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Biomedical subjects

M Ramsay

Publications and source records attributed to M Ramsay.

At least 19 recordsLinked to original sources

The epidemiology of measles in England and Wales since the 1994 vaccination campaign.

The incidence of measles in England and Wales has fallen since the national vaccination campaign in November 1994, in which 92% of children aged 5 to 16 years were vaccinated. A total of 148 confirmed cases with onsets in the 18 months from January 1995 to June 1996 have been ascertained. Notified cases did not provide a reliable measure of incidence: 11,343 suspected cases were notified in the same period, 6426 (57%) of whom were tested for salivary antibody. Only 90 (1.4%) of cases tested were confirmed. Many confirmed cases occurred in small clusters; 12 imported cases were identified. The pattern of small, local clusters is what would be expected from the introduction of imported cases into a population with herd immunity. Serological surveillance showed that the campaign produced a significant fall in the proportion of 5 to 16 year old children with low levels of measles antibody: the proportion with levels < 50 mIU/ml fell from 8.4% to 2.1%; the proportion with levels < 100 mIU/ml fell from 15.7% to 6.6%. About 15% of 2 to 4 year old children had antibody levels < 100 mIU/ml before and after the campaign. The addition of a routine second dose of measles vaccine (as measles, mumps, and rubella vaccine) to the vaccination schedule will provide another opportunity to immunise these children before they start school. The two dose vaccination programme should maintain the herd immunity of the population and the elimination of endemic measles transmission.

Adolescent

Mumps surveillance in England and Wales supports introduction of two dose vaccination schedule.

Sentinel surveillance in general practice and laboratory reports to the PHLS Communicable Disease Surveillance Centre show that the incidence of mumps has fallen to very low levels since vaccination against measles, mumps, and rubella was introduced in 1988. Hospital admissions for mumps show a 92% decline compared with the prevaccination era, to a rate of 0.2 per 100,000 population per year. Serological surveillance has shown an increase in the proportion of school age children who have no detectable antibody to mumps, which is consistent with the reduction in mumps virus transmission. The proportion of children aged 11 to 15 years with no detectable antibody is expected to peak at 19% in 1997. Mathematical models suggest that this increase in susceptibility is unlikely to allow a large resurgence of mumps in the short term but that school outbreaks may become more common. Outbreaks in universities and military establishments are possible in the medium term. Analysis of efficacy data for mumps vaccine indicates that mumps is unlikely to be eliminated with a single dose of vaccine at current coverage rates. A second dose of vaccine, which is now being offered to preschool children, will reduce morbidity and should eventually eliminate mumps if coverage is high enough.

Adolescent

The epidemiology of rubella in England and Wales before and after the 1994 measles and rubella vaccination campaign: fourth joint report from the PHLS and the National Congenital Rubella Surveillance Programme.

The national immunisation campaign carried out in the United Kingdom in November 1994 was designed to give children aged 5 to 16 years of age a single dose of a combined measles and rubella vaccine. Its main objective was to prevent an epidemic of measles predicted in school age children. The rubella component of the vaccine was included in order to reduce the high level of susceptibility to rubella in young adult males and thus reduce the risk of transmission from this group to pregnant women. Susceptibility to rubella in children aged 5 to 16 years has fallen from 15.7% to 3.4% since the measles and rubella campaign. Despite this the incidence of laboratory confirmed rubella rose substantially in 1996, largely on account of cases among males aged 17 to 24 years, who were not vaccinated in the 1994 campaign and about 16% of whom are susceptible. The impact of the resurgence on the incidence of infection in pregnancy has been relatively limited, due to the low level of susceptibility in the antenatal population (2% in nulliparous and 1.2% in parous women for 1994/5). No cases of congenital rubella arising from administration of measles and rubella vaccine during the campaign have been identified. The numbers of babies born with congenital rubella and terminations of pregnancy for rubella arising from the 1996 resurgence are expected to be similar to those that followed the 1993 resurgence. The reduction in susceptibility in future cohorts of young men who received measles and rubella vaccine in the 1994 campaign should prevent future resurgences after the year 2000. If a second dose of measles, mumps, and rubella (MMR) vaccine had not been introduced, susceptibility levels in the school age population would have risen to about 12% in the future. The effect of the second dose of MMR vaccine introduced for children aged 4 to 5 years in October 1996 will be assessed through serological surveillance.

