bluuebunny/crossref_metadata_2025 huggingface dataset:
A Family of
acr
-Coregulated
Mycobacterium tuberculosis
Genes Shares a Common DNA Motif and Requires Rv3133c (
dos
R or
dev
R) for Expression
Authors: Florczyk Matthew A. , McCue Lee Ann , Purkayastha Anjan , Currenti Egidio , Wolin Meyer J. , McDonough Kathleen A.
Published: August 2003

Previous work has shown that the divergently transcribed
Mycobacterium tuberculosis
genes
acr
(
hspX
, Rv2031c) and
acg
(Rv2032) are induced under conditions of shallow standing culture and low oxygen and intracellularly within macrophages. We used a combination of computational and experimental methods to identify promoters for eight additional genes that are regulated in a similar manner and that comprise an
acr
-coregulated promoter (ACP) family. Transcriptional regulation of these ACP family members was evaluated by using a plasmid-based promoter-green fluorescent protein fusion system and flow cytometry. All promoters showed increased expression in shallow standing versus shaking cultures, in low- versus high-oxygen conditions, and intracellularly within macrophages versus extracellularly in tissue culture medium. However, there were quantitative differences in expression among promoters and among conditions for each promoter. A conserved 18-bp palindromic sequence motif was identified in all ACPs by Gibbs sampling-based computational analyses. Two such motifs overlap regions in the
acr
and
acg
promoters that were previously shown to be required for their expression. In addition, we found that 5% carbon dioxide was required for growth of
Mycobacterium bovis
BCG under microaerophilic (1.3% O
2
) culture conditions and fully prevented the growth cessation typically associated with rapid removal of oxygen. These findings are likely to be relevant to the in vivo environment and will contribute to our understanding of the pathogenesis of tuberculosis infection.
Calcineurin Is Essential for Virulence in
Candida albicans
Authors: Bader Teresa , Bodendorfer Barbara , Schröppel Klaus , Morschhäuser Joachim
Published: August 2003

Calcineurin is a conserved Ca
2+
-calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast
Cryptococcus neoformans
, calcineurin is also essential for growth at 37°C and virulence. To investigate whether calcineurin plays a role in the virulence of
Candida albicans
, the major fungal pathogen of humans, we constructed
C. albicans
mutants in which both alleles of the
CMP1
gene, encoding the calcineurin catalytic subunit, were deleted. The
C. albicans
Δ
cmp1
mutants displayed hypersensitivity to elevated Na
+
, Li
+
, and Mn
2+
concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast
Saccharomyces cerevisiae
. Unlike
S. cerevisiae
calcineurin mutants, which exhibit reduced susceptibility to high Ca
2+
concentrations, growth of
C. albicans
was inhibited in the presence of 300 mM CaCl
2
after the deletion of
CMP1
, demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to
C. neoformans
, inactivation of calcineurin did not cause temperature sensitivity in
C. albicans
. In addition, hyphal growth, an important virulence attribute of
C. albicans
, was not impaired in the Δ
cmp1
mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in
C. albicans
.
Evidence for a Melanin Cell Wall Component in
Pneumocystis carinii
Authors: Icenhour Crystal R. , Kottom Theodore J. , Limper Andrew H.
Published: August 2003

Fluorescein isothiocyanate-labeled monoclonal antibodies specific for fungal melanin were used in this study to visualize melanin-like components of the
Pneumocystis carinii
cell wall. A colorimetric enzyme assay confirmed these findings. This is the first report of melanin-like pigments in
Pneumocystis
.
Intracellular Expression of the Plasmid-Encoded Toxin from Enteroaggregative
Escherichia coli
Authors: Sui Bao Quan , Dutta Pinaki R. , Nataro James P.
Published: August 2003

