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Biomedical subjects

John Macleod

Publications and source records attributed to John Macleod.

At least 19 recordsLinked to original sources
PubMed2006

Gluconic acid: an antifungal agent produced by Pseudomonas species in biological control of take-all.

Pseudomonas strain AN5 (Ps. str. AN5), a non-fluorescent Australian bacterial isolate, is an effective biological control (biocontrol) agent of the take-all disease of wheat caused by the fungus Gaeumannomyces graminis var. tritici (Ggt). Ps. str. AN5 controls Ggt by producing an antifungal compound which was purified by thin layer and column chromatography, and identified by NMR and mass spectroscopic analysis to be d-gluconic acid. Commercially bought pure gluconic acid strongly inhibited Ggt. Two different transposon mutants of Ps. str. AN5 which had lost take-all biocontrol did not produce d-gluconic acid. Gluconic acid production was restored, along with take-all biocontrol, when one of these transposon mutants was complemented with the corresponding open reading frame from wild-type genomic DNA. Gluconic acid was detected in the rhizosphere of wheat roots treated with the wild-type Ps. str. AN5, but not in untreated wheat or wheat treated with a transposon mutant strain which had lost biocontrol. The antifungal compounds phenazine-1-carboxylic acid and 2,4-diacetylphloroglucinol, produced by other Pseudomonads and previously shown to be effective in suppressing the take-all disease, were not detected in Ps. str. AN5 extracts. These results suggest that d-gluconic acid is the most significant antifungal agent produced by Ps. str. AN5 in biocontrol of take-all on wheat roots.

Antifungal Agents↗
PubMed2006

Enhanced detection and typing of human papillomavirus (HPV) DNA in anogenital samples with PGMY primers and the Linear array HPV genotyping test.

The Roche PGMY primer-based research prototype line blot assay (PGMY-LB) is a convenient tool in epidemiological studies for the detection and typing of human papillomavirus (HPV) DNA. This assay has been optimized and is being commercialized as the Linear Array HPV genotyping test (LA-HPV). We assessed the agreement between LA-HPV and PGMY-LB for detection and typing of 37 HPV genotypes in 528 anogenital samples (236 anal, 146 physician-collected cervical, and 146 self-collected cervicovaginal swabs) obtained from human immunodeficiency virus-seropositive individuals (236 men and 146 women). HPV DNA was detected in 433 (82.0%) and 458 (86.7%) samples with PGMY-LB and LA-HPV (P = 0.047), respectively, for an excellent agreement of 93.8% (kappa = 0.76). Of the 17,094 HPV typing results, 16,562 (1,743 positive and 14,819 negative results) were concordant between tests (agreement = 96.9%; kappa = 0.76). The mean agreement between tests for each type was 96.4% +/- 2.4% (95% confidence interval [CI], 95.6% to 97.2%; range, 86% to 100%), for an excellent mean kappa value of 0.85 +/- 0.10 (95% CI, 0.82 to 0.87). However, detection rates for most HPV types were greater with LA-HPV. The mean number of types per sample detected by LA-HPV (4.2 +/- 3.4; 95% CI, 3.9 to 4.5; median, 3.0) was greater than that for PGMY-LB (3.4 +/- 3.0; 95% CI, 3.1 to 3.6; median, 2.0) (P < 0.001). The number of types detected in excess by LA-HPV in anal samples correlated with the number of types per sample (r = 0.49 +/- 0.06; P = 0.001) but not with patient age (r = 0.03 +/- 0.06; P = 0.57), CD4 cell counts (r = 0.06 +/- 0.06; P = 0.13), or the grade of anal disease (r = -0.11 +/- 0.06; P = 0.07). LA-HPV compared favorably with PGMY-LB but yielded higher detection rates for newer and well-known HPV types.

Adolescent↗
PubMed2006

Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice.

