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Biomedical subjects

S Moffatt

Publications and source records attributed to S Moffatt.

25 records · Page 2Linked to original sources

Lung cancer, proximity to industry, and poverty in northeast England.

This study assesses whether deprived populations living close to industry experience greater mortality from lung cancer than populations with comparable socioeconomic characteristics living farther away. Mortality data, census data, a postal survey of living circumstances, historic and contemporary data on air quality and a historic land-use survey were used. Analysis was based on two conurbations in England, Teesside and Sunderland. Housing estates in Teesside were selected based on socioeconomic criteria and distinguished by proximity to steel and chemical industries; they were grouped into three zones: near (A), intermediate (B), and farther (C), with a single zone in Sunderland. We included 14,962 deaths in 27 estates. Standardized mortality ratios (SMR) for lung cancer [International Classification of Diseases #9 (ICD-9) 162] and cancers other than lung (ICD-9 140-239, excluding 162), and sex ratios were calculated. Mortality from lung cancer was well above national levels in all zones. For men, a weak gradient corresponding with proximity to industry at younger ages reversed at older ages. In women 0-64 years of age, stronger gradients in lung cancer mortality corresponded with proximity to industry across zones A, B, and C (SMR = 393, 251, 242, respectively). Overall rates in Teesside were higher than Sunderland rates for women aged 0-64 years (SMR = 287 vs. 185) and 65-74 years (SMR = 190 vs. 157). The association between raised lung cancer mortality and proximity to industry in women under 75 years of age could not be explained by smoking, occupation, socioeconomic factors, or artifact. Explanations for differences between men and women may include gender-specific occupational experiences and smoking patterns. Our judgment is that the observed gradient in women points to a role for industrial air pollution.

Adolescent↗

Induction of IL-1 beta-converting enzyme-independent apoptosis by IL-2 in human T cell lines.

Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. alpha, beta and gamma chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous alpha and gamma chains and exogenous beta chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant beta chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor beta chain, which are essential but not critical for IL-2-mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.

Apoptosis↗

A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces activation of interleukin-6 gene expression.

We examined the biological function of a nonstructural regulatory protein, NS1, of human parvovirus B19. Because of the cytotoxic activity of NS1, human hematopoietic cell lines, K562, Raji, and THP-1, were established as transfectants which produce the viral NS1 protein upon induction by using bacterial lactose repressor/operator system. NS1 was significantly produced in the three transfectant cells in an inducer dose- and time-dependent manner. Surprisingly, these three transfectants secreted an inflammatory cytokine, interleukin-6 (IL-6), in response to induction. However, no production of other related cytokines, IL-1beta, IL-8, or tumor necrosis factor alpha, was seen. Moreover, NS1-primed IL-6 induction was transiently demonstrated in primary human endothelial cells. Analysis with luciferase reporter plasmids carrying IL-6 promoter mutant fragments demonstrated that NS1 effect is mediated by a NF-kappaB binding site in the IL-6 promoter region, strongly implying that NS1 functions as a trans-acting transcriptional activator on the IL-6 promoter. Our novel finding, IL-6 induction by NS1, supports the possible relationship between parvovirus B19 infection and polyclonal activation of B cells in rheumatoid arthritis and indicates that NS1 protein may play a significant role in the pathogenesis of some B19-associated diseases by modulating the expression of host cellular genes.

Animals↗

'If this is what it's doing to our washing, what is it doing to our lungs?' Industrial pollution and public understanding in north-east England.

An epidemiological study of the impact of industrial pollution from a cokeing works in north-east England on the health of a population resident nearby uncovered strong but localised public concern about the possible dangers of air pollution. This paper discusses these popular concerns in the context of empirical findings from the study which examined evidence of ill-health alongside evidence on air quality levels. The substantive issues this paper examines relate to local variations in popular beliefs about health risks, and the relation between such beliefs and measurable differences in health states and status. The methodological issues addressed centre on the difficulties of interpreting this relationship between popular beliefs and concerns, on the one hand, and health experience, or apparent health experience, on the other.

Adult↗

Weaning from mechanical ventilation: physician-directed vs a respiratory-therapist-directed protocol.

