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Biomedical subjects

S I Anderson

Publications and source records attributed to S I Anderson.

At least 19 recordsLinked to original sources
PubMed2004

Chronic transcutaneous electrical stimulation of calf muscles improves functional capacity without inducing systemic inflammation in claudicants.

OBJECTIVES: To assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability. DESIGN: Prospective randomised controlled trial of calf muscle stimulation. MATERIALS AND METHODS: Stable claudicants were randomised to receive either active chronic low frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one leg, 3 x 20 min per day for four weeks. Leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (ACR), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention. RESULTS: Acute active muscle stimulation activated leucocytes less (28% increase) than a standard treadmill test (81% increase) and did not increase ACR. Chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70, P<0.05) while control treatment had no effect. Active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force. CONCLUSIONS: Chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.

Aged↗
PubMed2003

Linkage and comparative mapping of the locus controlling susceptibility towards E. COLI F4ab/ac diarrhoea in pigs.

In 1995, Edfors-Lilja and coworkers mapped the locus for the E. COLI K88ab (F4ab) and K88ac (F4ac) intestinal receptor to pig chromosome 13 (SSC13). Using the same family material we have refined the map position to a region between the microsatellite markers Sw207 and Sw225. Primers from these markers were used to screen a pig BAC library and the positive clones were used for fluorescent in situ hybridization (FISH) analysis. The results of the FISH analysis helped to propose a candidate gene region in the SSC13q41-->q44 interval. Shotgun sequencing of the FISH-mapped BAC clones revealed that the candidate region contains an evolutionary breakpoint between human and pig. In order to further characterise the rearrangements between SSC13 and human chromosome 3 (HSA3), detailed gene mapping of SSC13 was carried out. Based on this mapping data we have constructed a detailed comparative map between SSC13 and HSA3. Two candidate regions on human chromosome 3 have been identified that are likely to harbour the human homologue of the gene responsible for susceptibility towards E. COLI F4ab/ac diarrhoea in pigs.

Animals↗
PubMed2001

Appositions between cocaine and amphetamine-related transcript- and gonadotropin releasing hormone-immunoreactive neurons in the hypothalamus of the Siberian hamster.

Recent in vitro studies have provided evidence that cocaine and amphetamine-related transcript (CART) pathways in the hypothalamus mediate the effects of leptin upon gonadotropin releasing hormone (GnRH) secretion. The aim of the current study was to use dual label immunofluorescence to investigate the anatomical basis of such a pathway. CART-ir processes were found extensively in regions where GnRH cell bodies where located. Analysis using confocal microscopy showed that the majority of GnRH neurons (62%) had close appositions from CART-ir processes. The proportion of GnRH-ir perikarya with CART-ir appositions was significantly higher (P<0.05) in neurons located in the diagonal band of Broca (70%) compared to those more caudally located in the preoptic area (53%). This anatomical evidence for close appositions between CART-ir processes and GnRH cell bodies supports the hypothesis that one mechanism by which leptin causes its effect on the GnRH pulse generator is indirectly via CART neurons, thus allowing information about nutritional status and body fat stores to be conveyed to the reproductive system.

Animals↗
PubMed2001

Genetic and physical mapping, expression analysis and partial sequence of porcine PER1.

The porcine PER1 gene was mapped to chromosome 12q1.4-->q1.5 using fluorescence in situ hybridisation. A polymorphic microsatellite marker (S0601) was isolated from a BAC clone shown to contain the PER1 gene. Linkage analysis assigned S0601 distal to ALOX12 on SSC12, providing further evidence for the conservation of synteny between HSA17 and SSC12. RT-PCR analysis demonstrated the expression of PER1 in all 11 tissues tested, consistent with the data from other mammalian species. Part of the PER1 gene was sequenced, homologous to exons 2-14 of the human gene and encoding the N-terminus of porcine PER1. The predicted amino acid sequence of the partial pig PER1 protein shares over 96% identity with its human orthologue.

Animals↗
PubMed2000

Role of the cytoskeleton in rapid activation of CD11b/CD18 function and its subsequent downregulation in neutrophils.

When rolling adherent neutrophils are stimulated, they rapidly immobilize through activation of integrin CD11b/CD18, and then modulate attachment through this integrin to allow migration. We investigated links between cytoskeletal rearrangement and changes in function of integrin CD11b/CD18 in neutrophils stimulated with formyl peptide (fMLP). Neutrophils treated with the actin-polymerizing agent jasplakinolide became rolling adherent on monolayers of activated platelets, but could not use CD11b/CD18 to become immobilised when fMLP was perfused over them. If treated with jasplakinolide after fMLP, the cells stopped migrating but could not detach when fMLP was removed. Jasplakinolide did not inhibit changes in intracellular Ca(2+) seen after fMLP treatment, or inhibit neutrophil immobilisation induced by externally added Mn(2+). Thus cytoskeletal rearrangement was directly implicated in upregulation and, later, downregulation of CD11b/CD18 binding. Inhibition of RhoA with C3-transferase caused a dose-dependent reduction of initial rolling adhesion of neutrophils, and reduced the rate of migration after stimulation; however, neither the conversion of rolling to stationary adhesion, nor the ability of neutrophils to detach on removal of the stimulus, were inhibited. Thus, Rho may regulate actin polymerisation and motility in neutrophils, but did not appear to control integrin-mediated adhesion itself. Integrin binding may be promoted by disruption of links to the cytoskeleton, effected through depolymerisation of actin or cleavage of linking protein talin by calpain. Disruption of actin filaments with cytochalasin D did not, however, cause integrin-mediated immobilisation of rolling neutrophils. Although the calpain inhibitor calpeptin did inhibit the adhesion response to fMLP, this was only at doses where actin polymerisation was also ablated. We suggest that the cytoskeleton actively regulates binding conformation of CD11b/CD18 as well as its mobility in the membrane.

