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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 19 recordsLinked to original sources

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content.

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.

Brassica napus↗

Aggressive behaviour at first contact with services: findings from the AESOP First Episode Psychosis Study.

BACKGROUND: Aggressive behaviour is increased among those with schizophrenia but less is known about those with affective psychoses. Similarly, little is known about aggressive behaviour occurring at the onset of illness. METHOD: The main reasons for presentation to services were examined among those recruited to a UK-based first episode psychosis study. The proportion of individuals presenting with aggressive behaviour was determined and these individuals were compared to those who were not aggressive on a range of variables including sociodemographic, clinical, criminal history, service contact, and symptom characteristics. Among the aggressive group, those who were physically violent were distinguished from those who were not violent but who were still perceived to present a risk of violence to others. RESULTS: Almost 40% (n=194) of the sample were aggressive at first contact with services; approximately half of these were physically violent (n=103). Younger age, African-Caribbean ethnicity and a history of previous violent offending were independently associated with aggression. Aggressive behaviour was associated with a diagnosis of mania and individual manic symptoms were also associated with aggression both for the whole sample and for those with schizophrenia. Factors differentiating violent from non-violent aggressive patients included male gender, lower social class and past violent offending. CONCLUSIONS: Aggressive behaviour is not an uncommon feature in those presenting with first episode psychosis. Sociodemographic and past offending factors are associated with aggression and further differentiate those presenting with more serious violence. A diagnosis of mania and the presence of manic symptoms are associated with aggression.

Adolescent↗

Minor physical anomalies across ethnic groups in a first episode psychosis sample.

Minor physical anomalies (MPAs) are more prevalent amongst individuals with psychosis, supporting a neurodevelopmental model for psychotic disorders. The aim of this study was to investigate the possibility that neurodevelopmental adversity contributes to the excess of psychosis found in some ethnic groups in the UK. Subjects with first onset psychosis and healthy neighbourhood controls were enrolled in the AESOP study in South East London and Nottingham between 1997 and 1999. MPA rates were estimated in four broad ethnic groupings (White, African Caribbean, Black African and Other). Patients (n=245) had a higher mean total MPA score than healthy controls (n=158). This held true across each of the four ethnic groupings. The results of this study suggest that neurodevelopmental factors play a role in the aetiology of psychosis across all ethnic groups.

Adult↗

A computer model to simulate control of parasitic gastroenteritis in sheep on UK farms.

A computer model that simulates the population dynamics and epidemiology of three major species of parasitic nematodes of sheep found in the UK (Telodorsagia [Ostertagia] spp., Haemonchus spp. and Trichostrongylus spp.) is described. The model has been developed as a tool for veterinarians and advisors to aid in the implementation of integrated parasite control strategies designed to optimise anthelmintic usage and delay the development of resistance on UK farms. The model represents the parasite life cycle, flock dynamics and the response of individuals with different susceptible and resistant genotypes to the major broad-spectrum classes of anthelmintic available in the UK. Where possible, UK data have been used for the model parameters. The model allows worm control simulations on individual UK farms. Inputs include environmental and farm management variables which impact on the epidemiology of the disease, e.g. regional weather data; flock stocking rates; initial pasture larval contamination levels and species proportions; lambing dates; timing of flock movements to clean pastures; and removal of lambs during the year. Farm management data, as well as nematode egg outputs and grass larval counts, were collected from eight UK farms over a 1-year period for initial validation of the model outputs. The management data for each farm were used as inputs for each model run and model outputs for nematode egg counts from ewes and lambs were compared to the observed data for each farm. Statistical analysis of results shows a positive correlation for observed and simulated counts and regression analysis suggests an acceptable fit between the data. Comparison of observed and simulated outputs for resistance were possible for only one farm due to low numbers of worms developing in the laboratory tests. Additional studies will be necessary before resistance data can be reliably compared. Further validation studies are proposed to ensure that the model is robust and applicable across a diverse range of farm types. The model will be used to demonstrate the advantage, in terms of delaying resistance development, of current guidelines for anthelmintic use and management practices for worm control in sheep.

