Biomedical subjects

P Miller

Publications and source records attributed to P Miller.

At least 37 records · Page 2Linked to original sources

PubMed2002

Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings.

BACKGROUND: Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure. SUBJECTS: Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither. METHOD: Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance. RESULTS: In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001). CONCLUSIONS: In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.

Adult↗

PubMed2002

Maternal recall bias, obstetric history and schizophrenia.

BACKGROUND: This study sought to clarify the role of obstetric complications (OCs) and maternal recall bias for patients with first episodes of schizophrenia and those at increased risk of the disorder. METHOD: Subjects at high risk of schizophrenia were compared with people with first-episode schizophrenia and with healthy volunteers. Consenting mothers of subjects were interviewed using a standardised questionnaire for the recall of OCs, and OCs were also measured from records collected at the time of pregnancy and delivery. RESULTS: High-risk subjects and first-episode patients had higher rates of OCs recalled by their mother than controls, but hospital records showed no differences in OCs between groups. The number of OCs recalled by mothers of the high-risk group was not related to whether the mother had schizophrenia or not, but was related to the maternally rated abnormal childhood behaviour as measured by the Child Behaviour Checklist. CONCLUSIONS: These results suggest that studies that rely on maternal recall alone are susceptible to bias. The excess of OCs recalled by the mother could be related to abnormal behaviour in their child rather than maternal illness, family history or psychotic symptoms.

Adolescent↗

PubMed2001

Global analysis of protein activities using proteome chips.

To facilitate studies of the yeast proteome, we cloned 5800 open reading frames and overexpressed and purified their corresponding proteins. The proteins were printed onto slides at high spatial density to form a yeast proteome microarray and screened for their ability to interact with proteins and phospholipids. We identified many new calmodulin- and phospholipid-interacting proteins; a common potential binding motif was identified for many of the calmodulin-binding proteins. Thus, microarrays of an entire eukaryotic proteome can be prepared and screened for diverse biochemical activities. The microarrays can also be used to screen protein-drug interactions and to detect posttranslational modifications.

Amino Acid Motifs↗

PubMed2001

Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia.

BACKGROUND: Structural magnetic resonance imaging (MRI) of the brain in patients with schizophrenia has consistently demonstrated several abnormalities. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalities are evident, nor to what extent they are genetically or environmentally mediated. METHODS: One hundred forty-seven high-risk subjects (with at least two affected first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole brain. After inhomogeneity correction, regions of interest were traced by three group-blind raters with good inter-rater reliability. Regional brain volumes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. RESULTS: High-risk subjects had statistically significantly reduced mean volumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hippocampi and bilaterally smaller lenticular nuclei than the schizophrenics. High-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent associates of genetic liability. CONCLUSIONS: Subjects at high risk of developing schizophrenia have abnormalities of brain structure similar to but not identical to those found in schizophrenia. Our results suggest that some structural abnormalities are genetic trait or vulnerability markers, others are environmentally mediated, and that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease processes.

Amygdala↗

PubMed2001

Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms.

OBJECTIVES: To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference. DESIGN: Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes. SETTING: 31 general practices in Trent region. PARTICIPANTS: Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms. MAIN OUTCOME MEASURES: Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria. RESULTS: At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse. CONCLUSIONS: Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment.

Adult↗

PubMed2001

Radiography of the lumbar spine in primary care patients with low back pain: randomised controlled trial.

OBJECTIVE: To test the hypothesis that radiography of the lumbar spine in patients with low back pain is not associated with improved clinical outcomes or satisfaction with care. DESIGN: Randomised unblinded controlled trial. SETTING: 73 general practices in Nottingham, north Nottinghamshire, southern Derbyshire, north Lincolnshire, and north Leicestershire. 52 practices recruited participants to the trial. SUBJECTS: 421 patients with low back pain of a median duration of 10 weeks. INTERVENTION: Radiography of the lumbar spine. MAIN OUTCOME MEASURES: Roland adaptation of the sickness impact profile, visual analogue scale for pain, health status, EuroQol, satisfaction with care, use of primary and secondary care services, and reporting of low back pain at three and nine months after randomisation. RESULTS: The intervention group were more likely to report low back pain at three months (relative risk 1.26, 95% confidence interval 1.00 to 1.60) and had a lower overall health status score and borderline higher Roland and pain scores. A higher proportion of participants consulted their doctor in the three months after radiography (1.62, 1.33 to 1.97). Satisfaction with care was greater in the group receiving radiography at nine but not three months after randomisation. Overall, 80% of participants in both groups at three and nine months would have radiography if the choice was available. An abnormal finding on radiography made no difference to the outcome, as measured by the Roland score. CONCLUSIONS: Radiography of the lumbar spine in primary care patients with low back pain of at least six weeks' duration is not associated with improved patient functioning, severity of pain, or overall health status but is associated with an increase in doctor workload. Guidelines on the management of low back pain in primary care should be consistent about not recommending radiography of the lumbar spine in patients with low back pain in the absence of indicators for serious spinal disease, even if it has persisted for at least six weeks. Patients receiving radiography are more satisfied with the care they received. The challenge for primary care is to increase satisfaction without recourse to radiography.

