Incidence of HIV infection in homosexual men in London, 1988-94.
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Adult↗
Biomedical subjects
E Miller
Publications and source records attributed to E Miller.
Measles vaccination as a risk factor for inflammatory bowel disease.
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Bias↗
Cytomegalovirus infection in England and Wales: 1992 and 1993.
Cytomegalovirus causes illness through primary infection but also remains latent within the host and may be reactivated, especially if immunity is impaired. We have examined reports of cytomegalovirus infection from laboratories in England and Wales received by the PHLS Communicable Disease Surveillance Centre in 1992 and 1993. A total of 2938 reports were received, and 103 people had recurrent infections within the study period. The age distribution had peaks in infants (< 1 year of age) and in people aged 25 to 34 years. In almost a half of the patients (1371; 49%) factors were reported that indicated impaired immunity. Eighty-three of the 103 with recurrent infection (81%) were also reported to have impaired immunity. Children under 5 years accounted for 18% (543/2938) of reports. There were 930 reports of infections in people over 5 years of age who were not reported as immunocompromised. The data presented confirm that cytomegalovirus causes substantial morbidity in young children and people with impaired immunity. Cytomegalovirus infection causes considerable morbidity, especially hepatic, in patients whose immunity is thought to be normal.
Adolescent↗
A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.
The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase inhibitors (serpins). A neutral form of the protein is found in normal and some malignant squamous cells, whereas an acidic form is detected exclusively in tumor cells and in the circulation of patients with squamous cell tumors. In this report, we describe the cloning of the SCCA gene from normal genomic DNA. Surprisingly, two genes were found. They were tandemly arrayed and flanked by two other closely related serpins, plasminogen activator inhibitor type 2 (PAI2) and maspin at 18q21.3. The genomic structure of the two genes, SCCA1 and SCCA2, was highly conserved. The predicted amino acid sequences were 92% identical and suggested that the neutral form of the protein was encoded by SCCA1 and the acidic form was encoded by SCCA2. Further characterization of the region should determine whether the differential expression of the SCCA genes plays a causal role in development of more aggressive squamous cell carcinomas.
Amino Acid Sequence↗
A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines.
We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria/tetanus/pertussis (DTP) vaccination and febrile convulsion, and between measles/mumps/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an increased relative incidence for convulsions 0-3 days after DTP vaccination. The effect was limited to the third dose of vaccine for which the attributable risk (all ages) was 1 in 12,500 doses. Completion of vaccination by 4 months instead of 10 months after the change in the UK to an accelerated immunisation schedule may have resulted in a 4-fold decrease in febrile convulsions attributable to DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR vaccination were attributable to the measles component of the vaccine (risk 1 in 3000 doses). An excess of admissions for a convulsion 15-35 days after MMR vaccination was found only for vaccines containing the Urabe mumps strain (1 in 2600 Urabe doses). There was a causal association between MMR vaccination and ITP resulting in admission 15-35 days subsequently; there was no evidence of a mumps strain-specific effect. The estimated absolute risk of 1 in 24,000 doses was 5 times that calculated from cases passively reported by clinicians. This finding emphasises the need for active surveillance of adverse events. The record linkage method that we used is an effective way to identify vaccine-attributable adverse events.
Diphtheria-Tetanus-Pertussis Vaccine↗
Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis.
Atherosclerotic lesions contain oxidized LDL (OxLDL), immunoglobulins, and immune-competent cells. Low levels of circulating autoantibodies against malondialdehyde (MDA)-modified lysine, an epitope of OxLDL, occur in several species, and immune complexes between such autoantibodies and OxLDL are present in lesions. To study the potential role of autoantibodies against OxLDL in the atherogenic process, we prospectively hyperimmunized LDL receptor-deficient rabbits with homologous MDA-LDL and determined the effects of this intervention on the development of atherosclerosis. Immunization with MDA-LDL generated high titers of antibodies with similar specificity as naturally occurring autoantibodies. Immunized animals showed a significant reduction in the extent of atherosclerotic lesions in the aortic tree after 6.5 months, compared with "saline"-immunized controls (48% vs. 68%, P < 0.005). Immunization with keyhole limpet hemocyanin produced no change in lesion formation. Although the mechanisms by which immunization led to a protective effect are unknown, these results suggest an important role for the immune system in modulating the atherogenic process and may indicate a novel approach for inhibiting the progression of atherosclerosis.
Animals↗
Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines.
Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12-18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain (39/266, 15% vs 39/204, 19%, p = 0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27/3 rubella strain and the potential for elimination of rubella with a single dose strategy.