BACKGROUND: Opportunistic screening for genital chlamydia infection is being introduced in England, but evidence for the effectiveness of this approach is lacking. There are insufficient data about young peoples' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population-based approach. AIM: To estimate use of primary care services by young men and women; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach. DESIGN OF STUDY: Population based cross-sectional study. SETTING: Twenty-seven general practices around Bristol and Birmingham. METHOD: A random sample of patients aged 16-24 years were posted a chlamydia screening pack. We collected details of face-to-face consultations from general practice records. Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated 60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to 76.9%) of women aged 16-24 years attended their practice at least once in a 1-year period. During this period, an estimated 21.3% of patients would not attend their general practice but would be reached by postal screening, 9.2% would not receive a postal invitation but would attend their practice, and 11.8% would be missed by both methods. CONCLUSIONS: Opportunistic and population-based approaches to chlamydia screening would both fail to contact a substantial minority of the target group, if used alone. A pragmatic approach combining both strategies might achieve higher coverage.

Adolescent↗
PubMed2005

Partner notification of chlamydia infection in primary care: randomised controlled trial and analysis of resource use.

OBJECTIVE: To evaluate the effectiveness of a practice nurse led strategy to improve the notification and treatment of partners of people with chlamydia infection. DESIGN: Randomised controlled trial. SETTING: 27 general practices in the Bristol and Birmingham areas. PARTICIPANTS: 140 men and women with chlamydia (index cases) diagnosed by screening of a home collected urine sample or vulval swab specimen. INTERVENTIONS: Partner notification at the general practice immediately after diagnosis by trained practice nurses, with telephone follow up by a health adviser; or referral to a specialist health adviser at a genitourinary medicine clinic. MAIN OUTCOME MEASURES: Primary outcome was the proportion of index cases with at least one treated sexual partner. Specified secondary outcomes included the number of sexual contacts elicited during a sexual history, positive test result for chlamydia six weeks after treatment, and the cost of each strategy in 2003 sterling prices. RESULTS: 65.3% (47/72) of participants receiving practice nurse led partner notification had at least one partner treated compared with 52.9% (39/68) of those referred to a genitourinary medicine clinic (risk difference 12.4%, 95% confidence interval -1.8% to 26.5%). Of 68 participants referred to the clinic, 21 (31%) did not attend. The costs per index case were 32.55 pounds sterling for the practice nurse led strategy and 32.62 pounds sterling for the specialist referral strategy. CONCLUSION: Practice based partner notification by trained nurses with telephone follow up by health advisers is at least as effective as referral to a specialist health adviser at a genitourinary medicine clinic, and costs the same. Trial registration Clinical trials: NCT00112255.

Chlamydia Infections↗
PubMed2005

Bereavement and marriage are associated with antibody response to influenza vaccination in the elderly.

Stressful life events exposure including bereavement, an event commonly experienced by elderly people, social support, marital status, and satisfaction were examined in relation to antibody response to the annual trivalent influenza vaccination in an elderly community sample (N=184). Antibody response was assessed at baseline, and at 1 and 12 months following vaccination. Taking into account baseline antibody titer, overall life events exposure and social support were not associated with response to any of the influenza strains. However, bereavement in the year prior to vaccination was negatively associated with the 1-month response to the A/Panama and B/Shangdong strains. Being married and having higher marital satisfaction was also associated with higher peak responses to the A/Panama influenza strain at 1 month. The positive association between marital satisfaction and A/Panama response was particularly evident in the younger half of the married sample. These associations largely withstood adjustment for potential confounders. Thus, in the elderly, peak antibody response was associated with bereavement and marriage, and not the more general factors, life events and social support, related to antibody response in student samples. This suggests the importance of taking a life course approach to examining relationships between psychosocial factors and immunity, and that interventions to modify the impact of these factors should address those most salient for each age group.

Aged↗
PubMed2005

Cause-specific hospital admission and mortality among working men: association with socioeconomic circumstances in childhood and adult life, and the mediating role of daily stress.

