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Biomedical subjects

A V Swan

Publications and source records attributed to A V Swan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inter-laboratory validation of an ELISA for the determination of serum anti-ganglioside antibodies.

Anti-ganglioside antibodies are frequently sought in the sera of patients with autoimmune peripheral neuropathy, using an enzyme-linked immunosorbent assay (ELISA) as the principal method for antibody detection. Wide variations in assay performance between laboratories have been reported. In this study, we established a standardized ELISA method between laboratories within the European Inflammatory Neuropathy Cause and Treatment (INCAT) group and determined the inter-laboratory variance in assay performance using both the standardized INCAT method and in-house local methods. As expected, the inter-laboratory variances were greater using local methods than using the standardized method, producing titre estimates which could be 24.8 or 7.6 times larger or smaller, respectively, than the true means for these laboratories. Using the standardized method, the within laboratory measurement error accounted for 41% of the inter-laboratory variation, providing a theoretical upper limit to which technical improvements within laboratories could reduce inter-laboratory variation. These data describe the intrinsic weaknesses within the widely used ganglioside antibody ELISA methods and reinforce the importance of inter-laboratory cooperation within this area. Standardized serological reagents used in this study are available from INCAT members.

Antibodies↗
PubMed1999

Asymptomatic urethritis and detection of HIV-1 RNA in seminal plasma.

OBJECTIVE: To define risk factors for detection of HIV-1 RNA in semen in men attending the two largest HIV clinics in the West Midlands. METHODS: 94 HIV-1 seropositive men at any stage of infection donated matched semen and blood samples. 36 subjects (38%) were on no antiretroviral treatment, 12 (13%) were on dual therapy, and 46 (49%) were on three or more drugs. Median CD4 count was 291 cells x 10(6)/l. 87 subjects underwent a urethritis screen (Gram stained urethral smear and culture for gonococcus, and LCR for Chlamydia trachomatis on first pass urine). Quantitative cell free HIV-1 RNA was determined by commercial nucleic acid sequence based assay with a lower detection limit of 800 copies/ml for semen and 400 copies/ml for blood. Independent risk factors for seminal HIV RNA detection were defined by logistic regression. RESULTS: In univariate analysis, subjects not taking antiretrovirals were 11 times more likely to shed HIV RNA (21/36 (58%) v 6/58 (10%); p < 0.0001). Seven subjects (8%) had urethritis (including one C trachomatis infection). Urethritis was significantly associated with detection of seminal HIV RNA (adjusted OR, 80.2; p = 0.006), as was blood plasma viral load (adj OR, 19.3 per factor 10 increase; p < 0.001) and age (adj OR, 1.16 per 1 year older; p = 0.001). Antiviral treatment status, absolute CD4 and CD8 count, clinical stage, treatment centre, ethnicity, and risk factor were not independent predictors. No subject with undetectable blood viral load had detectable seminal HIV RNA. CONCLUSION: Asymptomatic urethritis is independently associated with seminal HIV RNA shedding.

Adult↗
PubMed1998

Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group.

We performed electrophysiological and serological testing within 15 days of symptom onset on 369 patients with Guillain-Barré Syndrome (GBS) enrolled in a trial comparing plasma exchange, intravenous immunoglobulin, and both treatments. Patients were classified into five groups by motor nerve conduction criteria; 69% were demyelinating, 3% axonal, 3% inexcitable, 2% normal, and 23% equivocal. Six of 10 (60%) patients with axonal neurophysiology had had a preceding diarrheal illness compared with 71 of 359 (20%) in other groups. Antiganglioside GM1 antibodies were present in a higher proportion of patients with axonal physiology or inexcitable nerves than other patients. The number dead or unable to walk unaided at 48 weeks was greater in the group with initially inexcitable nerves (6 of 12, 50%) compared with the rest (52 of 357, 15%), but was not significantly different between the axonal (1 of 10, 10%) and demyelinating (44 of 254, 17%) groups. Sensory action potentials and clinical sensory examination were both normal in 53 of 342 (16%) patients, and these "pure motor GBS" patients were more likely than other GBS patients to have IgG antiganglioside GM1 antibodies and to have had preceding diarrhea but had a similar outcome. The axonal group was more likely than other groups to have normal sensory action potentials. The outcomes in response to the three treatments did not differ in any subgroup (including patients with pure motor GBS or preceding diarrhea) or any neurophysiological category.

