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Biomedical subjects

R Robertson

Publications and source records attributed to R Robertson.

At least 19 recordsLinked to original sources
PubMed2006

Getting strategic about the environment and health.

Historically, the physical environment has been a target for public health policy across the globe. This remains the case in developing countries where the enduring infectious and toxic challenge posed by the environment is tangible and its health impact is manifest. However, in Western societies, the relevance of the environment to health has become obscured. Even when this is not the case, the perspective is usually narrow, centering on specific toxic, infectious or allergenic agents in particular environmental compartments. It is rare for importance to be given to a health-determining role for the environment acting through broader psychosocial mechanisms. The result is that environmental manipulation is seen as a cornerstone of the public health response for comparatively few health concerns. This paper considers how public health policies and action on the physical environment may be pursued more optimally. The need for a more strategic approach, which employs a new conceptual model that recognizes the complexity and contextual issues affecting the relationship between the environment and health but retains sufficient flexibility and simplicity to have practical application, is identified. Building on recent work, a model is proposed and pointers are given for its use in a practical context.

Causality↗
PubMed2006

Primary visual cortex neurons that contribute to resolve the aperture problem.

It is traditional to believe that neurons in primary visual cortex are sensitive only or principally to stimulation within a spatially restricted receptive field (classical receptive field). It follows from this that they should only be capable of encoding the direction of stimulus movement orthogonal to the local contour, since this is the only information available in their classical receptive field "aperture." This direction is not necessarily the same as the motion of the entire object, as the direction cue within an aperture is ambiguous to the global direction of motion, which can only be derived by integrating with unambiguous components of the object. Recent results, however, show that primary visual cortex neurons can integrate spatially and temporally distributed cues outside the classical receptive field, and so we reexamined whether primary visual cortex neurons suffer the "aperture problem." With the stimulation of an optimally oriented bar drifting across the classical receptive field in different global directions, here we show that a subpopulation of primary visual cortex neurons (25/81) recorded from anesthetized and paralyzed marmosets is capable of integrating informative unambiguous direction cues presented by the bar ends, well outside their classical receptive fields, to encode global motion direction. Although the stimuli within the classical receptive field were identical, their directional responses were significantly modulated according to the global direction of stimulus movement. Hence, some primary visual cortex neurons are not local motion energy filters, but may encode signals that contribute directly to global motion processing.

Action Potentials↗
PubMed2006

Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys.

Cortical processing is strongly influenced by the actions of neuromodulators such as acetylcholine (ACh). Early studies in anaesthetized cats argued that acetylcholine can cause a sharpening of orientation tuning functions and an improvement of the signal-to-noise ratio (SNR) of neuronal responses in primary visual cortex (V1). Recent in vitro studies have demonstrated that acetylcholine reduces the efficacy of feedback and intracortical connections via the activation of muscarinic receptors, and increases the efficacy of feed-forward connections via the activation of nicotinic receptors. If orientation tuning is mediated or enhanced by intracortical connections, high levels of acetylcholine should diminish orientation tuning. Here we investigate the effects of acetylcholine on orientation tuning and neuronal responsiveness in anaesthetized marmoset monkeys. We found that acetylcholine caused a broadening of the orientation tuning in the majority of cells, while tuning functions became sharper in only a minority of cells. Moreover, acetylcholine generally facilitated neuronal responses, but neither improved signal-to-noise ratio, nor reduced trial-to-trial firing rate variance systematically. Acetylcholine did however, reduce variability of spike occurrences within spike trains. We discuss these findings in the context of dynamic control of feed-forward and lateral/feedback connectivity by acetylcholine.

Acetylcholine↗
PubMed2005

Hyperphosphorylated tau and amyloid precursor protein deposition is increased in the brains of young drug abusers.