The plasmid-encoded toxin (Pet) from enteroaggregative
Escherichia coli
is a serine protease autotransporter that acts as an enterotoxin and cytotoxin. When applied to epithelial cells in culture, purified toxin induces cell elongation and rounding, followed by exfoliation of cells from the substratum. These effects are accompanied by loss of actin stress fibers and electrophysiologic changes. Although it has been hypothesized that Pet has an intracellular site of action, evidence for this is indirect. In addition, Pet has recently been shown to cleave spectrin in vitro and in vivo. If Pet requires intracellular localization to execute its toxic effects, then intracellular expression of the protein could induce cytopathic effects similar to those observed when the toxin is applied to the cell surface. To test this hypothesis, we expressed the mature Pet toxin (comprising only the passenger domain of the Pet precursor) in the cytoplasm of HEp-2 cells by using mammalian expression vectors. Separately, we expressed the Pet passenger domain mutated at the catalytic serine (PetS260A), a construct that has been reported to lack toxic effects. Forty-eight hours after transient transfection of pcDNA3.1-
pet
in HEp-2 cells, we observed cell elongation and other morphological changes similar to those induced by applied toxin. Cells transfected with pcDNA3.1 vector alone appeared normal, while cells expressing the PetS260A mutant displayed similar (though less pronounced) changes compared with those in cells expressing pcDNA3.1-
pet
. Notably, intracellular expression of Pet was accompanied by condensation of the spectrin cytoskeleton. These studies corroborate an intracellular site of action for the Pet toxin, further implicate a role for spectrin in Pet intoxication, and provide a powerful tool for Pet structure and function analyses.
Accumulation of
Clostridium perfringens
Epsilon-Toxin in the Mouse Kidney and Its Possible Biological Significance
Authors: Tamai Eiji , Ishida Tetsuya , Miyata Shigeru , Matsushita Osamu , Suda Hirofumi , Kobayashi Shoji , Sonobe Hiroshi , Okabe Akinobu
Published: August 2003

In this paper we show that
Clostridium perfringens
epsilon-toxin accumulates predominantly in the mouse kidney, where it is distributed mainly in glomeruli, capillaries, and collecting ducts. Although some pycnotic and exfoliated epithelial cells were observed in distal tubuli and collecting ducts, there were no findings indicative of severe renal injury. Bilateral nephrectomy increased the mouse lethality of the toxin, suggesting that the kidney contributes to the host defense against the lethal toxicity of epsilon-toxin.
Intracellular Survival of
Streptococcus pyogenes
in Polymorphonuclear Cells Results in Increased Bacterial Virulence
Authors: Medina Eva , Rohde Manfred , Chhatwal Gursharan S.
Published: August 2003

It has recently been shown that survival within phagocytic cells constitutes an additional strategy used by
Streptococcus pyogenes
to evade the host defenses. Here we provide evidence that
S. pyogenes
can escape from the phagosome into the cytoplasm of phagocytic cells. Furthermore, intracellular bacteria seem to undergo phenotypic switching that results in much more virulent microorganisms.
Two-Component Systems of
Helicobacter pylori
Contribute to Virulence in a Mouse Infection Model
Authors: Panthel Klaus , Dietz Patricia , Haas Rainer , Beier Dagmar
Published: August 2003

Helicobacter pylori
encodes three histidine kinases and five response regulators belonging to the family of two-component regulatory systems which are involved in transcriptional control. Here we demonstrate that isogenic mutants of
H. pylori
P76 with deletions of the response regulator open reading frame (ORF) HP1365 and ORFs HP244, HP165, and HP1364 encoding histidine kinases are unable to colonize the stomachs of BALB/c mice, suggesting an essential role of these systems in the regulation of important virulence properties of
H. pylori
. Furthermore, we demonstrate that the genes under the control of the P
HP1408
and P
HP119
promoters which are regulated by the two-component system HP166-HP165 are not essential for single mutant colonization of mice but are required under competitive colonization conditions.
Role of Periplasmic Peptidylprolyl Isomerases in
Salmonella enterica
Serovar Typhimurium Virulence
Authors: Humphreys Sue , Rowley Gary , Stevenson Andrew , Kenyon William J. , Spector Michael P. , Roberts Mark
Published: August 2003