Animals↗

Evidence of semantic disorganisation using semantic priming in individuals with high schizotypy.

Semantic processing deficits are present in schizophrenia and are particularly evident on semantic priming tasks. Using high schizotypes (psychosis-prone individuals) can overcome some confounds involved in studying actively symptomatic schizophrenics. In the current study, 26 high and 32 low scorers on the O-LIFE schizotypy scale (from a sample of 251 students) were selected for testing. All subjects were administered a lexical-decision semantic priming task where half the stimuli had a short 200 ms stimulus onset asynchrony (SOA, length of time from onset of prime to onset of target) and half the stimuli had a long 750 ms SOA. In addition, half the words were of high frequency and half of a low frequency. There were no group differences in priming for words of different frequencies. Low schizotypes showed greater priming at the 200 ms SOA than at the 750 ms SOA, whilst individuals with high schizotypy showed the opposite pattern. The pattern shown by the low schizotypes replicates earlier work by the authors using other normal control samples; establishing that there is greater priming under conditions of automatic spreading of activation. Furthermore, the data shows there is not an increase in automatic spreading of activation in individuals with high schizotypy. There has been controversy in the schizophrenia literature over whether there is increased priming under automatic conditions. The current study suggests that, when confounds are controlled for, schizophrenia-like symptoms are not related to an increase in automatic spreading of activation.

Adult↗

Anti-CD19 immunotoxin enhances the activity of chemotherapy in severe combined immunodeficient mice with human pre-B acute lymphoblastic leukemia.

The anti-CD19 immunotoxin (IT) (HD37-dgRTA) is effective in killing B-lineage leukemia cells and in curing severe combined immunodeficient mice with acute lymphoblastic leukemia. The present study aimed to identify effective combinations of HD37-dgRTA and chemotherapeutic agents. The in-vitro cytotoxicity assays demonstrate that the combination of HD37-dgRTA and either daunorubicin or vincristine is effective. The in-vivo experiments using HD37-dgRTA with vincristine prolonged the survival of mice compared to the chemotherapeutic agent or IT (90.7 vs. 147.1 days). Also, 80% of the mice treated with IT plus vincristine were long-term survivors.

Animals↗

Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro-organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD). OBJECTIVES: To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5-16-year-old children. METHODS: This was a randomized, placebo-controlled, double-blind, multi-centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index. RESULTS: There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4. CONCLUSIONS: M. vaccae was no more effective than the placebo in ameliorating the severity of AD.

Adolescent↗

The clinical and genetic spectrum of spinocerebellar ataxia 14.

Spinocerebellar ataxia 14 (SCA14) is associated with missense mutations in the protein kinase C gamma gene (PRKCG), rather than a nucleotide repeat expansion. In this large-scale study of PRKCG in patients with ataxia, two new missense mutations, an in-frame deletion, and a possible splice site mutation were found and can now be added to the four previously described missense mutations. The genotype/phenotype correlations in these families are described.

Adolescent↗

Awareness and use of smoking cessation treatments among diabetic patients.

AIMS: To investigate awareness of pharmacotherapeutic aids to smoking cessation in diabetic cigarette smokers. METHODS: A structured questionnaire-based interview was held by a research nurse individually with consecutively attending cigarette smokers. RESULTS: Of 597 diabetic patients attending a routine clinic, 100 (17%) were current cigarette smokers. Mean (+/-sd) age was 58+/-11 years, 58% were male, and 96% Type 2 diabetic patients. Mean daily cigarette consumption was 16/day, for a mean duration of 35 years. There were 34% who had never heard of nicotine replacement therapy (NRT), and of those who had, only 49% considered it safe with diabetes. Bupropion (Zyban) was unknown to 46%, and of those who knew of it, 39% thought it unsafe in diabetic patients. Only 31% of the group had been previously offered NRT, and 14% bupropion. The NHS Quitline was known of by 84%, but only 8% had used it. CONCLUSIONS: Cigarette smokers with diabetes have poor uptake, awareness and knowledge of NRT and bupropion as aids to smoking cessation. They comprise a high-risk group, for large and small vessel disease, and these findings are therefore of concern. More active education and support for these patients by medical and nursing staff is needed.