Drug abuse is a major problem worldwide. The incidence of drug-related deaths attributed to opiate abuse is increasing annually. Apart from routine examination, little is known of the neuropathology of drug abuse. We, and others, have shown previously that drug abuse is associated with microglial activation. We hypothesised that neuroinflammation might lead to premature neurodegeneration in drug abusers. We investigated the brains of young opiate abusers (n=34, all<40 years) for the presence of proteins associated with neurodegenerative diseases and compared them with the brains of age-matched, non-drug users (n=16) all of whom died suddenly. Detailed immunohistochemical analysis of the hippocampus, brainstem and basal ganglia for hyperphosphorylated tau, beta-amyloid, beta-amyloid precursor protein (betaAPP) and ubiquitin demonstrated an excess of AT 8-positive neurofibrillary tangles (NFT) in the drug abusers. These were not only more prevalent in the drug abusers than in controls (44%vs. 19%) but also involved more brain areas. In controls NFT were confined to the entorhinal cortex whereas in drug users they were also found in the subiculum, temporal neocortex, nucleus basalis of Meynert and the locus coeruleus. Virtually no amyloid plaques were present but betaAPP positivity was again much more common in drug abusers than controls (73%vs. 20% in the brainstem and 59%vs. 23% in the temporal lobe). There is no suggestion that these drug abusers had displayed major cognitive impairment although detailed neuropsychological assessment is difficult in this subject group. Likely causes of hyperphosphorylated tau deposition in drug abuse include hypoxic-ischaemic injury, microglial-associated cytokine release and possibly drug-associated neurotoxicity or hepatitis. Head injury, which is another major risk factor, does not appear to have contributed to our findings. Genetic factors also merit consideration. It is unclear at present how much of the hyperphosphorylated tau detected in these young drug abusers represents a transitory phenomenon.

Adolescent↗
PubMed2005

What happens when GPs proactively prescribe NRT patches in a disadvantaged community.

BACKGROUND AND AIMS: The high prevalence of smoking in disadvantaged communities gives serious cause for concern in terms of adverse effects on health and social outcomes. In Scotland, smoking -related lung cancer rates are particularly high and compare less favourably with the rest of the U.K. and Europe. GPs are increasingly being recognised as having an important role in smoking cessation and are allowed to prescribe NRT to those on a low income. This study aimed to follow up a group patientsfrom a disadvantaged area who had been prescribed nicotine patches by their GP. METHODS: An initial self-complete questionnaire gathered details on age, sex, motivation, marital status, employment history, contact with other smokers, concern about weight gain, and nicotine dependence. (Nicotine dependence was assessed by using the Fagerstrom Test). Follow up was carried out at three months after commencing NRT prescription. Data was also gathered from patient case notes as to whether the participant had a smoking-related diagnosis, periods of depression, drug and/or alcohol problems. Outcome was measured in terms of "smoke the same", "smoke less" and "stopped". The statistical methods used for testing each factor against smoking were Spearman rank correlation, chi-squared test for trend and Kruskal-Wallis test. Basic descriptive statistics were used to report general outcomes of the study. RESULTS: The study enrolled 120 patients but 19 were lost to follow up. Out of 101 who used their prescription, 35 were smoking the same, 46 were smoking less and 20 had stopped. The variables most strongly affecting outcome were age, with older smokers having more success (p < 0.001), and those who had a diagnosis of depression having a worse outcome in terms of smoking cessation (p < 0.05). CONCLUSION: This study's findings indicate that encouraging GPs to take a proactive approach in prescribing NRT is effective, even in an area of socio-economic deprivation, and particularly with older smokers.

Administration, Cutaneous↗
PubMed2004

Acetylcholine dynamically controls spatial integration in marmoset primary visual cortex.

Recent in vitro studies have shown that acetylcholine (ACh) selectively reduces the efficacy of lateral cortical connections via a muscarinic mechanism, while boosting the efficacy of thalamocortical/feed-forward connections via a nicotinic mechanism. This suggests that high levels of ACh should reduce center-surround interactions of neurons in primary visual cortex, making cells more reliant on feed-forward information. In line with this hypothesis, we show that local iontophoretic application of ACh in primate primary visual cortex reduced the extent of spatial integration, assessed by recording a neurons' length tuning. When ACh was externally applied, neurons' preferred length shifted toward shorter bars, showing reduced impact of the extra-classical receptive field. We fitted a difference and a ratio of Gaussian model to these data to determine the underlying mechanisms of this dynamic change of spatial integration. These models assume overlapping summation and suppression areas with different widths and gains to be responsible for spatial integration and size tuning. ACh significantly reduced the extent of the summation area, but had no significant effect on the extent of the suppression area. In line with previous studies, we also show that applying ACh enhanced the response in the majority of cells, especially in the later (sustained) part of the response. These findings are similar to effects of attention on neuronal activity. The natural release of ACh is strongly linked with states of arousal and attention. Our results may therefore be relevant to the neurobiological mechanism of attention.

Acetylcholine↗
PubMed2004

Factors influencing time from presentation to treatment of colorectal and breast cancer in urban and rural areas.

