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Biomedical subjects

L Clark

Publications and source records attributed to L Clark.

At least 19 recordsLinked to original sources
PubMed2006

How is place of death from cancer changing and what affects it? Analysis of cancer registration and service data.

We aimed to compare trends in place of cancer death with the growth of palliative care and nursing home services, and investigate demographic, disease-related and area influences on individual place of death, using registration data for 216404 patients with breast, lung, colorectal and prostate cancer and aggregate data on services in South East England. Between 1985 and 1994 there was a trend away from hospital death (67-44%), to home (17-30%) and hospice death (8-20%). After 1995, this partly reversed. By 2002, hospital death rose to 47%, home death dropped to 23%, hospice death remained stable and nursing home death rose from 3 to 8%. Numbers of palliative care services increased, but trends for hospice and nursing home deaths most clearly followed the beds available. Cancer diagnosis and treatment influenced individual place of death, but between 1998 and 2002, age and area of residence were associated with most variation. Older patients and those living in more deprived areas died more often in hospitals and less often at home. Despite more palliative care services the proportion of people dying at home has not increased. Variation by age, deprivation and area of residence is unlikely to reflect patient preference. More active surveillance and planning must support policies for choice in end of life care.

Age Factors↗
PubMed2006

Laparoscopic-assisted right lobe donor hepatectomy.

The major impediment to a wider application of living donor hepatectomy, particularly of the right lobe, is its associated morbidity. The recent interest in a minimally invasive approach to liver surgery has raised the possibility of applying these techniques to living donor right lobectomy. Herein, we report the first case of a laparoscopic, hand-assisted living donor right hepatic lobectomy. We describe the technical aspects of the procedure, and discuss the rationale for considering this option. We propose that the procedure, as described, did not increase the operative risks of the procedure; instead, it decreased potential morbidity. We caution that this procedure should only be considered for select donors, and that only surgical teams familiar with both living donor hepatectomy and laparoscopic liver surgery should entertain this possibility.

Adult↗
PubMed2006

Risk factors for colic in horses after general anaesthesia for MRI or nonabdominal surgery: absence of evidence of effect from perianaesthetic morphine.

REASON FOR PERFORMING STUDY: Post anaesthetic colic is a recognised risk of general anaesthesia (GA), but causes are poorly understood. OBJECTIVES: To identify risk factors for development of colic following GA for magnetic resonance imaging (MRI) or nonabdominal surgery and to test whether the use of perianaesthetic morphine was associated with an increased risk of post anaesthetic colic. METHODS: A total of 553 anaesthetic and clinical records of 500 horses anaesthetised at the Animal Health Trust were analysed, 342 (62%) involved MRI and 211 (38%) nonabdominal, predominantly orthopaedic surgery. Multivariable logistic regression analysis was used to examine the association between post anaesthetic colic and explanatory variables, including use of perianaesthetic morphine. RESULTS: Twenty horses (3.6%) developed colic within 7 days of GA. A significantly larger (P = 0.001) proportion of the surgical cases developed post anaesthetic colic (7.1%) compared with MRI cases (1.5%). Having controlled for the effect of MRI/surgeon, there was evidence for a significantly increased risk of colic associated with maintenance of anaesthesia with isoflurane and administration of benzyl penicillin and/or ceftiofur. A reduction in risk of colic was associated with premedication with romifidine, longer duration of anaesthesia and sedation within 2 days of GA. Perianaesthetic morphine administration was not associated with increased risk. CONCLUSIONS: This study identified apparently novel risk factors for colic in horses following GA. Use of morphine was not found, after controlling for other MRI and surgery related risk factors, to be associated with an increased risk. The low prevalence of colic after GA and resulting low study power mean that further larger, multicentre collaborative studies are warranted to corroborate findings in this study. POTENTIAL RELEVANCE: Better knowledge of risk factors should lead to achievable measures to reduce frequency of occurrence.

Anesthesia, General↗
PubMed2006

Post anaesthetic colic in horses: a preventable complication?

