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Biomedical subjects

S Keen

Publications and source records attributed to S Keen.

11 recordsLinked to original sources
PubMed2001

Enhanced muscle insulin receptor autophosphorylation with short-term aerobic exercise training.

Exercise training improves insulin action in skeletal muscle, but the mechanisms of this effect are not completely understood. In particular, the role of the insulin receptor (IR) is unclear. We examined the IR and an enzyme indicative of oxidative capacity in muscle in relation to improved insulin action in 20 previously sedentary individuals before and after a 7-day program of moderate-intensity cycle ergometry. After training, insulin sensitivity increased 33% (6.20 +/- 0.91 vs. 8.22 +/- 1.12 min. microU(-1). ml(-1) mean +/- SE, pre- vs. posttraining, respectively, P < 0.05). The mitochondrial marker enzyme cytochrome c oxidase (COX) increased in vastus lateralis biopsies by 21% (P < 0.05). After training, IR autophosphorylation, determined by ELISA, was significantly increased by approximately 40% at insulin concentrations from 1 to 100 nM (P < 0.05). The training-induced improvements in IR autophosphorylation were significantly correlated with changes in muscle COX content (r = 0.65, P < 0.05). These studies indicate that, in this model of increased physical activity, improvements in IR function are an early adaptation to exercise in humans, are correlated with increases in muscle oxidative capacity, and likely contribute to the beneficial effects of exercise training on insulin action.

Bicycling↗
PubMed2000

Can general practitioners influence the nation's health through a population approach to provision of lifestyle advice?

BACKGROUND: Lifestyle advice from general practitioners (GPs) has been shown to have a positive effect on population health. In practice, GPs provide lifestyle advice to a minority of their patients only, those who are high risk or already have symptoms. AIM: To look in depth at GPs' attitudes towards adopting a population approach to lifestyle advice and to use these results to identify ways of maximising the potential of GPs to affect population health. METHOD: Thirty-six GPs, purposively sampled by identifying characteristics likely to affect their health promotion activity, participated in a focus group study. Data from the focus groups were transcribed verbatim and analysed using standard methods. RESULTS: The main themes that emerged suggested that GPs do not take a population approach to lifestyle advice because they prefer a high risk approach and doubt their ability to be effective in a population approach. GPs believed that social, cultural, and environmental factors were the most important determinants of population health. Furthermore, they were concerned about the detrimental effects on the doctor-patient relationship of providing lifestyle advice to all patients. GPs believed that a multi-agency, centrally co-ordinated approach was the preferred way to improve population health and that their role should be limited to secondary prevention. CONCLUSION: Large amounts of resources would be necessary to convince GPs to adopt a population approach to lifestyle advice. Measures to tackle the social and environmental determinants of health may be a more effective and efficient means of improving the nation's health.

Attitude of Health Personnel↗
PubMed1999

Individuals with low back pain: how do they view physical activity?

BACKGROUND: Recent guidelines for those with acute low back pain have advocated early resumption of normal activity and increased physical activity. Little is known about the relationship between low back pain and physical activity, and on the impact of that relationship on the promotion of increased levels of physical activity within a general practice population. OBJECTIVES: We aimed to explore associations between factors that influence changes in physical activity and the way individuals perceive and behave with their low back pain, and the impact of those perceptions and behaviour on physical activity. METHODS: Twenty-seven informants were chosen using a purposive sample from a larger group of individuals who, because of their low back trouble, had been referred by their GPs to a community-based, single-blind, randomized controlled trial (RCT) at the University of York, which is evaluating the effectiveness and cost-effectiveness of a progressive exercise programme. Fifty-four interviews were conducted with this subgroup of the RCT; four informants were interviewed once, 19 twice and four of them three times. Interviews were transcribed and analysed using manual and computer-aided approaches. RESULTS: Physical activity was perceived as (i) activities of daily living, (ii) activities causing breathlessness that they went out of the way to do and (iii) more competitive-type activity. The avoidance of physical activity and fear of pain returning were the two main factors directly associated with informants' backs and changes in physical activity. These two factors hindered increases in physical activity, even though the majority of informants believed strongly that being physically active helped ease their low back pain. CONCLUSIONS: When advocating that individuals with acute low back pain return to or increase physical activity, it is important that clinicians identify avoidance of physical activity and/or fear of pain at the earliest stage in order to tailor advice and reassurance appropriately. If avoidance of activity and fear of pain is identified and clinicians want to encourage patients to take up and sustain increased physical activity, they should explore issues of fear of pain, and avoidance of and confidence to do physical activities, in addition to other factors influencing physical activity.

