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S Harding

Publications and source records attributed to S Harding.

At least 19 recordsLinked to original sources
PubMed2006

How affected is oxygen metabolism in DWI lesions?: A combined acute stroke PET-MR study.

OBJECTIVE: To use back-to-back diffusion-weighted imaging (DWI) and PET to obtain quantitative measures of the cerebral metabolic rate of oxygen (CMRO(2)) within DWI lesions, and to assess the perfusion-metabolism coupling status by measuring the cerebral blood flow and the oxygen extraction fraction within DWI lesions. METHODS: Six prospectively recruited acute carotid-territory stroke patients completed the imaging protocol, which was commenced 7 to 21 hours from onset and combined DWI derived from state-of-the-art diffusion tensor imaging sequencing using a 3-T magnet and fully quantitative (15)O-PET. The PET variables were obtained in individual DWI lesions in each patient. RESULTS: Across patients, the CMRO(2) was reduced in the DWI lesion relative to mirror (mean reduction 39.5%; p = 0.028). Examining individual DWI lesions, however, revealed considerable variability in the extent of this CMRO(2) reduction. The flow-metabolism coupling pattern underlying the DWI lesion was also variable, including ongoing ischemia, mild oligemia, and partial or complete reperfusion. DISCUSSION: Diffusion-weighted imaging (DWI) lesions generally reflect substantial disruption of energy metabolism. However, the degree of metabolic disruption is variable, indicating DWI lesions may not always represent irreversibly damaged tissue. Finally, because DWI lesions can persist despite reperfusion, assessment of perfusion is necessary for interpretation of DWI changes in acute stroke.

Aged↗
PubMed2006

Establishment of and first 20 months of operating an outreach geriatric clinic in a regional centre.

INTRODUCTION: Providing geriatric assessments to older people residing in rural or remote areas is a challenge due to the complexities of distance and a declining medical workforce. This study aimed to develop a feasible model of service delivery in a rural area, delivering specialised falls and memory clinics similar to those available in the metropolitan area. At the end of the first 20 months we evaluated the service in terms of patient access and the satisfaction of the local health care providers. METHODS: A meeting was held with key stakeholders to identify existing service provision in the region, and to determine which services were needed. Clinic attendance and information on services provided by the clinic were collected. Questionnaires regarding clinic performance were sent to health-care providers in the region. RESULTS: The stakeholder meeting identified communication, collaboration and continuing education as the main services required of the clinic. The clinic model included a specialist geriatrician and an extended practice nurse specialising in aged care. Between May 2003 and Dec 2004, 115 people were assessed by the extended practice nurse. Interventions relating to falls and cognition were accessed by clients. Time from referral to seeing a specialist and failure to attend rates were comparable to rates seen in the metropolitan clinics. All heath-care providers who responded to the survey found the service useful. CONCLUSION: Our clinic model is a possible mechanism for delivering ambulatory aged care services to rural and remote regions. This model of care did not improve access or shorten waiting times for attendees. Future models of specialised rural care need to explore innovative workforce strategies to improve access.

Aged↗
PubMed2005

Decline in, and lack of difference between, average birth weights among African and Portuguese babies in Portugal.

BACKGROUND: In preliminary data in Portugal, we found that African babies of migrant mothers were heavier than White Portuguese babies born in Lisbon. We investigate whether this pattern is replicated in the national data, and in addition the trends in birth weight in these groups. METHODS DESIGN AND SETTING: Births registered between 1995 and 2002 classified by reported nationality of mothers. PARTICIPANTS: 849,595 Portuguese births ('Portuguese' nationality, predominantly of European descent) and 22,463 African births ('Angola', 'Cape Verde', or 'Guinea Bissau, Republic of Guinea or Equatorial Guinea' nationality, predominantly of African origin). RESULTS: Among Portuguese births, there was a decline in births to teenaged mothers and an increase to mothers aged >or=35 years, with >9 years of education or in a non-manual class, but among African births there was an increase in births to teenaged mothers and a decline to mothers from advantaged socioeconomic backgrounds. Using the Wilcox-Russell method, overall mean birth weights of term Portuguese (3,303, SD 424 g) and African (3297, SD 441 g) babies were not different but the percentage of small preterm births was higher among African (4.7%) than among Portuguese (2.9%) births. Between 1995 and 2002, mean birth weight of term Portuguese babies declined by 58 g (3,334-3,276 g) and of African babies by 57 g (3,341-3,284 g). The left shift of the birth weight distributions was independent of maternal age, parity, and social factors among Portuguese babies, but among African babies the decrease appeared to be associated with socioeconomic advantage. CONCLUSION: There has been a downward trend in birth weights in Portugal among both Portuguese and African term births, but average birth weights of the two groups were similar.

