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Biomedical subjects

L Warren

Publications and source records attributed to L Warren.

At least 19 recordsLinked to original sources

Improving malaria surveillance in inner city London: is there a need for targeted intervention?

Malaria in south east London is under-notified, and a previous local study has described how available data can underestimate the incidence. An active surveillance system was established and data on malaria cases diagnosed between the 1st January and 31st December 2000 were gathered from local laboratories, the Malaria Reference Laboratory (MRL) and a neighbouring health authority. In total 320 cases were identified in local residents (42.33 per 100,000). Of these 320, 293 were laboratory confirmed (38.75 per 100,000) and there were 47 notifications on clinical suspicion. Only 6.8% (20) laboratory-confirmed cases were formally notified. Males of African descent aged 25-39 years who travelled to West Africa were most affected, and 92.5% of the cases were of P. falciparum infection. The surveillance programme confirmed that formal malaria notifications are unreliable. The most important group of residents for targeted health intervention are members of ethnic minority groups, born in endemic areas and travelling to their countries of origin to visit family or friends.

Adolescent↗

Temporal factors affecting cocaine-opioid interactions: a cocaine drug discrimination study in rats.

RATIONALE: Increasing concomitant abuse of cocaine and morphine-like opioids has prompted a number of studies aimed at understanding how these drugs interact. OBJECTIVE: The present study was designed to determine if variations in opioid pretreatment time would affect how mu opioid agonists interact with cocaine. METHODS: Rats were trained to discriminate 10 mg/kg cocaine from saline. One group of subjects (n=6) received morphine (5.6 mg/kg) 0.5 h, 1 h or 4 h prior to cumulative doses of cocaine (0.1-17.8 mg/kg). These pretreatment times were selected to overlap with states of acute opioid tolerance (approximately 1 h) or acute opioid dependence (approximately 4 h) as demonstrated by previous studies. A second group (n=6) was administered naloxone (0.3 mg/kg) 5 min prior to cumulative cocaine doses, with or without a 4-h morphine (5.6 mg/kg) or methadone (3.0 mg/kg) pretreatment. In a third procedure, the same subjects used in the second experiment were also tested for time-dependent changes in the analgesic effect of morphine using a hot-plate assay. RESULTS: Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine. However, neither 0.5-h or 4-h morphine pretreatment had any effect. In contrast, when naloxone was administered 4 h following either morphine or methadone and 5 min prior to assessment of the cocaine dose-response curve, the discriminative stimulus effects of cocaine were significantly attenuated. In assessing morphine-induced analgesia, paw-lick latency was significantly longer at 1 h and shorter at 4 h following morphine administration. CONCLUSIONS: The results illustrate the importance of temporal parameters for interactions between cocaine and mu opioid agonists.

Analgesics, Opioid↗

The use of ultrasound imaging to demonstrate reduced movement of the median nerve during wrist flexion in patients with non-specific arm pain.

Following clinical screening, we examined movement of the median nerve at the wrist using high-resolution (10-22 MHz) ultrasound in 16 controls and 12 patients with non-specific arm pain (also referred to as repetitive strain injury). Imaging was performed just proximal to the carpal tunnel with the wrist in neutral, 30 degrees of extension and 30 degrees of flexion. In control subjects the position of the median nerve was 4.8 (SE=0.4) mm more radial with the wrist flexed than with the wrist extended. In the twelve arm pain patients the average change was only 1.2 (SE=0.5) mm. It appears that ultrasound imaging may be helpful in diagnosing non-specific arm pain, a condition for which there are no well-defined diagnostic tests at present. The reduced nerve movement seen with ultrasound imaging confirms previous work with magnetic resonance imaging.

Adolescent↗

Cadmium accumulation by invertebrates living at the sediment-water interface.

Benthic animals can take up trace metals both from the sediment compartment in which they burrow and from the water column compartment above their burrows (we define both compartments as containing water and particles). If criteria for the protection of benthic animals are based on metal concentrations in one of these two compartments, then it should first be demonstrated that the majority of the metal taken up by these animals comes from the given compartment. To determine whether benthic animals take up the majority of their cadmium (Cd) from the sediment compartment, we created a Cd gradient in lake sediment and compared Cd accumulation by the invertebrates colonizing these sediments with Cd concentrations in the sediment compartment. On the basis of this relationship and using a bioaccumulation model, we estimate that indigenous benthic invertebrates take up the majority of their Cd from the water column compartment. The results of our experiment are similar to those from a previous study conducted on a different benthic community in a larger lake. Taxa common to both lakes obtained similar proportions of their Cd from the water column compartment, suggesting that Cd accumulation by the same species will be constant across lakes of differing size and chemistry. Our results strengthen the argument that the protection of benthic communities from metal pollution should consider metal in both the water column and sediment compartments. In this regard, the AVS model, which considers only sedimentary metals, was more effective in predicting Cd concentrations in pore waters than those in most animal taxa. We suggest that measurements of vertical chemical heterogeneity in sediments and of animal behavior would aid in predicting the bioaccumulation and effects of sedimentary pollutants.

