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Biomedical subjects

J Copeland

Publications and source records attributed to J Copeland.

At least 19 recordsLinked to original sources

Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial).

The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), Pounds 1703 vs Pounds 1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (Pounds 2930 vs Pounds 3176). The average cost to individuals for reoperations was higher in the lap group (Pounds 762 vs Pounds 553). Overall costs were slightly higher in the lap group (Pounds 6899 vs Pounds 6631), with mean difference of Pounds 268 (95%CI -689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (Pounds 8259 vs Pounds 5586) and open procedures (Pounds 7820 vs Pounds 5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery.

Colectomy↗

E-MSD: an integrated data resource for bioinformatics.

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

Algorithms↗

The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations. METHODS: Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points. RESULTS: No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg). CONCLUSIONS: The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp.

Aged↗

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Animals↗

Suicidal behavior in a young offender population.

Young offenders have numerous problems, including increased psychopathology, housing, and psycho-social stresses and increased rates of substance abuse. The current study investigated the contribution that substance use might make to a particularly vulnerable group of young people. Of the 300 young people approached for the study, 23.7% reported a prior suicide attempt. For this group, the most significant predictors of a prior suicide attempt were negative affect, prior exposure to violence, and housing stress. Life-time substance-use variables were most predictive of the number of suicide attempts a young person might make. Self-reported lethality (the expectation that on the last attempt the young person expected to die) was not strongly predicted by any variable. The research identifies the important role that dynamic risk factors (such as mood, substance use, and psychosocial stressors) play in increasing the risk of self-harm for young offenders, and raises the need to provide for more comprehensive discharge planning and support in order to manage these needs.

Adolescent↗

Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine--results at 24 months after transplantation.

BACKGROUND: The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine demonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The primary end. points of the present, prospective, randomized multicenter, double-blind trial were to compare the efficacy of the micro-emulsion form of cycolsporine (CsA-NL) with the oil-based formulation as determined by cardiac allograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SM) in the study population. The 6-month analysis of the study showed reduced number of CsA-NL patients requiring antilymphocyte antibody therapy for rejection, fewer International Society of Heart and Lung Transplantation grade > or =3A rejections in female patients and fewer infections. Our report represents the final analysis of the results 24 months after transplantation. METHODS: A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM. Acute allograft rejection was diagnosed by endomyocardial biopsy and graded according to the International Society of Heart and Lung Transplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test were used for comparisons between groups. RESULTS: After 24 months, allograft and recipient survival were identical in both groups. There were fewer CsA-NL patients (6.9%) requiring antilymphocyte antibody therapy for rejection than in the CsA-SM-treated patient group (17.7%, P=0.002). There were fewer discontinuations of study drug for treatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM group (18; 9.4%, P=0.037). The average corticosteroid dose was lower in the CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/day, P=0.034) over the 24-month study period. Overall, there was no difference in blood pressure or creatinine between the two study groups. CONCLUSIONS: The final results of this multi-center, randomized study of two forms of cyclosporine confirmed that there were fewer episodes of rejection requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated with CsA-SM. The use of CsA-NL did not predispose these patients to a higher risk of adverse events.

Adolescent↗

Persecutory symptoms and perceptual disturbance in a community sample of older people: the Islington study.

BACKGROUND: While there are extensive studies of paranoid symptoms and perceptual disturbance (PPD) in younger adults, relatively little is known about older adults with similar symptoms. METHOD: This study took place in Islington, an inner London borough. Enumeration Districts were randomised to provide a sampling frame. Residents aged 65 or over were interviewed at home. The Short-CARE was used to elicit psychiatric symptoms and diagnosis. Sociodemographic particulars were elicited using the Client Sociodemographic and Service Receipt Inventory. Questions were asked regarding sight and hearing. We used subsections of the geriatric mental scale to identify people who had PPD symptoms. Medications taken were recorded. We asked 'Do you have any health problems?' as a screening question for subjective health problems. RESULTS: We interviewed 720 people. Twenty-eight (3.9%) participants scored positively on the PPD sub-scales of the GMS. A forward logistic regression analysis for independent predictors of PPD found the significant independent predictors were dementia (p = 0.0000; odds ratio 6.8), drinking alcohol in last 6 months (p < 0.03; odds ratio 0.3), drinking alcohol to help sleep (p < 0.005; odds ratio 9.6), subjective memory loss (p < 0.007; odds ratio 3.3) and uncorrected visual impairment (p < 0.02; odds ratio 2.8). CONCLUSION: There is a relatively high prevalence of PPD in older people living in the community. This is not associated with higher use of services despite the increased needs. Further studies should consider interventions to meet this unmet need.