Aged↗

Pathways to care and ethnicity. 1: Sample characteristics and compulsory admission. Report from the AESOP study.

BACKGROUND: Many studies have found high levels of compulsory admission to psychiatric hospital in the UK among African-Caribbean and Black African patients with a psychotic illness. AIMS: To establish whether African-Caribbean and Black African ethnicity is associated with compulsory admission in an epidemiological sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: All patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas were included in the (AESOP) study. For this analysis we included all White British, other White, African-Caribbean and Black African patients from the AESOP sampling frame. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: African-Caribbean patients were significantly more likely to be compulsorily admitted than White British patients, as were Black African patients. African-Caribbean men were the most likely to be compulsorily admitted. CONCLUSIONS: These findings suggest that factors are operating at or prior to first presentation to increase the risk of compulsory admission among African-Caribbean and Black African patients.

Adolescent↗

Pathways to care and ethnicity. 2: Source of referral and help-seeking. Report from the AESOP study.

BACKGROUND: Previous research has found that African-Caribbean and Black African patients are likely to come into contact with mental health services via more negative routes, when compared with White patients. We sought to investigate pathways to mental health care and ethnicity in a sample of patients with a first episode of psychosis drawn from two UK centres. METHOD: We included all White British, other White, African-Caribbean and Black African patients with a first episode of psychosis who made contact with psychiatric services over a 2-year period and were living in defined areas. Clinical, socio-demographic and pathways to care data were collected from patients, relatives and case notes. RESULTS: Compared with White British patients, general practitioner referral was less frequent for both African-Caribbean and Black African patients and referral by a criminal justice agency was more common. With the exception of criminal justice referrals for Black African patients, these findings remained significant after adjusting for potential confounders. CONCLUSIONS: These findings suggest that factors are operating during a first episode of psychosis to increase the risk that the pathway to care for Black patients will involve non-health professionals.

Adolescent↗

Cryopreservation of viable hepatocyte monolayers in cryoprotectant media with high serum content: metabolism of testosterone and kaempherol post-cryopreservation.

Little work in the literature focuses on the cryopreservation of primary hepatocytes as monolayer cultures, yet this technique offers many distinct advantages over other cryopreservation systems, including high recovery, high post-thaw nutrient penetration, and low numbers of trapped dead cells. This article investigates the cryopreservation of primary rat hepatocytes at -78 degrees C attached as monolayers to collagen coated culture dishes, and describes efforts to increase post-thaw viability and function through manipulation of the freeze/thaw protocol. Different concentrations of foetal calf serum (FCS) with 10% (v/v) dimethyl sulphoxide (ME2SO) were tested as cryopreservation media, and high cryoprotectant serum levels were found to be important in maintaining membrane integrity and function in the cryopreserved rat hepatocyte monolayer cultures. Cultures cryopreserved with 90% (v/v) FCS plus 10% (v/v) ME2SO maintain 79.7+/-6.5% of the monolayer area as viable cells with normal morphology (by image analysis), 112.7+/-14.2% protein concentration, 55.4+/-4.2% carboxyfluorescein diacetate de-acetylation, 27.2+/-7.5% kaempherol glucuronidation (a measure of UDP-glucuronosyl transferase activity), and 39.3+/-7.3% testosterone hydroxylation (a measure of cytochrome P-450 activity) compared with non-cryopreserved controls. This method of cryopreservation may provide a simple, convenient means of long-term storage of hepatocytes for in vitro metabolism studies.

