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Biomedical subjects

L Ritchie

Publications and source records attributed to L Ritchie.

At least 19 recordsLinked to original sources

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Carcinogens↗

The health and lifestyle of Scottish fishermen: a need for health promotion.

It has long been known that fishing is one of the most dangerous occupations. In the year 2001, 33 boats were lost and 10 fishermen killed in UK waters. Despite the dangerous nature of the occupation, very little research has been conducted on fishermen's health and safety. The few studies that have been conducted are spread widely around the globe, and tend to focus on mortality rates and accidents. Few studies considered fishermen's lifestyle behaviours. To address this gap in current knowledge research was conducted to gain an understanding of health and lifestyle issues affecting Scottish fishermen. Data was collected using a postal questionnaire survey in the Scottish fishing population and health diaries in a small subsample. High rates of smoking were prevalent and passive smoking was a considerable problem. Fewer fishermen drank alcohol compared to the general population, but fishermen lacked knowledge about what safe levels of alcohol consumption were. Diet was lacking in fruit and vegetables, and meals were eaten at very erratic intervals. Fishermen may benefit from health promotion and education in the areas of smoking, diet and alcohol consumption.

Accidents, Occupational↗

Quantification of polynuclear aromatic hydrocarbons in transformer oils by enzyme immunoassay.

Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.

Carcinogenicity Tests↗

The health of fishermen in the catching sector of the fishing industry: a gap analysis.

Offshore fishing is a sizeable industry in the UK and it is one of the most dangerous occupations. Long hours, extreme weather and working with heavy machinery contribute to a high mortality rate in fishermen. Despite a long-standing acknowledgement of the dangers and high mortality associated with fishing, there has been little research in this field. Although there have been developments within the industry in terms of safety, there has been little emphasis on the relationship between health, the environment and performance at work. This paper reviews the international literature on the health of fishermen, and describes the main findings and highlights gaps in current evidence. Areas for further research that would inform the future development of an evidence-based occupational health service for the offshore fishing industry are discussed.

Accidents, Occupational↗

Empowerment and Australian community health nurses' work with aboriginal clients: the sociopolitical context.

A portion of a study designed to explore community health nurses' (CHNs) perceptions of the concept of empowerment in their work with Australian Aboriginal clients is discussed in this article. The 12 study participants were identified through purposive convenience sampling. During this exploration, contentions regarding the concept of empowerment emerged, revealing the sociopolitical context of CHN's work with Aboriginal people that shaped their practice in crucial ways. These issues emerged from the participants' discussions regarding the meaning of empowerment in their work with Aboriginal clients and the strategies for and challenges to working in empowering ways within the context of Aboriginal health. Selected components of Habermas's works provided a useful framework to facilitate an understanding of the forces that underpin community health nursing practice.

Attitude of Health Personnel↗

A novel sensor for monitoring leakage of petroleum and other liquid hydrocarbons into soil environments.

This paper describes the use of a potentially implantable infrared reflectometer for the qualitative detection of petroleum and a number of other hydrocarbon solvents. A rugged, low-power, re-useable sensor was evaluated in the laboratory for its ability to detect petrol in soil. A hydrophobic fluoropolymer was used as the sensing surface due to its high selectivity for petroleum hydrocarbons. The photocurrent reflected by this surface from a near IR source was measured to test for petroleum saturation within the membrane, which in turn was an indicator of petroleum in the surrounding soil. The simplicity in the sensor design enabled a stable, low cost detection method for petroleum and other hydrocarbons, ideal for use in sub-surface applications.

Environmental Monitoring↗

Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial.

