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Biomedical subjects

A Bennett

Publications and source records attributed to A Bennett.

At least 19 recordsLinked to original sources

Unusual middle-ear mischief: trans-tympanic trauma from a hair grip resulting in ossicular, facial nerve and oval window disruption.

A case of piercing of the tympanic membrane, resulting in unusual consequences, is described. This is the first reported case of the long process of a dislocated incus resulting in trauma to the horizontal portion of a dehiscent facial nerve. Simultaneous depression of the stapes footplate resulted in a perilymph leak, but with delayed presentation.

Accidents, Home↗

Quality of life and visual rehabilitation: an observational study of low vision in three general practices in West Glamorgan.

AIM: To survey low vision in an urban population and assess impact on quality of life, rehabilitation and support. METHODS: In a cross-sectional population survey, 66 patients were identified from databases of three general practices and surveyed by investigator administered questionnaire. Main outcome measures were ocular diagnoses, (US) National Eye Institute Visual Function-Questionnaire (NEI-VFQ) scores assessing visual and nonvisual disability, eligibility for, awareness and receipt of rehabilitation and support. RESULTS: Of 24,420 individuals on the lists of the three study practices, we found 101 registered as blind or partially sighted (prevalence 0.41%). A total of 66 patients participated with ocular diseases of age-related macular degeneration 39 (59%), glaucoma 11 (17%), diabetic retinopathy two (3%), retinitis pigmentosa two (3%), and 12 (18%) 'others'. Better eye visual acuity was counting fingers or worse in 32 (48.5%). NEI-VFQ scores were poor-overall mean 41.5% (SD 23.5). In all, 80% had a social services home visit with one-third of these still in contact. In all, 66% had undergone a low vision aid assessment and 57.6% of these used their aid. The awareness and receipt of benefits arising from registration as visually impaired were lower than for other supportive measures available for reasons unrelated to vision. None had a guide dog. CONCLUSIONS: We found expected patterns of low vision but poorer levels of function and support that may reflect age and deprivation in a population failed by the current systems for identification, registration, and rehabilitation based on legislation overtaken by demographic change and social provision independent of visual status.

Activities of Daily Living↗

Hepatic stellate cells on poly(DL-lactic acid) surfaces control the formation of 3D hepatocyte co-culture aggregates in vitro.

Evidence for the functional superiority of cells cultured as 3D aggregates or on 3D scaffolds over conventional 2D monolayer cultures has created interest in material and cell based methods that influence the formation and structure of multicellular aggregates in vitro. We have created a co-culture of primary rat hepatocytes and hepatic stellate cells on a poly(DL-lactic acid) surface, a poor substrate for rat hepatocyte adhesion, to study the dynamics of multicellular spheroid formation and the resultant cell arrangement. The poly(DL-lactic acid) surface allows dynamic and rapid interaction of hepatocytes and stellate cells to form co-culture spheroids in a complex multistage process (shown by time lapse microscopy). This spheroid morphology supports enhanced cell viability relative to a mono-culture mono-layer system (measured by lactate dehydrogenase leakage). The distribution of the aggregating cell type in the final structure is related to the mechanics of formation i.e. mainly central and peripheral. This study provides a unique and generically applicable insight into the dynamics of multicellular spheroid formation where aggregation is induced by one cell type and imposed on another. This has implications for 3D cell culture models and a wide number of currently used stromal co-culture systems.

Animals↗

Elevated serum alanine transaminase in patients with type 1 or type 2 diabetes mellitus.

