Biomedical subjects
Publications and source records attributed to M Stephens.
Particulate and histopathologic examination of atherosclerotic material collected during carotid artery stenting is presented, illustrating the limitations of current knowledge regarding the use of distal protection devices (DPD) during this novel vascular intervention.
AIMS: This study investigated the associations between xerostomia (dry mouth) (low, moderate and high) with other categorical variables (e.g. demographic and health status indicators). This paper aims to report on the severity of xerostomia in the elderly population and investigate the relationship with other aspects of perceived health. METHOD: Data were obtained from a cross-sectional survey of 225 elderly people from a large multilevel geriatric care centre. The centre consists of three levels of care: an apartment building in which residents live more or less independently, a home for the aged, and a chronic care hospital. Participants in the study were recruited when they attended the dental care facility. Data were collected by means of a personal interview conducted either at the dental care facility or the participant's residence. RESULTS: The mean age was 83 years. Most were females (72%) and almost all (99%) reported one or more chronic medical conditions; 88% had physical disabilities. Xerostomia was recorded on a seven-point scale. Scores were categorised as low, medium or high and the proportions were 49.3%, 30.3% and 20.4% respectively Bivariate analysis showed no association between dry mouth and sex, age, general health change or life satisfaction. However, when the high xerostomia group was separated out and odds ratios calculated they were 2.3 to 4.9 times more likely to experience a negative impact on health than the low group. Xerostomia did not have a significant impact on chewing capacity, morale or stress, although it contributed to the variability of the oral health-related quality of life measures. It was the only variable with a significant effect (OR 2.55) for the Oral Health Impact Profile-14 and displayed a higher odds ratio (2.76) for the Geriatric Oral Health Assessment Index. Self-reported xerostomia in the elderly population can be categorised into a severity scale. Those suffering most from xerostomia are more likely to experience a negative impact on general health. CONCLUSION: The key finding in this study is that xerostomia has a significant and negative impact on the quality of life of elderly individuals, though oral function may be less affected.
We report a case of angiolymphoid hyperplasia with eosinophilia (epithelioid haemangioma) involving multiple deep mediastinal, abdominal and intramammary lymph nodes in a 52-year-old woman with weight loss and raised CA-125 levels. The unusual clinical presentation with raised CA-125 levels and its occurrence within multiple deep visceral lymph nodes has never been reported in literature.
We report a 36-year-old man with atopic eczema who developed lymphomatoid papulosis while taking ciclosporin. Latent membrane protein 1 and in situ hybridization for Epstein-Barr virus were negative. There are only two reports in the literature of patients taking ciclosporin to control atopic eczema who developed primary cutaneous CD30+ T-cell lymphoproliferative disorders. The development of T-cell lymphoproliferative disorders including lymphomas is well described in patients with solid organ transplants who are taking ciclosporin. Also, it has been noted in patients taking ciclosporin for rheumatological conditions or psoriasis.
The hippocampus is sensitive to the effects of ethanol and appears to have a role in the development of alcohol tolerance. The objective of this study was to test the hypothesis that there are innate differences in gene expression in the hippocampus of inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats that may contribute to differences in sensitivity to ethanol and/or in the development of tolerance. Affymetrix microarrays were used to measure gene expression in the hippocampus of alcohol-naive male iP and iNP rats in two experiments (n=4 and 6 per strain in the two experiments). Combining data from the two experiments, there were 137 probesets representing 129 genes that significantly differed (P < or = 0.01); 62 probesets differed at P < or = 0.001. Among the 36% of the genes that were expressed more in the iP than iNP rat at this level of significance, many were involved in cell growth and adhesion, cellular stress reduction and anti-oxidation, protein trafficking, regulation of gene expression, synaptic function and metabolism. Among the 64% of the genes that had lower expression in the hippocampus of iP than iNP rats were genes involved in metabolic pathways, cellular signaling systems, protein trafficking, cell death and neurotransmission. Overall, the data indicate that there are significant innate differences in gene expression in the hippocampus between iP and iNP rats, some of which might contribute to the differences observed in the development of alcohol tolerance between the selectively bred P and NP lines.