Adult↗
PubMed1999

Guidelines for low back pain: changes in GP management.

BACKGROUND: Management guidelines are aimed at reducing inappropriate practice and improving efficiency; however, the effectiveness of many guidelines has yet to be confirmed. This study targets GPs' management of back pain and its relationship with the recent management guidelines. OBJECTIVES: We aimed to investigate changes in GP management of low back pain, low back pain episode duration and time before consultation, over a 5-year period. METHOD: A case series report of 574 patient notes was collected from a large practice in North Yorkshire (January 1992-March 1997). In addition, 713 referral notes from 26 practices across North Yorkshire were collected. The patients were potential subjects for a larger randomized controlled trial evaluating the effectiveness of an exercise programme. Both groups of data were analysed by identifying trends over time and using log linear regression. RESULTS: Recommendation of activity or exercise was found to be a trend increasing over time. In contrast, recommendation to rest was found to be a trend decreasing over time. Activity or exercise was more frequently recommended to younger patients. There was evidence that individuals are seeking a GP consultation more quickly. CONCLUSIONS: The gap between GP practice and the recent guidelines appears to be reducing. However, many variations in practice still exist. Evidence of decreasing time before consultations may indicate that the level of self-care by low back pain patients is decreasing. Although management guidelines may have some effect, there is some way to go before back pain management is optimized.

Adolescent↗
PubMed1999

Increasing population levels of physical activity through primary care: GPs' knowledge, attitudes and self-reported practice.

BACKGROUND: GPs have the potential to increase population levels of activity and thus produce important health gains. OBJECTIVES AND METHODS: The aim of this questionnaire survey was to determine the knowledge, attitudes and self-reported practice of GPs towards promoting regular physical activity and to assess the likely impact of GPs on population levels of physical activity. RESULTS AND CONCLUSIONS: A high response rate to the questionnaire was obtained and the results suggest that GPs have a good level of knowledge of the health benefits of regular physical activity and the levels required to achieve these, but do not promote activity in a way that will have an impact on the population level.

England↗
PubMed1998

Analysis of prostaglandin G/H synthase-2 inhibition using peroxidase-induced luminol luminescence.

The inducible form of the heme-protein prostaglandin G/H synthase (PGHS-2 or COX-2) has been established as a pivotal enzyme in the cascade of events leading to inflammation, hyperalgesia, and pyresis and represents a major therapeutic target in inflammatory disease. Accordingly, we have exploited the heme-catalyzed hydroperoxidase activity of recombinant hCOX-2 to generate luminescence in the presence of luminol, or a cyclic naphthalene hydrazide, and the substrate arachidonic acid. Arachidonate-induced luminescence was shown to be an index of real-time catalytic activity and demonstrated the turnover inactivation of the enzyme. Luminol luminescence was proportional to hCOX-2 concentration and gave accurate Km determinations for arachidonate. Inhibition of hCOX-2 activity, measured by luminescence, by a variety of selective (for COX-2) and nonselective inhibitors showed rank orders of potency similar to those observed with other in vitro and whole cell methods using the recombinant protein. The sensitivity of the luminescence assay also allowed determination of inhibitor potency at substrate concentrations below Km, distinguishing competitive inhibitors such as ibuprofen from time-dependent inhibitors such as DuP-697. Finally the use of higher quantum-yielding luminol analogues allowed measurement of cyclooxygenase activity at extremely low substrate and protein concentrations, enabling a variety of novel assay formats.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat.