Stage at diagnosis and survival from cancer vary according to where people live, suggesting some may have delays in diagnosis. The aim of this study was to determine if time from presentation to treatment was longer for colorectal and breast cancer patients living further from cancer centres, and identify other important factors in delay. Data were collected on 1097 patients with breast and 1223 with colorectal cancer in north and northeast Scotland. Women with breast cancer who lived further from cancer centres were treated more quickly than those living closer to cancer centres (P=0.011). Multilevel modelling found that this was largely due to them receiving earlier treatment at hospitals other than cancer centres. Breast lump, change in skin contour, lymphadenopathy, more symptoms and signs, and increasing age predicted faster treatment. Screen detected cancers and private referrals were treated more quickly. For colorectal cancer, time to treatment was similar for people in rural and urban areas. Quicker treatment was associated with palpable rectal or abdominal masses, tenesmus, abdominal pain, frequent GP consultations, age between 50 and 74 years, tumours of the transverse colon, and iron medication at presentation. Delay was associated with past anxiety or depression. There was variation between general practices and treatment appeared quicker at practices with more female general practitioners.

Adult↗
PubMed2004

All delays before radiotherapy risk progression of Merkel cell carcinoma.

Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy.

Carcinoma, Merkel Cell↗
PubMed2001

Cost effectiveness of computer tailored and non-tailored smoking cessation letters in general practice: randomised controlled trial.

OBJECTIVES: To develop and evaluate, in a primary care setting, a computerised system for generating tailored letters about smoking cessation. DESIGN: Randomised controlled trial. SETTING: Six general practices in Aberdeen, Scotland. PARTICIPANTS: 2553 smokers aged 17 to 65. INTERVENTIONS: All participants received a questionnaire asking about their smoking. Participants subsequently received either a computer tailored or a non-tailored, standard letter on smoking cessation, or no letter. MAIN OUTCOME MEASURES: Prevalence of validated abstinence at six months; change in intention to stop smoking in the next six months. RESULTS: The validated cessation rate at six months was 3.5% (30/857) (95% confidence interval 2.3% to 4.7%) for the tailored letter group, 4.4% (37/846) (3.0% to 5.8%) for the non-tailored letter group, and 2.6% (22/850) (1.5% to 3.7%) for the control (no letter) group. After adjustment for significant covariates, the cessation rate was 66% greater (-4% to 186%; P=0.07) in the non-tailored letter group than that in the no letter group. Among participants who smoked <20 cigarettes per day, the cessation rate in the non-tailored letter group was 87% greater (0% to 246%; P=0.05) than that in the no letter group. Among heavy smokers who did not quit, a 76% higher rate of positive shift in "stage of change" (intention to quit within a particular period of time) was seen compared with those who received no letter (11% to 180%; P=0.02). The increase in cost for each additional quitter in the non-tailored letter group compared with the no letter group was pound 89. CONCLUSIONS: In a large general practice, a brief non-tailored letter effectively increased cessation rates among smokers. A tailored letter was not effective in increasing cessation rates but promoted shift in movement towards cessation ("stage of change") in heavy smokers. As a pragmatic tool to encourage cessation of smoking, a mass mailing of non-tailored letters from general practices is more cost effective than computer tailored letters or no letters.

Adolescent↗
PubMed2001

Comparison of the timing of acute blood-brain barrier breakdown to rabbit immunoglobulin G in the cerebellum and spinal cord of mice with experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model for human multiple sclerosis (MS). Similar to MS patients, EAE animals can exhibit chronic or relapsing, remitting paralysis; leukocyte infiltration of the central nervous system (CNS); and breakdown of the blood-brain barrier (BBB), allowing access to serum components. EAE pathology in rodents is generally thought to progress from the spinal cord to the more rostral brain. This common notion is based on numerous reports on the severity and progression of cellular infiltration and BBB breakdown during the course of disease. We studied opening of the BBB in EAE mice immunized to the proteolipid protein (PLP) peptide, PLP 139-151, with or without the use of pertussis toxin. Peripherally injected rabbit immunoglobulin G showed significant penetration through a compromised BBB in EAE mice and was observed throughout the parenchyma as well as intracellularly in multiple neuronal types. Results demonstrate the novel finding that the cerebellar BBB is dramatically and briefly comprised, even before breakdown of the BBB in the thoracolumbar spinal cord and prior to symptomatic disease. The demonstration of susceptibility in the cerebellum provides an important target for studying the factors predisposing certain CNS regions to autoimmune-related compromise of the BBB, such as MS.

Animals↗
PubMed2001

Using phylogenetic analysis to trace HIV-1 migration among western European injecting drug users seroconverting from 1984 to 1997.

