Biomedical subjects
Publications and source records attributed to M Hickman.
Amebae have an Hsp60-associated, mitochondrion-derived organelle (crypton). In this study, the crypton was stained with multiple DNA-binding fluorochromes and a monoclonal anti-double-stranded DNA antibody. Transmission microscopy of partially purified cryptons revealed organelles bound by a double membrane.
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OBJECTIVE: To describe trends in HIV prevalence among female injecting drug users (IDU) in London between 1990 and 1996. DESIGN: HIV prevalence and risk behaviour were measured yearly between 1990 and 1993, and in 1996, in point prevalence HIV surveys of IDU recruited from both drug-treatment and community-based settings within Greater London. Sample sizes were 173 in 1990, 111 in 1991, 128 in 1992, 146 in 1993 and 200 in 1996. METHODS: Each survey used structured questionnaires and common sampling and interview strategies. Oral fluid specimens were collected for testing for antibodies to HIV (anti-HIV). Multiple logistic regression was used to assess the trend in HIV prevalence. RESULTS: The percentage of female IDU testing positive for antibodies to HIV showed a marked decline over the study period, from 15.0% in 1990 to 1.0% in 1996 (P < 0.001). This trend was independent of all other variables examined. Each year, higher HIV prevalences were found among IDU recruited from community settings compared with treatment agencies. CONCLUSIONS: These results concur with those of IDU recruited from treatment sites, although the yearly estimates in this study are higher. London benefits from low prevalence of HIV infection among IDU, coupled with behaviour change facilitated by early intervention. Continued surveillance of injectors recruited from both community and treatment settings is necessary in order properly to assess HIV prevalence among IDU.
AIMS: To provide an evidence base of estimates of the prevalence of problem drug use in inner London. DESIGN: Re-analysis of three capture-recapture studies using subjects aged 15-49 years, that aim to estimate the hidden population from analysing the overlaps between three data sources. SETTING: Newham (1995) Camden and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992). PARTICIPANTS: Each study collected data from three sources of problem drug users including: the Regional Drug Misuse Database, specialist drug agencies, HIV tests, social services, police arrests and court records. In LSL opiate users were analysed separately. The studies identified 1832 individuals in LSL, 543 in Newham, and 1321 in C&I. MEASUREMENTS: Poisson models were fitted to the data testing different interactions between the data sources representing potential dependencies. The simplest model was selected on the basis of its AIC score and log-likelihood ratio tests. FINDINGS: The number of hidden problem drug users were estimated to be 12,500 (95% CI 9600-16,100) in LSL with 4400 (3200-6100) opiate users; 7000 (5000-10,000) in C&I and 3800 (2000-7200) in Newham. The prevalence of problem drug use in those aged 15-49 was estimated to be 3.1% (2.5-3.9%) in LSL with 1.3% (1.0-1.6%) opiate users; and 3.6% (2.7-4.9%) and 3.3% (1.9-5.7%) in C&I and Newham, respectively. CONCLUSIONS: Despite the inherent problems with capture-recapture methods, our three studies establish an evidence base for estimates of problem drug use in London. It is important that a larger study is carried out in London.
A range of estimates for sickle cell and beta thalassaemia have been derived for the different ethnic groups living in the U.K., reflecting uncertainty over the true population value in certain countries and the heterogeneity within and between countries of origin comprising the same ethnic group. These were validated against six community screening programmes, with the estimated range correctly predicting the number of affected births observed by the programmes. In England approximately 3000 affected babies (0.47%) carry sickle cell trait and 2800 (0.44%) carry beta thalassaemia trait annually: with approximately 178 (0.28 per 1000 conceptions) affected by sickle cell disease (SCD) and 43 (0.07 per 1000) by beta thalassaemia major/intermedia. Allowing for termination, about 140-175 (0.22-0.28 per 1000) affected infants are born annually with SCD and from 10 to 25 (0.02-0.04 per 1000) with beta thalassaemia major/intermedia. These are the first evidence-based rates for sickle cell and beta thalassaemia for use in the U.K., and should underpin the future planning of services. The long-term solution to monitoring changes in the rates of trait and disease in the population is to introduce a standardized instrument for collecting ethnicity for all community screening programmes.