Antibodies, Viral↗
Antibody responses and reactions to the whole cell pertussis component of a combined diphtheria/tetanus/pertussis vaccine given at school entry.
To measure the clinical effect of adding a whole cell pertussis component to diphtheria/tetanus vaccine (DT) given as a pre-school booster, 190 children aged 4-5 years were randomised by a double-blind method to receive either diphtheria/tetanus/pertussis (DTP) or DT vaccine in a 1:1 ratio at selected clinics in England. The geometric mean antibody titres to each of the three pertussis antigens were at least sixfold higher in the DTP than the DT vaccine group and equalled or exceeded those in infants immediately after primary immunisation with DTP vaccine. There were no significant differences between DTP and DT vaccinated children in their diphtheria and tetanus antitoxin levels. The frequency of large local reactions and systemic symptoms such as crying and a disturbed night was 2-3-fold higher in the DTP vaccinees than in the DT vaccinees. Medication was given to 44% of DTP and 23% of DT vaccinees (p = 0.006). Although the change to whole cell DTP vaccine at school entry would result in good pertussis antibody titres, the 2-3-fold increase in reactogenicity that would be caused may be unacceptable at a time when whooping cough is not circulating widely. Evaluation of acellular DTP vaccines given as a pre-school booster in children vaccinated under the accelerated schedule is planned.
Antibody Formation↗
Antibody responses and symptoms after DTP and either tetanus or diphtheria Haemophilus influenzae type B conjugate vaccines given for primary immunisation by separate or mixed injection.
The safety and immunogenicity of two conjugate Haemophilus influenzae type B (Hib) vaccines administered either mixed with, or in separate limbs to, a whole-cell DTP vaccine, was compared in infants vaccinated at 2, 3 and 4 months of age. Antibody titres to purified polyribosylribitol phosphate, diphtheria, and to pertussis antigens between infants who received the Hib and DPT vaccines in separate limbs or in the same limbs were similar (P > 0.1) while antibody titres to tetanus toxoid were higher in the later group (P < 0.05). This study demonstrated that both Hib vaccines can be mixed with whole-cell DTP vaccine without reducing immunogenicity of either vaccine or increasing the incidence of adverse reactions.
Antibodies, Viral↗
Long-term monitoring of the diabetic dog and cat. Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins.
Management of diabetic dogs or cats requires the use of all available monitoring technology (Fig. 6). First, one should ask questions about the clinical control of DM. Are the clinical signs of DM resolved, and is the owner satisfied with insulin therapy? Other important questions would include: Is the dog or cat developing long-term complications of diabetes such as neuropathies or cataracts? Is body weight remaining stable? Is the dog or cat showing any signs of hypoglycemia? One should determine if the blood glucose curves are close to ideal for the type of insulin being administered. Urine glucose and ketones should be negative or trace as assessed by the at-home monitoring by the owner. In the problem diabetic, long-term glucose control can be assessed by serum fructosamine or glycosylated hemoglobin determinations. Regulation of the diabetic patient is accomplished when the owner is satisfied with the therapy and when the serum glucose monitoring parameters are acceptable.
Animals↗
Feasibility study for identifying adverse events attributable to vaccination by record linkage.
To investigate the feasibility of using a record linkage method for identifying vaccine attributable adverse events, computerized hospital admissions and vaccination records from South East Kent district were linked and checked for accuracy. Records for 90% of children under 2 years of age admitted to hospital over a 2-year period were matched with vaccination records using a computer algorithm based on name, date of birth, sex, and post-code supplemented by visual inspection. Relative to this gold standard, matching on date of birth, sex and postcode alone had a sensitivity of 60% and an incorrect match rate of 0.2% after matches to more than one vaccine recipient were excluded. Manual checking of a sample of admissions showed that only 4% had been assigned incorrect International Classification of Disease (ICD) codes. Routine record linkage of ICD admission codes to vaccination records therefore yields data of good quality which may be used for surveillance purposes.
Adverse Drug Reaction Reporting Systems↗
Predicting the impact of measles vaccination in England and Wales: model validation and analysis of policy options.
Measles incidence in England and Wales has fallen to an all-time low. Attention is now focused on preventing local outbreaks, and, in the long run, on the elimination of indigenous measles. A realistic age-structured (RAS) mathematical model of measles transmission is used to reconstruct the impact of measles vaccination in England and Wales from 1968 to the present and to evaluate the merits of future policy options. In general, the predictions of the model show good agreement with long-term age stratified case reports and seroprevalence surveys. The model underestimates the proportion of cases that are notified in 0-2-year-old children. However, recent work suggests a high degree of misdiagnosis in this age group. Projections on the basis of the existing vaccination strategy in the UK suggest that the present level of measles vaccine coverage will be insufficient to eliminate small seasonal outbreaks of measles. This result is, however, sensitive to the assumed level of vaccine efficacy. Explorations of a variety of changes to current vaccination strategy favour a 2-dose schedule with the second dose administered at age 4 years irrespective of vaccination history. A vaccination campaign in school-age children, to reduce deficits in herd immunity, would accelerate progress towards measles elimination.
