PubMed Health⌕ Search

Biomedical subjects

R Neale

Publications and source records attributed to R Neale.

At least 19 recordsLinked to original sources
PubMed2006

Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack.

BACKGROUND: Weak associations between total and LDL cholesterol and ischaemic stroke compared with coronary heart disease (CHD) are at odds with the similar effectiveness of statin drugs in preventing ischaemic stroke and CHD, suggesting that other lipid sub-fractions that are affected by statins might be better predictors of ischaemic stroke. Apolipoprotein B levels are reduced by statins and are a stronger predictor of CHD than total and LDL cholesterol in patients both on and off statins. However, there are very few published data on apolipoproteins and stroke risk and no studies in patients with previous transient ischaemic attack (TIA). METHODS: We performed a prospective cohort study of the associations of baseline total cholesterol, LDL, HDL, apolipoproteins A1 and B (apo A1; apo B) and risk of ischaemic stroke in 261 patients with previous TIA. Cox proportional hazards models were used to determine crude and multivariate-adjusted hazard ratios (HR) above versus below median values at 10-years follow-up. RESULTS: The apo B/apo A1 ratio was the strongest independent predictor of ischaemic stroke (HR=2.94, 95% CI 1.43-5.88, p=0.003) followed by apo B (HR=2.26, 95% CI 1.16-4.38, p=0.02). The associations between total cholesterol, LDL, HDL, LDL/HDL ratio and apo A1 and ischaemic stroke risk did not reach statistical significance. CONCLUSIONS: Apo B and the apo B/apo A1 ratio are predictive of ischaemic stroke in patients with previous TIA. Further studies are required to determine whether the prognostic value of apolipoprotein levels is maintained in patients on statins.

Aged↗
PubMed2004

Statin precipitated lactic acidosis?

An 82 year old woman was admitted with worsening dyspnoea. Arterial blood gases were taken on air and revealed a pH of 7.39, with a partial pressure of CO2 (pCO2) of 1.2 kPa, pO2 of 19.3 kPa, HCO3 of 13.8 mmol/litre, and base excess of -16.3 mmol/litre: a compensated metabolic acidosis with hyperventilation induced hypocapnia, which is known to be a feature of lactic acidosis. There was also an increased anion gap ((Na140 + K4.0) - (Cl 106 + HCO3 13.8) = 24.2 mEq/litre (reference range, 7-16)), consistent with unmeasured cation. Lactate was measured and found to be raised at 3.33 mmol/litre (reference range, 0.9-1.7). After exclusion of common causes of lactic acidosis Atorvastatin was stopped and her acid-base balance returned to normal. Subsequently, thiamine was also shown to be deficient. The acidosis was thought to have been the result of a mitochondrial defect caused by a deficiency of two cofactors, namely: ubiquinone (as a result of inhibition by statin) and thiamine (as a result of dietary deficiency).

Acidosis, Lactic↗
PubMed2002

Appropriate indicators for injury control?

Indicators are valuable tools used to measure progress towards a desired health outcome. Increased awareness of the public health burden due to injury has lead to a concomitant interest in monitoring the impact of national initiatives that aim to reduce the size of the burden. Several injury indicators have now been proposed. This study examines the ability of each of the suggested indicators to reflect the nature and extent of the burden of non-fatal injury. A criterion validity, population-based, prospective cohort study was conducted in Brisbane, a sub-tropical Metropolitan City on the eastern seaboard of Australia, over a 12-month period between 1 January and 31 December 1998. Neither the presence of a long bone fracture nor the need for hospitalisation for 4 or more days were sensitive or specific indicators for 'serious' or major injury as defined by the 'Gold Standard' Injury Severity Score (ISS). Subsequent analysis, using other public health outcome measures demonstrated that the major component of the illness burden of injury was in fact due to 'minor' not serious injury. However, the suggested indicators demonstrated low sensitivity and specificity for these outcomes as well. The results of the study support the need to include at least all hospitalisations in any population-based measure of injury and not attempt to simplify the indicator to a more convenient measure aimed at identifying just those cases of 'serious' injury.

Adolescent↗
PubMed2001

Cognition and survival: an exploration in a large multicentre study of the population aged 65 years and over.

