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Biomedical subjects

L London

Publications and source records attributed to L London.

At least 19 recordsLinked to original sources

Suicide and exposure to organophosphate insecticides: cause or effect?

BACKGROUND: Suicide using pesticides as agent is recognized as a major cause of pesticide poisoning. METHODS: A literature review of mortality and morbidity studies related to suicide among pesticide-exposed populations, and of human and animal studies of central nervous system toxicity related to organophosphate (OP) pesticides was performed. RESULTS: Suicide rates are high in farming populations. Animal studies link OP exposure to serotonin disturbances in the central nervous system, which are implicated in depression and suicide in humans. Epidemiological studies conclude that acute and chronic OP exposure is associated with affective disorders. Case series and ecological studies also support a causal association between OP use and suicide. CONCLUSIONS: OPs are not only agents for suicide. They may be part of the causal pathway. Emphasizing OPs solely as agents for suicide shifts responsibility for prevention to the individual, reducing corporate responsibility and limiting policy options available for control.

Agricultural Workers' Diseases↗

Challenges for improving surveillance for pesticide poisoning: policy implications for developing countries.

BACKGROUND: Surveillance is a critical public health tool for the control of pesticide poisoning. However, surveillance activities in developing countries are bedevilled by multiple problems, and inferences made from review of flawed data may lead to mistaken policy decisions. METHODS: Results of intensified surveillance from an intervention project in the Western Cape Province of South Africa were compared to the pattern of poisonings reported in routine notifications to the health authorities for a control farming district and in the study district over a 5-year period preceding the study. Intensified surveillance data results were also contrasted with policy approaches based on routine notifications and on Regional Poison Centre reports. RESULTS: Poisoning rates reported in the study area increased almost 10-fold during the intervention period. Compared to intensified surveillance, hospital and health authority sources greatly underestimate the proportion of cases due to occupational poisoning, and overestimate suicide as a proportional cause. In addition, the risks for women appear underestimated from routine notifications. Assumptions that a lack of awareness is responsible for most poisonings are not borne out by the empirical data when reporting is intensified. CONCLUSIONS: Current policy assumptions are faulty, may result in inappropriate blame being attributed to victims and, by relying on information as the main element of education, may shift responsibility onto the individual. Improvements in the surveillance system should aim to restructure the types of data collected, and facilitate intra-governmental and inter-sector collaboration. The culture of monitoring based on report writing must change to one of surveillance that leads to intervention.

Adolescent↗

Reovirus triggers cell type-specific proinflammatory responses dependent on the autocrine action of IFN-beta.

Resident cells of the respiratory and gastrointestinal tracts, including epithelial and fibroblast cells, are the initial sites of entry for many viral pathogens. We investigated the role that these cells play in the inflammatory process in response to infection with reovirus 1/L. In A549 human bronchial or HT-29 human colonic epithelial cells, interferon (IFN)-beta, regulated on activation T cell expressed and secreted (RANTES), IFN-gamma-inducible protein (IP)-10, and interleukin-8 were upregulated regardless of whether cells were infected with replication-competent or replication-deficient reovirus 1/L. However, in CCD-34Lu human lung fibroblast cells, IFN-beta, IP-10, and RANTES were expressed only after infection with replication-competent reovirus 1/L. Expression of interleukin-8 in CCD-34Lu fibroblast cells was viral replication independent. This differential expression of IFN-beta, RANTES, and IP-10 was shown to be due to the lack of induction of IFN regulatory factor-1 and -2 in CCD-34Lu fibroblast cells treated with replication-deficient reovirus 1/L. We have shown that cytokine and/or chemokine expression may not be dependent on viral replication. Therefore, treatment of viral infections with inhibitors of replication may not effectively alleviate inflammatory mediators because most viral infections result in the generation of replication-competent and replication-deficient virions in vivo.

Autocrine Communication↗

Alcohol consumption amongst South African farm workers: a challenge for post-apartheid health sector transformation.

A cross-sectional analytical study was conducted amongst farm workers in the deciduous fruit industry in South Africa to assess levels of alcohol consumption and abuse, and to explore the impact of the DOP system, whereby farm workers are paid in part with alcohol, on indicators of alcohol consumption. High levels of alcohol consumption were found. On the CAGE and a shortened version of the MAST questionnaires, 87 and 65%, respectively, had responses indicating problem drinking. Close to half of the sample consumed more grams of alcohol per week than considered safe drinking (210 g) and 9.3% consumed amounts in excess of dangerous drinking (>490 g/week). Almost one-fifth (19.4%) of workers interviewed reported current use of the DOP system, and 47.8% of workers had experience of one or more farms in the past where the DOP system had been used. Workers with past experience of the DOP system were 9.8 times less likely to be asbstainers than colleagues without exposure to the DOP system. The pervasive effects of excessive alcohol consumption, and its relationship to past and current DOP practices pose substantial public health challenges to the transformation of health services currently underway in South Africa.

