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Biomedical subjects

M Ramsay

Publications and source records attributed to M Ramsay.

At least 55 records · Page 3Linked to original sources

Molecular epidemiology of human group A rotavirus infections in the United Kingdom between 1995 and 1998.

The G and P types of 2,912 rotavirus-positive fecal specimens collected from eight geographical areas of the United Kingdom between 1995 and 1998 were determined by reverse transcription-PCR. Although 15 different G-P combinations were identified, G1P[8], G2P[4], G3P[8], and G4P[8] strains constituted 95% of all the rotaviruses typed. Other genotypes included G9P[6] and G9P[8], which were first identified in the United Kingdom in 1995, or other uncommon G and/or P types of strains that may have had an animal origin. Unusual combinations of G1 or G4 with P[4] and G2 with P[8] which may have arisen by reassortment between human strains were also identified. G1P[8] was the genotype most frequently found (57 to 87%) in each season, followed by G2P[4] in the 1995-1996 (18%) and 1997-1998 (16%) seasons, although the incidence of infection with this virus decreased significantly to 2% during the 1996-1997 season. Significant differences were seen in the distributions of G1P[8], G2P[4], and G9P[8] strains between children and adults, in the temporal distributions of G4P[8] and G9P[8] strains within a season, and in the geographical distributions of each of the four most common genotypes from one season to the next.

Adolescent↗

Active surveillance of hepatitis C infection in the UK and Ireland.

AIM: To investigate the prevalence, distribution, and clinical details of paediatric hepatitis C virus (HCV) infection in the UK and Ireland. METHODS: Active monthly surveillance questionnaire study coordinated through the British Paediatric Surveillance Unit, to all consultant paediatricians in 1997 and 1998. RESULTS: A total of 182 HCV infected children were reported from 54 centres and by paediatricians from eight different specialties. In 40 children HCV was acquired through mother to child transmission (MTC children); 142 were infected by contaminated blood products (n = 134), organ transplantation (n = 2), needles (n = 4), or unknown risk factor (n = 2). Intravenous drug use was the risk factor for 35 mothers of MTC children. Twelve children were coinfected with HIV and four with HBV. Recent serum aspartate aminotransferase or alanine aminotransferase values were at least twofold greater than the upper limit of normal in 24 of 152 children; this occurred in five of 11 HIV coinfected children. Liver histology, available in 53 children, showed normal (7%), mild (74%), moderate (17%), or severe (2%) hepatitis. Twenty eight children had received therapy with interferon alfa. CONCLUSION: Most current paediatric HCV infection in UK and Ireland has been acquired from contaminated blood products, and most children are asymptomatic. There is a need for multicentre trials to inform clinical practice and development of good practice guidelines in this area. Long term follow up of this cohort of HCV infected children is planned to help determine the natural history over the long term of HCV acquired during infancy and childhood.

Child↗

Invasive meningococcal disease among university undergraduates: association with universities providing relatively large amounts of catered hall accommodation.

The incidence of invasive meningococcal disease (IMD) among UK university students and non-students of similar age was investigated. In addition, we sought to identify structural risk factors associated with high rates of IMD in individual universities. Cases were ascertained via Consultants in Communicable Disease Control (or equivalent officers) between September 1994 and March 1997. Data on individual universities were obtained from university accommodation officers. University students had an increased annual rate of invasive meningococcal disease (13.2/10(5), 95% CI 11.2-15.2) compared with non-students of similar age in the same health districts (5.5/10(5), CI 4.7-6.4) and in those health districts without universities (3.7/10(5), CI 2.9-4.4). This trend was highly significant. Regression analysis demonstrated catered hall accommodation to be the main structural risk factor. Higher rates of disease were observed at universities providing catered hall places for > 10% of their student population (15.3/10(5), CI 11.8-18;8) compared with those providing places for < 10% of students (5.9/10(5), CI 4.1-7.7). The majority of IMD amongst students was caused by serogroup B organisms. University students in the UK are at increased risk of IMD compared with non-students of a similar age. The incidence of IMD tends to be greatest at universities with a high provision of catered hall accommodation.

Adolescent↗

High polymorphism at the human melanocortin 1 receptor locus.

Variation in human skin/hair pigmentation is due to varied amounts of eumelanin (brown/black melanins) and phaeomelanin (red/yellow melanins) produced by the melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eu- and phaeomelanin production in the melanocytes, and MC1R mutations causing coat color changes are known in many mammals. We have sequenced the MC1R gene in 121 individuals sampled from world populations with an emphasis on Asian populations. We found variation at five nonsynonymous sites (resulting in the variants Arg67Gln, Asp84Glu, Val92Met, Arg151Cys, and Arg163Gln), but at only one synonymous site (A942G). Interestingly, the human consensus protein sequence is observed in all 25 African individuals studied, but at lower frequencies in the other populations examined, especially in East and Southeast Asians. The Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, and at a low frequency (7%) in Indians, but is at an exceptionally high frequency (70%) in East and Southeast Asians. The MC1R gene in common and pygmy chimpanzees, gorilla, orangutan, and baboon was sequenced to study the evolution of MC1R. The ancestral human MC1R sequence is identical to the human consensus protein sequence, while MC1R varies considerably among higher primates. A comparison of the rates of substitution in genes in the melanocortin receptor family indicates that MC1R has evolved the fastest. In addition, the nucleotide diversity at the MC1R locus is shown to be several times higher than the average nucleotide diversity in human populations, possibly due to diversifying selection.