BACKGROUND: Understanding the patterns in determinants of survival becomes increasingly important as the population ages. Dementia is known to shorten survival as is impaired cognition. Whether this is a continuous phenomenon and independent of other explanatory variables is less clear. OBJECTIVES: To examine a population-based dataset in which a measure of cognitive function (Mini-Mental State Examination [MMSE]), self-reported physical health and lifestyle variables were measured at outset, with monitoring for mortality thereafter. METHODS: The five identical sites of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) were analysed, with populations in rural Cambridgeshire, Gwynedd, Newcastle, Nottingham and Oxford. Survival curves were modelled and stratified analyses carried out, with physical disease, sociodemographic variables and lifestyle variables as covariates. RESULTS: There was a strong and consistent reduction in survival probability for each decrement in MMSE. Adjustment for known confounders did not alter this pattern. Social class and education in particular had no additional effect. Self-reported health was the only other associated variable. CONCLUSION: Cognitive function appears to be a marker of capacity for survival in the UK. Terminal decline can account for some of this. Actuarial survival provided here can give carers and service providers an idea of prognosis at given ages and levels of cognition, and provide baseline data for those planning interventions in similar groups.

Aged↗
PubMed1999

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.

BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Adult↗
PubMed1998

The shady side of solar protection.

OBJECTIVE: To determine the value of shade in protecting humans from solar ultraviolet (UV) radiation. DESIGN AND SETTING: Measurement with photometers of protection factors for ultraviolet B radiation (UVB) and for total solar radiation for different types of trees and other structures during the summer months (1995-1997) in south-east Queensland. (The protection ratio is the ratio of the intensity of UVB or total solar radiation in direct sunlight to that in shade.) RESULTS: For summer sun at midday, the mean (SD) UV protection ratio for the shade of trees (n = 65) was 4.21 (1.36) on a horizontal surface and 1.33 (0.30) on a vertical surface. In contrast, the mean (SD) protection ratio for total solar energy (primarily infrared) was much higher (12.1 [1.4]). Trees common in recreational areas in Australia (eucalypts: UV protection ratio, 3.52 [0.79]; Norfolk Island pines: UV protection ratio, 3.72 [0.98]) offered reduced protection compared with trees with more dense foliage (UV protection ratio, 5.48 [1.44]). Over a whole day, measurement of shade by trees and other structures showed that the UV protection ratio was lower in the morning and afternoon. Shade from awnings, buildings and hats gave similar results to those for trees. Both at midday and over a whole day satisfactory protection (UV protection ratio > 15) was obtained only in shade which eliminated exposure to the sky as well as to direct sunlight; for example, in thickly wooded areas and under low, widely overhanging structures. CONCLUSIONS: Most forms of shade, while useful, offer people insufficient protection from solar UV. A fair-skinned person sheltering under a tree could suffer sunburn after less than one hour. There is a need for appropriate design of structural shade, use of other solar protection measures in conjunction with shade, and research on behavioural responses to shade.

Facility Design and Construction↗
PubMed1997

Sun exposure, sunscreen and their effects on epidermal Langerhans cells.

This study examined the effects of chronic and current sun exposure on the number of Langerhans cells in epidermal sheets of UV-exposed and unexposed skin of the arms and assessed the effect of sunscreens. Participants were enrolled in a skin cancer prevention trial and had been using sunscreen daily for the previous 3 years. There were significantly fewer Langerhans cells on the exposed (463 cells/mm2) than on the unexposed forearm (528 cells/mm2) (P = 0.0001). High sun exposure in the previous 2 weeks and a history of predominantly outdoor occupations were both associated with a reduced number of Langerhans cells, although age and other biological indicators of chronic exposure were not associated. Sunscreen use was protective against the effects of current but not chronic sun exposure, with a suggestion of a greater effect at higher levels of exposure. Unexpectedly, people with a past history of nonmelanoma skin cancer had more Langerhans cells in both the exposed and the unexposed skin. These results emphasize the need for continued public health education to protect the immune system from the damaging effects of UV radiation.

Adult↗
PubMed1996

An animal model for human melanoma.