BACKGROUND: The risk of chronic liver disease is higher in diabetics, and serum alanine transaminase (ALT) is a sensitive predictor of mortality from liver disease. AIM: To estimate the prevalence of elevated ALT in type 1 and type 2 diabetes, and identify possible risk factors. METHODS: We identified all patients (n = 2077) attending review between September 2002 and August 2003. We excluded those with no ALT measurement (n = 73); those whose alcohol consumption was >14 units/week (women) (n = 276) or >21 units/week (men) (n = 324); and those with a diagnosis of Maturity Onset Diabetes of the Young, secondary diabetes, gestational diabetes or uncertain type of diabetes (n = 51). We calculated the prevalences of elevated ALT in both type 1 and type 2 diabetes patients, and compared the demographic, microvascular risk factors and current drug use between each group using multivariate logistic regression. RESULTS: Of 1353 patients included, 836 (61.9%) had type 2 diabetes. Elevated ALT was found in 9.5% (95%CI 7.1-12.3%) of patients with type 1 diabetes, and 12.1% (95%CI 9.9-14.5%) of those with type 2 diabetes. The risk of elevated ALT in patients with type 2 diabetes increased with increasing body mass index (p(trend) = 0.04), and was lower in those taking insulin (OR 0.38, 95%CI 0.22-0.65). DISCUSSION: The prevalence of elevated ALT is 3-4 times higher in patients with either type 1 or type 2 diabetes than in the general population. Further studies investigating the aetiology and mechanisms of this elevation may suggest appropriate early interventions.

Adolescent↗

Microbial aerosol generation during laboratory accidents and subsequent risk assessment.

AIM: To quantify microbial aerosols generated by a series of laboratory accidents and to use these data in risk assessment. METHODS AND RESULTS: A series of laboratory accident scenarios have been devised and the microbial aerosol generated by them has been measured using a range of microbial air samplers. The accident scenarios generating the highest aerosol concentrations were, dropping a fungal plate, dropping a large bottle, centrifuge rotor leaks and a blocked syringe filter. Many of these accidents generated low particle size aerosols, which would be inhaled into the lungs of any exposed laboratory staff. Spray factors (SFs) have been calculated using the results of these experiments as an indicator of the potential for accidents to generate microbial aerosols. Model risk assessments have been described using the SF data. CONCLUSIONS: Quantitative risk assessment of laboratory accidents can provide data that can aid the design of containment laboratories and the response to laboratory accidents. SIGNIFICANCE AND IMPACT OF THE STUDY: A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.

Accidents, Occupational↗

Determining the performance of a commercial air purification system for reducing airborne contamination using model micro-organisms: a new test methodology.

The performance of a duct-mounted air disinfection system, designed to reduce airborne pathogens in the hospital environment, was determined using a new testing methodology. The methodology places the equipment in a test duct, a microbial aerosol is generated and then sampled simultaneously before and after the test system. This allows a percentage efficiency value to be calculated. The air disinfection system is a novel chemical-coated filter and ultraviolet (UV) radiation air purification system, operating at a flow rate of 500 m(3)/h, against aerosols of MS2 phage and Mycobacterium vaccae (surrogates of viral and mycobactericidal pathogens). A three UV lamp system was effective against airborne phages, removing an average of 97.34% of the aerosolized challenge. With the UV component switched off, the average efficiency dropped to 61.46%. This demonstrates that the chemical-coated filter component plays a more significant role than the UV radiation in destroying phages. When six UV lamps were used, the system was able to remove mycobacteria with an efficiency exceeding 99.99%. This test methodology can be used to assess manufacturers' claims of efficacy of equipment against airborne micro-organisms in the hospital environment.

Air Microbiology↗

No association between insulin gene variation and adult metabolic phenotypes in a large Finnish birth cohort.

