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Biomedical subjects

A J Robinson

Publications and source records attributed to A J Robinson.

At least 19 recordsLinked to original sources

Chlamydia trachomatis and Neisseria gonorrhoeae infection and the sexual behaviour of men who have sex with men.

BACKGROUND: Rates of bacterial sexually transmitted infections (STIs) continue to rise among men who have sex with men (MSM) in the UK. OBJECTIVE: To evaluate factors associated with Chlamydia trachomatis and Neisseria gonorrhoeae among MSM attending a genitourinary medicine clinic in inner London. STUDY DESIGN: 599 MSM undergoing testing for STIs were recruited. Specimens for ligase chain reaction (LCR), strand displacement amplification (SDA) assay and culture were collected from the pharynx, urethra and rectum for the detection of C trachomatis and N gonorrhoeae. Details regarding demographics, symptoms, signs and sexual behaviour were recorded. Associations of these factors with each infection were tested, adjusting for other risk factors. RESULTS: The prevalence of C trachomatis and N gonorrhoeae was 11.0% and 16.0%, respectively. LCR and SDA performed well for the detection of C trachomatis and N gonorrhoeae from urethra and rectum. Using either method, compared with our current testing policy, over 18% of those with C trachomatis and N gonorrhoeae would not have had their infection diagnosed or treated. Age, sexual behaviour, urethral and rectal symptoms and signs were strongly associated with both infections. A total of 33.7% of men reported at least one episode of unprotected anal intercourse in the previous month. Men reporting multiple episodes were markedly more likely to be HIV positive. CONCLUSION: The prevalence of infection, rates of partner acquisition and unprotected anal intercourse reported among these MSM are alarming. Improved detection of C trachomatis and N gonorrhoeae using nucleic acid amplification tests has major public health implications for STI and possibly HIV transmission in this population.

Adolescent↗

The Department of Health recurrent-targeted funding for GU medicine clinics: what happened to the funding?

The Department of Health provided two recurrent targeted funding of 5 million pounds sterlings and 3 million pounds sterlings for genitourinary (GU) medicine services in 2003 in response to the increasing waiting times for appointments. The British Association for Sexual Health and HIV conducted a survey to find out if the clinics continued to receive their full allocation, if not, the reasons for it, and the workload change from 2002 to 2004. Out of a total of 91 responders, 78 were from acute trusts and 13 from primary care trusts (PCTs). Of the acute trusts and PCTs, respectively, 67.9% and 76.9% received the full allocation; overall 30.8% did not receive their full allocation. In all, 86% of clinics had increases in their workload and of the 26 clinics with shortfall of funds, 24 (92.3%) still managed to increase the workload. This survey showed that the funding and other measures have increased the workload capacity, and also highlights the continuing problem of many clinics in not receiving their full allocation. Such clinics should be targeted for early review by Medical Foundation for AIDS and Sexual Health with involvement of the Special Health Authorities and PCTs in the current national review of GU services.

Financing, Government↗

Immunocontraceptive effects on female rabbits infected with recombinant myxoma virus expressing rabbit ZP2 or ZP3.

Recombinant myxoma viruses expressing rabbit zona pellucida 2 (rZP2) or rabbit zona pellucida 3 (rZP3) glycoproteins were constructed and tested in domestic rabbits to assess their potential to induce autoimmune infertility. The recombinant virus expressing rZP2 had no effect on fertility or ovarian histology, despite all animals developing antibodies against the rZP2 antigen. However, recombinant viruses expressing rZP3 induced infertility in 70% of animals at the first breeding. Serum antibodies were relatively short-lived, but antibody was bound to zona pellucida of all rabbits from Day 10 onward. There was no obvious correlation between infertility and rZP3 antibody titer. There was a transient inflammatory response in the ovaries of rZP3-immunized rabbits at Day 15 but no T-cell response to rZP3 could be detected at any time. Dysfunctional follicular formation was present in ovaries from rabbits infected with rZP3-expressing viruses 15-40 days postinfection but this had disappeared at later time points. A recombinant myxoma virus expressing a modified rZP3 antigen with the C-terminal hydrophobic putative anchor sequence deleted was also tested. This virus did not induce either infertility or an antibody response against the zona pellucida. Thus, the context of antigen presentation was crucial for an autoimmune response.