Autoantibodies↗
PubMed1998

New cases seen at genitourinary medicine clinics: England 1997.

Statistics from genitourinary medicine (GUM) clinics provide the most comprehensive source of data on the epidemiology of sexually transmitted infections (STI) in England. Between 1996 and 1997, the total number of diagnoses made in GUM clinics rose by 7% and total diagnoses of acute STIs by 9%. Diagnoses of genital Chlamydia trachomatis, genital warts and gonorrhoea rose by 20%, 8%, and 5%, respectively. Cases of infectious syphilis rose by 26%, most of which was attributable to an outbreak in Bristol. These rises followed substantial rises in acute STIs between 1995 and 1996, and were most pronounced among teenagers and homosexual and bisexual men. The continued growth in numbers of acute STIs is occurring despite the targeting of known risk groups in sexual health education and intervention programmes, and suggests that renewed efforts to improve sexual health are needed.

Adolescent↗
PubMed1996

An investigation of the role of fathers in immunization uptake.

BACKGROUND: Mothers, but not fathers, are the usual focus of strategies to maximize immunization coverage in low income countries. METHODS: A study of the immunization determinants of children aged 12-18 months was conducted in 1991 in the Eastern Region of Ghana using structured interviews of a population sample of 294 mothers and 170 (67%) of the children's fathers. RESULTS: Fathers were more likely than mothers to perceive that the fathers had participated in the decision to send children for immunizations. Where both parents reported that the father had participated in the decision, and he could speak English, the child was more likely to have completed the immunization schedule by 12 months (OR = 5.7, 95% confidence interval [CI]: 1.5-21.7), independently of other factors. Neither the father's participation, nor his ability to speak English, was independently associated with the child's immunization status. CONCLUSIONS: The results of the study suggest that, where fathers have a higher level of education, programmes which are designed to involve them in decisions about their children's use of preventive health services have the potential to increase timely immunization coverage levels.

Child, Preschool↗
PubMed1996

Risk factors associated with Epstein-Barr virus replication in oral epithelial cells of HIV-infected individuals.

OBJECTIVE: To examine risk factors associated with Epstein-Barr virus (EBV) replication in the oral epithelium of an HIV-infected cohort. DESIGN: Longitudinal study of behavioural, medication and immunological parameters of HIV-1-seropositive outpatients attending a genitourinary clinic. Outcome measure was EBV DNA positivity in curetted oral squames, as detected by in situ hybridization. Logistic regression for repeated observations of the same individuals was used to analyse how risk changed over time. RESULTS: Fifty six individuals were studied; 158 patient-visits were made in total (mean, 2.8). Of 137 samples curetted from the tongue, 36 were positive for EBV DNA. Recreational drug use, oral sexual practices, therapy with zidovudine and aciclovir, and changes in CD4 and total lymphocyte counts were not associated with changes in risk. Alcohol drinking, elevated CD8 lymphocyte counts and fluconazole therapy were associated with a decreased risk, and cigarette smoking with increased risk. CONCLUSION: Behavioural and HIV-specific immunological changes may play important roles in promoting and affecting the course of oral EBV replication. Rigorous anticandidal therapy and avoidance of cigarette smoking may retard the development of oral hairy leukoplakia.

AIDS-Related Opportunistic Infections↗
PubMed1996

United Kingdom AIDS survival in adults.

OBJECTIVE: To examine the impact of age, year and region of AIDS diagnosis on early (up to 12 months) and late survival of AIDS patients in different exposure categories; to describe the hazard pattern from 12 months after AIDS diagnosis. PATIENTS: A total of 4577 UK adult AIDS diagnoses to the end of 1991 in men who have sex with men, 273 AIDS cases in injecting drug users, 411 AIDS patients infected by blood products, and 535 other adult AIDS cases, mainly ascribed to heterosexual transmission. Deaths have been recorded for 4739 of these 5796 AIDS patients. RESULTS: The influence of calendar year and region of AIDS diagnosis on survival were short-term, for the most part operative only within the first year of follow-up. The monthly death-rate was roughly constant from 12 to 48 months post-AIDS [pooled estimate, 0.055 with 95% confidence interval (CI), 0.053-0.057] but was more than halved for 4-year survivors (pooled estimate, 0.022; 95% CI, 0.017-0.027). About 7% of AIDS cases diagnosed in 1990-1991 survive for at least 48 months. Survival after AIDS diagnosis shortens with advancing age at AIDS diagnosis: the relative hazard per decade of age (1.35; 95% CI, 1.29-1.41 in the first year after AIDS) is significantly greater (P < 0.001) in the first year after AIDS diagnosis than from 12 to 48 months (1.19; 95% CI, 1.13-1.25 in the second epoch). CONCLUSIONS: The influence of covariates, including age, is strongest in the first year of follow-up after AIDS diagnosis. Monthly death-rate is roughly constant at 0.055 from 12 to 48 months post-AIDS and at 0.022 thereafter.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database.