CONTEXT: Recent research suggests that variation in the gene encoding dystrobrevin binding protein (DTNBP1) confers susceptibility to schizophrenia. Thus far, no specific risk haplotype has been identified in more than 1 study. OBJECTIVES: To confirm DTNBP1 as a schizophrenia susceptibility gene, to identify and replicate specific risk and protective haplotypes, and to explore relationships between DTNBP1 and the phenotype. DESIGN: Genetic association study based on mutation detection and case-control analysis. SETTING: All subjects were unrelated and ascertained from general (secondary care) psychiatric inpatient and outpatient services. PARTICIPANTS: The Cardiff, Wales, sample included 708 white subjects from the United Kingdom and Ireland (221 females) who met DSM-IV criteria for schizophrenia and were individually matched for age, sex, and ethnicity to 711 blood donor controls (233 females). Mean +/- SD age at first psychiatric contact for cases was 23.6 +/- 7.7 years; mean age at ascertainment was 41.8 +/- 13.5 years. The Dublin, Ireland, sample included 219 white subjects from the Republic of Ireland who met DSM-III-R criteria for schizophrenia or schizoaffective disorder and 231 controls. The mean age of the Irish cases was 46.0 +/- 8.5 years; mean age at first psychiatric contact was 25.2 +/- 12.4 years. MAIN OUTCOME MEASURE: Evidence for association between the DTNBP1 locus and schizophrenia. RESULTS: In the Cardiff sample, there was no evidence for association with previously implicated haplotypes but strong evidence for association with multiple novel haplotypes. Maximum evidence was found for a novel 3-marker haplotype (global P<.001), composed of 1 risk haplotype (P =.01) and 2 protective haplotypes, 1 common (P =.006) and 1 rare (P<.001). Specific risk and protective haplotypes were replicated in the Dublin sample (P =.02,.047, and.006, respectively). The only phenotypic variable associated with any haplotype was between the common protective haplotype and higher educational achievement (P =.02, corrected for multiple tests). CONCLUSIONS: DTNBP1 is a susceptibility gene for schizophrenia. Specific risk and protective haplotypes were identified and replicated. Association with educational achievement may suggest protection mediated by IQ, although this needs to be confirmed in an independent data set.
Attention deficit hyperactivity disorder (ADHD) is a childhood onset disorder, for which there is good evidence that genetic factors contribute to the aetiology. Recently reported linkage findings suggested evidence of a susceptibility locus on chromosome 16p13 (maximum LOD score of 4.2, P=5 x 10(-6)). The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this region of linkage. As this is also a good functional candidate gene for ADHD, we undertook family-based association analysis in a sample of 238 families. We found significant evidence of association with a GRIN2A exon 5 polymorphism (chi(2)=5.7, P=0.01). Our data suggest that genetic variation in GRIN2A may confer increased risk for ADHD and that this, at least in part, might be responsible for the linkage result on 16p reported by Smalley et al. We conclude that replication is required and that further work examining for association of GRIN2A polymorphisms with ADHD is warranted.
Succinate-semialdehyde dehydrogenase (SSADH) deficiency is a rare cause of learning disability. We have investigated SSADH to assess its contribution to cognitive ability in the general population in both case-control- and family-based analyses. Sequence analysis of SSADH revealed four changes affecting the encoded protein, only one of which had a minor allele whose frequency is even moderately common. We genotyped this functional polymorphism in 197 high-IQ cases, 201 average-IQ controls and 196 parent high-IQ offspring trios. The minor allele was significantly less frequent in high-IQ cases and was significantly less frequently transmitted by parents to high-IQ subjects than chance expectation. A previous study has shown that the minor allele encodes a lower activity enzyme than the major allele. These data suggest that higher SSADH activity is associated with higher intelligence across the general population. The effect is small, with each allele having an effect size translating to about 1.5 IQ points.