BACKGROUND: The aim of this study was to investigate the association of childhood and adulthood social class with the occurrence of specific diseases, including those not associated with a high mortality rate, and to investigate daily stress as the mechanism for that part of any association which cannot be accounted for by established risk factors. METHODS: This was a prospective cohort study with 25 years of follow-up for cause-specific morbidity and mortality. A total of 5577 Scottish men were recruited from 27 workplaces in the West of Scotland. Childhood social class was determined from the occupation held by the individual's father, and adulthood social class from the individual's occupation at enrolment. Daily stress was measured at enrolment using the Reeder Stress Inventory. RESULTS: Health differentials were found for cardiovascular diseases, lung cancer, peptic ulcer, asthma, accidents and violence, alcohol-related diseases, and perhaps psychiatric illness. Adulthood circumstances were associated with the incidence of most diseases in adulthood, the exception being stroke, which was strongly associated with less privileged circumstances in childhood. Both childhood and adulthood circumstances contributed to the incidence of coronary heart disease. Daily stress did not underlie any of these associations once the influence of established risk factors had been taken into account. CONCLUSIONS: Socioeconomic circumstances in childhood and adulthood both contribute to health differentials in adulthood, the relative contributions depending upon the particular disease. Where known risk factors explained only part of the excess of a disease among individuals raised or living in less-privileged circumstances, there was no evidence to suggest that daily stress was the reason for the unexplained excess.

Activities of Daily Living↗
PubMed2005

Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study.

OBJECTIVE: To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures. DESIGN: Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home. SETTING: England. PARTICIPANTS: 19,773 men and women aged 16-39 years invited to participate in screening. MAIN OUTCOME MEASURES: Coverage and uptake of screening; prevalence of chlamydia. RESULTS: Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year. CONCLUSIONS: Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.

Adolescent↗
PubMed2005

Is subjective social status a more important determinant of health than objective social status? Evidence from a prospective observational study of Scottish men.

Both subjective and objective measures of lower social position have been shown to be associated with poorer health. A psychosocial, as opposed to material, aetiology of health inequalities predicts that subjective social status should be a stronger determinant of health than objective social position. In a workplace based prospective study of 5232 Scottish men recruited in the early 1970s and followed up for 25 years we examined the association between objective and subjective indices of social position, perceived psychological stress, cardiovascular disease risk factors and subsequent health. Lower social position, whether indexed by more objective or more subjective measures, was consistently associated with an adverse profile of established disease risk factors. Perceived stress showed the opposite association. The main subjective social position measure used was based on individual perceptions of workplace status (as well as their actual occupation, men were asked whether they saw themselves as "employees", "foremen", or "managers"). Compared to foremen, employees had a small and imprecisely estimated increased risk of all cause mortality, whereas managers had a more marked decreased risk. The strongest predictors of increased mortality were father's manual as opposed to non-manual occupation; lack of car access and shorter stature, (an indicator of material deprivation in childhood). In the fully adjusted analyses, perceived work-place status was only weakly associated with mortality. In this population it appears that objective material circumstances, particularly in early life, are a more important determinant of health than perceptions of relative status. Conversely, higher perceived stress was not associated with poorer health, presumably because, in this population, higher stress was not associated with material disadvantage. Together these findings suggest that, rather than targeting perceptions of disadvantage and associated negative emotions, interventions to reduce health inequalities should aim to reduce objective material disadvantage, particularly that experienced in early life.

Administrative Personnel↗
PubMed2005

Enhanced enzyme immunoassay with negative-gray-zone testing compared to a single nucleic Acid amplification technique for community-based chlamydial screening of men.

We evaluated a low-cost diagnostic strategy for detecting Chlamydia trachomatis in a low-prevalence population. We used an amplified enzyme immunoassay (EIA) with a reduced-cutoff "negative gray zone" to identify reactive specimens for confirmation by a nucleic acid amplification test. As part of the Chlamydia Screening Studies project, men provided a first-pass urine specimen, which they returned by post for testing. We tested 1,003 specimens by IDEIA PCE EIA (Dako) and Cobas PCR (Roche). There were 32 (3.2%) true positive specimens according to a combined standard using an algorithm requiring concordant results from at least two independent tests. All of these were positive by Cobas PCR and 24 were confirmed to be positive by PCE EIA, including 2 that gave results in the negative gray zone. There were 971 true negative specimens, 2 of which were positive by Cobas PCR and 19 of which were initially inhibitory for PCR. The relative sensitivity, specificity, positive predictive value, and negative predictive value of PCE EIA with PCR confirmation were 75.0% (95% confidence interval [CI], 56.6 to 88.5%), 100% (95% CI, 99.7 to 100%), 100% (95% CI, 88.3 to 100%), and 99.2% (95% CI, 98.4 to 99.6%), respectively. The corresponding values for Cobas PCR were 100% (95% CI, 89.1 to 100%), 99.8% (95% CI, 99.3 to 100%), 94.1% (95% CI, 76.9 to 98.2%), and 100% (95% CI, 99.6 to 100%), respectively, with 1.9% (19/1003) of the samples being initially indeterminate. When the prevalence of C. trachomatis is low, the use of an amplified EIA on urine specimens, with confirmation of results in the negative gray zone by use of a nucleic acid amplification technique, is not suitable for screening asymptomatic men. In addition, positive nucleic acid amplification test results should be confirmed and an inhibition control should be used.