The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of 1989-90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10,000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21-92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups.

Aged↗
PubMed1995

An investigation assessing the fraction of human immunodeficiency virus infection attributable to ethnic group variations in risk.

Considerable speculation and a recent publication has suggested that much of the human immunodeficiency virus (HIV-1) infection in the subset of the UK population represented by women having babies in Metropolitan London is substantially imported from Africa. Other data are supportive of this hypothesis. Ades et al. (1992) concluded that the fraction of HIV seroprevalence, identified in a large London-based study using neonatal blood from the dried blood spots on Guthrie cards, attributable to mothers born in Africa was 92.4% with 95% CI: 82-100%. This is an important observation which requires confirmation. This paper reports on an attempt to do this with closely similar methodology using the Unlinked Anonymous Survey (UAS) of HIV-1 seroprevalence in pregnant women attending antenatal centres, together with data from the Office of Population Censuses and Surveys (OPCS) on the country of origins of mothers delivering in 1991 at the 15 London centres included in the UAS. As in Ades' analysis there appeared to be a strong association between centre prevalences and the proportions of women of African origin delivering at those centres. This was consistent with a high fraction of seroprevalence attributable to such women, but it was also clear that the assumptions required for the estimation of the attributable fractions were not fully met. Analyses modified to justify the assumptions produced attributable fraction estimates ranging from 44% to 96% with lower 95% confidence limits 20% or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗
PubMed1994

The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing.

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p < 0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p < 0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counselees reported a deterioration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.

Adolescent↗
PubMed1994

Total lymphoid irradiation in multiple sclerosis.

Following a report of the efficacy of total lymphoid irradiation (TLI) in the treatment of chronic progressive multiple sclerosis a further randomised double-blind placebo-controlled study was undertaken with the intention of entering 56 patients. In the event it was possible to recruit only 27 patients in a 2.5 year period. Three patients received active treatment openly and 24 were randomised to either active (14) or sham (10) treatment. Treatment was 1980 cGy to the lymphoid system and spleen or sham treatment after full simulation. The primary outcome measure was a comparison of the mean rates of change between treatment groups on the expanded Kurtzke disability scale (EDSS) over the two year follow up period. Patients were also assessed on other clinical outcome measures, psychometry, and serial MRI of the brain. Active treatment resulted in a profound and prolonged fall in T lymphocytes especially those with the CD4 marker and a reversal in CD4:CD8 ratio. No significant benefit was demonstrated on the rate of clinical disease progression (EDSS). A small but significant benefit was found on a score of bladder function. No significant benefit was demonstrated on other clinical or psychometric indices or on subjective visual analogue scales. There was a small but significant difference in the rate of accumulation of lesions on brain MRI favouring the treatment group. The treated group had a higher incidence of clinically relevant side effects, notably amenorrhoea and infections: three deaths (one in the TLI group, two in the sham treated group) occurred. A post hoc calculation indicates that the study had a possible 35% risk of a false negative result using the principal outcome measure. The study fails to confirm the previously reported clinical benefit of TLI although there may be a minor benefit on disease progression as indicated by MRI lesion counts. It is concluded that TLI cannot be recommended for the routine treatment of chronic progressive multiple sclerosis but the beneficial effect on MRI lesions, though modest, suggests that further research into immune modulation of this condition may be worthwhile.

Adult↗
PubMed1993

Sexually transmitted diseases and HIV-1 infection among homosexual men in England and Wales.