FkpA is a peptidylprolyl isomerase whose expression is regulated by the alternative sigma factor, sigma factor E (σ
E
). In contrast to the results of a previous report, inactivation of
fkpA
was found to have only a minor effect on the ability of
Salmonella enterica
serovar Typhimurium to invade and survive within epithelial and macrophage cell lines and cause infection in mice. However, an effect of the
fkpA
mutation on serovar Typhimurium virulence was seen if the mutation was combined with mutations in
surA
or
htrA
, two other σ
E
-regulated genes, which encode proteins involved in protein folding and/or degradation in the periplasm.
Twitching Motility Contributes to the Role of Pili in Corneal Infection Caused by
Pseudomonas aeruginosa
Authors: Zolfaghar Irandokht , Evans David J. , Fleiszig Suzanne M. J.
Published: August 2003

Twitching motility is a form of surface-associated bacterial movement mediated by type IV pili of
Pseudomonas aeruginosa
. Others have shown that
pilT
and
pilU
mutants, which are piliated but defective in twitching motility, display reduced cytotoxic capacity towards epithelial cells in vitro. Although these mutants efficiently infected lungs in vivo, they were defective in dissemination to the liver. In this study the role of twitching motility in
P. aeruginosa
epithelial cell invasion and corneal disease pathogenesis was explored.
pilU
and
pilT
mutants of
P. aeruginosa
strain PAK were compared to a nonpiliated
pilA
mutant and to wild-type bacteria in their ability to associate with and to invade corneal epithelial cells in vitro and to cause disease in a murine model of corneal infection. As expected, the
pilA
mutant demonstrated reduced association and invasion of corneal epithelial cells (
P
< 0.05 in both cases). The
pilT
mutant, but not the
pilU
mutant, was less invasive than wild-type PAK was (
P
< 0.05 versus
P
= 0.43), while both
pilU
and
pilT
mutants exhibited association levels similar to those of the wild type (
P
= 0.31 and 0.52, respectively). In vivo, all mutants were markedly attenuated in virulence and showed reduced ability to colonize the cornea at 4 and 48 h (all
P
values < 0.02). Thus, twitching motility contributed to the role of pili in corneal disease but was not involved in the role of pili in adherence to or invasion of corneal epithelial cells.
Differential Interleukin-8 and Nitric Oxide Production in Epithelial Cells Induced by Mucosally Invasive and NoninvasiveTrypanosoma cruziTrypomastigotes
Authors: Eickhoff C. S. , Eckmann L. , Hoft D. F.
Published: August 2003

Trypanosoma cruzimetacyclic trypomastigotes (MT), but not blood form trypomastigotes (BFT), are highly mucosally infective. We investigated the abilities of MT and BFT to induce inflammation and/or intracellular killing activity within mucosal epithelia. BFT, but not MT, induced marked increases in interleukin-8, GRO-α, MCP-1, and nitric oxide production in HeLa and AGS cells, despite similar infectivities. MT may avoid induction of inflammation as an important biological mechanism facilitating mucosal invasion.
Genetic Variation Influences the B-Cell Response to Immunization with a Pneumococcal Polysaccharide Conjugate Vaccine
Authors: McCool T. L. , Schreiber J. R. , Greenspan N. S.
Published: August 2003

CBA/J mice immunized with pneumococcal 23F-CRM
197
vaccine produce significantly lower titers of 23F-specific antibodies and fewer 23F-specific antibody-secreting cells (ASC) than did BALB/c or (CBA/J × BALB/c)F
1
(CCBAF
1
) mice. The reduced 23F-specific titers of CBA/J versus BALB/c or CCBAF
1
mice are presumably related to lower frequencies of 23F-specific ASC influenced by genetic variation.
Signaling via Toll-Like Receptor 5 Can Initiate Inflammatory Mediator Production by Murine Osteoblasts
Authors: Madrazo Denise R. , Tranguch Susanne L. , Marriott Ian
Published: August 2003