Activities of Daily Living↗

Perflubron emulsion reduces inflammation during extracorporeal circulation.

The recovery from cardiac surgery and cardiopulmonary bypass can be complicated by an acute inflammatory response. Circulating blood through an extracorporeal circuit (ECC) contributes to this complication. Perfluorocarbon-based blood substitutes (PFCs) are under investigation for use as a component of the ECC "prime" solution, because PFCs increase the oxygen-carrying capacity of the diluted blood. Some PFCs may provide the additional benefit of attenuating the ECC-induced inflammatory response. Earlier, we reported that perflubron emulsion (PFE, Alliance Pharmaceutical Corp.) reduced neutrophil (PMN) activation in vivo. However, the potential of PFE to reduce ECC-induced PMN activation has not been investigated. In this study, we used a small-scale ECC model to quantify the extent of PMN activation during circulation and to examine if PFE treatment attenuated PMN activation. ECC circuits were filled with a mixture of blood and Plasmalyte. Two groups were studied: an untreated group containing blood plus PlasmaLyte and a treated group in which some of the Plasmalyte was substituted with PFE (4.5 g/100 ml). Hematology and measures of whole blood PMN activation were made from blood samples taken periodically throughout the 120-min ECC circulation period. We found, for the untreated group, a significant decrease in the number of circulating PMNs and an increase in PMN activation with time. PMN activation was demonstrated as a significant increase in the expression of the PMN adhesion protein CD11b (P < 0.05) and an increase in PMN oxygen free radical production (reactive oxygen species (ROS)). After 120 min of circulation, the PMNs remained capable of a significant response to a second inflammatory stimulus, but PFE treatment significantly attenuated the fMLP-induced increase in PMN ROS at t = 120 min (P < 0.05). These results suggest that PFE may have dual utility in cardiac surgery, to increase oxygen delivery and to serve as an antiinflammatory agent.

Animals↗

Clinical profile of participants in a brief intervention program for cannabis use disorder.

The increasing demand for cannabis dependence treatment has led to the identification of significant gaps in the knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and allocated to either a 6-session CBT program, a single-session brief intervention, or a delayed-treatment control group. This paper demonstrates that individuals with cannabis use disorder will present for a brief intervention program. While they report similar patterns of cannabis use to nontreatment samples, they report a range of serious health and psychosocial consequences. While they appear relatively socially stable, they typically demonstrated severe cannabis dependence and significantly elevated levels of psychological distress, with the most commonly cited reason for cannabis use being stress relief. There were clinically relevant gender differences among the sample. This study provides more evidence of the demand for, and nature of issues relevant to, interventions for cannabis use disorders, and supports the need for further research into how best to assist individuals with these disorders.

Adolescent↗

A randomized controlled trial of brief cognitive-behavioral interventions for cannabis use disorder.

The increasing demand for treatment for cannabis dependence in Australia and internationally has led to the identification of significant gaps in knowledge of effective interventions. A randomized controlled trial of brief cognitive-behavioral interventions (CBT) for cannabis dependence was undertaken to address this issue. A total of 229 participants were assessed and randomly assigned to either a six-session CBT program (6CBT), a single-session CBT intervention (1CBT), or a delayed-treatment control (DTC) group. Participants were assisted in acquiring skills to promote cannabis cessation and maintenance of abstinence. Participants were followed-up a median of 237 days after last attendance. Participants in the treatment groups reported better treatment outcomes than the DTC group. They were more likely to report abstinence, were significantly less concerned about their control over cannabis use, and reported significantly fewer cannabis-related problems than those in the DTC group. Those in the 6CBT group also reported more significantly reduced levels of cannabis consumption than the DTC group. While the therapist variable had no effect on any outcome, a secondary analysis of the 6CBT and 1CBT groups showed that treatment compliance was significantly associated with decreased dependence and cannabis-related problems. This study supports the attractiveness and effectiveness of individual CBT interventions for cannabis use disorders and the need for multisite replication trials.