Alleles↗

An estimate of the proportion of diarrhoeal disease episodes seen by general practitioners attributable to rotavirus in children under 5 y of age in England and Wales.

Mean weekly incidence rates for a 4-week period of new episodes of infectious intestinal disease (IID) and laboratory reports of faecal isolations in children under 5 y of age presenting in general practice were used to estimate the incidence of IID due to rotavirus infection in England and Wales. Between January 1992 and December 1996, a total of 92452 new episodes of IID were seen at sentinel general practices and reported to the Royal College of General Practitioners (RCGP) Research Unit in Birmingham, UK. Of these 32% (29592) were in children under 5 y of age. During the same period the Communicable Disease Surveillance Centre (CDSC) in London, UK received 159532 reports of faecal identifications in children under 5 y of age; 69219 (43%) of these were due to rotavirus. By modelling RCGP data and laboratory reports, the proportion of episodes attributable to rotavirus infection was estimated to be 29% (95% CI: 24% to 34%). By extrapolation of RCGP data it was estimated that rotavirus accounted for 762000 of new episodes of IID nationally in children under 5 y of age between January 1992 and December 1996. Implementation of a rotavirus vaccination programme could substantially reduce the incidence of childhood diarrhoea.

Child, Preschool↗

Cystic fibrosis carrier frequencies in populations of African origin.

Cystic fibrosis (CF) is a common autosomal recessive disorder in populations of European descent. However, very little is known about CF in populations of African origin among whom it has been believed to be extremely rare. The aim of this study was to determine if this is the case or whether it is under-reported. A CFTR mutation, 3120+1G-->A, which was first reported in three African-American CF patients, has been shown to account for 9-14% of African-American CF chromosomes. It has also been found in 4/6 CF chromosomes in South African blacks and one CF chromosome of Cameroonian origin. In order to determine the carrier frequency of the 3120+1G-->A mutation in Africa, 1360 unrelated, healthy subjects were screened. Nine carriers were identified. In addition, two out of five black CF patients with positive sweat tests were found to be heterozygous for the 3120+1G-->A mutation and two out of another four black patients with symptoms suggestive of CF, but unconfirmed by sweat tests, were heterozygous for the D1270N mutation. A further three CFTR mutations, A559T, S1255X, and 444delA, which had been found in African-American CF patients, were not identified in the patients or in over 373 healthy subjects tested. The 3120+1G-->A mutation has a carrier frequency of 1 in 91 (8/728) in South African blacks with a 95% confidence interval of 1 in 46 to 1 in 197. Since this mutation accounts for between 15% and 65% of CF chromosomes in South African blacks, a corrected CF carrier frequency would be between 1 in 14 and 1 in 59. Hence, the incidence of CF would be predicted to be between 1 in 784 and 1 in 13924 births in this population. There are several possible reasons why these people are not being detected. Some of these are misdiagnosis as chronic pulmonary infection, malnutrition, tuberculosis, infantile diarrhoea, failure to thrive, or a high infant mortality rate.

Africa↗

Human pigmentation genetics: the difference is only skin deep.

There is no doubt that visual impressions of body form and color are important in the interactions within and between human communities. Remarkably, it is the levels of just one chemically inert and stable visual pigment known as melanin that is responsible for producing all shades of humankind. Major human genes involved in its formation have been identified largely using a comparative genomics approach and through the molecular analysis of the pigmentary process that occurs within the melanocyte. Three classes of genes have been examined for their contribution to normal human color variation through the production of hypopigmented phenotypes or by genetic association with skin type and hair color. The MSH cell surface receptor and the melanosomal P-protein are the two most obvious candidate genes influencing variation in pigmentation phenotype, and may do so by regulating the levels and activities of the melanogenic enzymes tyrosinase, TRP-1 and TRP-2.

Albinism↗

Control of hepatitis B in the United Kingdom.

Control of hepatitis B in the UK is based upon selective vaccination of persons in high-risk groups. To assess the likely cost-effectiveness of changes to this policy, information on the current burden of HBV infection in the UK is required. Laboratory reports of acute hepatitis B suggest that the vast majority of new hepatitis B infections acquired in the UK occur in adults, even after adjustment for unapparent infection. In childhood, perinatal transmission remains the most significant known risk factor. Universal antenatal screening has the potential to prevent perinatal infections in UK births and a substantial proportion of those UK acquired infections which lead to carriage. In addition, to antenatal screening, universal infant vaccination (at 2, 3 and 4 months) can, in the short term, only prevent the small number of infections acquired in childhood. Economic analysis using current surveillance data is required to assess the possible cost-benefit of universal vaccination. Regardless of this, there is an urgent need to improve selective vaccination and to ensure that a high proportion of antenatal carriers is identified.

Acute Disease↗