Algorithms↗
PubMed2005

Substance misuse and psychiatric illness: prospective observational study using the general practice research database.

OBJECTIVES: To quantify the relation between substance misuse and psychiatric illness in the UK general practice population in terms of (a) the relative risk of developing one condition given prior exposure to the other and (b) the proportion of cases of one condition attributable to exposure to the other. DESIGN: Population based prospective observational study using the general practice research database (GPRD) between 1993 and 1998. The 230 GP practices represent 3.1% of the population. SETTING: England and Wales. PARTICIPANTS: 1.4 million registered patients of whom 3969 had both substance misuse and psychiatric diagnoses between 1993 and 1998. MAIN OUTCOME MEASURES: Relative risk (RR) for subsequent psychiatric illness among participants exposed to substance misuse and RR for subsequent substance misuse among participants exposed to psychiatric illness. Population attributable risk (PAR) of psychiatric illness attributable to substance misuse and of substance misuse attributable to psychiatric illness. RESULTS: The baseline prevalence of psychiatric illness over the study period was 15% and 0.3% for substance abuse. RR for psychiatric illness for substance misusers compared with non-substance misusers was 1.54 (95% CI 1.47 to 1.62). RR for substance misuse among psychiatric compared with non-psychiatric cases was 2.09 (95% CI 1.99 to 2.22). PAR for psychiatric illness attributable to substance misuse was 0.2%. PAR for substance misuse attributable to psychiatric illness was 14.2%. DISCUSSION: Only a comparatively small proportion of psychiatric illness seems possibly attributable to substance use whereas a more substantial proportion of substance use seems possibly attributable to psychiatric illness. This study does not support the hypotheses that comorbidity between substance misuse and psychiatric illness is primarily the result of substance misuse or that increasing comorbidity is largely attributable to increasing substance misuse.

Comorbidity↗
PubMed2004

Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies.

BACKGROUND: Use of illicit drugs, particularly cannabis, by young people is widespread and is associated with several types of psychological and social harm. These relations might not be causal. Causal relations would suggest that recreational drug use is a substantial public health problem. Non-causal relations would suggest that harm-reduction policy based on prevention of drug use is unlikely to produce improvements in public health. Cross-sectional evidence cannot clarify questions of causality; longitudinal or interventional evidence is needed. Past reviews have generally been non-systematic, have often included cross-sectional data, and have underappreciated the extent of methodological problems associated with interpretation. METHODS: We did a systematic review of general population longitudinal studies reporting associations between illicit drug use by young people and psychosocial harm. FINDINGS: We identified 48 relevant studies, of which 16 were of higher quality and provided the most robust evidence. Fairly consistent associations were noted between cannabis use and both lower educational attainment and increased reported use of other illicit drugs. Less consistent associations were noted between cannabis use and both psychological health problems and problematic behaviour. All these associations seemed to be explicable in terms of non-causal mechanisms. INTERPRETATION: Available evidence does not strongly support an important causal relation between cannabis use by young people and psychosocial harm, but cannot exclude the possibility that such a relation exists. The lack of evidence of robust causal relations prevents the attribution of public health detriments to illicit drug use. In view of the extent of illicit drug use, better evidence is needed.

Adolescent↗