Experimental animal models that are directly relevant to human melanoma are lacking. We propose the Angora goat as a potentially useful field model with experimental potential and to this end have examined the prevalence and site distribution of all skin cancers in 28 Angora goat herds in Queensland, Australia. The prevalence of benign melanocytic lesions (lentigines) and their experimental induction by sunlight were also investigated. Among 1731 goats over 2 years of age, 139 malignant skin tumors were excised from 95 affected animals. The prevalence of squamous cell carcinoma (SCC) was 3.8% and of melanoma, 2.2%. Main site of occurrence of melanoma (83%) was the dorsal surface of the ear; in contrast SCC occurred mostly (84%) on the perineum. Lentigines were darker and more prevalent on the exposed compared with the unexposed surface of the ear in Angoras, analogous to the higher prevalence of nevi on the exposed compared with the less exposed inner surface of the arm in humans. Lentigines, which were also found on the perineum though lighter in color than on the dorsal ear, were absent in young animals under 3 months but were numerous in 1-3 year olds. Furthermore in an experimental substudy eight goats, having one flank repeatedly shorn and the contralateral flank left unshorn, revealed consistently more solar lentigines on the shorn flank (P < 0.05) when both sides were examined after 9 months. Histopathological examination of paired skin biopsies from five of these goats also showed more abundant pigmentation in skin from the exposed, as compared with the unexposed flank. These findings indicate that sunlight induces tumors and lentigines in goats in a highly site-specific manner. The Angora goat model may suggest paradigms for explaining the site differences observed for human melanoma and may also be useful in the future clarification of molecular changes following carcinogenic levels of sun exposure.

Animals↗
PubMed1995

Complications of urogynaecological surgery.

Operations to correct stress urinary incontinence are common procedures and are performed by both urologists and gynaecologists. Many surgeons, however, have not received subspecialty training. This review is intended to guide the surgeon in the prevention and management of the more common complications that may occur, such as de novo detrusor instability, voiding dysfunction, and the colposuspension syndrome.

Female↗
PubMed1991

CGS 22745: a selective orally active inhibitor of 5-lipoxygenase.

CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50 = 0.6 microM). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 microM for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formation ex vivo after 5 min. Its effective biological half-life was greater than 160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibited ex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat.

Administration, Oral↗
PubMed1989

Vitamin C status and other nutritional indices in patients with stroke and other acute illnesses: a case-control study.

Sixty-three patients with acute thrombotic stroke were compared with 47 age and sex-matched patients admitted concurrently with acute ischaemic cardiac pain and a further 44 with acute noncardiovascular illnesses. Overall the stroke patients scored highest on a questionnaire designed to estimate mean daily intake of vitamin C before hospital admission. There were problems with this retrospective dietary assessment, however, and the diet scores of the 27 stroke patients able to answer the questionnaire themselves fell between those of the other two groups. There were no significant differences between the three patient groups in plasma ascorbic acid or uric acid levels, but plasma magnesium and albumin levels were higher in the stroke patients. These findings were similar for patients aged over and under 70 but intergroup differences in magnesium and albumin levels were more marked in the elderly. These results do not support the postulated inverse relationship between vitamin C status and the risk of stroke.

Acute Disease↗
PubMed1985

Antagonism of L-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist?

Lisuride antagonized L-5-hydroxytryptophan (5-HTP)-induced head twitches at doses lower than those sufficient to induce the serotonin (5-HT) syndrome. Among several other 5-HT agonists tested, only LSD and 1-(m-trifluoromethylphenyl)-piperazine (TFMPP) shared this paradoxical profile. Assessment of various dopamine (DA) agonists revealed a lack of correlation between DA-mediated stereotyped behavior (indicative of postsynaptic DA agonism) and blockade of 5-HTP-induced head twitches. Lisuride displaced specific ligand binding from putative S1a, S1b and S2 receptors at nanomolar concentrations, and other drugs that blocked 5-HTP-induced head twitches also displaced binding at S2 sites. It is proposed that lisuride may have agonist properties at S1a receptors mediating the 5-HT syndrome but antagonist properties at S2 receptors mediating 5-HTP-induced head twitching.