Murine osteoblasts express Toll-like receptor 5 (TLR5), and this expression is upregulated following exposure to bacteria or to the TLR5 agonist, flagellin. Importantly, flagellin activates transcriptional regulators and elicits proinflammatory cytokine production, suggesting TLR5 functionality. TLR5 may represent an important mechanism underlying the recognition of bacterial pathogens by osteoblasts during bone infections.
The Small Nucleoid-Binding Proteins H-NS, HU, and Fis Affect
hilA
Expression in
Salmonella enterica
Serovar Typhimurium
Authors: Schechter Lisa M. , Jain Sumita , Akbar Samina , Lee Catherine A.
Published: August 2003

hilA
encodes an activator of
Salmonella enterica
serovar Typhimurium virulence genes and is transcriptionally modulated by environmental conditions. We show that H-NS represses
hilA
under low-osmolarity conditions. H-NS, HU, and Fis also appear to affect the derepression of
hilA
by HilD. Modulation of
hilA
by counteracting repressing and derepressing mechanisms may allow
Salmonella
serovar Typhimurium to regulate its virulence genes in response to different situations in vivo.
Production of FaeG, the Major Subunit of K88 Fimbriae, in Transgenic Tobacco Plants and Its Immunogenicity in Mice
Authors: Huang Yahong , Liang Wanqi , Pan Aihu , Zhou Zhiai , Huang Cheng , Chen Jianxiu , Zhang Dabing
Published: August 2003

Transgenic tobacco plants stably expressing recombinant FaeG, which is the major subunit and adhesin of K88ad fimbriae, were obtained. Analysis of sera from immunized mice indicates that in mice, the immunogenicity induced by plant-derived FaeG protein is comparable to that generated with traditional approaches.
Signature-Tagged Mutagenesis of
Pasteurella multocida
Identifies Mutants Displaying Differential Virulence Characteristics in Mice and Chickens
Authors: Harper Marina , Boyce John D. , Wilkie Ian W. , Adler Ben
Published: August 2003

Pasteurella multocida
is the causative agent of fowl cholera in birds. Signature-tagged mutagenesis (STM) was used to identify potential virulence factors in a mouse septicemia disease model and a chicken fowl cholera model. A library of
P. multocida
mutants was constructed with a modified Tn
916
and screened for attenuation in both animal models. Mutants identified by the STM screening were confirmed as attenuated by competitive growth assays in both chickens and mice. Of the 15 mutants identified in the chicken model, only 5 were also attenuated in mice, showing for the first time the presence of host-specific virulence factors and indicating the importance of screening for attenuation in the natural host.
Occupational health guidelines for the management of low back pain: an international comparison
Authors: Staal J B , Hlobil H , van Tulder M W , Waddell G , Burton A K , Koes B W , van Mechelen W
Published: August 2003

Background:The enormous socioeconomic burden of low back pain emphasises the need for effective management of this problem, especially in an occupational context. To address this, occupational guidelines have been issued in various countries.

Aims:To compare available international guidelines dealing with the management of low back pain in an occupational health care setting.

Methods:The guidelines were compared regarding generally accepted quality criteria using the AGREE instrument, and also summarised regarding the guideline committee, the presentation, the target group, and assessment and management recommendations (that is, advice, return to work strategy, and treatment).

Results and Conclusions:The results show that the quality criteria were variously met by the guidelines. Common flaws concerned the absence of proper external reviewing in the development process, lack of attention to organisational barriers and cost implications, and lack of information on the extent to which editors and developers were independent. There was general agreement on numerous issues fundamental to occupational health management of back pain. The assessment recommendations consisted of diagnostic triage, screening for “red flags” and neurological problems, and the identification of potential psychosocial and workplace barriers for recovery. The guidelines also agreed on advice that low back pain is a self limiting condition and, importantly, that remaining at work or an early (gradual) return to work, if necessary with modified duties, should be encouraged and supported.
A mortality and morbidity study of refinery and petrochemical employees in Louisiana
Authors: Tsai S P , Wendt J K , Cardarelli K M , Fraser A E
Published: August 2003

Aims:To examine the mortality experience of 4221 employees from 1973 to 1999 and the illness absence patterns for 2203 employees from 1990 to 1999 of a chemical and refinery facility in Louisiana.