Adolescent

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women.

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.

Adult

Hospital admissions attributable to rotavirus infection in England and Wales.

Laboratory reports and data on hospital admissions were used to estimate the number of hospitalizations due to group A rotavirus infection in England and Wales. Between January 1990 and December 1994, there were 75,059 laboratory reports of rotavirus infection, and 66,062 of these were in children <5 years old; rotavirus represented 39% of all pathogens identified in fecal specimens from this age group. Between April 1993 and March 1994, 1904 hospital admissions coded as "infectious intestinal disease" and 2354 coded as "noninfective gastroenteritis" occurred in children <5 in the North Thames region (a health authority representing 13% of the population in England and Wales). By modeling admission and laboratory reporting data, it was estimated that 54% of hospitalizations for intestinal infectious disease and 34% for noninfective gastroenteritis were attributable to rotavirus. By extrapolation of the North Thames data, it was estimated that 17,810 rotavirus-related hospitalizations (5/1000 children <5 years old) occurred in England and Wales during the same period. Effective vaccines have the potential to substantially reduce the number of hospital admissions due to group A rotavirus infection.

Adolescent

Ethnicity and myotonic dystrophy: a possible explanation for its absence in sub-Saharan Africa.

The CTG trinucleotide repeat, in the myotonic dystrophy (DM) myotonin protein kinase gene, was studied by PCR analysis in a total of 246 unrelated South African Bantu-speaking Negroids, 116 San and 27 Pygmies. The size and distribution of the CTG repeat were determined and showed that the alleles ranged in length from 5 to 22 repeats. The most common CTG repeat is 5 (25% of chromosomes) in the South African Negroids but 11 (27% of chromosomes) in the San population and 12 (22% of chromosomes) in the Pygmies. The southern African Bantu-speaking Negroids and San were found to have significantly fewer large repeat length alleles than do Caucasoid and Japanese populations. Since DM has not been observed in southern African Negroids, it is possible that the occurrence of fewer large CTG repeats in the normal range may, in part, explain this absence. It seems likely, that the rare DM mutation event postulated to have occurred on a specific chromosomal haplotype, occurred after the migration of humans from Africa.

Africa South of the Sahara

Neonatal sucking and maternal feeding practices.

This study is the first to demonstrate an association between neonatal and later sucking ability, clinical signs of feeding ability and maternal feeding practices. Of 49 infants followed to a mean age of six weeks, 20 had some feeding problems (compensatory group), based on changes in feeding practices by their mothers, and 29 did not (non-compensatory group). Infants in the compensatory group performed less well on initial and follow-up sucking measures than infants in the non-compensatory group, indicating that they were feeding less efficiently from birth. Also, infants in the compensatory group ingested less during follow-up testing and were reported to be fed more frequently at home by their mothers than infants in the non-compensatory group. These findings strongly suggest that even among healthy infants, there may be more with problematic feeding abilities than have been previously recognized and that mothers are a reliable source of information about their infants' feeding abilities.

Age Factors

First report of CFTR mutations in black cystic fibrosis patients of southern African origin.

Cystic fibrosis (CF) is thought to be rare in the black populations of Africa who have minimal white admixture. Only a few cases have been reported but have not been studied at the molecular level. We report the detection of CFTR mutations in three southern African black patients. One was homozygous for the 3120 + 1G-->A mutation, while the other two were compound heterozygotes each with this mutation on one chromosome. The other mutations were G1249E and a previously unreported in frame 54 bp deletion within exon 17a involving nucleotides 3196-3249 (3196del54). The 3120 + 1G-->A mutation was first described in American black patients and has been shown to be a common mutation in this population (9-14% of CF chromosomes). It was also found in a black CF patient whose father, the 3120 + 1G-->A carrier, is from Cameroon. These data suggest that it is an old mutation which accounts for many of the CFTR mutations in African blacks.

Adult

Founder effect and prevalence of myotonic dystrophy in South Africans: molecular studies.