Animals↗

Over-expression of human lysosomal alpha-mannosidase in mouse embryonic stem cells.

Alpha-mannosidosis is a lysosomal storage disorder characterised by the lysosomal accumulation of mannose-containing oligosaccharides and a range of pathological consequences, caused by a deficiency of the lysosomal enzyme alpha-mannosidase. One of the major features of alpha-mannosidosis is progressive neurological decline, for which there is no safe and effective treatment. Implantation of stem cells into the central nervous system has been proposed as a potential therapy for these disorders. We report the construction and characterisation of mouse embryonic stem cell lines for the sustained over-expression of recombinant human lysosomal alpha-mannosidase (rhalphaM). Two vectors (involving recombinant human alpha-mannosidase expression driven by either the chicken beta-actin promoter/CMV enhancer or by the elongation factor 1-alpha promoter) were constructed and used to transfect mouse D3 embryonic stem cells. Selected clonal cell lines were isolated and tested to evaluate their expression of recombinant human alpha-mannosidase. Stem cell clones transfected with the chicken beta-actin promoter/CMV enhancer maintained rhalphaM expression levels throughout differentiation. This expression was not markedly elevated above background. In contrast, the vector incorporating the elongation factor 1-alpha promoter facilitated substantial over-expression of alpha-mannosidase when analysed out to 21 days of differentiation in stably transfected cell lines. The highest expressing cell line was found to qualitatively retain a similar differentiation potential to untransfected cells, and to secrete alpha-mannosidase that could mediate a reduction in the level of oligosaccharides stored by human alpha-mannosidosis skin fibroblasts. These results suggest potential for the use of this cell line for investigation of a stem cell therapy approach to treat alpha-mannosidosis.

Animals↗

The value of ultrasonic examination of the lumbar spine in infants with specific reference to cutaneous markers of occult spinal dysraphism.

AIM: To present part of the rationale behind the recent update to the M12 guideline in The Royal College of Radiologists' publication "Making the best use of a department of clinical radiology", 4th edition 1998, which stated that ultrasound was useful in screening for dysraphism in infants with cutaneous markers such as sacral dimple or hairy patch. MATERIALS AND METHODS: Over a 10-year period a total of 223 infant lumbar spines were scanned, for various clinical indications. Forty of these patients had already had abnormalities detected antenatally by foetal ultrasonography. One hundred and eight-three patients had abnormalities detected on postnatal clinical examination; most of these had various cutaneous markers, some had other congenital abnormalities. RESULTS: There were a total of 29 patients with dysraphism; 24 were detected antenatally and five postnatally. Of the five, two had two or more cutaneous markers and three had anorectal anomalies. All 86 of the patients with simple sacral dimples, pits or sinuses were normal. CONCLUSION: As an isolated abnormality, simple dimples or pits are not useful markers of spinal dysraphism. The authors suggest a new imaging protocol, resulting in improved diagnostic efficiency.

Female↗

Survival and engraftment of mouse embryonic stem cell-derived implants in the guinea pig brain.

alpha-Mannosidosis is a lysosomal storage disease resulting from a deficiency of the enzyme alpha-D-mannosidase. A major feature of alpha-mannosidosis is progressive neurological decline, for which there is no safe and effective treatment available. We have a guinea pig model of alpha-mannosidosis that models the human condition. This study investigates the feasibility of implanting differentiated mouse embryonic stem cells in the neonatal guinea pig brain in order to provide a source of alpha-mannosidase to the affected central nervous system. Cells implanted at a low dose (1.5 x 10(3)cells per hemisphere) at 1 week of age were found to survive in very low numbers in some immunosuppressed animals out to 8 weeks. Four weeks post-implantation, cells implanted in high numbers (10(5) cells per hemisphere) formed teratomas in the majority of the animals implanted. Although implanted cells were found to migrate extensively within the brain and differentiate into mature cells of neural (and other) lineages, the safety issue related to uncontrolled cell proliferation precluded the use of this cell type for longer-term implantation studies. We conclude that the pluripotent cell type used in this study is unsuitable for achieving safe engraftment in the guinea pig brain.