ADP Ribose Transferases↗
PubMed1999

Physical mapping of porcine seasonality genes.

Seasonal infertility in sows is a problem in the pig industry characterized by delayed onset of puberty in summer and decreased farrowing rate resulting from silent oestrus and aborted pregnancy. Summer infertility is thought to be influenced by heat, sunburn and stress. However, the strongest contributory factor is photoperiod. The difference in seasonality between wild boar and commercial pig breeds suggests that there may be a genetic component to this trait. The maps and associated molecular tools emerging from the pig genome project have created opportunities to examine the genetic component of seasonal infertility. We are identifying and mapping genes that are likely to be involved in biological clock mechanisms and the melatonin pathways as candidate seasonality genes.

Abortion, Veterinary↗
PubMed1999

Mood disorders in patients after treatment for primary intracranial tumours.

The frequency of mood disorder was studied in a cohort of patients with treated intracranial glioma or meningioma, where psychological morbidity was related to physical and neuropsychological functioning and to the patients' knowledge of their disease. Forty patients were assessed on a range of physical, psychological and neuropsychological measures, with additional interview of a relative to obtain supplementary information regarding each patients' knowledge of their disease. Two (5%) of the 40 patients had clinically significant levels of anxiety, six (15%) clinically significant levels of depression and 92% full or intermediate knowledge about their prognosis. Psychological morbidity was associated with high levels of physical disability and also with cognitive dysfunction, but was not related to the grade of the patient's tumour or the extent to which the patient was aware of the nature of his or her disease. A proportion of patients with intracranial tumours suffer levels of psychological distress sufficient to warrant psychological and/or pharmacological intervention.

Adolescent↗
PubMed1998

Evaluation of the osteoblast response to a silica gel in vitro.

Many bioactive glasses and glass ceramics contain silica, yet the effect of silica on the osteoblast is not well understood. The osteoblast cell response to a silica surface, without the interference of the other ions present in glasses and glass ceramics has been investigated. A silica sol-gel was prepared which gave a molar ratio of 1:4:4 tetraethyl orthosilicate (TEOS): ethanol:acidified water 0.2 M HCl) and spin cast on to thermanox discs. The gel was characterized in terms of bioactivity and release of silicic acid. Primary human osteoblasts (HOBs) were seeded on the surface of upright or inverted silica discs. Cell activity (alamar blue reduction), number (DNA content) and differentiation (alkaline phosphatase activity, nodule formation and mineralization) were measured. There was no apparant difference in cell number, activity or alkaline phosphatase activity between silica discs and controls. Nodules formed much earlier on the silica surfaces and these eventually mineralized. Nodule formation was reproducibly enhanced on the silica surface and less markedly on the inverted discs. It is likely that both the surface characteristics of the silica gel and silicic acid release from the disc affect osteoblast behaviour.

Journal Article↗
PubMed1997

Capillary red blood cell flow and activation of white blood cells in chronic muscle ischemia in the rat.

Increased activity of ischemic skeletal muscles in which functional hyperemia is impaired has been linked with capillary endothelial swelling postcapillary white blood cell (WBC) adherence. The perfusion pattern of capillaries under these conditions and time course of WBC activation is not known. Capillary microcirculation was studied by videomicroscopy at rest and after muscle contractions (1 Hz, 10 min) in extensor digi-torum longus muscles of pentobarbital sodium-anesthetized rat during the early stages of chronic ischemia (unilateral ligation of the common iliac artery for 3 days) and in ischemic muscles subjected to increased activity (7 days of ischemia or 3 days of ischemia plus indirect electrical stimulation via planted electrodes, 10 Hz, 7 x 10 min on-90 min off/day) to investigate how perfusion was affected. All ischemic muscles had more intermittently flowing capillaries than did unoperated control) muscles. Temporal heterogeneity of perfusion at rest, assessed by velocity, time spent stationary, and stop/start frequency of red blood cells, was similar to control values in ischemic muscles but greater in ischemic muscles subjected to additional activity. Hyperemic responses to contractions were severely blunted in all ischemic groups. The portion of morphologically nonspherical WBCs, taken to indicate activation, was 24 +/- 3% in venous blood after 3 days of ischemia vs. 14 +/- 1% in control muscles and increased further by 7 days (42 +/- 2%) when activated cells were also found in arterial blood. Thus increased muscular activity may exacerbate the adverse effects of ischemia on capillary perfusion, and WBC activation, evident before endothelial swelling is apparent, provides the potential as a circulating signal for capillary swelling in the ischemic and other muscles.