OBJECTIVES: (1) To establish recruitment rates of newly presenting asthmatic children. (2) To establish acceptability of study protocols. (3) To pilot age-specific quality of life (QoL) assessment. (4) To assess short-term (6 months) outcomes of inhaled corticosteroids (ICS) treatment. (5) To refine sample size calculations for a definitive study. DESIGN: A randomised pragmatic longitudinal trial design was used, with no blinding or placebo, to examine early ICS introduction similar to its use in practice. Subjects were assessed at entry, 3 and 6 months. SETTING: Subjects were recruited from six general practices. Children under 6 years were assessed at the Craig Research and Investigation Unit, Royal Aberdeen Children's Hospital, or their family home, and subjects 6 years and over were assessed at their general practice. SUBJECTS: Children (aged 6 months-16 years) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospectively from general practices. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness. INTERVENTIONS: Subjects were randomised to ss2-agonist (ss2-only group) or ss2-agonist and ICS (ICS group) for 6 months. Physicians could later prescribe ICS in controls if needed. MAIN OUTCOME MEASURES: (1) Pulmonary function. (2) Asthma symptom diary. (3) Symptomatic health status questionnaire. (4) Caregiver's and child's QoL. (5) Growth. (6) Bone mass. (7) Bone turnover. (8) Economic issues. RESULTS: Of over 15,000 children yielded from general practice records, 11% had symptoms suggestive of asthma/wheeze, and two-thirds of these already used ICS. Of the remaining, 141 subjects met the criterion of early asthma, and 86 were randomised. Two-thirds of those randomised were < 6 years old, the males:females ratio was 2:1, and 67% had a family history of atopy. RESULTS - PHYSIOLOGICAL DEVELOPMENT: Pulmonary function did not significantly improve in the older children. Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group, there was great variability. Incidence of wheeze and night-time cough reduced equally in both groups. Reduction of night-time symptom score and reliever use, and increase in symptom-free days were only significant in the ss2-only group. No significant differences were found in growth and bone mass between the two groups, but bone metabolism was significantly reduced at 6 months in the ICS group. RESULTS - PSYCHOLOGICAL DEVELOPMENT: The caregiver's QoL questionnaire was sensitive to child symptom changes over 3 months, but absolute impact of child symptoms on their QoL varied, whereas the child-centred questionnaire was not sensitive to change. RESULTS - ECONOMICS: There were no significant differences in medical consultation costs between the groups, but, as expected, prescription costs in the ICS group were higher over 6 months. Combined healthcare costs were significantly higher for patients assigned to ICS, but there were no significant differences in any effectiveness measures between the groups. CONCLUSIONS: Most (96%) of the proposed sample was recruited, and the low drop-out rate (8%) demonstrated acceptability of the study protocol. Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma, or virally induced wheeze. The caregiver's QoL questionnaire was found to better reflect a child's symptom changes than a child-centred instrument. In the short term, no adverse effects were seen on growth, but ICS treatment significantly reduced bone metabolism. Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone, and clinical benefits of early ICS intervention amongst these children were not detected; however, there was inadequate power in this pilot study to establish this. (AB

Adolescent↗

Call to needle times after acute myocardial infarction in urban and rural areas in northeast Scotland: prospective observational study.

OBJECTIVE: To determine call to needle times and consider how best to provide timely thrombolytic treatment for patients with acute myocardial infarction. DESIGN: Prospective observational study. SETTING: City, suburban, and country practices referring patients to a single district general hospital in northeast Scotland. SUBJECTS: 1046 patients with suspected acute myocardial infarction given thrombolytic treatment. MAIN OUTCOME MEASURES: Time from patients' calls for medical help until receipt of opiate or thrombolytic treatment, measured against a call to needle time of 90 minutes or less, as proposed by the British Heart Foundation. RESULTS: General practitioners were the first medical contact in 97% (528/544) of calls by country patients and 68% (340/502) of city and suburban patients. When opiate was given by general practitioners, median call to opiate time was about 30 minutes (95% within 90 minutes) in city, suburbs, and country; call to opiate delay was about 60 minutes in city and suburban patients calling "999" for an ambulance. One third of country patients received thrombolytic treatment from their general practitioners with a median call to thrombolysis time of 45 minutes (93% within 90 minutes); this compares with 150 minutes (5% within 90 minutes) when this treatment was deferred until after hospital admission. In the city and suburbs, no thrombolytic treatment was given outside hospital, and only a minority of patients received it within 90 minutes of calling; median call to thrombolysis time was 95 (46% within 90 minutes) minutes. CONCLUSIONS: The first medical contact after acute myocardial infarction is most commonly with a general practitioner. This contact provides the optimum opportunity to give thrombolytic treatment within the British Heart Foundation's guideline.