OBJECTIVE: To reconstruct the epidemiological relationships of the HIV epidemics among injecting drug users (IDU) in western Europe. METHODS: HIV env V3 sequences of and epidemiological data were obtained from 145 IDU who seroconverted in three sequential periods: 1984-1988, 1989-1992 and 1993-1997. The sequences were phylogenetically analysed and examined for signature patterns characteristic of northern European IDU, including the conserved GGC codon in the V3 loop. RESULTS: Subpopulations of genetically related HIV strains were observed in Italy, France, Scotland and Spain, in contrast to the Netherlands, Austria and Switzerland. This difference between the two groups of countries suggests that the HIV epidemics amongst IDU in the latter group was caused by multiple virus introductions. In Edinburgh and the surrounding area, most IDU were infected with the same GGC strain over the 12-year study period. The epidemic among IDU in north-western Europe started with GGC viruses, whereas in south-western Europe non-GGC viruses predominated. This geographical separation has faded during the course of the epidemic, most likely because of virus exchange among IDU populations.

Base Sequence↗
PubMed2001

Effect of potassium phosphate supplementation on perceptual and physiological responses to maximal graded exercise.

This investigation evaluated the effect of oral potassium phosphate supplementation on ratings of perceived exertion (RPE) and physiological responses during maximal graded exercise tests (GXT). Eight highly trained endurance runners completed a GXT to anchor the Borg 15-point RPE scale and two double-blind counterbalanced GXTs. Subjects ingested either 4,000 mg x day(-1) of phosphate (PHOS) or a placebo (PLA) for 2 days. Two weeks separated GXTs. Phosphate levels obtained immediately prior to the GXTs were greater in PHOS than PLA. No differences between PHOS and PLA were noted for the submaximal and maximal physiological responses. RPE for the overall body were lower during PHOS than PLA at intensities corresponding to 70-80% of VO2max. This suggests that oral potassium phosphate supplementation mediates perceived exertion during moderately intense exercise.

Adult↗
PubMed2000

Symptoms, quality of life, and health service contact among young adults with mild asthma.

This report assesses Quality of Life (QoL) and its relationship to current symptoms and prospective medical contact among 396 adult patients with asthma. Patients were 16 to 52 yr of age and in the care of family physicians in the northeast of Scotland. All patients had been prescribed asthma medication within the previous 3 mo. Mean %pred FEV(1) was 87.4, mean %pred PEF was 85.1; 41% reported respiratory symptoms every week in the month before interview. Patients completed the SF-36, SF-12, and St. George's Respiratory Questionnaire (SGRQ) scales. Although mean scores on the SF-36 and SF-12 were close to population norms for patients without chronic illness, the presence of any respiratory symptoms in the month before interview was related to significantly lower QoL scores on the SF-36 scales of Physical Functioning, Energy, Mental Health, Pain, and Health Perception: the SF-12 Physical Functioning scale, and the SGRQ Symptoms, Impact and Activities scales. Physician contact for asthma in the 12 mo after interview was significantly related to SF-36, SF-12, and SGRQ scores at time of interview; however, when adjusted for symptoms at time of interview, only the SGRQ scales remained significant predictors of prospective physician contact. We conclude that respiratory symptoms have significant impact on QoL among patients with mild asthma, measured by generic and respiratory QoL scales, but that a specific respiratory scale is better able to discriminate patients who will seek physician care for asthma.

Adolescent↗
PubMed2000

Audit of bloodborne virus infections in injecting drug users in general practice.

Two hundred and ninety patients attending a single general practice in Edinburgh were known to have used illegal drugs, 145 of whom were identified as past or present injectors. Data on bloodborne virus infections and immunisation against hepatitis B virus (HBV) were gathered during 1998, attempts were made to improve the level of testing for bloodborne viruses and immunisation against HBV, and follow up was carried out between October 1999 and February 2000. One hundred and fifteen patients were studied in detail. Evidence of previous HBV infection was found in 31 of 71 tested in 1998 (44%) and 40 of 99 tested at follow up (40%). In 1998 54 out of the 75 tested for hepatitis C antibodies (72%) were positive compared with 73 out of 108 (68%) at follow up. Twenty-six of the 80 tested for HIV antibodies were positive in 1998 (33%) and 26 of 105 at follow up (25%). Large numbers of injecting drug users in our study were found to be not immune to hepatitis B and required immunisation. An abbreviated protocol for immunisation was devised, including post vaccination checks and boosting as necessary. Hepatitis C testing was requested after counselling in most cases, resulting in important and positive interventions. Prevention opportunities for all three bloodborne viruses were identified.

Blood-Borne Pathogens↗