Adult↗

People, pesticides, and the environment: who bears the brunt of backward policy in South Africa?

Whereas international trends show that many developed countries are adopting policies that promote pesticide reduction, use of pesticides in South Africa continues to expand. In particular, macroeconomic policies encourage pesticides use among emergent small-scale black farmers, while potential exposures of workers on commercial farms remain high. Despite having legal controls that seem to conform to international standards, the present health and environmental impacts of pesticide use in South Africa are substantial and generally underestimated. The reasons lie in the fragmentation of regulatory mechanisms as well as the absence of public awareness and participation in policy-making related to pesticides. Failure to enforce existing legislation, an ambivalent relationship between government and industry, and the existence of a "pesticide culture" will continue to prevent implementation of meaningful control measures. As a result, it is marginalized groups, such as small-scale farmers and farm workers, who bear the brunt of policies that have not kept pace with a growing international awareness of the hazards of widespread pesticide use for human health and for the environment. Opportunities for fundamental transformation of the legal and policy framework relating to pesticides in order to promote environmental justice are explored.

Journal Article↗

Utility of vibration sense testing for use in developing countries: comparison of extinction time on the tuning fork to vibration thresholds on the Vibratron II.

The measurement of vibration sense loss is a useful tool to detect early impacts of neurotoxic chemicals. Measurement methods are needed for developing countries that are culturally unbiased, and which can be used under field conditions where electricity may be unavailable. Extinction time on a 256 Hz tuning fork was compared to vibration threshold measured on the Vibratron II for precision and agreement amongst 306 fruit farm workers as part of a study investigating neurobehavioural impacts of organophosphates in South Africa in 1993. Simultaneous data were also available from a 1 g accelerometer attached to the post of the Vibratron for comparisons. Precision of the tuning fork and Vibratron II appeared comparable and CVs (2.5 to 8.9%) were lower than that reported in the literature. Agreement of the tuning fork with the Vibratron was moderate (Spearmans correlation coefficient of the order of 0.39 to 0.42) whereas agreement between Vibratron and Accelerometer was high (Spearmans correlation of coefficient of the order of 0.78 to 0.83). Height, age and schooling were predictors of vibration sense for the Vibratron and accelerometer but only schooling for extinction time on the tuning fork. Height modified the variability of the Vibratron and accelerometer. Delays in application of the tuning fork to the base of the medial malleolus of 3 seconds or more were associated with average increases in extinction time of 1.7 s. The tuning fork, as standardised in this study, represents a relatively quick, easy and low-technology device with good utility, that is relatively resistant to the usual confounders for vibration threshold measurement. Further studies to explore its validity in relation to other well-recognised methods for detection of subtle neurotoxic impacts should be encouraged.

Adult↗

Heterogeneous cytokine production by acutely stimulated bronchoalveolar T lymphocytes in reovirus 1/Lang-infected mice.

While the in vitro properties of CD4(+) and CD8(+) cytokine-producing lymphocytes have been well studied, the in vivo cytokine production patterns and relative roles of CD4(+) and CD8(+) T lymphocytes during a primary in vivo immune response remain unclear. In this study, mice were inoculated intranasally with reovirus 1/L, and respiratory T lymphocyte populations were analyzed using multicolor flow cytometric analysis for the production of cytokine within and between classical type 1/type 2 patterns. Cytokine production observed in vivo following infection did not correlate with classical T cell cytokine expression patterns; instead, multiple types of lymphocyte populations that produced one of several possible cytokine combinations were present. Cytokine production by CD4(+) lymphocytes appears in the early and middle stages of the immune response, while CD8(+) lymphocytes produce more cytokine in the later stages. Early cytokine responses occurred predominantly in the whole lung and lung-associated lymph node populations. The complex patterns of cytokine expression seen in this study likely influence local cell-mediated immunity as well as the complex interaction of T cell subsets and the interaction of T cells with B cells which are necessary for the generation of cell-mediated and humoral immune responses required for effective broad-spectrum immunity.

Animals↗

Polychlorinated biphenyl mixtures (Aroclors) inhibit LPS-induced murine splenocyte proliferation in vitro.

