Helen Brown

Case-control study of sudden infant death syndrome in Scotland, 1992-5.

Abstract Objective: To investigate the relation between routine infant care practices and the sudden infant death syndrome in Scotland. Methods: National study of 201 infants dying of the sudden infant death syndrome (cases) and 276 controls by means of home interviews comparing methods of infant care and socioeconomic factors. Results: Sleeping prone (odds ratio 6.96 (95% confidence interval 1.51 to 31.97)) and drug treatment in the previous week (odds ratio 2.33 (1.10 to 4.94)) were more common in the cases than controls on multivariate analysis. Smoking was confirmed as a significant risk factor (odds ratio for mother and father both smoking 5.19 (2.26 to 11.91)). The risk increased with the number of parents smoking (P<0.0001), with the number of cigarettes smoked by mother or father (P=0.0001), and with bed sharing (P<0.005). A new finding was an increased risk of dying of the syndrome for infants who slept at night on a mattress previously used by another infant or adult (odds ratio 2.51 (1.39 to 4.52)). However, this increased risk was not established for mattresses totally covered by polyvinyl chloride. Conclusions: Sleeping prone and parental smoking are confirmed as modifiable risk factors for the sudden infant death syndrome. Sleeping on an old mattress may be important but needs confirmation before recommendations can be made. Key messages Parental smoking is currently the most important modifiable risk factor in the sudden infant death syndrome In this study sleeping prone and, to a lesser extent, sleeping on the side increased the risk of the syndrome, so babies should be put down to sleep only on their back Bed sharing with an infant should be discouraged if the mother smokes Sleeping on an old mattress may carry an increased risk

Impact of Cadaveric Renal Transplantation on Survival in Patients Listed for Transplantation

The aim of this study was to assess the magnitude of the survival benefit of renal transplantation compared with dialysis in patients selected for transplantation in Scotland. Longitudinal study of survival and mortality risk in all adult patients (1732) listed for a first transplant between January 1, 1989, and December 31, 1989, in Scotland. A time-dependent Cox regression analysis adjusted for comorbidity, sociodemographic and geographic factors, primary renal disease, time on dialysis, and year of listing compared the risk of death for patients receiving a first cadaveric transplant versus all patients on dialysis listed for transplantation. After adjustment for the covariates, the relative risk (RR) of death during the first 30 days after transplantation was 1.35 (95% confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR = 1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI, 0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long-term risk of death was present in all patients undergoing transplantation, irrespective of their age group or primary renal disease. Similar results were seen when survival with a transplant was censored for graft failure. The projected life expectancy with a transplant was 17.19 yr compared with only 5.84 yr on dialysis. Despite an initial higher risk of death, long-term survival for patients who undergo transplantation is significantly better compared with patients who are listed but remain on dialysis. A successful transplant triples the life expectancy of a listed renal failure patient.

Equity of access to renal transplant waiting list and renal transplantation in Scotland: cohort study

Abstract Objective To examine the access to the renal transplant waiting list and renal transplantation in Scotland. Design Cohort study. Setting Renal and transplant units in Scotland. Participants 4523 adults starting renal replacement therapy in Scotland between 1 January 1989 and 31 December 1999. Main outcome measures Impact of age, sex, social deprivation, primary renal disease, renal or transplant unit, and geography on access to the waiting list and renal transplantation. Results 1736 of 4523 (38.4%) patients were placed on the waiting list for renal transplantation and 1095 (24.2%) underwent transplantation up to 31 December 2000, the end of the study period. Patients were less likely to be placed on the list if they were female, older, had diabetes, were in a high deprivation category, and were treated in a renal unit in a hospital with no transplant unit. Patients living furthest away from the transplant centre were listed more quickly. The only factors governing access to transplantation once on the list were age, primary renal disease, and year of listing. A significant centre effect was found in access to the waiting list and renal transplantation. Conclusions A major disparity exists in access to the renal transplant waiting list and renal transplantation in Scotland. Comorbidity may be an important factor.