REASONS FOR PERFORMING STUDY: There is little information on the prevalence of, and risk factors associated with, post anaesthetic colic (PAC) in horses undergoing nonabdominal operations. OBJECTIVES: To undertake the first prospective study of prevalence of PAC and identify risk factors in its development in nonabdominal procedures. METHODS: A multicentre prospective case-control study was conducted, on every horse undergoing anaesthesia for a nonabdominal procedure between April 2004 and June 2005. Colic cases were defined as any horse with recognised signs of abdominal pain within 72 h of general anaesthesia that could not be attributed to any concurrent disease. Five control horses per case were selected randomly from the study population at all hospitals. Multivariable logistic regression analysis was used to examine the relationship between predictor variables and the risk of developing PAC. RESULTS: The estimated mean prevalence of PAC in the study population was 5.2% (95% CI, 2.8, 8.0). However, the prevalence of colic varied between each centre. The most commonly diagnosed cause of colic was impaction. Multivariable analyses showed that the centre involved and the type of surgery performed were associated with an increased risk of PAC. Preoperative food deprivation and the use of opioid drugs were confounding factors. CONCLUSIONS: Prevalence of PAC varied significantly between the 4 hospitals studied; there may be hospital-related covariates that account for this. The type of surgery performed influenced the risk of PAC. POTENTIAL RELEVANCE: Identifying the risk factors for PAC is a prerequisite for its prevention. This study indicates horses at increased risk of PAC that might benefit from a more critical evaluation of post anaesthetic gastrointestinal function and/or the provision of preventative measures. Further investigation is required to explain the variation in prevalence of PAC between centres.

Anesthesia↗
PubMed2005

Microbial indicators of heavy metal contamination in urban and rural soils.

Urban soils and especially their microbiology have been a neglected area of study. In this paper, we report on microbial properties of urban soils compared to rural soils of similar lithogenic origin in the vicinity of Aberdeen city. Significant differences in basal respiration rates, microbial biomass and ecophysiological parameters were found in urban soils compared to rural soils. Analysis of community level physiological profiles (CLPP) of micro-organisms showed they consumed C sources faster in urban soils to maintain the same level activity as those in rural soils. Cu, Pb, Zn and Ni were the principal elements that had accumulated in urban soils compared with their rural counterparts with Pb being the most significant metal to distinguish urban soils from rural soils. Sequential extraction showed the final residue after extraction was normally the highest proportion except for Pb, for which the hydroxylamine-hydrochloride extractable Pb was the largest part. Acetic acid extractable fraction of Cd, Cu, Ni, Pb and Zn were higher in urban soils and aqua regia extractable fraction were lower suggesting an elevated availability of heavy metals in urban soils. Correlation analyses between different microbial indicators (basal respiration, biomass-C, and sole C source tests) and heavy metal fractions indicated that basal respiration was negatively correlated with soil Cd, Cu, Ni and Zn inputs while soil microbial biomass was only significantly correlated with Pb. However, both exchangeable and iron- and manganese-bound Ni fractions were mostly responsible for shift of the soil microbial community level physiological profiles (sole C source tests). These data suggest soil microbial indicators can be useful indicators of pollutant heavy metal stress on the health of urban soils.

Biological Availability↗
PubMed2005

Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity.

RATIONALE: Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear. OBJECTIVES: To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition. METHODS: Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 5-7 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated. RESULTS: ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change. CONCLUSIONS: We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects.

Adolescent↗
PubMed2005

Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals.