The immune system is believed to be a sensitive indicator for adverse polychlorinated biphenyl (PCB)-induced health effects. Four commercial PCB mixtures (Aroclors) or six individual PCB congeners were evaluated for their effect on splenocyte viability and lipopolysaccharide (LPS)-induced splenocyte proliferation in vitro in two strains of mice, C57B1/6 (high affinity aromatic hydrocarbon receptor (AhR) complex) and DBA/J (low affinity AhR complex). All four Aroclors, the selected individual noncoplanar congeners, or two tertiary mixtures containing one congener from each class significantly decreased the in vitro LPS-induced proliferation of murine splenocytes in either strain of mice without inducing a significant decrease in viability. In contrast, selected individual coplanar or mono-ortho-coplanar congeners did not inhibit splenocyte proliferation or viability at any concentration. These results suggest that mixtures of PCBs and/or congener class (specifically, noncoplanar congeners) may be more highly immunotoxic than individual planar and mono-ortho-coplanar congeners alone. Thus, this in vitro assay has revealed a more complex pattern of immunotoxicity of Aroclors versus individual congeners than has previously been reported or anticipated based on both in vivo derived immunotoxic data and standard comparisons to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These results have important practical significance since mixtures of PCB congeners were used industrially and now contaminate the environment.

Animals↗

Transcriptional pause, arrest and termination sites for RNA polymerase II in mammalian N- and c-myc genes.

Using either highly purified RNA polymerase II (pol II) elongation complexes assembled on oligo(dC)-tailed templates or promoter-initiated (extract-generated) pol II elongation complexes, the precise 3" ends of transcripts produced during transcription in vitro at several human c- and N- myc pause, arrest and termination sites were determined. Despite a low overall similarity between the entire c- and N- myc first exon sequences, many positions of pol II pausing, arrest or termination occurred within short regions of related sequence shared between the c- and N- myc templates. The c- and N- myc genes showed three general classes of sequence conservation near intrinsic pause, arrest or termination sites: (i) sites where arrest or termination occurred after the synthesis of runs of uridines (Us) preceding the transcript 3" end, (ii) sites downstream of potential RNA hairpins and (iii) sites after nucleotide addition following either a U or a C or following a combination of several pyrimidines near the transcript 3" end. The finding that regions of similarity occur near the sites of pol II pausing, arrest or termination suggests that the mechanism of c- and N- myc regulation at the level of transcript elongation may be similar and not divergent as previously proposed.

Base Sequence↗

Optimal induction of upper respiratory tract immunity to reovirus 1/L by combined upper and lower respiratory tract inoculation.

There has been an increasing interest in developing vaccines which are both easy to administer and which elicit functionally protective immune responses at mucosal and/or systemic sites. Intranasally administered vaccines meet the criteria of ease of administration and are thought to stimulate respiratory-mucosal immunity via interaction with nasal associated lymphoid tissues (NALT). The aim of this study was to gain a better understanding of how best to stimulate respiratory-mucosal immunity using a murine model of respiratory reovirus infection. Either a predominantly upper respiratory tract infection or a combination upper and lower respiratory tract infection was established by administering the same virus dose in either a small or large inoculum volume. These studies demonstrate that stimulation of NALT alone by an upper respiratory tract infection does not induce an optimal primary antibody response even in the nasal cavity. Effective immunity of both the upper and lower respiratory tract was obtained when a combination upper and lower respiratory tract infection was established. These results have important clinical implications since they suggest that effective respiratory mucosal immunity will be best achieved by the combined stimulation of both the upper and lower respiratory tract and will likely require both intranasal as well as inhaled aerosol delivery of antigen to the lower respiratory tract in humans.

Administration, Intranasal↗

Prolonged induction of IL-8 gene expression in a human fibroblast cell line infected with reovirus serotype 1 strain Lang.

Viruses which infect mucosal surfaces commonly infect these particular anatomical sites based on both the virion structure and the interaction of the virus with a particular microenvironment. We infected a human lung epithelial cell line, a human gut epithelial cell line, and a human lung fibroblast cell line with reovirus 1/L to explore how this natural isolate of both the lung and the gut may interact with mucosal surfaces. While reovirus infection of the gut and lung epithelial cell lines was lytic, a chronic infection was established in the human lung fibroblast cell line. All three cell lines also produced interleukin-8 (IL-8) after infection with reovirus 1/L, and IL-8 production was not dependent upon viral replication. A prolonged production of IL-8 was observed in the chronically infected lung fibroblast cell line, suggesting that this mucosal population may be involved in the generation of inflammatory responses after the resolution of the initial lytic infection of the epithelium. These studies provide an in vitro model system for analyzing the interaction of reovirus 1/L with resident mucosal cell populations.

Cell Line↗