Animals↗

Prevalence of serum antibodies to canine adenovirus and canine herpesvirus in the European red fox (Vulpes vulpes) in Australia.

OBJECTIVES: To determine the seroprevalence and aspects of the epidemiology of canine adenovirus (CAdV) and canine herpesvirus (CaHV-1) in European red foxes (Vulpes vulpes) in Australia. DESIGN: Serum samples were collected opportunistically from foxes in 1991-1994 in Western Australia (WA) and South Australia (SA) and in 1980-1984 and 1990-1994 in New South Wales (NSW) and the Australian Capital Territory (ACT). The sera were examined for antibody to CAdV and CaHV-1 using ELISAs. Seroprevalence in the different regions was determined for both viruses and the CAdV data were analysed for interactions between decade of collection, age, season, region and gender using logistic regression. RESULTS: The overall prevalence of antibody to CAdV was 23.2% (308/1326) but was significantly higher in sera collected in the eastern states of Australia (47%: 233/498) than in WA (9%: 75/828). Overall, in NSW and the ACT, there was a significantly lower prevalence in juveniles than in adults and the prevalence in juveniles in the 1990s was significantly lower than in the 1980s. The prevalence was also significantly lower in the autumn than in the winter for juveniles but the reverse held for adults. The NSW and ACT data were subdivided into eastern (including the ACT) and western regions. This revealed a significantly higher prevalence in the winter than in the autumn for the west and the reverse in the east. In WA, the northern rangeland regions of WA had lower prevalence (1.9%) than the southern agriculture regions (10.7%). Seasonally, there was a peak prevalence in the spring dropping through the summer and autumn and rising again in the winter. This seasonal pattern was also found in the combined data for all sites in the 1990s. There was no gender difference in prevalence of CAdV either overall or in different regions. The overall prevalence of antibody to CaHV-1 was 2.2% (28/1300). The small number of positives allowed only limited statistical analysis that did not reveal any differences in decade of collection, age, season or region. CONCLUSIONS: CAdV infection is common in the Australian fox population whereas CaHV-1 infection is rare. For CAdV, the age and seasonal patterns of seroprevalence were generally consistent with the recruitment of young susceptible foxes into the population in the spring and the accumulation of infections with age. The differences in regional prevalences correlated with fox density. The low prevalence of antibody to CaHV-1 suggests that CaHV-1 may be a more suitable vector than CAdV for bait delivery of immunocontraceptive antigens to foxes in Australia.

Adenoviridae Infections↗

Survival of Escherichia coli O157:H7, O111:H- and O26:H11 in artificially contaminated chocolate and confectionery products.