A high prevalence of myotonic dystrophy (DM) has been described in South African Caucasoid Afrikaans-speaking families in the northern Transvaal. Evidence is presented for a strong founder effect, with a single haplotype occurring on 68% of all Caucasoid DM chromosomes; among the Afrikaans speakers, the proportion was 83%. In addition to this major haplotype, five minor DM haplotypes in the Caucasoids and two minor haplotypes in DM individuals of mixed ancestry were found. All DM chromosomes, however, had a common haplotype core, namely, Alu (ins), HinfI-2 (intron 9), and TaqI-2 (D19S463). We have detected significant linkage disequilibrium between the DM mutation and particular alleles of the extragenic markers D19S112 and D19S207. Significant differences were found in allele and haplotype distributions in the Caucasoid DM and non-DM chromosomes and Negroid non-DM chromosomes. These findings together with the strong association of allele 3 at the D19S63 locus on 93% (14/15) of the South African DM chromosomes suggest that the majority of present-day DM mutations in South African Caucasoids may have originated from a common initial founder who introduced one of the European ancestral mutations.

Alleles

Distinct components of spatial learning revealed by prior training and NMDA receptor blockade.

Synaptic plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory. In support of this, both hippocampal long-term potentiation and spatial learning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5) or by a mutation in one of the receptor subunits. Here we report, however, that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. This is not because of stimulus generalization, and occurs despite learning of the second task remaining hippocampus dependent. An AP5-induced learning deficit is, however, still seen if the animals are pretrained using a non-spatial task. Thus, despite its procedural simplicity, the watermaze may involve multiple cognitive processes with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be required for encoding the spatial representation of a specific environment.

2-Amino-5-phosphonovalerate

Maternal origin of extra haploid set of chromosomes in third trimester triploid fetuses.

Twenty-six highly polymorphic markers were used to determine the origin of the extra haploid chromosome set in 6 triploid fetuses of type II phenotype. All had reached the third trimester of pregnancy. The extra set was maternal in origin in all cases, supporting previous research indicating longer in utero survival of maternally-derived triploid fetuses. These findings provide evidence for an instance of genomic imprinting in humans.

Adult

Presence of Y chromosome sequences and their effect on the phenotype of six patients with Y chromosome anomalies.

The extent of Y chromosome material was determined in 6 southern African subjects with sex chromosome anomalies. Four of the subjects were phenotypically female, and 2 were phenotypically male. Molecular and cytogenetic findings were correlated with phenotypic expression. An X;Y translocation was found in both male subjects, and in one female subject. The remaining female subjects were characterized by an isodicentric Y, an isochromosome Yq, and a micromarker of undetermined origin, respectively. The individuals were tested for the presence of a number of Y-specific DNA sequences. Molecular findings were generally compatible with the cytogenetic findings, and also with the phenotypic sex of the patients. All the female subjects had Y material and all but one were negative for the sex determining region of the Y (SRY). The somatic Ullrich-Turner-like findings present in 3 of the females were attributed to either the presence of a 45,X cell line and/or a single copy of Xp. The males both showed X;Y translocations without any detectable loss of Y DNA. Although molecularly very similar, the disparate clinical findings in these 2 subjects could have been accounted for by different X inactivation patterns.

Adolescent

XX true hermaphroditism in southern African blacks: exclusion of SRY sequences and uniparental disomy of the X chromosome.

A molecular investigation of 16 Bantu-speaking Black XX true hermaphrodites was undertaken in an attempt to determine the cause of the disorder. Y-specific sequences, including sequences mapping to the sex-determining region of the Y, were shown to be absent from lymphocyte tissue of all 16 patients tested. Y chromosome sequences were also absent from the ovarian and testicular components of both ovotestes of a single XX true hermaphrodite, thus excluding gonadal mosaicism involving Y chromosome sequences. Since there is evidence for Xp genes involved in testis determination/differentiation, uniparental disomy of the X chromosome was investigated in 14 XXTH families. Uniparental disomy was excluded in 12 of the 14 families, and isodisomy was excluded in the remaining two cases.

Africa, Southern