Adult↗

PubMed2001

Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia.

BACKGROUND: Studies of groups at high risk of developing schizophrenia have tended to be based on subjects recruited to the study in their infancy. This paper reports on subjects at genetic high risk for schizophrenia assessed as young adults, close to the age when most onsets of schizophrenia occur. METHODS: One hundred and fifty-five young people at elevated risk for the development of schizophrenia and 36 controls not at increased risk were assessed on entry to the Edinburgh High Risk Study. The measures included current psychotic symptoms, past and present cannabis and other drug use, lifetime life events and two aspects of genetic liability to schizophrenia. RESULTS: Cannabis and other illicit drug use were significantly associated with symptoms in both groups. The same held true for the more upsetting life events experienced, but not for less upsetting ones. Within the high-risk group, there was no relationship between symptoms and a measure of genetic loading, but there was some slight evidence of a higher risk of symptoms when affected relatives were on the father's rather than the mother's side of the family. CONCLUSIONS: Cannabis use, use of other illicit substances and upsetting life events may all lead to psychotic symptoms in vulnerable young people.

Adolescent↗

PubMed2001

A principal component analysis of facial expressions.

Pictures of facial expressions from the Ekman and Friesen set (Ekman, P., Friesen, W. V., (1976). Pictures of facial affect. Palo Alto, California: Consulting Psychologists Press) were submitted to a principal component analysis (PCA) of their pixel intensities. The output of the PCA was submitted to a series of linear discriminant analyses which revealed three principal findings: (1) a PCA-based system can support facial expression recognition, (2) continuous two-dimensional models of emotion (e.g. Russell, J. A. (1980). A circumplex model of affect. Journal of Personality and Social Psychology, 39, 1161-1178) are reflected in the statistical structure of the Ekman and Friesen facial expressions, and (3) components for coding facial expression information are largely different to components for facial identity information. The implications for models of face processing are discussed.

Adolescent↗

PubMed2001

Human and automatic face recognition: a comparison across image formats.

Human subjects perform poorly at matching different images of unfamiliar faces. When images are taken by different capture devices (cameras), matching is difficult for human perceivers and also for automatic systems. We test an automatic face recognition system based on principal components analysis (PCA) and compare its performance with that of human subjects tested on the same set of images. A number of variants of the PCA system are compared, using different matching metrics and different numbers of components. PCA performance critically depends on the choice of distance metric, with a Mahalanobis metric consistently outperforming a Euclidean metric. Under optimal conditions, the automatic PCA system exceeds human performance on the same images. We hypothesise that unfamiliar face recognition may be mediated by processes corresponding to rather simple functions of the inputs.

Face↗

PubMed2001

Evaluating telemedicine in an accident and emergency setting.

This paper outlines the methodology of an evaluation of telemedicine in an Accident and Emergency (A&E) setting. Telemedicine technology consisting of ISDN 2 based videoconferencing and 'store & forward' software has been installed and is currently being evaluated in two minor injury units (MIUs) and a District General Hospital (DGH) A&E department in Lincolnshire. A cost-benefit analysis will be conducted using a pragmatic prospective case-control study with both a concurrent and retrospective control group. Any differences in resource use (including direct and indirect costs) between the intervention (Telemedicine) and the control (No Telemedicine) groups will be identified from both a patient and NHS perspective. A variety of health and non-health outcome measures will be recorded including staff and patient acceptability of the new technology.

Accidents↗

PubMed2001

Redefining leadership responsibilities following organizational redesign.

A redefinition of leadership roles was necessitated by the adoption of program management, which accompanied the merger of two large academic hospitals, each of which consisted of two sites. Directors of professional departments were removed when staff were deployed to programs. Program directors were selected to manage the new programs, and profession leaders were identified to monitor standards of practice. The roles and accountabilities of the new program and profession leaders needed to be clarified for incumbents and other hospital staff. This article describes the process undertaken to clarify those responsibilities. The resulting Guide outlines 14 specific and collaborative responsibilities of program and profession leaders. Plans for review and future development of the Guide are discussed.

Guidelines as Topic↗

PubMed2001

Interdisciplinary health professional education: a historical review.