Methods:Mortality and illness absence data were extracted from the Shell Oil Company’s health surveillance system (HSS). The standardised mortality ratio was used as a measure of mortality risk. Morbidity frequency and duration of absence were calculated by age, sex, and four health risk factors (cigarette smoking, high blood pressure, hypercholesterolaemia, and obesity).

Results:Male employees experienced a significant deficit in mortality for all causes of death, all cancers, lung cancer, heart disease, and respiratory disease compared with the corresponding US population. Brain cancer was non-significantly increased, with six observed and five expected deaths; mortality from leukaemia was consistently lower than expected. The majority of employees had no illness absences of six days or longer during the 10 year study period. The loss of productivity (in terms of days of absence) was greater for employees with health risk factors. Ever smoking male employees had a 79% increase of heart disease and more than 50% higher rates of respiratory disease and musculoskeletal disorders compared to non-smokers. Smokers were absent 2.9 and 1.6 more days than non-smokers and ex-smokers, respectively.

Conclusions:Regardless of the comparison population, significantly fewer deaths were seen for all causes combined, all cancers, lung cancer, heart disease, or non-malignant respiratory disease. Illness absence rates and duration were higher among employees with health risk factors.
Occupation related pesticide exposure and cancer of the prostate: a meta-analysis
Authors: Van Maele-Fabry G , Willems J L
Published: August 2003

Aims:To summarise recent literature on the risk of prostate cancer in pesticide related occupations, to calculate the meta-rate ratio, and to compare it to data from meta-analyses previously published.

Methods:A meta-analysis of 22 epidemiological studies, published between 1995 and 2001, was conducted in order to pool their rate ratio estimates. Studies were summarised and evaluated for homogeneity and publication bias.

Results:The meta-rate ratio estimate, based on 25 estimators of relative risk from 22 studies, was 1.13 (95% CI 1.04 to 1.22). Significant heterogeneity of rate ratios existed among the different studies. Therefore, a stratified analysis was carried out. Major sources of heterogeneity identified were geographic location, study design, and healthy worker effect. Overall, pooled risk estimates for studies derived from Europe were lower than those derived from the USA/Canada. A significant increase in rate ratio was observed for the occupation category of pesticide applicators, whereas no significant increase was observed for farmers. There was no evidence of publication bias.

Conclusion:This increased meta-rate ratio for prostate cancer in different pesticide related occupations, including farmers, is very similar to three, previously published, meta-rate ratios for prostate cancer in farmers calculated from studies published before 1995. Although the underlying data do not identify pesticide exposure as an independent cause for prostate cancer, the fact that an increased meta-rate ratio is again obtained points to occupational exposure to pesticides as a possible factor. Future epidemiological studies should focus, as far as possible, on reliable methods to estimate actual exposure.
Smoking and occupation from the European Community Respiratory Health Survey
Authors: McCurdy S A , Sunyer J , Zock J-P , Antó J M , Kogevinas M ,   European Community Respiratory Health Survey Study Group
Published: August 2003

Background:Smoking is among the most important personal and modifiable risk factors for adverse health outcomes. The workplace offers a potentially effective venue for tobacco prevention programmes; identifying occupational groups with high smoking prevalence may assist in targeting such programmes.

Aims:To examine smoking prevalence among occupational groups in the European Union.

Methods:The European Community Respiratory Health Survey (ECRHS), a cross sectional health survey conducted in 1992–93, was used to examine smoking prevalence by occupation among 14 565 subjects from 30 centres in 14 participating countries.

Results:There was an approximately twofold range in smoking prevalence by occupation. For occupational groups with at least 50 subjects, the highest smoking prevalence was seen in metal making and treating for men (54.3%) and cleaners for women (50.7%). Increased smoking prevalence by occupation persisted after adjustment for age, country, and age at completion of education. Smoking was also increased among occupations with high exposure to mineral dust and gas or fumes.