Rats with cytotoxic lesions of the perirhinal, postrhinal, and TE cortices (Rh+TE, n = 7) were compared with surgical control animals (n = 7) on a series of spontaneous object recognition tests. The Rh+TE group was associated with a failure to select the novel object. This recognition deficit contrasted with the apparently normal ability of the same animals to learn and perform a spatial working memory test (T-maze alternation). The animals were also tested on the acquisition of an automated visual discrimination task in which the stimuli were presented on a visual display unit (VDU) equipped with a touch screen. The animals with Rh+TE lesions showed only a borderline deficit on this task. These findings are consistent with other evidence implicating the rhinal region in recognition memory. More importantly, they also provide a dissociation between spatial working memory and object recognition and, hence, show that extensive rhinal lesions are not sufficient to disconnect the hippocampus functionally.

Animals↗
PubMed1997

Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis.

alpha 4 beta 1 integrin (VLA-4) is crucial for the adhesion of leukocytes to human vascular cell adhesion molecule-1 (VCAM-1) on inflamed endothelium. This cell adhesion event is the first step in leukocyte extravasation across the blood-brain barrier in inflammatory diseases of the central nervous system (CNS) such as experimental autoimmune encephalomyelitis (EAE). Prevention of leukocyte infiltration by antibodies against the alpha 4 integrin, which block the alpha 4 beta 1 integrin/VCAM-1 interaction, have been shown to suppress clinical and pathological features of EAE. In this study, two mouse monoclonal antibodies (MAb) directed against human alpha 4 integrin were analyzed in vitro for their ability to block the interaction of leukocytes with VCAM-1 under different assay conditions. The best blocking MAb, AN100226m, was humanized by complementarily-determining region grafting, associated with human C regions and expressed. We found that modification of two structural determinants (H27 and H29) for the heavy chain CDR1 loop in one hand, and modification of framework amino acid H38, H40 and H44 in the other hand, had no effect on antigen binding. In contrast, modification of a structural determinant (H71) for the heavy chain CDR2 loop resulted in loss of binding. The humanized antibody. AN100226, was equivalent to the murine antibody. AN100226m, in binding to alpha 4 beta 1 integrin and in blocking cell adhesion. More importantly, AN100226 was as effective as AN100226m in the reversal of active EAE in guinea pigs and thus may be useful in the treatment of autoimmune diseases such as multiple sclerosis. AN100226 is currently in phase II clinical trials in the UK for the treatment of multiple sclerosis exacerbations.

Amino Acid Sequence↗
PubMed1982

Studies on the regulation of insulin binding by liver plasma membranes from Zucker fatty rats.

The hyperinsulinemia of obese rodents has been associated with a reduced number of hepatic insulin receptors except in hepatocytes from fatty Zucker rats. We isolated liver plasma membranes from 10-11-wk-old lean and fatty Zucker rats, some of which were injected with streptozotocin 2--4 wk earlier. We have determined that although the number of hepatic insulin receptors is not reduced in young hyperinsulinemic fatty Zucker rats, the number of receptors can be increased when the hyperinsulinemia of the fatty rats is reduced by treatment with streptozotocin. In the fatty rats, this reduction in circulating insulin is accompanied by a reduction in plasma triglyceride concentration, consistent with a decreased stimulation of hepatic lipogenesis. Competitive binding curves for insulin were obtained with isolated liver plasma membranes and 125I-insulin. Analysis of these curves for affinity and number of receptors indicated that the number of insulin receptors was unchanged for the fatty control rats relative to the lean control rats but was increased in streptozotocin-treated animals. These data indicate that the regulation of hepatic insulin receptors is altered in the young fatty Zucker rat as characterized by a lack of downregulation of hepatic insulin receptors by hyperinsulinemia and an upregulation of hepatic insulin receptors at insulin concentrations higher than those found in lean rats. An altered state of hepatic insulin receptor regulation may be characteristic of developing obesity.

Animals↗
PubMedDate not supplied

Subcutaneous administration of adrenaline for anaphylaxis.

Seventeen children who have had life-threatening anaphylaxis and who are treated in one clinic are all attending mainstream schooling and carry adrenaline. This paper looks at the education of their teachers in emergency procedures.

Anaphylaxis↗