Adult↗

Anabolic-androgenic steroid use disorders among a sample of Australian competitive and recreational users.

Illicit anabolic-androgenic steroid (AAS) use, for body building and body image purposes, is increasing internationally. This study describes the prevalence and symptoms of AAS use disorders obtained using a semi-structured interview among a mixed-gender sample of 100 current Australian users, that were recruited from a variety of sources. The median age of the sample was 27 years and 94% were male. The full range of DSM IV symptoms of AAS abuse and dependence were reported and over three quarters (78%) of the sample exhibited at least one symptom of abuse or dependence on AAS. A total of 23% of the participants qualified for a diagnosis of AAS dependence using DSM IV criteria and a further 25% met criteria for AAS abuse. There were no gender differences in AAS abuse or dependence diagnoses. The only variable related to an AAS substance use disorder was reporting the experience of AAS-related aggression, which may be a useful clinical indicator of the disorder.

Adolescent↗

One year follow-up of cannabis dependence among long-term users in Sydney, Australia.

Eighty one percent of a sample of long-term cannabis users was followed up at 1 year (162/200). Half (51%) were daily smokers, while 20% had substantially decreased or ceased use. More than half received a dependence diagnosis on each of three measures in the last year, with 44% dependent on all three. Remission was much more common than incidence of dependence. Nevertheless, use and dependence patterns were strongly related over time. Longitudinal analyses revealed that quantity of use and severity of dependence at baseline were the primary predictors of those same variables at follow-up. These data suggest that cannabis use and dependence are fairly stable among long-term users.

Adolescent↗

Validation of the Hamilton Depression Rating Scale and Montgommery and Asberg Rating Scales in terms of AGECAT depression cases.

OBJECTIVE: To validate the Hamilton Depression (17) and Montgommery and Asberg Depression Scales as research instruments in older depressed community residents. DESIGN: External validation against GMS/AGECAT case level in the recruitment of older community residents for an antidepressant trial. ANALYSES: Receiver operator curves were generated for each rating scale, using GMS/AGECAT case level in external criterion. The sensitivity, specificity, positive and negative predictive values of both rating instruments were examined in the whole sample and age and gender subgroups. MADRS and HAM-D cut-off scores differentiating GMS/AGECAT cases from subcases were identified. RESULTS: HAM-D cut-off score of 16 and MADRS score of 21 were identified as differentiating case from sub-case. Diagnostic accuracy of both instruments was good, reflecting good sensitivity and specificity across both genders and sub-age groups. CONCLUSIONS: Both scales performed well in this population. These scores provide researchers with externally validated and clinically relevant cut-off scores in designing trials in the management of older depressed community residents.

Aged↗

Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema.

Resolution of pulmonary oedema is mediated by active absorption of liquid across the alveolar epithelium. A key component of this process is the sodium-potassium ATPase (Na+K+-ATPase) enzyme located on the basolateral surface of epithelial cells and up-regulated during oedema resolution. We hypothesised that lung liquid clearance could be further up-regulated by lipid-mediated transfer and expression of exogenous Na+K+-ATPase cDNA. We demonstrate proof of this principle in a model of high permeability pulmonary oedema induced by intraperitoneal injection of thiourea (2.5 mg/kg) in C57/BL6 mice. Pretreatment of mice (24 h before thiourea) by nasal sniffing of cationic liposome (lipid #67)-DNA complexes encoding the alpha and beta subunits of Na+K+-ATPase (160 microg per mouse), significantly (P<0.01) decreased the wet:dry weight ratios measured 2 h after thiourea injection compared with control animals, pretreated with an equivalent dose of an irrelevant gene. Whole lung Na+K+-ATPase activity was significantly (P<0.05) increased in mice pretreated with Na+K+-ATPase cDNA compared both with untreated control animals as well as animals pretreated with the irrelevant gene. Nested RT-PCR on whole lung homogenates confirmed gene transfer by detection of vector-specific mRNA in three of four mice studied 24 h after gene transfer. This demonstration of a significant reduction in pulmonary oedema following in vivo gene transfer raises the possibility of gene therapy as a novel, localised approach for pulmonary oedema in clinical settings such as ARDS and lung transplantation.

