the right. After 1 month of culture under conditions where neurons die, the production curves for NO and TNFalpha in LPS-stimulated glia shifted back to the left compared to mixed neuron-glia cultures. Immunostaining of rat microglia for the marker CR3 (the receptor for complement component C3) demonstrated that high concentrations of LPS (1 microg/mL) reduced the number of microglia in mixed-glial cultures. In contrast, reduction of CR3 immunostaining was not observed in LPS-stimulated mixed neuron-glia cultures. Taken together, the results demonstrate that disinhibition of the glial response to LPS occurs after neurons die in aged cultures. Once neurons have died, the responsiveness of glia to LPS is restored. Neurons prevented injury to microglia by reducing their responsiveness to LPS. This study broadens our understanding of the ways in which the CNS microenvironment affects cerebral inflammation.

Animals↗

Comparison of the effects of two early intervention strategies on the health outcomes of malnourished hemodialysis patients.

OBJECTIVE: To determine the efficacy and cost-effectiveness of providing oral supplementation early in the course of malnutrition for hemodialysis (HD) patients. DESIGN: The study design consisted of 3 groups: an experimental group, a control group of patients with mild hypoalbuminemia (HA) (serum albumin [SA] = 3.5 to 3.7 g/dL), and a comparison group of patients with moderate to severe HA (SA = 2.5 to 3.4 g/dL). SETTING: Ten outpatient hemodialysis centers in southeast lower Michigan. PATIENTS: Treatment and control groups consisted of 32 HD patients with mild HA. Fourteen HD patients with moderate to severe HA comprised the comparison group. INTERVENTION: The experimental group received diet counseling and oral supplementation, and the control group received diet counseling only. The comparison group received physician-prescribed oral supplements and dietary counseling to permit comparison of the experimental treatment with current supplementation practices. MAIN OUTCOME MEASURES: Differences between groups in the number of patients reaching nutritional repletion, change in SA levels at the end of the study, and follow-up periods, were tested using chi-square analysis. Analysis of variance was used to compare group differences in treatment duration to repletion and number of hospitalization days. RESULTS: During the study period, significantly more patients reached nutritional repletion in the experimental group and control group (50% and 57%, respectively) than in the comparison group (7%). Overall, repletion occurred more quickly in the experimental group (3.2 +/- 1.7 months) than in the control group (3.5 +/- 1.2 months), with a larger number of patients in the experimental group repleted by month 2 of the study phase. During follow-up, patients in the experimental group were far more likely to maintain nutritional repletion or continue to improve (61%) than patients in the control group (14%). Although too few patients were hospitalized to show statistical significance, there was a trend toward greater numbers of hospital days in more malnourished patients (208 days for the comparison group), followed by those with mild HA who did not receive oral supplements (107 days), and the experimental group (71 days). CONCLUSION: Although the sample size for this study was too small for the results to be conclusive, it appears that use of nutritional supplements early in the course of malnutrition may provide benefits such as, attaining nutritional repletion more quickly, which results in less product usage. It is also more likely that good nutritional status will be maintained after supplementation is discontinued.

Aged↗