5-Hydroxytryptophan↗
PubMed1984

Inducing labour with vaginally administered prostaglandin E2.

In 50 consecutive pregnant women at a 125-bed community hospital with 1000 deliveries annually, labour was induced with prostaglandin E2 administered intravaginally. There were no stillbirths or neonatal deaths, and complications in the mothers were few. In nine women (18%) oxytocin was subsequently administered because of a failure of labour to progress; in spite of this, cesarean section was required in two (4%) of the patients. The overall cesarean section rate was 6%. Prostaglandins have been used routinely to induce labour in the United Kingdom for several years. This noninvasive method is safe, effective and well received by women in a community hospital setting, including those wanting "natural childbirth".

Adult↗
PubMed1984

Effects of dopamine agonists, catecholamine depletors, and cholinergic and GABAergic drugs on acute dyskinesias in squirrel monkeys.

It has been suggested that the neuroleptic-induced acute dyskinetic syndrome in monkeys may be a useful model of extrapyramidal dysfunction. Various drugs that have well-characterized effects on clinical extrapyramidal syndromes and on catecholaminergic, cholinergic, or GABAergic neurotransmission were assessed in dyskinesia-susceptible squirrel monkeys. Catecholamine depletors (alpha-methyl-p-tyrosine, tetrabenazine) induced the syndrome, as do dopamine (DA) receptor antagonists, and d-amphetamine reversed the effects of tetrabenazine. The haloperidol-induced syndrome was reversed by the indirectly acting DA agonists amantadine and L-dopa. Neither of the DA autoreceptor agonist TL-99 or 3-PPP elicited this syndrome, suggesting that these agents lack extrapyramidal involvement. Anticholinergics reversed haloperidol-induced dyskinesias and the cholinomimetic arecoline was capable of inducing dyskinesias. When coadministered repeatedly with haloperidol, benztropine suppressed the emergence of susceptibility to neuroleptic-induced dyskinesias. These results confirm that the acute dyskinetic syndrome in the monkey is characterized by DA deficiency and acetylcholine excess. Diazepam and baclofen, which have been reported to have some clinical benefit in tardive dyskinesia, suppressed haloperidol-induced acute dyskinesias without causing gross motor depression. Pharmacological manipulation of GABAergic pathways from striatum may constitute a fruitful approach to the treatment of dyskinetic motor disorders.

Acute Disease↗
PubMed1983

Avoidance and ICSS behavioral models dissociate TL-99 and 3-PPP from dopamine receptor antagonists.

The behavioral effects of the putative dopamine autoreceptor agonists, TL-99 and 3-PPP, were explored in animal procedures that reveal highly characteristic effects of neuroleptics currently in clinical use. Sidman avoidance responding in rats was not altered appreciably by doses up to 10 mg/kg TL-99 or 30 mg/kg 3-PPP. Higher doses of TL-99 attenuated Sidman avoidance performance in squirrel monkeys, although 3-PPP had no effect. Lever pressing for intracranial self-stimulation (ICSS) was attenuated in a dose-related fashion by TL-99 and 3-PPP, with relatively shallow dose-response relationships. A low dose of haloperidol (0.03 mg/kg) partly reversed the effects of 3-PPP (3 mg/kg) on lever pressing ICSS, but not those of TL-99 (3 mg/kg). Yohimbine (3 mg/kg) failed to alter the effects of TL-99 at a dose that abolished the suppressant effect of clonidine on ICSS. Analysis of within-session ICSS response decrement patterns indicated that TL-99 reduced ICSS to a greater extent towards the end of the session than during the first 5 min. No such within-session trend was produced by 3-PPP, suggesting that 3-PPP attenuates ICSS by virtue of a performance deficit. Similar conclusions were reached using a shuttlebox task that involved self-regulation of ICSS duration by rats. Therefore, the clinical profile of neuroleptics is unlikely to be mimicked precisely by 3-PPP or TL-99. Clinical trials of DA autoreceptor agonists for antipsychotic efficacy will indicate whether or not avoidance and ICSS behaviors are relevant to the detection of the intrinsic antipsychotic activity of drugs.

Animals↗