Adolescent↗
Interpretation of serological surveillance data for measles using mathematical models: implications for vaccine strategy.
Serological surveillance of measles immunity has been carried out in England since 1986/7. Results from sera collected in 1989-91 revealed that the proportion of school age children who were susceptible to measles was increasing, following the introduction of the measles, mumps and rubella vaccination programme in October 1988. Mathematical models are used to interpret these data and determine whether this increasing susceptibility is sufficient to allow a resurgence of disease from the low levels achieved by 1993. The models summarize serological profiles by a single parameter, the reproduction number R, which quantifies the level of herd immunity in the population. Results showed that there was cause for concern over the levels of susceptibility to measles, with an epidemic of over 100,000 cases likely in 1995/6. These predictions are consistent with trends in the incidence and age distribution of measles and have enabled the planning of a major vaccination campaign.
Adolescent↗
Telemedicine: an annotated bibliography: Part I.
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Humans↗
Telemedicine: an annotated bibliography: Part II.
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Humans↗
Micronucleus frequencies in lymphoblastoid cell lines measured with the cytokinesis-block technique and flow cytometry.
In these experiments, the cytokinesis-block technique was used to measure the spontaneous and radiation-induced micronucleus frequencies in lymphoblastoid cell lines from normal individuals and individuals with radiation-sensitive syndromes. The radiation-induced micronucleus frequencies were measured at different harvest times to investigate the optimum time to measure radiation-induced cytogenetic damage with the cytokinesis-block technique. The frequency of radiation-induced micronuclei was found to be independent of the frequency of binucleate cells in these cell lines. Longer incubation times were complicated by increasing numbers of mononucleate and multinucleate cells, and scoring slides at an early incubation time after the maximum frequency of binucleate cells is reached was recommended. Two of the cell lines (one established from an individual with ataxia telangiectasia, and one from an infant with mitotic instability) had significantly higher radiation-induced micronucleus frequencies than the control cell lines. Finally, the radiation-induced micronucleus frequencies in three of the cell lines were measured by flow cytometry, and the results ranked the cell lines in the same order of radiosensitivity as the cytokinesis block technique.
Cell Division↗
Pigmentation of the posterior lens capsule central to Wieger's ligament and the Scheie line: a possible indication of the pigment dispersion syndrome.
Observation of pigment deposition on the posterior lens central to Wieger's ligament and the position of the so-called Scheie line is reported as a clinical sign of the pigment dispersion syndrome (PDS). Although abnormal pigmentation of the posterior lens surface is well-known to occur as scattered deposition among the zonule insertions as well as in the shape of a line formed within the crevice just anterior to the junction between the posterior capsule and the anterior hyaloid face, pigmentation has not been well-known to occur more centrally, nearer the polar capsular region. Pigment in this location is a relatively unknown finding in PDS and may lead to suspicion and diagnosis of this disorder.
Adolescent↗
Adverse events and antibody response to accelerated immunisation in term and preterm infants.
A study was performed to compare adverse events and antibody response in term and preterm children vaccinated with diphtheria, tetanus, and pertussis vaccine at 2, 3, and 4 months of age. A total of 124 children were recruited and grouped according to gestational age: 37 weeks or more (n = 52), 34 to 36 weeks (n = 40), and less than 34 weeks (n = 32). Study nurses followed up children 24 hours after each vaccination to record temperature, redness, and swelling at the injection site and any systemic symptoms. Proportions of children experiencing adverse events did not differ between groups. Blood samples were obtained six weeks after the vaccination course at which time all children had protective levels of diphtheria and tetanus antitoxins. Geometric mean antibody titres (95% confidence interval) to pertussis toxin were 2754 (2042 to 3715), 5495 (4074 to 7413), and 3690 (2951 to 4677), to filamentous haemagglutinin were 541 (282 to 1023), 951 (537 to 1698), and 614 (426 to 1023), and to agglutinogens 2 and 3 were 12,106 (6918 to 21,380), 21,330 (13,183 to 34,674), and 22,387 (15,136 to 33,113) in children born at a gestational age of less than 34 weeks, 34 to 36 weeks, and 37 weeks or more respectively. These findings support the current recommendations that preterm children are vaccinated at chronological age according to the national schedule.
Age Factors↗