Animals↗
PubMed1996

Late rehabilitation for closed head injury: a follow-up study of patients 1 year from time of discharge.

Subsequent to the setting up of an outpatient psychological service for head-injured patients, 50 patients were interviewed a year from the time of their discharge from our neurorehabilitation unit. The problems which persisted at this stage are presented and discussed. Some of the difficulties encountered in the evaluation of rehabilitation effects are identified. We conclude that: (1) there is a desperate need in the UK for more long-term support and rehabilitation services for this group of patients and (2) it is essential that such services are carefully monitored and evaluated despite the difficulties involved.

Adolescent↗
PubMed1994

Role of intracranial pressure monitoring in severely head-injured patients without signs of intracranial hypertension on initial computerized tomography.

Previous studies have suggested that only a small proportion (< 15%) of comatose head-injured patients whose initial computerized tomography (CT) scan was normal or did not show a mass lesion, midline shift, or abnormal basal cisterns develop intracranial hypertension. The aim of the present study was to re-examine this finding against a background of more intensive monitoring and data acquisition. Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or less, whose admission CT scan did not show a mass lesion, midline shift, or effaced basal cisterns, underwent minute-to-minute recordings of arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) derived from blood pressure minus ICP. Intracranial hypertension (ICP > or = 20 mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients; in five cases the rise was pronounced in terms of both magnitude (ICP > or = 30 mm Hg) and duration. Reduced CPP (< or = 60 mm Hg lasting longer than 5 minutes) was recorded in five patients. Severely head-injured (comatose) patients whose initial CT scan is normal or does not show a mass lesion, midline shift, or abnormal cisterns nevertheless remain at substantial risk of developing significant secondary cerebral insults due to elevated ICP and reduced CPP. The authors recommend continuous ICP and blood pressure monitoring with derivation of CPP in all comatose head-injured patients.

Adolescent↗
PubMed1994

Measuring the burden of secondary insults in head-injured patients during intensive care.

Primary traumatic brain damage may be compounded by secondary pathophysiological insults that can occur soon after trauma, during transfer to hospital or subsequent treatment of the head-injured patient. The aim of this prospective study was to quantify the burden of a wide range of secondary insults occurring after head injury and to relate these to 12-month outcome. In 124 adult head-injured patients studied during intensive care using a computerized data collection system, < or = 14 clinically indicated physiological variables were measured minute-by-minute. Verified values falling outside threshold limits for > or = 5 min, as defined by the Edinburgh University Secondary Insult Grading scheme, were analysed by insult grade and duration. A greater incidence of secondary insults was detected than previous studies have indicated. Insults were found in 91% of patients and occurred in all severities of head trauma, at all ages, and at every level of Injury Severity Score (ISS). The cumulative durations were much greater than previously recorded although 85% of the total time was at the least severe grade. Short duration insults were common. In 71 patients, in whom 8 insults could be assessed (intracranial pressure, arterial hypo- and hypertension, cerebral perfusion pressure, hypoxemia, pyrexia, brady- and tachycardia), outcome at 12 months was analysed using logistic regression to determine the relative influence of age, admission Glasgow Coma Sumscore, ISS, pupil response on admission, and insult duration on both mortality and morbidity. The most significant predictors of mortality in this patient set were durations of hypotensive (p = .0064), pyrexic (p = .0137), and hypoxemic (p = .0244) insults. When good versus poor outcome was considered, hypotensive insults (p = .0118) and pupil response on admission (p = .0226) were significant.

Adult↗
PubMedDate not supplied

A comparison of the Glasgow Coma Scale and the Swedish Reaction Level Scale.

The Glasgow Coma Scale (GCS) and the Swedish Reaction Level Scale (RLS85), two level-of-consciousness scales used in the assessment of patients with head injury, were compared in a prospective study of 239 patients admitted to a regional head injury unit over a 4-month period. Assessments were made by nine staff members ranging from house officer to registrar, after briefing about the two scales. Data were also collected on age, nature of injuries, surgical treatment, and condition at discharge or transfer using the Glasgow Outcome Scale. Both the GCS and the RLS85 reliably identified comatose patients and those with minor head injury, but were much less effective in defining the response level in patients considered to have a moderate head injury. Only 41% of the patients allocated to a moderate-head-injury category by the GCS and the RLS85 were common to both groups. Where a mismatch occurred, neither scale allocated patients to a 'better' or 'worse' category more frequently than the other. Assessment of patients' conscious levels using the GCS was difficult in only two cases. One patient had facial injuries, and the other was intubated. The RLS85 was reported by all users to be simpler to use than the GCS, but the latter is much more widespread in use. Both scales function well in cases of severe and minor head injury, but have weaknesses when defining moderate head injury. Level-of-consciousness scales are only an aid to assessment and the final choice between the two scales must remain a matter of personal or departmental preference.

Activities of Daily Living↗