Acute Disease↗

Calcium influx via L-type voltage-gated channels mediates the delayed, elevated increases in steady-state c-fos mRNA levels in cerebellar granule cells exposed to excitotoxic levels of glutamate.

The altered kinetics of steady-state c-fos mRNA production in cultured cerebellar granule cells under excitotoxic conditions was investigated in neurons subjected to depolarising stimuli, namely, high KCl and L-glutamate (Glu), in which Ca2+ influx occurs by differing routes. Increases in intracellular-free calcium levels ([Ca2+]i) stimulated by nontoxic or toxic levels of Glu were blocked by selective N-methyl-D-aspartate (NMDA) receptor antagonism; were blocked only partially by the L-type channel blocker, nifedipine; and were unaffected by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonists. Glu-induced cell death was prevented only by NMDA receptor blockade. Exposure of cells to nontoxic levels of Glu resulted in a transient increase in c-fos mRNA levels, whereas an excitotoxic dose produced a delay in the appearance of c-fos mRNA but a subsequent, progressive, and sustained (>4 hr) increase. An excitotoxic dose of Glu in combination with either nifedipine or selective NMDA receptor antagonists resulted in the normal, transient increase of c-fos mRNA levels. Chronic exposure to 55 mM KCl caused no cytotoxicity, although it resulted in a delayed, elevated increase in c-fos mRNA levels that was unaffected by NMDA receptor blockade but reverted to the normal, transient profile of c-fos mRNA formation when it was coadministered with nifedipine. The KCl-induced increase in [Ca2+]i levels was inhibited dramatically by nifedipine but was unaffected by any of the ionotropic Glu receptor antagonists. The results support the notion that the appearance of a delayed but elevated increase in steady-state c-fos mRNA levels following exposure to excitotoxic doses of Glu is mediated specifically by calcium influx via L-type voltage-gated channels.

Animals↗

Audit of prehospital thrombolysis by general practitioners in peripheral practices in Grampian.

BACKGROUND: In the Grampian region early anistreplase trial (GREAT), domiciliary thrombolysis by general practitioners was associated with a halving of one year mortality compared with hospital administration. However, after completion of the trial and publication of the results, the use of this treatment by general practitioners declined sharply. OBJECTIVE: To increase the proportion of eligible patients receiving timely thrombolytic treatment from their general practitioners. SETTING: Practices in Grampian located > or = 30 minutes' travelling time from Aberdeen Royal Infirmary, where patients with suspected acute myocardial infarction were referred after being seen by general practitioners. AUDIT STANDARD: A call-to-needle time of 90 minutes, as proposed by the British Heart Foundation (BHF). METHODS: Findings of this audit of pre-hospital management of acute myocardial infarction were periodically fed back to the participating doctors, when practice case reviews were also conducted. RESULTS: Of 414 administrations of thrombolytic treatment, 146 (35%) were given by general practitioners and 268 (65%) were deferred until after hospital admission. Median call-to-needle times were 45 (94% < or = 90) and 145 (7% < or = 90) minutes, respectively. Survival at one year was improved with prehospital compared with hospital thrombolysis (83% v 73%; p < 0.05). The proportion of patients receiving thrombolytic treatment from their general practitioners did not increase during the audit. CONCLUSIONS: In practices > or = 30 minutes from hospital, the BHF audit standard was readily achieved if general practitioners gave thrombolytic treatment, but not otherwise. Knowledge of the benefits of early thrombolysis, and feedback of audit results, did not lead to increased prehospital thrombolytic use. Additional incentives are required if general practitioners are to give thrombolytic treatment.

Aged↗

Association of c-fos mRNA expression and excitotoxicity in primary cultures of mouse neocortical and cerebellar neurons.