RATIONALE: There is converging evidence for impairments in decision-making in chronic substance users. In the light of findings that substance abuse is associated with disruptions of the functioning of the striato-thalamo-orbitofrontal circuits, it has been suggested that decision-making impairments are linked to frontal lobe dysfunction. We sought to investigate this possibility using functional neuroimaging. METHODS: Decision-making was investigated using the Cambridge Risk Task during H2(15)O PET scans. A specific feature of the Risk Task is the decisional conflict between an unlikely high reward option and a likely low reward option. Four groups, each consisting of 15 participants, were compared: chronic amphetamine users, chronic opiate users, ex-drug users who had been long-term amphetamine/opiate users but are abstinent from all drugs of abuse for at least 1 year and healthy matched controls without a drug-taking history. RESULTS: During decision-making, control participants showed relatively greater activation in the right dorsolateral prefrontal cortex, whereas participants engaged in current or previous drug use showed relatively greater activation in the left orbitofrontal cortex. CONCLUSION: Our results indicate a disturbance in the mediation by the prefrontal cortex of a risky decision-making task associated with amphetamine and opiate abuse. Moreover, this disturbance was observed in a group of former drug users who had been abstinent for at least 1 year.

Adult↗
PubMed2004

The neuropsychology of ventral prefrontal cortex: decision-making and reversal learning.

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that measures of decision-making and reversal learning may be useful as functional markers of ventral prefrontal cortex integrity in psychiatric and neurological disorders. Whilst existing measures of decision-making may have superior sensitivity, reversal learning may offer superior selectivity, particularly within prefrontal cortex. Effective decision-making on existing measures requires the ability to adapt behaviour on the basis of changes in emotional significance, and this may underlie the shared neural circuitry with reversal learning.

Animals↗
PubMed2003

Cost effectiveness of defibrillation by targeted responders in public settings.

BACKGROUND: Out-of-hospital cardiac arrest is frequent and has poor outcomes. Defibrillation by trained targeted nontraditional responders improves survival versus historical controls, but it is unclear whether such defibrillation is a good value for the money. Therefore, this study estimated the incremental cost effectiveness of defibrillation by targeted nontraditional responders in public settings by using decision analysis. METHODS AND RESULTS: A Markov model evaluated the potential cost effectiveness of standard emergency medical services (EMS) versus targeted nontraditional responders. Standard EMS included first-responder defibrillation followed by advanced life support. Targeted nontraditional responders included standard EMS supplemented by defibrillation by trained lay responders. The analysis adopted a US societal perspective. Input data were derived from published or publicly available data. Future costs and effects were discounted at 3%. Monte Carlo simulation and sensitivity analyses assessed the robustness of results. Standard EMS had a median of 0.47 (interquartile range [IQR]=0.32 to 0.69) quality-adjusted life years and a median of 14 100 dollars (IQR=8600 dollars to 21 900 dollars) costs per arrest. Targeted nontraditional responders in casinos had an incremental cost of a median 56 700 dollars (IQR=44 100 dollars to 77 200 dollars) per additional quality-adjusted life year. The results were sensitive to changes in time to defibrillation, incidence of arrest, and number of devices required to implement rapid defibrillation. CONCLUSIONS: Where cardiac arrest is frequent and response time intervals are short, rapid defibrillation by targeted nontraditional responders may be a good value for the money compared with standard EMS. The incidence of arrest should be considered when choosing locations to implement public access defibrillation.

Adult↗
PubMed2003

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗
PubMed2003

A comparison of the anti-inflammatory activities of conjugated estrogens and 17-beta estradiol.

OBJECTIVE AND DESIGN: Unregulated chronic inflammatory process partly due to an estrogen deficiency may render postmenopausal women vulnerable to degenerative conditions such as arthritis, osteoporosis, atherosclerosis, and Alzheimer's disease. Current confusion regarding therapeutic efficacy of estrogen replacement therapy may be due to different estrogen formulations used, short term therapy, as well as advanced stage of the disease. MATERIALS AND METHODS: We compared anti-inflammatory activities of two major estrogen preparations, conjugated equine estrogen (CEE) and 17-beta estradiol, using an animal model (rat mesentery) of in vivo inflammatory reaction to intravenously infused amyloid-beta, examined by video recording and subsequently analyzed by transmission electron microscopy. Cellular markers of inflammation were monitored: leukocyte migration, platelet activation, mast cell activation/degranulation, and endothelial disruption. RESULTS: Low doses of CEE (0.3 mg/kg for 3 weeks) demonstrated significant anti-inflammatory activity, whereas even at high doses (2.0 mg) 17-beta estradiol had only minimal activity. CONCLUSION: CEE, a mixture of several compounds, may have some component(s) with significant anti-inflammatory activity. The anti-inflammatory activity of CEE may have a role in prevention of several degenerative diseases associated with menopause.