OBJECTIVE: To examine surveillance data for evidence of changing sexual behaviour and continuing transmission of HIV-1 among men who have sex with men. DESIGN: Analytic study of surveillance data on sexually transmitted diseases. SETTING: England and Wales. MAIN OUTCOME MEASURES: Number of cases of rectal gonorrhoea and newly diagnosed HIV infection in homosexual men. RESULTS: New cases of gonorrhoea among men attending genitourinary medicine clinics increased by 7.7% in 1989 and by 4.2% in 1990. Reports of rectal isolates of Neisseria gonorrhoeae also rose and the male to female ratio for patients with rectal gonorrhoea changed from 0.3:1 during 1988-9 to 2.6:1 in 1990-1. Although the overall number of cases of acute hepatitis B fell during 1988-91, 81 and 82 homosexual men were infected in 1990 and 1991 respectively compared with 50 and 42 in 1988 and 1989. 1526 men had HIV-1 infection diagnosed in 1991, the largest number since 1987. Twenty eight of the 97 (29%) men who seroconverted between January 1989 and December 1991 were aged less than 25. The proportion of men aged 15-19 who were found to be infected with HIV-1 at their first test increased from an average of 2.4% up to 1990 to 4.7% in the first nine months of 1991. The prevalence of HIV infection in men under 25 attending genitourinary medicine clinics in London was 17% compared with 7.8% outside London. CONCLUSION: Unsafe sexual behaviour and HIV transmissions have increased among homosexual men after a period of decline. Recent HIV transmissions may disproportionately affect younger men.

Acquired Immunodeficiency Syndrome↗
PubMed1993

HIV infection in injecting drug users attending centres in England and Wales, 1990-1991.

OBJECTIVE: To monitor trends in HIV infection and associated risk behaviours in injecting drug users (IDU) in England and Wales. DESIGN: Ongoing voluntary unlinked anonymous cross-sectional survey. METHOD: IDU attending centres in 1990 and 1991 were invited to complete a brief questionnaire requesting demographic and behavioural information, and to provide a saliva sample to be tested for antibodies to HIV and to the core antigen of hepatitis B virus (HBV). RESULTS: In 1990, 1.2% (19 out of 1543) of samples from 33 centres, and in 1991 1.8% (25 out of 1417) of samples from 37 centres contained antibody to HIV. Antibody t9 HBV core-antigen was found in 33 and 31% of IDU in 1990 and 1991, respectively. The prevalence of HIV infection in IDU attending centres in London (4.2%) was higher than in those attending centres elsewhere (0.8%). The prevalence of HIV infection in 1991 varied between individual centres from 0 to 10.6%, and at many centres outside London no IDU were infected with HIV. In the same year the prevalence of past infection with HBV varied from 14 to 54%, and IDU who had evidence of HBV infection were found among attenders in nearly all centres. The prevalences of sharing injecting equipment and risky sexual behaviour were high at many centres. The prevalence of HIV infection was higher in IDU who had started to inject in 1985 or earlier, than in those who started injecting later. In each year, approximately half the IDU surveyed reported having had a voluntary confidential HIV-antibody test, and the prevalence of HIV infection was five times higher in those tested than in those who had not been tested. CONCLUSIONS: HIV prevalence in IDU attending centres in England and Wales was low in 1990-1991. There is some indication that IDU have modified their injecting or sexual behaviour, but even at existing reduced levels of risk behaviour, transmission can occur in HIV is introduced into previously unexposed groups.

Adolescent↗
PubMed1993

Acute renal failure treated by haemofiltration: factors affecting outcome.

Two hundred and fifty consecutive patients with acute renal failure treated by continuous haemofiltration on one intensive care unit (ICU) were studied prospectively to investigate the possibility of predicting outcome at the time of referral. Logistic regression analysis was used to identify important prognostic factors and the regression coefficients were used to weight a scoring system for the severity of illness of patients with acute renal failure. Overall survival was 53% with improvement over the course of the study. Multivariate analysis showed that outcome was related to age, need for artificial ventilation, use of inotropes, urine volume, serum bilirubin, arterial base deficit and serum creatinine. The scoring system based on the first five of these variables had a specificity of predicting death of 67% and a sensitivity of 76%.

Acute Kidney Injury↗
PubMed1992

Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)

To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations.

Angina Pectoris↗
PubMed1992

A methodology for simulating the impact of DNA-probe services on the outcomes of pregnancies.

For certain single-gene disorders, DNA probes allow individuals to make more informed decisions about family size and the outcomes of pregnancies. They may also have important psychological effects. We present a method of assessing their impact on the outcomes of pregnancy. We conclude that the traditional approach, which focuses solely on the potential of prenatal diagnostic services to reduce affected births, is limited. It neglects the potential of such services to promote an increase in unaffected births by reducing the number of unnecessary terminations.

DNA Probes↗
PubMed1992

DNA probe technology: implications for service planning in Britain.

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.

Adolescent↗