OBJECTIVES: To examine ethnic group differences in HIV testing history and sexual HIV risk behaviours that may account for such differences, among men in England who have sex with men (MSM), in order to inform HIV prevention planning priorities. METHODS: A self completion survey in the summer of 2001 was carried out in collaboration with community based health promoters. Three recruitment methods were used: "gay pride" festivals, health promoter distributed leaflets, internet version advertised with gay service providers. The leaflet was produced with an alternative cover for targeted recruitment of black men. RESULTS: In a sample of 13,369 MSM living in England, 17.0% were from minority ethnic groups and 5.4% had tested HIV positive. Compared to the white British majority, Asian men were 0.32 times as likely to be living with diagnosed HIV infection, while black men were 2.06 times as likely to be doing so. Among men who had not tested HIV positive, Asian men were less likely to have sex with a known HIV positive partner, while black men were more likely to have insertive unprotected anal intercourse both with a partner they knew to be HIV positive and with a partner whose HIV status they did not know. CONCLUSIONS: Among MSM in England, HIV prevalence is higher among black men and lower among Asian men compared with the white British majority. Increased sexual HIV risk behaviour, especially exposure during insertive anal intercourse, accounts for some of this difference. HIV prevention programmes for MSM and African people should both prioritise black MSM.
Oral-health-related quality of life measures that exist are designed for adults. This study aimed to develop and evaluate the CPQ(11-14), a self-report measure of the impact of oral and oro-facial conditions on 11- to 14-year-old children. An item pool was generated with the use of a literature review and interviews with health professionals, parents, and child patients. The 36 items rated the most frequent and bothersome by 83 children were selected for the CPQ(11-14). Validity testing involved a new sample of 123 children. Test-retest reliability was assessed in a subgroup of these children (n = 65). Mean CPQ(11-14) scores were highest for oro-facial (31.4), lower for orthodontic (24.3), and lowest for pedodontic (23.3) patients. There were significant associations between the CPQ(11-14) score and global ratings of oral health (p < 0.05) and overall well-being (p < 0.01). The Cronbach's alpha and intraclass correlation coefficient for the CPQ(11-14) were 0.91 and 0.90, respectively. These results suggest that the CPQ(11-14) is valid and reliable.
Current routine genotyping methods typically do not provide haplotype information, which is essential for many analyses of fine-scale molecular-genetics data. Haplotypes can be obtained, at considerable cost, experimentally or (partially) through genotyping of additional family members. Alternatively, a statistical method can be used to infer phase and to reconstruct haplotypes. We present a new statistical method, applicable to genotype data at linked loci from a population sample, that improves substantially on current algorithms; often, error rates are reduced by > 50%, relative to its nearest competitor. Furthermore, our algorithm performs well in absolute terms, suggesting that reconstructing haplotypes experimentally or by genotyping additional family members may be an inefficient use of resources.
This work characterizes solvation effects in reversed-phase liquid chromatography in the presence of 1-propanol. The solvatochromic method combined with a multivariate curve resolution-alternating least-squares analysis method has been used to characterize two modified silica surfaces--phenyl bonded and C18 bonded silica in mobile-phase mixtures of methanol--water and acetonitrile--water in the presence of 1-propanol. The presence of a small amount of 1-propanol has been shown to affect mainly the polarity properties of the stationary phases while the mobile-phase properties are largely unaffected. The chain collapse mechanism for the C18 stationary phase at higher concentrations of water seems to be inhibited in the presence of 1-propanol, and partitioning is the predominant solute retention mechanism. The phenyl-based phase shows considerably different behavior from that of the C18 phase, and propanol appears to disrupt the pi-stacking interactions between the solute and the phenyl rings anchored to the silica support.
OBJECTIVES: This paper compares the performance of the GOHAI and the OHIP-14 as measures of the oral health-related quality of life of the compromised elderly. METHODS: Data were obtained from a cross-sectional survey of 225 participants, most of whom lived in a large geriatric care centre. RESULTS: The mean age of subjects was 83 years and the majority had one or more chronic medical conditions and physical disabilities. Their main oral problems were high rates of tooth loss and xerostomia. Additive and simple count methods were used to derive GOHAI and OHIP-14 scores. Using the additive method, 8.4% had a GOHAI score of zero and 30.3% an OHIP-14 score of zero. Using the simple count method the percentage with a score of zero was 15.1% and 45.8%. Both measures discriminated between dentate subjects with and without one or more dentures, with and without a chewing problem and with and without dry mouth. Both also showed significant associations with self-rated oral health and satisfaction with oral health status. Associations tended to be stronger between GOHAI scores and these variables. The measures were equally good at predicting overall psychological well-being and life satisfaction. Although the GOHAI identified more oral functional and psychosocial impacts than the OHIP-14, neither was markedly superior to the other when used as discriminatory measures. However, the high prevalence of subjects with zero scores may compromise the ability of the OHIP-14 to detect within-subject change.