BACKGROUND: We report detailed findings of the first systematic validation of a Regional Drug Misuse Database (RDMD); such databases constitute the main investment in routine drug statistics in the UK by the Department of Health. METHODS: A retrospective case-finding study in a stratified random sample of one in three specialist drug agencies was carried out. Agency records of clients attending during 1994 were matched with reports (episodes) to the North Thames RDMD to assess the level of under-reporting, and the relationship between RDMD reports (episodes) and the number of problem drug users in contact with agencies. Under-ascertainment of cases was estimated using two-sample capture-recapture. RESULTS: Under-reporting was associated with agency records missing full date of birth or initials (attributers), and agency type. Compared with drug dependency units (DDU) the odds of under-reporting were 3-18 times higher by the other specialist drug agencies. Even after excluding episodes with missing attributers the odds ratio (OR) of not being reported was significantly higher among needle exchanges (OR 2.7), non-statutory community based drug teams (OR 3.2), statutory community based drug teams (OR 4.9) and residential rehabilitation units (OR 8.7) compared with DDUs. Overall database episodes represented 60 per cent of the number of clients attending specialist agencies as a result of a mixture of under-reporting and the proportion of clients retained in treatment, which also varied by agency type. A total of 727 individuals (16 per cent) had never been reported. CONCLUSIONS: Surveillance of drug misuse through RDMDs does not yet fulfil its objectives. It is essential that a system of following up reports is introduced to improve their utility, and to contribute to the monitoring of the UK Government's new drugs strategy, and wider European surveillance.
OBJECTIVE: To evaluate universal antenatal screening for haemoglobinopathies. SETTING: District general hospital serving a London borough with 45% ethnic minorities. METHODS: Retrospective cohort study of 1444 women referred in 1688 pregnancies and 95 tertiary referrals during 101 pregnancies. RESULTS: Unselected women at risk for sickle cell disease booked 2.7 weeks (95% confidence interval (CI) 0.14 to 5.1) later in gestation than those at risk for beta thalassaemia were less likely to attend counselling (83% v 93%, relative risk (RR) 0.89; 95% CI 0.85 to 0.94), their partners were less likely to be tested (77% v 95%, RR 0.81; 0.77 to 0.83), and they were less likely to accept prenatal diagnosis (22% v 90%, RR 0.37; 0.24 to 0.57). Over 99% of tertiary referrals attended counselling and had their partners tested. There were no significant differences in acceptance of prenatal diagnosis between those at risk of sickle cell disease and beta thalassaemia (55% v 67%). Unselected women at risk of sickle cell disease were significantly less likely to have their partner tested or to accept prenatal diagnosis than tertiary referrals, but not those at risk of beta thalassaemia. 80% of beta thalassaemia and 16% of SS births were prevented. CONCLUSIONS: Uptake of prenatal diagnosis among unselected women at risk of beta thalassaemia is similar to that reported by tertiary centres. It is considerably lower for sickle cell disease but could increase considerably if screening occurred earlier in gestation. Acceptance of counselling is universally high, suggesting that informed choices are made, and indicating a need to measure these outcomes for cost effectiveness studies.
OBJECTIVES: To describe the incidence of gonorrhoea diagnosed in genitourinary medicine (GUM) clinics in South Thames (West) between 1995 and 1996, and how it changed among population subgroups. SETTINGS AND SUBJECTS: Cases of uncomplicated and complicated gonorrhoea diagnosed at 13 GUM clinics in the former South Thames West (STW) Regional Health Authority that reported disaggregate data to the South Thames GUM Clinic Collaborative STD Surveillance Scheme. METHODS: Annual incidence rates (per 100,000) of gonorrhoea diagnoses by sex, age group, ethnic group, area of residence, and year were calculated. Poisson regression models were used to calculate risk ratios (RR) to describe the key differences in the variation of gonorrhoea cases by these variables. Relative differences in the incidence of diagnosed gonorrhoea between 1995 and 1996 were investigated by including an interaction between year and the other variables (age group, sex, ethnic group, region) and testing whether any were significant using a likelihood ratio test. RESULTS: Area of residence, sex, age group, and ethnic group were key predictors of the rates of diagnosed gonorrhoea. The risk ratio for gonorrhoea (after adjustment for the other variables) was: 13 times higher among blacks than the white population; twice as high in inner London compared with outer London; and three times lower in the "shire" region compared with outer London. The rate of diagnosed gonorrhoea was significantly higher in the black population in the shire region than the inner London white population. The rate of gonorrhoea diagnosed by GUM clinics from 1995 to 1996 almost doubled in the white population aged 15-44 years, from 16 cases per 100,000 to 30 cases per 100,000 (adjusted RR 2.0, 95% CI 1.6 to 2.4), whereas increased rates in the black and Asian/other ethnic groups were not statistically significant (adjusted RR 1.1, 95% CI 0.9 to 1.4; and 1.4, 95% CI 0.7 to 2.7 respectively). CONCLUSION: The observed increase in gonorrhoea between 1995 and 1996 occurred mostly among heterosexual white men and women. Overall, the rates of gonorrhoea among young people, especially in the black population and in inner London represent a significant public health problem that may merit further targeted interventions, the effectiveness of which could be monitored through further development of routine surveillance data.