To date, the survival of Escherichia coli O157:H7 and other verocytotoxin-producing E. coli (VTEC) in chocolate and other confectionery products has not been fully established, unlike Salmonella, which have been responsible for occasional outbreaks of infection linked to contaminated chocolate and related products, although none of these outbreaks have been related to products produced in the United Kingdom. The United Kingdom Biscuit, Cake, Chocolate and Confectionery Alliance commissioned this study to obtain information on the decline and potential survival of E. coli, particularly verocytotoxin-producing strains, in reduced aw confectionery products chocolate, biscuit cream and mallow. These products were artificially contaminated with high (4 log10 cfu/g) and low (2 log10 cfu/g) levels of E. coli O157:H7, O111:H- and O26:H11 and their survival, as affected by storage temperature (10, 22 and 38 degrees C), was monitored over 12 months. Preliminary studies to establish the best inoculation and recovery procedures indicated that differences between counts on selective and non-selective media used were not sufficiently different to influence the outcome of this study. Irrespective of sample type, rapid decline was observed in products stored at 38 degrees C and increased survival occurred in products stored at 10 degrees C. In chocolate (average aw 0.40), these bacteria were detected for up to 43 days in samples stored at 38 degrees C. At 22 degrees C they survived for up to 90 days and in product stored at 10 degrees C they could still be detected after 366 days storage. In biscuit cream (average aw 0.75) they survived for 2 days at 38 degrees C, 42 days at 22 degrees C and 58 days at 10 degrees C. Whilst mallow (aw ca. 0.73) was not stored at 38 degrees C, these bacteria could still be detected in samples stored for up to 113 and 273 days at 22 and 10 degrees C, respectively. The observed prolonged survival of these bacteria under conditions of reduced aw and lowered storage temperature in this study is supported by previous studies with Salmonella and E. coli O157:H7 in other foods. In the same way that Salmonella bacteria can survive for long periods, in excess of 12 months, in chocolate, this study provides evidence that E. coli, including pathogenic strains, can also survive for similar periods of time. Assuming the routes of transmission are similar, controls currently used by the confectionery industry to prevent contamination by Salmonella should also be effective against E. coli, including VT-producing strains, providing that all raw materials have been suitably processed, stored and handled before and during manufacture.

Cacao↗

BASHH survey of additional genitourinary medicine-targeted allocations in 2003 and 2004.

In response to the increasing waiting times for appointments at genitourinary (GU) medicine clinics, the Department of Health has made three targeted funding allocations to improve access consisting of a non-recurrent allocation of 5 million pounds in 2002-03, followed by an 8 million pounds recurrent and a further 5 million pounds non-recurrent allocation in 2003-04. The British Association for Sexual Health and HIV (BASHH) conducted a survey of lead consultants for GU medicine clinics in March 2004 to determine if they could confirm whether all of the targeted funding had been allocated to their budgets. A total of 122 individuals representing 132 (65%) clinics in England, responded to the questionnaire for either calendar year. Of the first 5 million pounds non-recurrent allocation, made in January 2003, the number and percentage of the 117 respondents who had received their full allocation was 96 (82%) compared to 13 (11%) who received less than the allocated amount and 8 (7%) who were uncertain. These individuals were able to confirm that 3,155,000 pounds (92%) of the 3,424,500 pounds allocation to their clinics had reached its intended target. Of the second 8 million pounds recurrent allocation in financial year 2003-04, 76 (64%) of 119 respondents received their full allocation, 30 (25%) respondents received less than the allocated amount, and 13 (11%) respondents were uncertain. The total amount of the allocation for the clinics represented by these 106 recipients was 4,566,500 pounds of which 3,619,663 pounds (79%) had reached their clinic budgets. Of the final non-recurrent 5 million pounds allocation in financial year 2003-04, 61 (51%) respondents received their full allocation, 49 (41%) respondents received less than their allocated amount, and nine (8%) respondents remained uncertain. The total amount of the allocation for the clinics represented by these 110 recipients was 3,258,000 pounds of which 1,638,000 pounds (50%) had reached their clinic budgets. Thus, of the total 7,824,500 pounds allocation to the Primary Care Trusts (PCTs) with lead sexual health responsibilities for the GU medicine clinics of recipients in 2003-04, only 5,257,663 pounds (67%) was confirmed to have reached clinic budgets. Overall, only 51 (43%) of 119 respondents could confirm having received all of their recurrent and non-recurrent allocations, 58 (49%) had received either a reduced allocation or none at all and 10 (8%) were uncertain. This survey suggests that a significant proportion of the additional funding to improve access to GU medicine clinics failed to reach its intended target. The deficit between the amounts allocated and received by clinics was larger in financial year 2003-04, when the funding was given to PCTs with lead roles for sexual health, as compared with the preceding year when it was allocated directly to clinics. Moreover, the late allocation of non-recurrent funding and the inability of many clinics to arrange for this funding to be carried forward at year-end may have further prevented its intended use to increase service capacity and reduce waiting times.