Conclusions:Smoking rates vary significantly by occupation. Prevention efforts in the workplace should focus on occupations with high smoking prevalence and large employment bases.
Risk factors in the onset of neck/shoulder pain in a prospective study of workers in industrial and service companies
Authors: Andersen J H , Kaergaard A , Mikkelsen S , Jensen U F , Frost P , Bonde J P , Fallentin N , Thomsen J F
Published: August 2003

Aims:To quantify the relative contribution of work related physical factors, psychosocial workplace factors, and individual factors and aspects of somatisation to the onset of neck/shoulder pain.

Methods:Four year prospective cohort study of workers from industrial and service companies in Denmark. Participants were 3123 workers, previously enrolled in a cross sectional study, where objective measurement of physical workplace factors was used. Eligible participants were followed on three subsequent occasions with approximately one year intervals. Outcomes of interest were: new onset of neck/shoulder pain (symptom cases); and neck/shoulder pain with pressure tenderness in the muscles of the neck/shoulder region (clinical cases).

Results:During follow up, 636 (14.1%) participants reported neck/shoulder pain of new onset; among these, 82 (1.7%) also had clinical signs of substantial muscle tenderness. High shoulder repetition was related to being a future symptom case, and a future clinical case. Repetition was strongly intercorrelated with other physical measures. High job demands were associated with future status as a symptom case, and as a clinical case. A high level of distress predicted subsequent neck/shoulder pain, and neck/shoulder pain with pressure tenderness.

Conclusions:High levels of distress, and physical and psychosocial workplace factors are predictors of onset of pain in the neck and/or shoulders, particularly pain with pressure tenderness in the muscles.
Prevalence and association of welding related systemic and respiratory symptoms in welders
Authors: El-Zein M , Malo J-L , Infante-Rivard C , Gautrin D
Published: August 2003

Background:The prevalence of welding related respiratory symptoms coexisting with welding related systemic symptoms in welders is unknown.

Aims:To determine in a sample of welders the prevalence of coexisting welding related systemic symptoms indicative of metal fume fever (MFF) and welding related respiratory symptoms suggestive of occupational asthma (OA), and the strength and significance of any association between these two groups of symptoms.

Methods:A respiratory symptoms questionnaire, a systemic symptoms questionnaire, and a questionnaire on occupational history were administered by telephone to 351 of a sample of 441 welders (79.6%) from two cities in Québec, Canada.

Results:The co-occurrence of possible MFF (defined as having at least two symptoms of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, and shortness of breath, occurring at the beginning of the working week, 3–10 hours after exposure to welding fumes) together with welding related respiratory symptoms suggestive of OA (defined as having at least two welding related symptoms of cough, wheezing, and chest tightness) was 5.8%. These two groups of symptoms were significantly associated (χ2= 18.9, p < 0.001).

Conclusion:There is a strong association between welding related MFF and welding related respiratory symptoms suggestive of OA. As such, MFF could be viewed as a pre-marker of welding related OA, a hypothesis that requires further investigation.
Increased plasma homocysteine levels in shift working bus drivers
Authors: Martins P J F , D’Almeida V , Vergani N , Perez A B A , Tufik S
Published: August 2003

Background:Previous studies have indicated an association between shift work and cardiovascular disease. There is also considerable epidemiological evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular disorders.

Aims:To analyse plasma homocysteine levels in shift work bus drivers, and to investigate possible relations with sleep parameters and other biochemical factors.

Methods:Blood samples were collected from 30 male shift working long-haul bus drivers in a Brazilian sample and analysed for plasma levels of homocysteine, folic acid, vitamin B12, and serum lipids. A group of 22 daytime workers, matched for age and body mass index served as controls. The incidence of mutations in the gene coding for methylene tetrahydrofolate, an enzyme which is related to hyperhomocysteinemia, was also assessed. Polysomnographic recordings were obtained from the target group.