Adolescent↗
PubMed2005

Effects of unconditioned and conditioned social defeat on alcohol self-administration and reinstatement of alcohol seeking in rats.

RATIONALE AND OBJECTIVES: We and others have shown that a stressor commonly used in laboratory studies, intermittent footshock, reinstates alcohol seeking in a rat relapse model. The effects of more ethologically relevant stressors on reinstatement have not been examined. Here, we characterized the effects of social defeat (a naturalistic stressor) or a cue associated with the defeat experience on reinstatement of alcohol seeking. We also examined the effect of unconditioned and conditioned social defeat on alcohol self-administration. METHODS: Rats were trained to self-administer alcohol (12% w/v, 1 h day(-1)), and after stable responding, one group of animals received five exposures to social defeat paired with peppermint odor prior to daily self-administration sessions. After three more self-administration sessions, these rats were tested for the effects of the peppermint odor cue on self-administration. In another group of rats, the effects of three daily exposures to social defeat paired with peppermint odor on extinction of responding were examined. After further extinction sessions, the effect of the odor cue on reinstatement was tested in these animals. The acute effect of social defeat on reinstatement was examined in another group of animals. RESULTS: Acute exposure to social defeat decreased alcohol self-administration, reduced rates of responding during extinction, and did not reinstate alcohol seeking. Exposure to a discrete odor cue previously paired with social defeat decreased alcohol self-administration but induced modest reinstatement of alcohol seeking. CONCLUSIONS: Results provide the first demonstration of reinstatement of alcohol seeking by a cue paired with social defeat and are also in agreement with previous findings on the suppressive effect of social defeat stress on alcohol self-administration.

Animals↗
PubMed2005

Urocortin 1 expression in five pairs of rat lines selectively bred for differences in alcohol drinking.

RATIONALE: There is accumulating evidence that the neuropeptide urocortin 1 (Ucn1) is involved in alcohol consumption. Thus far, however, most studies have been performed in mice. OBJECTIVES: The purpose of the present study was to characterize Ucn1 expression in rats selectively bred for either high or low alcohol intake. METHODS: Brains from naive male rats of five pairs of independently selected lines (iP/iNP, AA/ANA, HARF/LARF, HAD1/LAD1, and HAD2/LAD2) were analyzed by immunohistochemistry. RESULTS: Significant differences were found between iP/iNP, HARF/LARF, and HAD2/LAD2 in number of Ucn1-containing cells in the Edinger-Westphal (EW) nucleus (the main source of Ucn1 in the brain), whereas no significant differences were found between HAD1/LAD1 and AA/ANA. Similarly, significant differences in the optical density of Ucn1 immunoreactivity in EW were found between iP/iNP, HARF/LARF, and HAD2/LAD2, whereas no differences on this measure were found between HAD1/LAD1 and AA/ANA. In the lateral septum (LS, the main projection area of Ucn1-containing neurons in the rat), significant differences were found only between AA/ANA and HAD2/LAD2; however, a meta-analysis indicated that across all five lines, preferring animals had a significantly greater number of Ucn1-positive fibers than nonpreferring animals. CONCLUSIONS: These results provide evidence that, in rats, Ucn1 may be involved in regulation of alcohol intake, and that this regulation may occur through the Ucn1 projections to LS.

Alcohol Drinking↗
PubMed2005

Trends in socioeconomic disparities in stroke mortality in six european countries between 1981-1985 and 1991-1995.