A historical review was conducted to examine the advances made, nationally and internationally, in interdisciplinary health professional education since the mid-1960s. One hundred and nineteen articles were reviewed and divided by decade into the following subheadings: models, courses, communication/group process issues, and international perspectives. Twenty-seven articles, categorized as models, defined the conceptual field, described curriculum and program development, or provided a framework for evaluation. Thirty-two articles dealt with interdisciplinary courses, focusing on objectives, content areas, or innovative methods. Nine articles contributed content on interdisciplinary communication and group process issues, from which guidelines were abstracted. Fifty-one articles contributed an international perspective, leading to the recognition that interdisciplinary health professional education, practice, and research is a global movement.

Education, Professional↗

PubMed2001

Bromine and iodine in 1997 UK total diet study samples.

Concentrations of bromine and iodine were analysed in samples from the 1997 UK Total Diet Study (TDS) using ICP-MS. The data has been used to estimate dietary exposures of UK consumers to these elements from the typical UK diet. Samples for the 20 TDS food groups were obtained from 20 towns in the UK in 1997 and analysed in 1998/99 for total bromine and total iodine concentrations. These samples were also analysed for 12 other elements. The UK regulatory authority had considered iodine recently, but had not considered bromine before. This survey provides up-to-data baseline data for those two elements. Iodine concentrations are similar to those found in recent surveys. Levels of bromine were consistent with previous data where available. Dietary exposures to bromine and iodine were calculated to see if there were any risks to health from the levels of these elements found in the UK diet. The estimated population average exposure to iodine was 0.25 mg d-1, which is within the range of previous estimates (1995, 0.21 mg d-1; 1991, 0.17 mg d-1; 1985, 0.28 mg d-1). The estimated population average exposure to bromine was 3.6 mg d-1.

Adult↗

PubMed2001

Effects of 17 beta-estradiol and trimegestone alone, and in combination, on the bone and uterus of ovariectomized rats.

Trimegestone is a novel norpregnane progestin, which is being developed, in combination with 17 beta-estradiol, for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis. A model of osteoporosis in the ovariectomized rat has been used to evaluate the effects of 17 beta-estradiol and trimegestone, alone and in combination, on bone and uterus in these animals. Two treatment protocols were investigated, preventive with treatment starting immediately after ovariectomy and curative with treatment starting 1 or 6 months after ovariectomy. 17 beta-Estradiol was administered subcutaneously at a dose of 10 micrograms/kg/day with trimegestone or norethisterone being administered orally at a dose of 1 mg/kg/day; treatment was given 5 days per week. Treatment on both protocols was for 6 months. Given alone, 17 beta-estradiol maintained bone mass, either partially or completely, when given on the preventive protocol, or on the curative protocol with treatment starting 1 month after ovariectomy; it did not restore bone mass when given on the curative protocol with 6 months lapsing between ovariectomy and start of treatment. Trimegestone did not block the beneficial effects of 17 beta-estradiol on bone. 17 beta-Estradiol induced uterine hypertrophy on all these protocols and this was blocked completely by trimegestone. Trimegestone administered alone had no effect on bone or uterus but, when given in combination with 17 beta-estradiol, it did not inhibit the effect of 17 beta-estradiol in maintaining bone mass but completely blocked its uterotropic effect. Norethisterone at a similar dose did not inhibit the effects of 17 beta-estradiol on bone but also did not block its uterotropic effect.

Animals↗

PubMed2001

Evidence for higher-order structure formation by the c-myb 18-mer phosphorothioate antisense (codons 2-7) oligodeoxynucleotide: potential relationship to antisense c-myb inhibition.

We have demonstrated the formation of higher-order structures (presumably tetraplexes) by an 18-mer phosphorothioate antisense c-myb oligodeoxyribonucleotide that has been shown to have activity in the treatment of leukemia xenograft models. Although not observable by conventionally employed techniques, such as PAGE and dimethyl sulfate (DMS) protection, the formation of such higher-order structures by this oligonucleotide was revealed by several techniques. These included capillary gel electrophoresis (CGE), which demonstrated the presence of molecules with greatly increased retention time compared with the monomer; magnetic circular dichroism spectroscopy, which demonstrated a band at 290 nm, a characteristic of antiparallel tetraplexes; and fluorescence energy transfer measurements. For the last, the 18-mer phosphorothioate oligonucleotide was synthesized with a 5'-fluorescein group. Similar to the molecular beacon model, its fluorescence was quenched when combined in solution with tetraplex-forming oligomers that contained a 3'-Dabcyl moiety. 7-Deazaguanosine inhibits the formation of tetraplexes by eliminated Hoogsteen base pair interactions. The wild-type and 7-deazaguanosine-substituted antisense c-myb oligomers differentially downregulated the expression of the c-myb proto-oncogene in K562 and HL60 cells, with the wild-type oligomer being the least active. The 18-mer c-myb molecule can, therefore, form highly complex structures, whose analysis in solution cannot be limited to examination of slab gel electrophoresis results alone.