The effect of excitatory amino acids (EAAs) on c-fos mRNA expression was studied in primary cultures of mouse cerebellar granule cells and in neocortical neurons after 2 and 7 days in vitro (div). In cultured granule cells at 2 and 7 div, and in cortical neurons at 2 div, exposure to low levels (< or = 10 microM) of a variety of EAAs (viz. glutamate [Glu], S-sulpho-L-cysteine [SC], N-methyl-D-aspartate [NMDA], alpha-amino-3-hydroxy-5-methyl-4-isoxazole [AMPA], and kainate [KA]) resulted in a transient increase in the level of c-fos mRNA which peaked at 30 min but returned to a basal level by 120 min. However, exposure of granule cells (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC and of cortical neurons (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC, or AMPA and to low levels (< or = 10 microM) of Glu and AMPA resulted in a delay in c-fos mRNA induction but a subsequent, progressive increase that was sustained for at least 240 min. Furthermore, this effect was accompanied by a dose-related increase in the release of the cytosolic enzyme, lactate dehydrogenase, used as an indicator of excitotoxicity. A ratio (Q240/30) for the steady-state levels of c-fos mRNA after 30 min and 240 min of exposure to EAAs was determined which showed that Q240/30 >2 correlated reproducibly with excitotoxic cell death, whereas a ratio of < or = 1 correlated with a nonexcitotoxic event. In both cell types at 7 div, coadministration of the selective NMDA receptor antagonist, DL(+/-)-2-amino-5-phosphonopentanoic acid (APV) with cytotoxic levels of Glu 1) protected against EAA-induced neurotoxicity and 2) exhibited a transient c-fos mRNA expression (Q240/30 values approximately 1). In contrast, the AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), provided no protection against excitotoxicity and had no significant effect on the Glu-induced delay in c-fos mRNA expression. These results suggest that the Q240/30 c-fos mRNA ratio may 1) be used as a predictive index for excitotoxic neuronal death, 2) provide information on the identity of the receptor subtype mediating excitotoxicity in different brain cell types, and 3) aid in establishing the role of excitotoxicity during the development of neurons in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

NMDA receptor-mediated cGMP synthesis in primary cultures of mouse cerebellar granule cells appears to involve neuron-astrocyte communication with NO operating as the intercellular messenger.

The possibility that neuron-astrocyte communication may be responsible for glutamate (Glu)-stimulated cGMP formation even in relatively homogeneous primary cultures of mouse cerebellar granule cells (7 days in vitro) was investigated. Pharmacological analysis using selective excitatory amino acid (EAA) receptor antagonists showed that cGMP production, stimulated in these cultures by Glu and a variety of endogenous EAAs structurally-related to Glu (namely, L-aspartate, L-cysteine sulphinate, L-homocysteate, S-sulpho-L-cysteine), was mediated wholly by N-methyl-D-aspartate (NMDA) receptor activation. Moreover, EAA-induced responses were dependent on the presence of extracellular calcium but unaffected by addition of the L-type voltage-sensitive calcium channel blockers nifedipine (10 microM) or verapamil (5 microM). The mode of calcium entry was also shown to be important since the calcium ionophore, A23187 (10 microM), was unable to stimulate cGMP levels above basal. cGMP formation was blocked by the competitive nitric oxide synthase inhibitor, L-NG-nitroarginine (100 microM), consistent with a role of nitric oxide (NO) in this signalling pathway. In the presence of added haemoglobin (1 microM), acting as a membrane-impermeable NO scavenger, Glu-stimulated cGMP formation was abolished implying that NO must act as an intercellular messenger. When the neuronal population was destroyed following a 24 hr exposure to the excitotoxin, S-sulpho-L-cysteine (200 microM), Glu-stimulated cGMP formation was abolished; whereas responses to the NO donor, sodium nitroprusside (SNP), although markedly reduced were still double that stimulated by Glu in the absence of the excitotoxin, suggesting the presence of non-neuronal cells that can generate cGMP if supplied directly with NO. Consistent with this suggestion, low levels of the glial specific enzyme, glutamine synthetase, were detected in granule cell cultures. Furthermore, omission or delayed addition of the antimitotic agent, cytosine arabinoside (20 microM), to the growth medium caused a significant increase in the level of Glu-stimulated cGMP formation.

Animals↗

Glutamate toxicity in primary cerebellar cultures from mouse brain is unaffected by changes in cGMP levels.