Animals↗

Beyond multidisciplinary care: a new conceptual model for spina bifida services.

Medical care for people who are born with spina bifida (myelodysplasia) is complex and challenging, but the goal of such care is to optimize health and function for people with this condition. Despite years of expert agreement that multidisciplinary care is the medical standard for individuals with spina bifida, this model does not seem to go far enough towards accomplishing the goal of improved function as well as health for all people with spina bifida. Advances in the medical and surgical management of people with spina bifida and society's increased desire to include those with disabilities in family and community life has heightened our expectations for functional/participatory improvement for people with this condition. Some large spina bifida programs have added a separate rehabilitation component to the comprehensive package of services offered to people with spina bifida. The problem with adding further services to the traditional multidisciplinary spina bifida program is the increased complexity and potential for fragmentation that it presents, particularly for the patient and family. We performed a MEDLINE literature search to find information on integrating these services. Although several articles address the importance of either the multidisciplinary spina bifida clinic or a rehabilitation approach, there is little information about integration of medical and rehabilitation services. We propose a new model for spina bifida services throughout the lifespan that integrates the medical and functional/rehabilitative perspectives. Our model for conceptualizing spina bifida services builds on the WHO framework for coding disability (ICIDH-2). This framework includes not only health and functional perspectives, but a participation dimension as well. Furthermore, our new model emphasizes the importance of anticipatory guidance and transitional planning as an integrating dimension applicable across the lifespan. The model is based on three main conceptual dimensions--comprehensiveness, coordination and longitudinality. We are using the model to create standards of care, integrate services and improve their efficiency, and to develop policies regarding spina bifida services. Through this effort we hope to provide better medical and rehabilitation services to those with spina bifida and meet the complex challenge the condition presents throughout the lifespan.

Comprehensive Health Care↗

Eating attitudes, body shape perceptions and mood of elite rowers.

The study assessed the influence of age, gender and weight category upon eating attitudes, body shape perceptions, and mood. Elite rowers (N = 103) participating in the 1996 World Championships or Great Britain National Championships completed the Eating Attitude Test (EAT), the Body Shape Questionnaire (BSQ), and a short form of the Profile of Mood States (POMS-C). Participants were grouped as lightweight (Female: < 59 kg, n = 19; Male: < 72.5 kg, n = 31) or heavyweight (Female: n = 25; Male: n = 28) competitors. Results showed higher EAT scores among the lightweight group, 12.0% of whom reported scores above the threshold associated with eating disorders. Body shape concerns were higher for heavyweights than lightweights and for females than males. The interaction effect was not significant. BSQ scores were negatively correlated with age. Depression, Confusion and Tension scores collectively predicted 37% of the variance in BSQ scores while Depression scores predicted 9% of the variance in EAT scores. The results provide further evidence that the risk of eating disorders among elite rowers is moderated by age, gender and weight category. Further, they suggest that measures of mood may help identify athletes at risk from eating disorders.

Adolescent↗

Postischemic infusion of Cu/Zn superoxide dismutase or SOD:Tet451 reduces cerebral infarction following focal ischemia/reperfusion in rats.

Oxygen-free radicals play a major role in neuronal cell injury following cerebral ischemia/reperfusion. The free-radical scavenging enzyme, Cu/Zn superoxide dismutase (SOD-1), ameliorates various types of brain injury resulting from temporary CNS ischemia. We have compared the cerebroprotective properties of human SOD-1 (hSOD-1) with a novel recombinant SOD-1 hybrid protein, SOD:Tet451, composed of hSOD-1 linked to the neuronal binding fragment of tetanus toxin (TTxC). Following 2 h of temporary middle cerebral artery occlusion, rats infused with equivalent activities of either hSOD-1 or SOD:Tet451 for the initial 3 h of reperfusion showed reductions in cerebral infarct volume of 43 and 57%, respectively, compared to saline-treated controls (P < 0.01). Serum hSOD-1 concentrations in rats receiving SOD:Tet451 were seven-fold higher than those in rats receiving the native enzyme. Animals treated with SOD:Tet451 also demonstrated an extended persistence of hSOD-1 in the bloodstream during drug washout as compared to animals given free enzyme. Immunohistochemical examination of brain sections from an SOD:Tet451-treated ischemic rat showed positive immunoreactivity in the ipsilateral cerebral cortex using either anti-TTxC or anti-human SOD-1 antibodies. Our results document that both hSOD-1 and SOD:Tet451 significantly reduce brain infarct volume in a model of transient focal ischemia/reperfusion in rats. Additionally, our findings suggest that the cerebroprotective effects of SOD-1 may be enhanced by neuronal targeting as seen with the hybrid protein SOD:Tet451.