This study assesses whether stroke mortality trends have been less favorable among lower than among higher socioeconomic groups. Longitudinal data on mortality by socioeconomic status were obtained for Finland, Norway, Denmark, Sweden, England/Wales, and Turin, Italy. Data covered the entire population or a representative sample. Stroke mortality rates were calculated for the period 1981-1995. Changes in stroke mortality rate ratios were analyzed using Poisson regression and compared with rate ratios in ischemic heat disease mortality. Trends in stroke mortality were generally as favorable among lower as among higher socioeconomic groups, such that socioeconomic disparities in stroke mortality persisted and remained of a similar magnitude in the 1990s as in the 1980s. In Norway, however, occupational disparities in stroke mortality significantly widened, and a nonsignificant increase was observed in some countries. In contrast, disparities in ischemic heart disease mortality widened throughout this period in most populations. Improvements in hypertension prevalence and treatment may have contributed to similar stroke mortality declines in all socioeconomic groups in most countries. Socioeconomic disparities in stroke mortality generally persisted and may have widened in some populations, which fact underlines the need to improve preventive and secondary care for stroke among the lower socioeconomic groups.

Europe↗
PubMed2005

Metallic neurosurgical implants for cranial reconstruction and fixation: assessment of magnetic field interactions, heating and artefacts at 3.0 Tesla.

The objective of this study was to evaluate the magnetic resonance imaging (MRI) compatibility of metallic neurosurgical implants commonly used for cranial reconstruction and fixation, in association with a 3.0 Tesla (T) MR system. Ten metallic neurosurgical implants used for cranioplasty operations were evaluated. The implants were tested ex vivo for magnetic field interactions (translational attraction and torque), heating (using saline and gel phantoms), and artefact production [using dual echo spin echo (DSE) and gradient echo (GRE) sequences] at 3.0 Tesla. None of the implants displayed translational attraction or torque, and heating was physiologically insignificant (maximal temperature elevation was 0.5 degrees C). MR artefacts were minimal with spin echo sequences; gradient echo sequences produced much larger artefacts. The neurosurgical implants evaluated in this study should not present a risk to patients undergoing MRI in the 3.0 T MR system. Although the implants do produce susceptibility artefacts, especially with gradient echo sequences, useful imaging should still be possible.

Artifacts↗
PubMed2005

Optical coherence tomography in photodynamic therapy for subfoveal choroidal neovascularisation secondary to age related macular degeneration: a cross sectional study.

AIMS: To introduce new terminology and validate its reliability for the analysis of optical coherence tomography (OCT) scans, compare clinical detection of cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to study the effect of photodynamic therapy (PDT) on the foveal morphology. METHODS: Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV) secondary to age related macular degeneration (AMD) undergoing PDT were evaluated with refraction protocol best corrected logMAR visual acuity (VA), slit lamp biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New terminologies introduced to interpret the OCT scans were: neuroretinal foveal thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and vitreomacular hyaloid attachment (VMHA). RESULTS: Fifty six eyes of 53 patients were studied. VA was better in eyes with a thinner outer high reflectivity band (OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a greater number of PDT treatments (p = 0.04). There was poor agreement between OCT and clinical examination in the detection of CMO and subretinal fluid (kappa = 0.289 and kappa = 0.165 respectively). To validate the interpretation and measurements on OCT, two groups of 20 scans were analysed by two independent observers. There was good agreement between the observers in the detection of IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high reproducibility, and of OHRBT reproducibility was low. CONCLUSIONS: New terminology has been introduced and tested. OCT appears to be superior to clinical examination and FFA in the detection of CMO. In this study, better vision was associated with a thinner OHRBT and/or the absence of SRF giving insight into the biological effect of PDT.

Aged↗
PubMed2004

Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats.

RATIONALE AND OBJECTIVES: Alpha-2 adrenoceptors are known to be involved in stress-induced reinstatement of heroin and cocaine seeking in laboratory animals. Here, we studied the involvement of these receptors in stress-induced reinstatement of alcohol seeking by using an agonist (lofexidine) and an antagonist (yohimbine) of these receptors, which inhibit and activate, respectively, noradrenaline transmission. We also tested the effect of lofexidine and yohimbine on alcohol self-administration. Lofexidine is used clinically for treating opiate withdrawal symptoms and yohimbine induces stress-like responses in humans and non-humans. METHODS: Rats were trained to self-administer alcohol (12% w/v, 1 h/day) and after extinction of the alcohol-reinforced behavior, they were tested for the effect of lofexidine (0, 0.05 and 0.1 mg/kg, IP) on reinstatement of alcohol seeking induced by intermittent footshock stress (10 min, 0.8 mA) or for the effect of yohimbine (0, 1.25 and 2.5 mg/kg, IP) on reinstatement of alcohol seeking. Other rats were trained to self-administer alcohol, and after stable responding, the effects of lofexidine and yohimbine on alcohol self-administration were determined. RESULTS: Pretreatment with lofexidine (0.05 mg/kg and 0.1 mg/kg) attenuated stress-induced reinstatement of alcohol seeking and also decreased alcohol self-administration. In contrast, yohimbine pretreatment potently reinstated alcohol seeking after extinction and also induced a profound increase in alcohol self-administration. CONCLUSIONS: Results indicate that activation of alpha-2 adrencoceptors is involved in both stress-induced reinstatement of alcohol seeking and alcohol self-administration. To the degree that the present results are relevant to human alcoholism, alpha-2 adrencoceptor agonists should be considered in the treatment of alcohol dependence.