ABCG1 encodes a transporter protein that may be involved in the cellular uptake of tryptophan. Tryptophan is the precursor for serotonin, which is implicated in the regulation of mood. The gene maps to chromosome 21q22.3, a region implicated in bipolar disorder I (BPI) in genetic linkage studies. ABCG1 is thus a suitable candidate gene for study in BP1. We screened all 15 exons and 700 bases of the 5' flanking region of ABCG1 for mutations, using Denaturing High Performance Liquid Chromatography (DHPLC). A total of 13 single nucleotide polymorphisms (SNPs) were identified. Ten of the SNPs were intronic, two lie within the 5' flanking region and one within the 3' UTR. We identified a GCC repeat within Exon 1 and two novel intronic VNTRs. Eight of the SNPs, the two VNTRs, the GCC repeat and two known microsatellite markers within the gene were tested for association with BP1 in a sample of 110 parent-offspring trios using the Extended Transmission Disequilibrium Test (ETDT). No alleles or haplotypes were significantly preferentially transmitted from parents to affected offspring. However, the trend for preferential transmission of markers in the 3'UTR is in the same direction as in a previous report for association with mood and panic disorders and therefore warrants attempts at replication. Marker-to-marker linkage disequilibrium (LD) showed that strong LD was present over relatively short distances of up to 20 kb and was present for SNPs as well as for polymorphic repeats. The polymorphisms identified in this study will be useful in examining the role of this gene in other neuropsychiatric disorders and behavioural traits.
Research in bioinformatics in the past decade has generated a large volume of textual biological data stored in databases such as MEDLINE. It takes a copious amount of effort and time, even for expert users, to manually extract useful information embedded in such a large volume of retrieved data and automated intelligent text analysis tools are increasingly becoming essential. In this article, we present a simple analysis and knowledge discovery method that can identify related genes as well as their shared functionality (if any) based on a collection of relevant retrieved relevant MEDLINE documents. The relative computational simplicity of the proposed method makes it possible to process and analyze large volumes of data in a short time. Hence, it significantly contributes to and enhances a user's ability to discover such embedded information. Two case studies are presented that indicate the usefulness of the proposed method.
BACKGROUND: While established as an initial screening tool for the evaluation of injured patients at the trauma center, sonographic evaluation of the patient in the prehospital setting remains untested. The purpose of this study was to determine the feasibility of this procedure during prehospital helicopter transport. METHODS: Two qualified flight surgeons performed all imaging studies. Confirmatory endpoints were documented for all images obtained in flight. RESULTS: For this preliminary study, 100 patients are presented; 84 studies were analyzed; 16 were excluded due to patient weight (8), hemodynamic instability (6), or problems with machine calibration (2). Sensitivity was 81.3%; specificity was 100%. The positive predictive value was 100%; the negative predictive value was 95.7%. The accuracy was 96.4%. CONCLUSION: Sonographic studies obtained during air-medical transport are of similar quality and consistency as those obtained in the emergency department. The ability to detect hemoperitoneum in the field may challenge traditional algorithms for prehospital care as a result.
Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. In IBD, growth failure may be the only clinical presentation; it is imperative to perform a detailed history and physical examination to search for other systemic and gastrointestinal manifestations of the disease. IBD can have a significant impact on linear growth, weight gain, and bone mineralization, and can cause delays in the onset of puberty. Delays in growth and sexual development can be early indicators of disease activity, and assessment of growth and development should be performed frequently. Nutritional therapy is important not only to correct undernutrition, but also as therapy for IBD. Delayed puberty can have a significant impact on the self-esteem of the adolescent patient and diminish final adult height. Loss of bone mineral density is especially significant during a period in which the majority of bone accretion is expected to occur. These issues present unique problems to the gastroenterologist caring for a child or adolescent with IBD and require specific types of monitoring and interventions.
The use, in association studies, of the forthcoming dense genomewide collection of single-nucleotide polymorphisms (SNPs) has been heralded as a potential breakthrough in the study of the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favor of family-based tests of association, such as the transmission/disequilibrium test (TDT), but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and to estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings and may substantially outperform it if there are conflicting associations in different subpopulations.