Circular Dichroism↗

PubMed2001

Inhibition of potentially anti-apoptotic proteins by antisense protein kinase C-alpha (Isis 3521) and antisense bcl-2 (G3139) phosphorothioate oligodeoxynucleotides: relationship to the decreased viability of T24 bladder and PC3 prostate cancer cells.

Isis 3521 and G3139 are 20- and 18-mer phosphorothioate oligonucleotides, respectively, targeted to the protein kinase C (PKC)-alpha and bcl-2 mRNAs. Treatment of T24 bladder and PC3 prostate carcinoma cells with full-length and 3'-truncation mutants of Isis 3521 causes down-regulation of PKC-alpha protein and mRNA. However, at the level of a 15-mer and shorter, down-regulation of mRNA expression is no longer observed. Further, no diminution in cellular viability, as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide assay, in response to increasing concentrations of paclitaxel, can be observed for these shorter oligomers. These observations not only indicate that PKC-alpha protein expression can be down-regulated by both RNase H-dependent and -independent mechanisms but also that down-regulation of PKC-alpha is insufficient by itself to "chemosensitize" cells. G3139, which down-regulates bcl-2 protein and mRNA expression, also down-regulates PKC-alpha protein and mRNA expression but not that of PKC-betaI, -epsilon, or -zeta. However, the down-regulation of PKC-alpha and bcl-2 are not linked. When the carrier Eufectin 5 is employed, only bcl-2 is down-regulated in both T24 and PC3 cells at 50 nM oligonucleotide concentration. At 100 nM, both bcl-2 and PKC-alpha expression are down-regulated, and only at this concentration can "chemosensitization" to paclitaxel and carboplatin be observed. In contrast, the down-regulation of bcl-2 seems to be linked with that of RelA (p65). However, this too is also not sufficient for chemosensitization, even though it leads to the loss of expression of genes under the putative control of nuclear factor-kappaB and to detachment of the cells from plastic surfaces. These results underscore the complexity of the intracellular requirements for the initiation of chemosensitization to anti-neoplastic agents.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Effect of experience of severe stroke on subjective valuations of quality of life after stroke.

Previous work suggests that the quality of life associated with severe disability after stroke is rated very poorly by members of the public, often as being worse than death. Other evidence suggests that experience of illness alters perceptions of its severity. This was tested for severe stroke. Eleven patients with severely disabling stroke, but able to complete a standard gamble interview, 22 age and sex matched controls, and 20 health professionals participated. A standard gamble interview was carried out to determine the quality of life (utility) associated with three hypothetical scenarios representing mild, moderate, and severe stroke, and current health. A sample was retested for reliability, and comparisons were made with other measures of health status. All three subject groups showed wide variation in the utilities they attached to each of the scenarios. The control subjects' valuations were lower than those of either patients or staff members, especially for moderate stroke (median 0.30, 0.73, and 0.68 respectively). There were weak to moderate correlations between utilities and other measures of health status including the Barthel index (r=0.51) and Rivermead mobility score (r=0.24). Test retest-reliability was modest (reliability coefficient 0.75), but indicators of the internal validity of the results were good. In conclusion, it cannot be assumed that general population valuations are valid for patient groups. In clinical practice it is unsafe to make any assumption about subjective quality of life after stroke, due to the wide range of valuations given, although many people rate severe and moderate stroke at least as bad as death.

Aged↗

PubMed2001

Programme approach to managing informed commissioning.

The objective of this paper is to examine possible organizational reasons for why UK NHS commissioners have not adopted programme budgeting and marginal analysis (PBMA). This is despite increasing evidence of discontent with current commissioning and priority-setting processes, increasing research evidence demonstrating the potential of PBMA and support for the principles of PBMA. Two separate semistructured surveys of the views of commissioning decision-makers on the use of PBMA were carried out at Grampian Health Board and Newcastle & North Tyneside Health Authority. Twenty-nine decision-makers were interviewed. Both surveys found common barriers to implementation of PBMA, described by respondents as 'institutional inertia'. These were the reactive rather than proactive environment; the fear of 'unnecessary' explicitness; an aversion to unilateral innovation in the current NHS environment; and the demand for concrete evaluation evidence. It is concluded that these qualitative surveys have small samples and cannot claim to be representative. It may be significant that many issues were common to both surveys carried out separately in organizations. It is unlikely that NHS commissioning will independently adopt techniques such as PBMA, given the current commissioning environment and organizational structures. Implementation strategies and future research on such commissioning innovations may need to focus on institutions as well as the interventions.

Budgets↗