AIMS/HYPOTHESIS: Although the variable number tandem repeat (VNTR) minisatellite 5' to the insulin gene is among the most studied polymorphisms in diabetes, the relationships between VNTR variation, diabetes-related traits and predisposition to type 2 diabetes remain unclear. Since inadequate sample size is likely to have been an obstacle to reliable inference, we examined the relationship between VNTR variation and a range of diabetes-related traits in a cohort of 5,753 Finnish adults. MATERIALS AND METHODS: VNTR genotypes were derived, by typing at the -23HphI variant site, for 5,646 individuals from the Northern Finland Birth Cohort 1966. Associations were sought between these genotypes and a range of anthropometric (BMI, WHR), physiological (blood pressure) and biochemical (fasting glucose, insulin, lipids, indices of insulin sensitivity and beta cell function) measures obtained at clinical examination at 31 years. RESULTS: We found no evidence that VNTR genotype was significantly associated with measures of insulin secretion, insulin sensitivity, glycaemia, adiposity or blood pressure. CONCLUSIONS/INTERPRETATION: Despite evidence from several relatively small studies suggesting that INS-VNTR genotypes are associated with predisposition to type 2 diabetes, reduced beta cell function and measures of adiposity, the present study failed to detect any association with a range of diabetes-related traits. Taken with other recent studies in large population-based cohorts, these data suggest that previous studies have, at the very least, overestimated the influence of the INS-VNTR on type 2 diabetes-related traits. The effects of INS-VNTR variation on insulin transcription observed in vitro appear not to translate into detectable differences in basal insulin secretion in humans.

Adult↗

Intranasal immunisation with defective adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus.

There is no vaccine licensed for human use to protect laboratory or field workers against infection with Venezuelan equine encephalitis virus (VEEV). Infection of these groups is most likely to occur via the airborne route and there is evidence to suggest that protection against airborne infection may require high antibody levels and the presence of antibody on the mucosal surface of the respiratory tract. Recombinant defective type 5 adenoviruses, expressing the E3E26K structural genes of VEEV were examined for their ability to protect mice against airborne challenge with virulent virus. After intranasal administration, good protection was achieved against the homologous serogroup 1A/B challenge virus (strain Trinidad donkey). There was less protection against enzootic serogroup II and III viruses, indicating that inclusion of more than one E3E26K sequence in a putative vaccine may be necessary. These studies confirm the potential of recombinant adenoviruses as vaccine vectors for VEEV and will inform the development of a live replicating adenovirus-based VEEV vaccine, deliverable by a mucosal route and suitable for use in humans.

Adenoviruses, Human↗

ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Adenosine Triphosphatases↗

Transcriptional regulation of human SREBP-1c (sterol-regulatory-element-binding protein-1c): a key regulator of lipogenesis.

Sterol-regulatory-element-binding protein 1c (SREBP-1c) is one member of the family of transcription factors that stimulate sterol and fatty-acid biosynthesis in animal cells. Human SREBP-1c, mapped to chromosome 17p11.2, is expressed in liver, intestine, skeletal muscle and adipocytes. A section of genomic sequence from a chromosome 17 library, thought to contain the SREBP-1c promoter, was cloned. Putative transcription-factor-binding sites and a potential transcriptional start site were identified using the Genomatix Suite of sequence analysis tools (MatInspector). Sequence analysis showed the human promoter to be 42% identical with the previously published mouse sequence. Two novel transcription-factor-binding sites were identified: those for PDX-1 (pancreatic-duodenal homoeobox-1) and HNF-4 (hepatic nuclear factor-4). Co-transfection experiments with overexpression plasmids for PDX-1 and HNF-4 suggested that both factors stimulate SREBP-1c gene expression, although further work is required to ascertain their mechanisms of action.

Animals↗

A realistic field facility to simulate reactor spectra.

The design construction and characterisation of a simulated realistic neutron workplace field is described. Utilising a low-energy primary source of neutrons based on the 7Li(p,n) reaction, and a heavy water moderator, a broad spectrum is produced with energies extending from thermal to about 1 MeV. The field simulates the type of spectra encountered around UK gas-cooled reactors.

Body Burden↗

Successful treatment of severe psoriasis and psoriatic arthritis with adalimumab.