Results:Bus drivers showed significantly higher levels of plasma homocysteine than the control group (18.57v9.43 μM). Most of the other biochemical, behavioural, and molecular parameters did not differ between groups. Likewise, sleep parameters appeared to be within the normal range.

Conclusions:The significantly increased plasma homocysteine levels in long-haul bus drivers did not appear to be secondary to other biochemical or behavioural problems in this group. These results suggest that hyperhomocysteinemia may be involved in the increased incidence of cardiovascular diseases observed in shift workers.
Agreement between hearing thresholds measured in non-soundproof work environments and a soundproof booth
Authors: Wong T W , Yu T S , Chen W Q , Chiu Y L , Wong C N , Wong A H S
Published: August 2003

Aims:To study the agreement between audiometric test results measured in non-soundproof environments at the worksite, and in a soundproof booth.

Methods:In a cross sectional prevalence study on noise induced hearing loss, 885 transport workers whose hearing thresholds were measured by a standard audiometric test method in non-soundproof environments at the worksite were identified to have some hearing loss (>25 dB), and were retested in a soundproof booth.

Results:At 4–8 KHz, the mean of the absolute differences in hearing threshold obtained by these two methods was 2 dB or less. When the proportions of hearing loss (⩾30 dB for any frequencies at 3–8 KHz, or ⩾90 dB for three low frequencies at 0.5–2 KHz, or ⩾90 dB for three high frequencies at 3–6 KHz) were compared, considerable differences existed. A much better agreement was obtained when the criteria for hearing loss as measured in the field test under non-soundproof conditions were relaxed by 5 dB. At 4 KHz, the difference between the proportion of subjects with hearing loss as measured in the field and that as measured in the booth was the smallest. The kappa statistic was highest at 3 and 4 KHz.

Conclusions:Audiometric test results conducted in non-soundproof environments in the field are comparable to those obtained in a soundproof environment among transport workers with a hearing loss of >25 dB. The hearing threshold at 4 KHz appears suitable for the estimation of the prevalence of hearing loss when appropriate adjustments are made in the diagnostic criteria.
Cancer risk for chemical workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
Authors: Bodner K M , Collins J J , Bloemen L J , Carson M L
Published: August 2003

Aims:To describe the long term mortality experience of a cohort of 2187 male chemical production workers previously exposed to substantial levels of dioxin.

Methods:Vital status for a previously identified cohort was determined for an additional 10 years, to 1995. Dioxin exposures took place before 1983 and were sufficient to result in chloracne in 245 individuals. Mortality rates were compared with national figures and with a large pool of co-workers in unrelated production jobs.

Results:All cancers combined (standardised mortality ratio (SMR) = 1.0, 95% CI 0.8 to 1.1) and lung cancer (SMR = 0.8, 95% CI 0.6 to 1.1) were at or below expected levels. Rates for soft tissue sarcoma (SMR = 2.4, 95% CI 0.3 to 8.6) and non-Hodgkin’s lymphoma (SMR = 1.4, 95% CI 0.6 to 2.7) were greater than expected overall, but below expectation in the update period. No trend of increasing risk with increasing exposure was observed for these cancers. Workers who developed chloracne had very low all-cancer rates (SMR = 0.5, 95% CI 0.3 to 1.0), and lung cancer rates (SMR = 0.3, 95% CI 0.0 to 1.1).

Conclusions:We found no coherent evidence of increased cancer risk from dioxin exposure in this cohort. Our study highlights the wide range of cancer rates and the lack of consistency across dioxin studies.
Lymphohaematopoeitic cancer mortality among workers with benzene exposure
Authors: Collins J J , Ireland B , Buckley C F , Shepperly D
Published: August 2003