Animals↗

Correction of intraoperative coagulopathy in a patient with neurofibromatosis type I with intravenous desmopressin (DDAVP).

A patient with the genetic condition neurofibromatosis type I and no known coagulopathy undergoing cesarean delivery, had diffuse uterine and surgical site bleeding that was not correctable by oxytocin, methylergonovine and PGF2 alpha. Despite good uterine tone, hemorrhage continued from the uterus and the surrounding tissues, persisting even after surgical ligation of the uterine arteries. With no change in her condition, which was behaving clinically as a coagulopathy, an infusion of desmopressin acetate (DDAVP) was begun. The patient's bleeding promptly resolved shortly after infusion of this agent. A review of relevant literature suggests that platelet reactivity of patients with neurofibromatosis type 1 is attenuated in some in vitro conditions. Thus, there may be some theoretical basis for using DDAVP in patients with neurofibromatosis type 1 who have bleeding problems with no other known source, such as in the case presented here.

Adult↗

Detection of p53 mutations in precancerous gastric tissue.

Intestinal-type gastric cancer is preceded by gastritis and intestinal metaplasia. There is uncertainty regarding the stage at which genetic alterations in the p53 gene occur. Reactive oxygen species (ROS) may participate in the production of mutations and the inactivation of p53 is due to infection by the bacterium Helicobacter pylori. We have investigated whether alterations of the p53 gene can be detected in gastritis and intestinal metaplasia using the restriction site mutation assay. We also assessed the potential contribution of ROS to p53 inactivation using electron spin resonance spectroscopy (ESR) and correlated with the presence of H. pylori. In all, 35% of the gastritis samples and 45% of the intestinal metaplasia samples were found to contain mutations in exons 5-8 of the p53 gene. Electron spin resonance spectroscopy analysis showed a significant increase in free radical levels in gastritis samples compared with normal, intestinal metaplasia and cancer samples, suggesting that free radicals present in gastritis may contribute to p53 mutations. There was no significant difference in free radical levels between the H. pylori-positive and -negative groups. However, a small subpopulation of the H. pylori-negative patients had much higher levels of free radicals. This suggests a more prominent role for other factors in ROS production.

Acute Disease↗

Contribution of patient related differences to multidrug resistance in rheumatoid arthritis.

BACKGROUND: There is a wide variation in responses to standard disease modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Whether multidrug resistance, failure to respond to several DMARDs, is a specific entity over and above that expected by chance alone is unclear. OBJECTIVE: To identify patients with RA who demonstrate a multidrug resistant phenotype and to determine what proportion of the variance in drug responses is due to patient related factors. METHODS: Patients with RA (1987 American College of Rheumatology criteria) were identified from clinics at Manchester Royal Infirmary and through the Arthritis Research Campaign National RA Repository. The clinic records were reviewed and multidrug resistance was defined as stopping three or more DMARDs owing to lack of efficacy after an adequate trial of the drug. Logistic regression measured by a random effects model was used to determine the relative contribution of the drug and subject related differences to the multidrug resistance. RESULTS: 265 patients (210 (79.3%) female) were studied. The mean (SD) age and disease duration were 52.2 (12.9) and 10.7 (8.8) years, respectively. Patients had a median (range) of 2 (1-8) DMARD courses. Failure of at least one DMARD due to inefficacy occurred in 105 (40%) and 13 (5%) were multidrug resistant. Overall, 35% of the variance in drug responses was due to between-subject differences (p=0.02). Rheumatoid factor (RF) status contributed significantly to this (OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained only 3% of the total variance in drug inefficacy. CONCLUSION: Multidrug resistance occurs in an uncommon (5%) but important subgroup of patients with RA. The between-subject variance is not fully explained by demographics and RF status. Understanding the biological mechanisms that contribute to multidrug resistance may suggest new therapeutic approaches and targets in RA.

Adult↗