OBJECTIVE: To describe the impact of HIV on mortality in men and women aged 15-54 in London. DESIGN: Combination of routine mortality statistics with reports of AIDS deaths adjusted for underreporting and change in address from time of report to time of death. Calculation of standardised mortality ratios (SMRs) for males including and excluding HIV comparing inner London and outer London with the rest of England and Wales. METHODS: Comparison of trends in all cause mortality and SMRs in males over time. Comparison of trends in HIV related deaths with other main causes of deaths in males and females in London. RESULTS: Age standardised rates for the rest of England and Wales showed a continual decline from 1979 to 1996 but rates in inner London males (ages 15-54) stopped declining around 1984-5 leading to a considerable increase in the SMR for inner London from 127 for 1985-7 to 171 for 1994-6. SMRs excluding HIV related deaths for inner London, however, showed no significant change over this time. There was a fall in HIV related mortality in 1996, though HIV was still the leading cause of death in males and second leading cause of death in females in inner London, and the fourth commonest cause of death in males in outer London. CONCLUSION: These data are the first to indicate the impact of HIV on mortality within a significant population in England and Wales. They show that public health priorities in London are different from the rest of the country. Analyses of trends of all cause mortality in people under 65 may mislead unless they take account of HIV.
The planning of renal replacement therapy is based on assessment of population need for the white population, but uses historical trends in treatment uptake for black and Asian ethnic minority groups, for whom the incidence of chronic renal failure (CRF) is not known. Epidemiological studies of CRF are based upon follow-up of plasma creatinine results obtained from clinical biochemistry laboratories. We conducted a postal questionnaire survey of UK National Health Service (NHS) and private clinical biochemistry laboratories in Greater London and the south east of England to arrange the design and test the feasibility of carrying out a study to determine ethnic-specific rates of CRF. Fifty-five NHS laboratories (90%) and 19 private laboratories (57%) responded. Few pathology computer systems recorded ethnic group, patient post code, or diagnosis; although 31 of the laboratory computers (42%) were linked with the hospital Patient Administration System which could supply these data. Approximately 5.5 million electrolyte profiles and 20 million individual renal function tests are carried out annually in south east England. Ninety per cent of those were performed within NHS laboratories, implying that a study can use NHS sources alone without risk of any undue bias. Sixty laboratories (81%) included creatinine in their routine electrolyte profile, which would be a requirement for any study. Thirty-one laboratories (42%) archived tests within 1 year of entry, which would rule out a retrospective study design. A prospective study is feasible and should be carried out as soon as is practicable.
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AIM: To compare the costs and cost effectiveness of universal and targeted screening for the haemoglobinopathies; to compare the cost of two laboratory methods; and to estimate the cost effectiveness of programmes at different levels of prevalence and mix of haemoglobinopathy traits. METHODS: A retrospective review of laboratory and follow up records to establish workload and costs, and estimation of costs in a range of circumstances was made in a haematology department and sickle cell and thalassaemia centre, providing antenatal and neonatal screening programmes in Inner London. The costs for 47,948 babies, screened during 1994, of whom 25 had clinically significant haemoglobinopathies and 704 had haemoglobinopathy traits, were retrospectively assessed. RESULTS: The average cost per baby tested (isoelectric focusing and high power liquid chromatography) was 3.51 Pounds /3.83 Pounds respectively; the cost per case of sickle cell disease identified (IEF/HPLC) was 6738 Pounds /7355 Pounds; the cost per trait identified (IEF/HPLC) was 234 Pounds /255 Pounds; the cost per extra case of SCD and trait identified by universal programme varied. CONCLUSIONS: IEF and HPLC are very similar in terms of average cost per test. At 16 traits/1000 and 0.5 SCD/1000 there was no significant identification cost difference between universal and targeted programmes. Below this prevalence, a targeted programme is cheaper but likely to miss cases of SCD. If targeted programmes were 90-99% effective, universal programmes would cease to be good value except at very high prevalence. Greater use of prenatal diagnosis, resulting in termination, and therefore fewer affected births, reduces the cost effectiveness of universal screening. Screening services should aim to cover a screened population which will generate a workload over 25,000 births a year, and preferably over 40,000.