Ambulatory Care Facilities↗

How useful are high vaginal swabs in general practice? Results of a multicentre study.

Vulvovaginal symptoms are a common reason for consultation with a general practitioner (GP). High vaginal swabs (HVS) are used to investigate symptoms, but their usefulness is poorly evaluated and microbiological tests performed vary between laboratories. In this multicentre study of 797 women with genital symptoms attending GPs, diagnostic yield of HVS was poor except for Candida spp. (22%). There is an urgent need to establish the most cost-effective approach for the management of these women.

Adolescent↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. III. Release, persistence and rate of spread of an identifiable strain of myxoma virus.

An identifiable strain of myxoma virus was introduced into four local populations of wild rabbits Oryctolagus cuniculus on the southern tablelands of New South Wales (NSW) and its spread in the presence of other field strains was monitored for 6 months. The main vector in this region was considered to be the European rabbit flea Spilopsyllis cuniculi. Each population of rabbits was of a high density and living in groups of warrens covering areas from 59 to 87 hectares. Rabbits occupying centrally located warrens were inoculated with the virus in late September or early October (spring) and the subsequent appearance of myxomatosis across the sites monitored by trapping, shooting and visual observations. Samples, taken from rabbits with myxomatosis, were examined by polymerase chain reaction (PCR) that allowed identification of the introduced strain. On all four sites the introduced virus spread from the inoculated rabbits in the centrally located warrens to rabbits in surrounding warrens. On Sites 1 and 3, this spread continued across the entire site persisting for at least 118 and 174 days respectively. On Sites 2 and 4, the virus was detected for 78 and 62 days respectively and the subsequent inability to detect the introduced virus correlated with the appearance of an unrelated field strain. Using three different methods of calculation, rates of spread ranged from 3.7 to 17.8 m d(-1).

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. I. Natural occurrence of myxomatosis.

A survey of rabbit populations in the southern tablelands of New South Wales, Australia, was carried out to establish the pattern of occurrence of myxomatosis in preparation for a deliberate release of myxoma virus. Myxomatosis was first detected in December and cases were found on most sites through to May. The serological profiles of rabbit populations suggested that their susceptibility to myxoma virus was generally low in winter and highest in spring and summer reflecting the presence of increasing numbers of susceptible young rabbits. This was consistent with the pattern of rabbit breeding, as determined from the distribution of births and reproductive activity in females and males, which occurred maximally in spring and early summer. The serology and age structure of rabbit populations on sites suggested that some rabbit populations can escape an annual myxomatosis epizootic. Although fleas were present on rabbits throughout the year and therefore not considered to be a limiting factor in the spread of myxomatosis, their numbers peaked at times coincident with peak rabbit breeding. It was concluded that mid to late spring was an optimal time for a deliberate release.

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. II. Selection of a strain of virus for release.

To be able to study the dynamics of myxoma virus spread following a release in the field, a strain of virus is required that is both highly transmissible and readily differentiated from other field strains. Eight strains of virus of known virulence for laboratory rabbits and with previously mapped and sequenced restriction fragment length polymorphisms, were used to infect groups of seronegative wild rabbits. Based on these trials, and on the nature of the DNA polymorphism, a virus designated Brooklands/2-93 was chosen as a strain suitable for experimental release. These trials confirmed that resistance to myxomatosis within wild rabbit populations continues to be substantial and that some rabbits are highly resistant. These rabbits probably have little role in transmission of virus. Most of the virus strains tested induced very small or invisible primary lesions at the inoculation site. Thus the secondary skin sites such as eyelids, face and ears may be critical for transmission.

Animals↗