UNLABELLED: To speed weaning and free physicians for other duties, we changed from a physician-directed to a respiratory therapist (RT)-directed protocol for weaning cardiac surgery patients from mechanical ventilation. METHODS: Eligible patients were identified by physicians after which RTs initiated and directed an intermittent mandatory ventilation weaning in accordance with a written weaning protocol. Eligibility criteria for entry into the weaning protocol (Phase 1) were expanded at the end of 4 months to include more complicated and unstable patients to be weaned by the RT-directed protocol (Phase 2). Total ventilation time and the duration of weaning were recorded for all patients during both phases and during the 2-months prior to implementing RT-directed weaning (control period). All patients were physician weaned during the control period. RESULTS: No complications were associated with the introduction of RT-directed weaning. The percentage of all cardiac surgery patients weaned by the RTs increased progressively from 41 to 90% over the 7-month study period. When compared to a similar group of physician-weaned patients in the control period, the RT-weaned patients in Phase 1 and Phase 2 of the study had a significantly shorter median total ventilation time (18.6 vs 16.8 hours [p = 0.02, chi 2.95,1] for Phase 1 and 19.7 vs 17.8 hours [p = 0.04] for Phase 2). CONCLUSIONS: We have demonstrated that respiratory therapists can safely and efficiently wean cardiac surgery patients from mechanical ventilation.

Aged↗

Acute necrotizing myopathy of intensive care: electrophysiological studies.

A series of recent reports have identified cases of a quadriplegic myopathy characterized by myofiber necrosis and loss of myosin filaments associated with the use of nondepolarizing muscle blocking agents and glucocorticoids. We report electrophysiological findings in 7 intensive care unit patients who developed evidence of an acute myopathy in association with the use of nondepolarizing muscle blocking agents. Several important features were identified: (i) a neuromuscular transmission deficit was observed in 3 patients up to 7 days following withdrawal of vecuronium; (ii) motor M potentials were of low amplitude, there was mild abnormal spontaneous activity on needle electromyography, and sensory conduction was relatively preserved; (iii) not all patients received glucocorticoids or were asthmatic; (iv) 2 patients given vecuronium had very high creatine kinase levels and developed acute renal failure associated with myoglobinuria; and (v) rises in motor M potentials accompanied clinical recovery. This complication of intensive care may be severe, but is reversible and possibly avoidable. Our findings implicate nondepolarizing muscle blocking agents in the development of the myopathy. Electrophysiological studies provide important prognostic guidance.

Action Potentials↗

Is living near a coking works harmful to health? A study of industrial air pollution.

OBJECTIVE: To determine whether there was excess ill health in people living near a coking works, and if so whether it was related to exposure to coking works' emissions. DESIGN: Populations varying in proximity to the coking works were compared with control populations. Health data were correlated with available environmental data. METHODS: Analysis of routinely collected mortality, cancer registration, and birth statistics; community survey using self completed postal questionnaires; retrospective analysis of general practice (GP) records; tests of respiratory function; and analysis of available environmental data. MAIN RESULTS: Study and control populations were comparable in terms of response rates, gender, and most socioeconomic indicators. For adults, age standardised mortality and cancer rates of the population closest to the coking works were comparable with those for the district as a whole. Gender ratios, birthweight, and stillbirth rates were comparable in the study and control populations. For several indicators of respiratory health including cough, sinus trouble, glue ear, and wheeze (but not for asthma and chronic bronchitis) there was a gradient of self reported ill health, with the highest prevalence in areas closest to the works. For example, sinus trouble was reported by 20% of adults and 13% of children in the area closest to the works compared with 13% and 6% respectively in the control area. GP consultations for respiratory disorders increased when pollution (measured by SO2 levels) was high: annual consultation rates per 1000 varied from 752 in the top group of daily pollution levels to 424 in the bottom group. Analysis of locally collected smoke and SO2 data indicated that SO2 concentrations were highest closest to the works and, after closure of the coking works, the number of days on which SO2 and smoke levels exceeded 100 micrograms/m3 and 90 micrograms/m3, respectively, fell steeply. CONCLUSION: Routinely available indicators failed to provide convincing evidence that the coking works had harmed health. Self report and GP consultations indicated that respiratory ill health in the people living close to the works was worse than expected. Some of the excess probably resulted from exposure to coking works emissions. The health effects of relatively low level but intermittently high air pollution from a point source may be subtle, contributing to respiratory morbidity, but not apparent in analysis of routine health indicators.

Adolescent↗