Adrenergic alpha-Agonists↗
PubMed2004

Lack of change in birthweights of infants by generational status among Indian, Pakistani, Bangladeshi, Black Caribbean, and Black African mothers in a British cohort study.

AIM: To test the hypothesis that an intergenerational increase would occur in birthweights of babies born to UK-born compared with overseas-born (migrant) minority women. METHOD: Live singleton births to mothers present at the 1991 Census in a national longitudinal study were classified by mother's country of birth and ethnic origin as reported in the census. During 1983-2000, 52,554 White, 1788 Indian, 1538 Pakistani, 995 Bangladeshi, 300 Black Caribbean, and 299 Black African live singleton births were identified. Mean birthweights were adjusted for maternal age, socio-economic circumstances, gender, year of birth, and birth order. RESULTS: Adjusted mean birthweights were: 3400 g (95% CI: 3395, 3405) for infants of UK-born White mothers; 3033 g (95% CI: 2980, 3087) of UK-born Indian mothers and 3066 g (95% CI: 3034, 3097) of migrant Indian mothers; 3110 g (95% CI: 3049, 3172) of UK-born Pakistani mothers and 3123 g (95% CI: 3087, 3159) of migrant Pakistani mothers; 3026 g (95% CI: 2922, 3130) of UK-born Bangladeshi mothers and 3110 g (95% CI: 3076, 3145) of migrant Bangladeshi mothers; 3268 g (95% CI: 3177, 3359) of UK-born Black Caribbean mothers and 3238 g (95% CI: 3089, 3388) of migrant Black Caribbean mothers; and 3167 g (95% CI: 3004, 3330) of UK-born Black African mothers and 3302 g (95% CI: 3208, 3395) of migrant Black African mothers. The proportions of low birthweight infants (<2500 g), generally greater among migrant mothers than White UK-born mothers, were similar by generational status within the ethnic groups. CONCLUSION: There are no significant differences in mean birthweights of infants by generational status among mothers from these main ethnic minority groups in the UK.

Africa↗
PubMed2004

Review article: supra-oesophageal manifestations of gastro-oesophageal reflux disease and the role of night-time gastro-oesophageal reflux.

Gastro-oesophageal reflux disease (GERD) has been associated with a variety of supra-oesophageal symptoms, including asthma, laryngitis, hoarseness, chronic cough, frequent throat clearing and globus pharyngeus. GERD may be overlooked as the underlying mechanism for these symptoms because typical GERD symptoms may be absent, despite abnormal oesophageal acid exposure. Two basic mechanisms linking GERD with laryngeal symptoms have been proposed: direct contact of gastric acid with the upper airway, in some cases due to micro-aspiration, and a vagovagal reflex triggered by acidification of the distal portion of the oesophagus. Gastro-oesophageal reflux (GER) during sleep is believed to be an important mechanism for the development of supra-oesophageal complications of GERD, such as asthma and idiopathic pulmonary fibrosis (IPF). Several physiological changes during sleep, including prolonged oesophageal acid contact time, decreased upper oesophageal sphincter pressure, increased gastric acid secretion, decreased salivation, decreased swallowing and a decrease in conscious perception of acid, render an individual more susceptible to reflux-induced injury. Supra-oesophageal symptoms often improve in response to aggressive acid-suppressive therapy. However, many unanswered questions remain regarding the appropriate approach to diagnosis and treatment of patients with GERD-related supra-oesophageal symptoms. In this article we review the relationship between supra-oesophageal symptoms and GERD and, where possible, highlight the evidence supporting the role of night-time reflux as a contributing factor to these symptoms.