Animals↗

Intrathecal administration of recombinant human superoxide dismutase 1 in amyotrophic lateral sclerosis: a preliminary safety and pharmacokinetic study.

We undertook a safety and pharmacokinetic study of intrathecal (i.t.) recombinant human superoxide dismutase (rhSOD1). We administered rhSOD1 as an acute bolus in three sheep and 16 human subjects with amyotrophic lateral sclerosis (ALS). Two sheep received chronic i.t. infusion of rhSOD1 (one at 17.7 mg per day, the second at 38.0 mg per day) for six months. Two of the 16 subjects had familial ALS and mutations in the gene for Cu/Zn SOD1. They both received i.t. infusion of rhSOD1 (5 to 10 mg per day) for 3 to 6 months. Intrathecal rhSOD1 administration was safe. Bolus i.t. administration of 0.25 mg rhSOD1 in sheep revealed a mean elimination half-life of 0.4 (SD +/- 0.06) hours, clearance of 12.2 +/- 3.2 ml per hour, and volume of distribution of 7.3 +/- 0.9 ml. After chronic i.t. infusion, the initial alpha-phase half-life was estimated as 1.2 hours and the extended beta-phase half-life was 15.0 hours. The mean clearance rate was 25.9 ml per hour and the steady-state volume of distribution was 920.6 ml. Bolus i.t. administration of 20 micrograms of rhSOD1 in ALS subjects revealed a mean elimination half-life of 2.2 +/- 0.8 hours, clearance of 1.2 +/- 0.6 ml per hour, and volume of distribution of 3.5 +/- 0.4 ml. With chronic i.t. infusion of 5 mg per day, cerebrospinal SOD1 levels increased approximately fortyfold. We detected no benefit of this treatment in the two patients with familial ALS.

Adult↗

Effects of blood alcohol concentrations on negative punishment: implications for decision making.

OBJECTIVE: A series of studies examined how various blood ethanol concentrations influenced the effectiveness of a negative punishment procedure in a risk-taking/decision-making task. Based on the animal punishment literature plus the impression that ethanol diminishes the effects of punishment and impairs decision making, it was predicted that individuals receiving alcohol would increase their risk- taking behavior despite the presence of a negative punishment stimulus (point loss) given on a variable schedule. METHODS: In Experiment 1, a within-subjects design with repeated measures was used where 10 male subjects played a modified computer-generated choice game under three levels of punishment certainty, three levels of punishment severity and four ranges of blood ethanol (0.00%, 0.01-0.049%, 0.050-0.099%, 0.10-0.15%) RESULTS: Results indicated significant decreases in risk taking as either punishment certainty or severity was increased. However, no significant effects were found for ethanol, or interactions of ethanol with punishment certainty or punishment severity. Two additional studies examining aspects of the experimental procedure produced similar results CONCLUSIONS: Overall, the results of these studies do not support the hypothesis that high concentrations of blood alcohol are sufficient in and of themselves to eliminate the suppression function of negative punishment contingencies leading to increased risk-taking behavior. The implications of these results for understanding blood alcohol effects are discussed.

Adult↗

Factors associated with life satisfaction among a sample of persons with neurotrauma.

Factors were examined that are associated with life satisfaction one year post-discharge for persons with a spinal cord (SCI) or traumatic brain injury (TBI). Findings show persons with SCI or TBI should be considered as two distinct groups with regard to factors affecting life satisfaction. Different strategies might be considered to affect either group. Three psychosocial variables significantly increased life satisfaction for persons with SCI: closeness to family, the level of family activities, and blaming oneself for the injury. For persons with TBI, total family satisfaction, blaming oneself for the injury, being employed, being married, and having memory and bowel independence significantly increased life satisfaction. For persons with TBI, there was a difference in the number of factors affecting life satisfaction dependent on whether the persons blamed themselves or not. Those who do not blame themselves show a greater number of functional activities as indicators for their self-satisfaction.

Activities of Daily Living↗