Animals↗

Cannabis use among Australian adolescents: findings of the 1998 National Drug Strategy Household Survey.

OBJECTIVE: To describe the prevalence, context and recent trends in cannabis use among Australian adolescents. METHOD: Data was collected from 1,581 adolescents aged 14-19 years as part of the 1998 National Drug Strategy Household Survey, and comparisons were made with data from 350 adolescents who participated in the 1995 survey. RESULTS: Among 14-19 year olds, 47.8% have had the opportunity to use cannabis in the past year and 45.2% have used cannabis at least once in their lifetime. Substantial increases have occurred since 1995 in the prevalence of use among young females. While most cannabis use was fairly infrequent, a minority of 14-19 year olds (9.4%) used cannabis at least weekly. Cannabis use was associated with regular tobacco and alcohol use, and other illicit drug use. Regular cannabis users had lower levels of health on the general health and vitality dimensions of the SF-36. IMPLICATIONS: These results show that cannabis availability and use is common among Australian adolescents, and confirm that there has been an increase in use between 1995 and 1998, although only among young females. Future research is required to understand why this recent increase has occurred, and trends in cannabis uptake and use patterns among this group should be carefully monitored. Interventions may need to be developed and made available to the group of young people who are using cannabis heavily.

Adolescent↗

Safety, tolerability and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil based formulation of cyclosporine--results at six months after transplantation.

BACKGROUND: The introduction of cyclosporine has resulted in significant improvement in the survival of cardiac allograft recipients due to decreased mortality from infection and rejection. The original oil-based cyclosporine formulation exhibits variable and unpredictable bioavailability that correlates with an increased incidence of acute and chronic rejection in those patients in whom this is most pronounced. The primary objectives of this prospective, multicenter, randomized, double-blind study in cardiac transplant patients were: to compare the efficacy of cyclosporine microemulsion (CsA-NL) with oil-based cyclosporine (CsA-SM) as measured by cardiac allograft and recipient survival and the incidence and severity of acute rejection episodes; and to assess the safety and tolerability of CsA-NL compared with CsA-SM in this population. This report represents the analysis of results 6 months after transplantation. METHODS: A total of 380 patients undergoing their first cardiac transplant at 24 centers in the United States, Canada, and Europe were enrolled in this double-blind, randomized trial examining the safety and efficacy of CsA-NL versus CsA-SM. Rejection was diagnosed using endomyocardial biopsy and were graded according to standardized criteria of the International Society of Heart and Lung Transplantation (ISHLT). Clinical parameters were monitored during the study. Survival and freedom from were used for analysis as was Fisher's exact test for comparisons between groups. RESULTS: At 6 months after transplantation, allograft and patient survival were the same for both groups. The frequency of ISHLT grade 3A or greater episodes in the two groups was identical. Fewer CsA-NL patients (5.9%) required antilymphocyte antibody (ATG or OKT-3) therapy for rejection compared with the CsA-SM-treated patients (14.1%, P=0.01). Females with ISHLT rejection grade > or = 3A treated with CsA-NL had a 46% lower incidence of rejection compared with the CsA-SM-treated group (31.3% vs. 57.6%, P=0.032). Fewer infections were seen in the CsA-NL. With the exception of baseline and 1 week posttransplant creatinines which were higher in the CsA-NL group, the overall creatinine was not significantly different between the two groups. CONCLUSIONS: This multicenter, randomized study of cardiac transplant recipients documented less severe rejection (in particular those requiring antibody therapy) and a lower incidence of infection in CsA-NL-treated patients. Results from the female subgroup analysis suggest that the improved bioavailability of CsA-NL might reduce the frequency of rejection episodes in female patients. The use of CsA-NL was not associated with an increased risk of adverse events.

Adolescent↗