Asthma↗
PubMed2003

Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats.

RATIONALE AND OBJECTIVE: Alcohol and tobacco are often co-abused in humans and previous studies found that nicotine increases alcohol consumption in rats. Here, we studied whether nicotine would reinstate alcohol-taking behavior in drug-free rats and whether this effect would be enhanced by prior exposure to nicotine during alcohol self-administration training. METHODS: Rats were trained to press a lever for alcohol (12% w/v, 1 h/day), and following stable alcohol intake groups of rats ( n=11-12) were given daily vehicle or nicotine (0.2, 0.4 or 0.8 mg/kg, SC) injections just prior to the self-administration sessions for 10 days. Rats were then given 6 days of alcohol self-administration in the absence of nicotine and an additional 5-10 drug-free days during which lever presses were not reinforced (extinction). Subsequently, rats were tested for reinstatement of alcohol seeking following exposure to priming injections of vehicle or nicotine (0.4 mg/kg, SC). RESULTS: Nicotine increased alcohol self-administration in a dose- and time-dependent manner over the 10-day period. Nicotine also reinstated alcohol seeking after extinction of the alcohol-reinforced behavior, and this effect was strongly enhanced by prior nicotine exposure. CONCLUSIONS: The present data extend previous studies on the effect of nicotine on alcohol self-administration, and further indicate that nicotine is an effective stimulus for reinstatement of alcohol seeking during drug-free periods.

Alcohol Drinking↗
PubMed2003

Grading and disease management in national screening for diabetic retinopathy in England and Wales.

AIMS: A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight-threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false-positive referral to the hospital eye service. METHODS: Expert panel structured discussions between 2000 and 2002 with review of existing evidence and grading classifications. PROPOSALS: Principles of the protocol include: separate grading of retinopathy and maculopathy, minimum number of steps, compatible with central monitoring, expandable for established more complex systems and for research, no lesion counting, no 'questionable' lesions, attempt to detect focal exudative, diffuse and ischaemic maculopathy and fast track referral from primary or secondary graders. Sight-threatening diabetic retinopathy is defined as: preproliferative retinopathy or worse, sight-threatening maculopathy and/or the presence of photocoagulation. In the centrally reported minimum data set retinopathy is graded into four levels: none (R0), background (R1), preproliferative (R2), proliferative (R3). Maculopathy and photocoagulation are graded as absent (M0, P0) or present (M1, P1). DISCUSSION: The protocol developed by the Diabetic Retinopathy Grading and Disease Management Working Party represents a new consensus upon which national guidelines can be based leading to the introduction of quality-assured screening for people with diabetes.

Clinical Protocols↗
PubMed2002

The role of corticotropin-releasing factor in the median raphe nucleus in relapse to alcohol.

Using an animal model of drug relapse, we found that intermittent footshock stress reinstates alcohol seeking, an effect attenuated by the 5-HT reuptake blocker fluoxetine and by corticotropin-releasing factor (CRF) receptor antagonists. Here we studied the role of the 5-HT cell body region of the median raphe nucleus (MRN) and CRF receptors in this site in reinstatement of alcohol seeking. Rats were given alcohol in a two-bottle choice procedure (water vs alcohol) for 25 d and were then trained for 1 hr/d to press a lever for alcohol (12% w/v) for 23-30 d. Subsequently, lever pressing for alcohol was extinguished by terminating drug delivery for 5-9 d. Tests for reinstatement of alcohol seeking were then performed under extinction conditions. Intra-MRN infusions of 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] (a 5-HT1A agonist that decreases 5-HT cell firing and release) reinstated alcohol seeking. Reinstatement of alcohol seeking also was observed after intra-MRN infusions of low doses of CRF (3-10 ng), which mimicked the effect of ventricular infusions of higher doses of the peptide (300-1000 ng). Finally, intra-MRN infusions of the CRF receptor antagonist d-Phe CRF (50 ng) blocked the effect of intermittent footshock (10 min) on reinstatement. These data suggest that an interaction between CRF and 5-HT neurons within the MRN is involved in footshock stress-induced reinstatement of alcohol seeking.

Alcoholism↗