During evaluation of potential end-points for in vitro neurotoxicity screening we investigated what influence changes in cyclic GMP (cGMP) levels might exert on the degree of glutamate (Glu)-induced neurotoxicity in primary cultures of mouse cerebellar granule cells. Depletion of Glu-stimulated cGMP levels by N-methyl-D-aspartate receptor antagonists fully protected against Glu-induced toxicity. However, when Glu-stimulated cGMP levels were either depleted or elevated by the use of a variety of pharmacological agents acting intracellularly at various points of the NO/cGMP signalling pathway the degree of cytotoxicity exerted by Glu was unaltered. These results imply that cGMP and NO do not modulate the toxic effects of Glu and are therefore unsuitable as biomarkers of excitotoxicity in these cells.

Animals↗

A prototypic intracellular calcium antagonist, TMB-8, protects cultured cerebellar granule cells against the delayed, calcium-dependent component of glutamate neurotoxicity.

The effect(s) of a prototypic intracellular Ca2+ antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), on glutamate-induced neurotoxicity was investigated in primary cultures of mouse cerebellar granule cells. Glutamate evoked an increase in cytosolic free-Ca2+ levels ([Ca2+]i) that was dependent on the extracellular concentration of Ca2+ ([Ca2+]o). In addition, this increase in [Ca2+]i correlated with a decrease in cell viability that was also dependent on [Ca2+]o. Glutamate-induced toxicity, quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining, was shown to comprise two distinct components, an "early" Na+/Cl(-)-dependent component observed within minutes of glutamate exposure, and a "delayed" Ca(2+)-dependent component (ED50 approximately 50 microM) that coincided with progressive degeneration of granule cells 4-24 h after a brief (5-15 min) exposure to 100 microM glutamate. Quantitative analysis of cell viability and morphological observations identify a "window" in which TMB-8 (at > 100 microM) protects granule cells from the Ca(2+)-dependent, but not the Na+/Cl(-) -dependent, component of glutamate-induced neurotoxic damage, and furthermore, where TMB-8 inhibits glutamate-evoked increases in [Ca2+]i. These findings suggest that Ca2+ release from a TMB-8-sensitive intracellular store may be a necessary step in the onset of glutamate-induced excitotoxicity in granule cells. However, these conclusions are compromised by additional observations that show that TMB-8 (1) exhibits intrinsic toxicity and (2) is able to reverse its initial inhibitory action on glutamate-evoked increases in [Ca2+]i and subsequently effect a pronounced time-dependent potentiation of glutamate responses. Dantrolene, another putative intracellular Ca2+ antagonist, was completely without effect in this system with regard to both glutamate-evoked increases in [Ca2+]i and glutamate-induced neurotoxicity.

Animals↗

Stroke units.

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Cerebrovascular Disorders↗

Is Bell's palsy a reactivation of varicella zoster virus?

Despite various pointers to an infectious aetiology, the cause of Bell's palsy remains obscure. We examined paired sera from 62 patients with facial palsy and 50 age and sex matched contemporaneous controls. Significantly more patients than controls had IgM antibodies by ELISA to varicella zoster virus (56.5% vs. 20%, P = 0.0001) and herpes simplex virus (41.9% vs. 18%, P = 0.006). Additionally, significantly more patients than controls were positive for CF antibody to varicella zoster virus (14.5% vs. 0%, P = 0.004) but not to herpes simplex or cytomegalovirus. Significantly more controls than patients (54% vs. 25.8%, P = 0.002) had no evidence of antigenic stimulation by any of the herpesvirus group. No significant difference between patients and controls in seropositivity by IgM ELISA to cytomegalovirus. Epstein-Barr virus and IFA for human herpes virus 6 was found. Furthermore, there was no significant difference between the two groups as to evidence of recent infection by the following agents: rubella virus and Borrelia burgdorferi by IgM ELISA, influenza A. influenza B, adenovirus, respiratory syncytial virus, mumps and measles. Mycoplasma pneumoniae, Coxiella burnetii and chlamydia spp. by complement fixation test. The first reported case of clinically and serologically proven Mycoplasma pneumoniae pneumonia associated with Bell's palsy is described. The rate of complete recovery at 6-8 weeks after onset was not significantly different in patients who were given steroids compared to those who were not. Ear related symptoms were the most common, occurring in 12 of 65 cases, but only three (4.6%) had clinical shingles (vesicles in ear).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