Amyloid beta-Peptides↗
PubMed2003

Progestins initiate adverse events of menopausal estrogen therapy.

OBJECTIVE: Recent report, particularly the Women's Health Initiative, demonstrated that hormone therapy with combined estrogen plus progestin increased the incidence of heart attacks, stroke, blood clots, breast cancer and dementia in women over 65 years old. We investigated the role of synthetic progestins in initiating the adverse events associated with estrogen therapy. METHODS: We used a fluorescence imaging technique, which allows video microscopic recordings of blood flow, blood vessel morphology and activities of various blood cells in a live animal. The acute peripheral and cerebrovascular responses were measured following intraperitoneal (5 or 10 mg) or intravenous (10 or 100 microg) administration of progesterone, synthetic progestins (medroxyprogesterone acetate and norethindrone) or estrogens (conjugated equine estrogens and 17 beta-estradiol). RESULTS: In both peripheral and cerebral vasculature, synthetic progestins caused endothelial disruption, accumulation of monocytes in the vessel wall, platelet activation and clot formation, which are early events in atherosclerosis, inflammation and thrombosis. Natural progesterone or estrogens did not show such toxicity. CONCLUSION: The risk associate with combined estrogen plus progestin therapy may be a consequence of vascular actions of progestins. Using progestins with minimal vascular toxicity may lead to safer estrogen preparations for menopausal women.

Animals↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

5-HT(2C) receptor activation by m-chlorophenylpiperazine detected in humans with fMRI.

Functional brain imaging using selective drug probes offers the opportunity to investigate regional neuronal activation linked to receptor stimulation or inhibition. In a placebo-controlled, balanced order design in eight male volunteers, the 5-HT(2c) agonist, m-chlorophenylpiperazine (mCPP) increased blood oxygen level dependent (BOLD) signal in the hypothalamus, caudate, pallidum, amygdala and pyriform cortex, anterior cingulate gyrus and choroid plexus (p < 0.001 uncorrected), areas with high density of 5-HT(2c) receptors. Activation in the hypothalamus correlated significantly with the prolactin response (p < 0.05 small volume corrected). In a subsequent Go/NoGo task, mCPP enhanced activation in right lateral orbitofrontal cortex (p < 0.05 small volume corrected). These findings suggest that pharmacoMRI is a potentially powerful tool for investigating neurotransmitter function in humans.

Brain↗
PubMed2002

The Ensembl genome database project.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

Computational Biology↗
PubMed2001

Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library.

A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.

Animals↗
PubMed2001

Estrogen and raloxifene activities on amyloid-beta-induced inflammatory reaction.

The prevalence of Alzheimer's disease (AD) in women is double that of men. Several studies indicate that use of estrogen after menopause by women may reduce the risk of developing AD. The risk of estrogen-dependent tumors associated with estrogen replacement therapy has prompted the use of alternatives, like the SERM raloxifene, which exert estrogen agonist effects on selected target tissues. Whether SERMS provide cognitive and cardiovascular benefits comparable to those of estrogens is an active area of investigation in women's health. A chronic inflammatory process is central to the pathology of Alzheimer's disease. Using an animal model we compared the anti-inflammatory activity of orally administered estrogens (2 mg/kg) and raloxifene (3 mg/kg) in ovariectomized rats. Morphological analysis of Abeta(1-40)-induced inflammatory reaction featured adhesion and transmigration of leukocytes across the vessel wall, endothelial disruption, and platelet activation. Estrogen showed remarkable anti-inflammatory action, whereas raloxifene had no significant beneficial effect. Inhibition of the inflammatory process may contribute to the reported efficacy of estrogen in the treatment of AD.

Administration, Oral↗