Effective T-Cell Responses Select Human Immunodeficiency Virus Mutants and Slow Disease Progression

ABSTRACT The possession of some HLA class I molecules is associated with delayed progression to AIDS. The mechanism behind this beneficial effect is unclear. We tested the idea that cytotoxic T-cell responses restricted by advantageous HLA class I molecules impose stronger selection pressures than those restricted by other HLA class I alleles. As a measure of the selection pressure imposed by HLA class I alleles, we determined the extent of HLA class I-associated epitope variation in a cohort of European human immunodeficiency virus (HIV)-positive individuals (n = 84). We validated our findings in a second, distinct cohort of African patients (n = 516). We found that key HIV epitopes restricted by advantageous HLA molecules (B27, B57, and B51 in European patients and B5703, B5801, and B8101 in African patients) were more frequently mutated in individuals bearing the restricting HLA than in those who lacked the restricting HLA class I molecule. HLA alleles associated with clinical benefit restricted certain epitopes for which the consensus peptides were frequently recognized by the immune response despite the circulating viruss being highly polymorphic. We found a significant inverse correlation between the HLA-associated hazard of disease progression and the mean HLA-associated prevalence of mutations within epitopes (P = 0.028; R2 = 0.34). We conclude that beneficial HLA class I alleles impose strong selection at key epitopes. This is revealed by the frequent association between effective T-cell responses and circulating viral escape mutants and the rarity of these variants in patients who lack these favorable HLA class I molecules, suggesting a significant pressure to revert.

An expression atlas of human primary cells: inference of gene function from coexpression networks

BackgroundThe specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets derived from human primary cells and analysed large correlation graphs of these data.ResultsUsing the network analysis tool BioLayout Express3D we identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control.ConclusionsWe consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (http://biogps.org/dataset/2429/primary-cell-atlas/) and on macrophages.com (http://www.macrophages.com/hu-cell-atlas).

Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus.

Detection of antibody to recombinant proteins derived from hepatitis C virus (HCV) genotype 1 represents the principal method for diagnosis of HCV infection. A method was developed for quantifying antibody reactivity in two third‐generation enzyme immunoassays (Ortho EIA 3.0 and Murex VK48), and the influence of viraemia, HCV genotype, and host factors such as age, gender, and risk group upon antibody levels were investigated in a consecutive series of 117 anti‐HCV‐positive volunteer blood donors. Viraemic donors (as assessed by the polymerase chain reaction; PCR) showed significantly higher levels of anti‐HCV by the Ortho EIA than those who were nonviraemic (adjusted mean difference of 10.1 fold after multiple regression analysis). The only other factor to influence significantly antibody level was genotype, where it was found that donors infected with type 1 showed 4 to 4.5 times greater serological reactivity by the Ortho assay than those infected with type 2 or 3. Antibody levels by the Ortho assay correlated closely to those detected by the Murex VK48 assay, and similar differences between PCR‐positive and negative donors and between those infected with different genotypes were found. Differences in serological reactivity between genotypes indicate that a large proportion of epitopes of the type 1a or 1b recombinant proteins used in current assays are genotype specific. Variation in sensitivity of screening assays for different genotypes is of potential concern when used in countries where non‐type 1 genotypes predominate in the blood donor or patient population.

Unique acquisition of cytotoxic T-lymphocyte escape mutants in infant human immunodeficiency virus type 1 infection.