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The cytoplasmic juxtamembrane domain of the human insulin receptor (hIR) contains a single copy of the tetrameric amino acid sequence Asn-Pro-Glu-Tyr (NPEY) (residues 969-972 in the exon 11-containing B-isoform), which exists in the context of NPXY. In this study, we examined the role of NPEY972 in mediating insulin signal transduction and cellular biological effects. Transfected Chinese hamster ovary cell lines expressing either the wild-type hIR-B isoform (hIR.WT) or a mutant receptor lacking the NPEY972 sequence (hIRDeltaNPEY) and control Chinese hamster ovary.Neo cells were used to comparatively analyze the following insulin effects: in vivo receptor tyrosine autophosphorylation and kinase activity, signal transduction to downstream signaling molecules, and stimulation of glycogen and DNA synthesis. The results showed that in comparison to hIR.WT, the hIRDeltaNPEY mutant demonstrated the following: (a) normal insulin-mediated receptor tyrosine phosphorylation, but approximately 50% reduction in phosphorylation of p185-(insulin receptor substrate-1) and binding of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase), (b) an enhanced stimulation of PI 3-kinase enzymatic activity, (c) a complete inability to phosphorylate Shc, (d) minimal impairment of insulin sensitivity for glycogen synthesis, and (e) an augmented response to insulin-stimulated DNA synthesis via a high capacity, low sensitivity pathway. These results demonstrate the following: 1) the NPEY972 sequence is important but not absolutely essential for coupling of hIR kinase to insulin receptor substrate-1 and p85 or for mediating insulin's metabolic and mitogenic effects, 2) the NPEY972 sequence is necessary for Shc phosphorylation, and 3) the absence of Shc phosphorylation releases the constraints on maximal insulin-stimulated mitogenic response, thus indicating that alternate signaling pathway(s) exist for this insulin action. This alternate pathway appears to be associated with enhanced activation of PI 3-kinase and is of high capacity and low sensitivity.
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OBJECTIVES: To explore geographical variation in sexual behaviour in Great Britain with reference to the prevalence of HIV infection. DESIGN: The National Survey of Sexual Attitudes and Lifestyles comprises a randomly selected, representative sample of almost 19,000 men and women aged 16-59 years living in Great Britain. METHODS: The survey was carried out using a combination of face-to-face interview and self-completion questionnaires and a wide range of data was collected. In this study, data on numbers and sex of sexual partners, condom use, injecting drug use, perception of risk of AIDS and lifestyle change were analysed, and comparisons were made between the different geographical areas in Great Britain. RESULTS: In the last 5 years, men living in Inner London were more likely to have a male partner [odds ratio (OR), 5.6; 95% confidence interval (CI), 3.1-10.0] or to have had 10 or more female partners (OR, 2.4; 95% CI, 1.6-3.6) than men living in other parts of the country. Similar results were observed for women living in Inner London: OR for a female partner in the last 5 years was 4.1 (95% CI, 1.6-10.2) and for five or more male partners in the last 5 years was 2.1 (95% CI, 1.5-2.8). More complex, but less striking patterns of behaviour were seen in different parts of the country. Both men and women living in Inner London were more likely to recognize that they were at some risk of acquiring HIV and were also more likely to report a change in sexual lifestyle. CONCLUSIONS: These analyses highlight the difficulties inherent in extrapolating from sexual behaviour data gathered using purposive samples to the population as a whole. The results are consistent with the known epidemiology of HIV and sexually transmitted diseases in Britain. The data suggest that cases of HIV will continue to be concentrated in Inner London, but Londoners are particularly aware of their risk. Reported behaviour change in response to perception of risk of AIDS underlines the importance of effective health promotion.
OBJECTIVE: To describe the epidemiology and associated clinical features of gonorrhoea and chlamydial infection and to develop a profile of sexually transmitted diseases (STDs) in an outer London health district. DESIGN: Hospital-based retrospective study. SETTING: Genitourinary medicine clinic, Northwick Park Hospital, Harrow and Brent Health Authority. SUBJECTS: 70 male and female individuals with gonorrhoea and 129 with chlamydial infection, diagnosed consecutively over 28 months in 1992-94. RESULTS: More men than women had gonorrhoea (43 versus 27) but more women than men had chlamydial infection (84 versus 45), p < 0.001. There was a clear tendency for cases with either infection to locate along major road and rail transport routes. Foci of gonococcal infection were concentrated mainly in the densely populated areas, whereas chlamydial cases were more evenly spread. There was no significant effect of gender or type of STD on the odds ratio for residence in Harrow, single marital status or attendance for test of cure. However, the odds ratios for women having sexual intercourse with a regular partner only or previous STD were 5 (95% CI 2.4 to 10.2), p < 0.001 and 0.3 (95% CI 0.18 to 0.69), p = 0.002 times the odds for men, respectively. The odds ratios for patients with gonococcal infection being employed or having sex with a regular partner only were 0.5 (95% CI 0.27 to 0.98), p = 0.04 and 0.30 (95% CI 0.15 to 0.60), p < 0.001 times the odds for patients with chlamydial infection, respectively. Of the women with gonorrhoea and previous pregnancy, 68% gave a history of abortion compared with 44% of those with chlamydial infection (p = 0.03). CONCLUSION: The identification of foci gonococcal and chlamydial infection and apparent location of these infections along the major transport routes in our health district require further study. That chlamydial infection, unlike gonorrhoea, is evenly distributed irrespective of population concentration and deprivation, suggests urgent need for a comprehensive local effort to control both STDs.