Adalimumab, a fully human-derived recombinant monoclonal antibody against tumour necrosis factor-alpha, has been shown to be effective for the treatment of patients with moderately to severely active rheumatoid arthritis. We report two patients with long-standing recalcitrant psoriasis and psoriatic arthritis who, after multiple treatment failures with conventional and experimental antipsoriatic medications, both responded to treatment with adalimumab. Significant clinical improvement was noted in both skin and joint disease in the two patients after several weeks of treatment with adalimumab. We are unaware of previous published reports of adalimumab therapy in patients with psoriasis and psoriatic arthritis.

Adalimumab↗

Sexual behaviour of young people in international tourist resorts.

BACKGROUND/OBJECTIVES: Increasingly, young people travel abroad to experience nightlife in international resorts. Although media coverage of such resorts suggests high levels of sexual activity, little empirical data are currently available. We have measured: 3 year trends in sexual behaviour of young people visiting Ibiza, levels of sexual risk taking, and their relation to substance use. Additionally, in 2002 we identified levels of homosexual sex and sexual interactions between UK residents and individuals from other countries. METHODS: Data were collected from visitors to Ibiza between 2000 and 2002 just before they left the island. Information on sexual health was surveyed using a short anonymous questionnaire. RESULTS: Over half of individuals (56.0%) visiting Ibiza had sex with at least one person, with 26.2% of males and 14.5% of females having sex with more than one individual. However, of those arriving without sexual partners (75.5%) just under half (47.5%) have sex in Ibiza and most of these (62.4%) always used condoms. Having any sex abroad was associated with using illicit drugs and having more sexual partners in the 6 months before visiting Ibiza. However, having unprotected sex or sex with more than one person was associated with smoking as well as having higher numbers of sexual partners before their visit. Overall, 8.6% of individuals had sex with a non-UK resident in Ibiza although such individuals were no more likely to have sex without condoms. CONCLUSIONS: Substantial numbers of individuals visiting international nightlife resorts have unprotected sex with people they meet while abroad. This poses an increasing threat to the sexual health of UK residents but as yet little attention has been paid to developing interventions that might reduce sexual risk taking among young people holidaying abroad.

Adolescent↗

Gender politics and secure services for women: reflections on a study of staff understandings of challenging behaviour.

This paper discusses the findings of a Q methodological study that investigated the complexity of professional understandings of (attitudes towards) residents in a secure unit for women with learning disabilities and challenging behaviours. Particular attention is afforded to the critical debate regarding women in psychiatric and secure care, including the significant contribution made to this literature by feminist perspectives. A multiprofessional group of staff (n = 38) participated in the study and nine distinct accounts of women's challenging behaviour are described. Despite a considerable amount of recent policy concern with the position of women in psychiatric services, the findings of this research suggest that many front line staff are reluctant to highlight gender in their explanations of women's behaviour. This supports the assertion by Williams et al. (2001), who were involved in the National Gender Training Initiative (NGTI), that most critical theorizing about women's mental health has had minimal impact at the level of individuals' understandings of these important issues. This state of affairs suggests a powerful case for the expansion of staff training as provided in the NGTI, which makes gender central to understanding and emphasizes feminist perspectives.

Female↗

Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates.

A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association study was conducted on 115 rhesus macaque infants either homozygous for the long 5HTTLPR variant (l/l) or heterozygous for the short and long form (l/s). To assess contributions of genotype and early rearing environment, 36 mother-reared monkeys (l/l = 26, l/s = 10) and 79 nursery-reared monkeys (l/l = 54, l/s = 25) were assessed on days 7, 14, 21, and 30 of life on a standardized primate neurobehavioral test designed to measure orienting, motor maturity, reflex functioning, and temperament. Both mother-reared and nursery-reared heterozygote animals demonstrated increased affective responding relative to l/l homozygotes. Nursery-reared, but not mother-reared, l/s infants exhibited lower orientation scores than their l/l counterparts. These results demonstrate the contributions of rearing environment and genetic background, and their interaction, in a nonhuman primate model of behavioral development.

Aging↗

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