ABSTRACT The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

Cohort Profile: Scottish Health and Ethnicity Linkage Study of 4.65 million people exploring ethnic variations in disease in Scotland

: imported for journal id 300 on Dec 03, 2001, no letter sent Sent to referee - Referee Sent: 16-Nov-00 Expected: 16-Dec-00 Arrived: 12-Dec-00 MsID: IJE/2000/000462 - Major Revision - Last reminder: Sent to referee - Referee Sent: 05-Mar-01 Expected: 05-Apr-01 Arrived: 26-Apr-01 MsID: IJE/2001/000086 - Reject - Last reminder: 06-Apr-01 Thank you - Referee Sent: Expected: Arrived: MsID: IJE/2001/000086 - - Last reminder: Acknowledgement - Correspond Sent: 04-Jul-01 Expected: Arrived: MsID: IJE/2001/000382 - - Last reminder: decision - Correspond Sent: 30-Jul-01 Expected: Arrived: MsID: IJE/2001/000382 - - Last reminder: (Bhopal, Raj S)

Myocardial infarction incidence and survival by ethnic group: Scottish Health and Ethnicity Linkage retrospective cohort study

Objective Inequalities in coronary heart disease mortality by country of birth are large and poorly understood. However, these data misclassify UK-born minority ethnic groups and provide little detail on whether excess risk is due to increased incidence, poorer survival or both. Design Retrospective cohort study. Setting General resident population of Scotland. Participants All those residing in Scotland during the 2001 Census were eligible for inclusion: 2 972 120 people were included in the analysis. The number still residing in Scotland at the end of the study in 2008 is not known. Primary and secondary outcome measures As specified in the analysis plan, the primary outcome measures were first occurrence of admission or death due to myocardial infarction and time to event. There were no secondary outcome measures. Results Acute myocardial infarction (AMI) incidence risk ratios (95% CIs) relative to white Scottish populations (100) were highest among Pakistani men (164.1 (142.2 to 189.2)) and women (153.7 (120.5, 196.1)) and lowest for men and women of Chinese (39.5 (27.1 to 57.6) and 59.1 (38.6 to 90.7)), other white British (77 (74.2 to 79.8) and 72.2 (69.0 to 75.5)) and other white (83.1 (75.9 to 91.0) and 79.9 (71.5 to 89.3)) ethnic groups. Adjustment for educational qualification did not eliminate these differences. Cardiac intervention uptake was similar across most ethnic groups. Compared to white Scottish, 28-day survival did not differ by ethnicity, except in Pakistanis where it was better, particularly in women (0.44 (0.25 to 0.78)), a difference not removed by adjustment for education, travel time to hospital or cardiac intervention uptake. Conclusions Pakistanis have the highest incidence of AMI in Scotland, a country renowned for internationally high cardiovascular disease rates. In contrast, survival is similar or better in minority ethnic groups. Clinical care and policy should focus on reducing incidence among Pakistanis through more aggressive prevention.

Sexual Transmission of Single Human Immunodeficiency Virus Type 1 Virions Encoding Highly Polymorphic Multisite Cytotoxic T-Lymphocyte Escape Variants

ABSTRACT Antigenic variation inherent in human immunodeficiency virus type 1 (HIV-1) virions that successfully instigate new infections transferred by sex has not been well defined. Yet this is the viral “challenge” which any vaccine-induced immunity must deal with. Closely timed comparisons of the virus circulating in the “donor” and that which initiates new infection are difficult to carry out rigorously, as suitable samples are very hard to get in the face of ethical hurdles. Here we investigate HIV-1 variation in four homosexual couples where we sampled blood from both parties within several weeks of the estimated transmission event. We analyzed variation within highly immunogenic HIV-1 internal proteins encoding epitopes recognized by cytotoxic Tlymphocytes (CTLs). These responses are believed to be crucial as a means of containing viral replication. In the donors we detected virions capable of evading host CTL recognition at several linked epitopes of distinct HLA class I restriction. When a donor transmitted escape variants to a recipient with whom he had HLA class I molecules in common, the recipients CTL response to those epitopes was prevented, thus impeding adequate viral control. In addition, we show that even when HLA class I alleles are disparate in the transmitting couple, a single polymorphism can abolish CTL recognition of an overlapping epitope of distinct restriction and so confer immune escape properties to the recipients seroconversion virus. In donors who are themselves controlling an early, acute infection, the precise timing of onward transmission is a crucial determinant of the viral variants available to compose the inoculum.