Lymphohaematopoeitic cancer mortality was examined among 4417 workers at a chemical plant by cumulative and peak benzene exposure. There was little evidence of increasing risk with increasing cumulative exposure for all leukaemias or acute non-lymphocytic leukaemias (ANL), or the other lymphohaematopoeitic cancers with the exception of multiple myeloma. For multiple myeloma, the SMRs were 1.1 (95% CI 0.3 to 2.5) in the non-exposed group, 1.4 (95% CI 0.2 to 5.1) in the <1 ppm-years, 1.5 (95% CI 0.2 to 5.4) in the 1–6 ppm-years, and 2.6 (95% CI 0.7 to 6.7) in the >6 ppm-years group. We found no trends by peak exposures for any of the cancers. However, when peak exposures over 100 ppm for 40 or more days were considered, the observed number of all leukaemias (SMR = 2.7, 95% CI 0.8 to 6.4), ANL (SMR = 4.1, 95% CI 0.5 to 14.9), and multiple myeloma (SMR = 4.0, 95% CI 0.8 to 11.7) were greater than expected. While the observed number of deaths is small in this study, the number of peak exposures greater than 100 ppm to benzene is a better predictor of risk than cumulative exposure. The dose rate of benzene and a threshold for exposure response may be important factors for evaluating lymphohaematopoietic risk.
Risk of soft tissue sarcomas and residence in the neighbourhood of an incinerator of industrial wastes
Authors: Comba P , Ascoli V , Belli S , Benedetti M , Gatti L , Ricci P , Tieghi A
Published: August 2003

Aims:To investigate the association between occurrence of soft tissue sarcomas (STS) in Mantua and residence near an incinerator of industrial wastes.

Methods:Cases were subjects with histologically confirmed primary malignant STS diagnosed 1989–98 in the population resident in Mantua and in the three neighbouring municipalities. Controls were randomly extracted from population registries, matched for age and sex. Residential history was reconstructed for all study subjects since 1960. Main residence was geographically positioned according to GPS standards.

Results:The study included 37 STS cases (17 men and 20 women) and 171 controls. The incidence of STS in the area of study was estimated as 8.8 per 100 000 in men and 5.6 per 100 000 in women. The odds ratio associated with residence within 2 km, standardised by age and sex, was 31.4 (95% CI 5.6 to 176.1), based on five exposed cases. At greater distances, risk rapidly decreased, showing a fluctuation around the null value of 1.

Conclusion:The study shows a significant increase in risk of STS associated with residence within 2 km of an industrial waste incinerator; an aetiological role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can be hypothesised.
Risk factors among elderly for short term deaths related to high levels of air pollution
Authors: Filleul L , Baldi I , Dartigues J-F , Tessier J-F
Published: August 2003

Background:Air pollution has been linked to increased rates of mortality, but little is known about individual characteristics related to the increase in risk.

Aims:To examine short term effects of air pollution on daily mortality in elderly people in Bordeaux and compare characteristics of subjects ⩾65 years old who died with levels of particulate air pollution.

Methods:Daily mortality data from Bordeaux were used to determine the core model of mortality for the period 1988–97. The air pollution indicator was regressed on the core model of mortality, allowing control of the main effect modifiers and confounding factors of air pollution on the same day. The residual series of this regression model was classified from the lowest to the highest to determine “low level days” and “high level days”. A sample of 1469 elderly people in a French cohort study were studied.

Results:From 1988 to 1997, 543 subjects died; 55 deaths were during days with low air pollution and 51 during days with high air pollution. Only gender differed significantly according to both types of days, with a proportion of women significantly higher in high air pollution days than men. After adjustment for smoking habits, the odds ratio was 5.2 for women.

Conclusion:The risk of mortality between women and men was determined on days with “high air pollution levels” above the 50–90th centiles compared to below the 10th centile. No clear pattern was observed between days with low levels of air pollution and the different centiles of exposure.
Driving impairment due to sleepiness is exacerbated by low alcohol intake
Authors: Horne J A , Reyner L A , Barrett P R
Published: August 2003

Aims:To assess whether low blood alcohol concentrations (BACs), at around half the UK legal driving limit, and undetectable by police roadside breathalysers, further impair driving already affected by sleepiness, particularly in young men, who are the most “at risk” group of drivers for having sleep related crashes.

Methods:Twelve healthy young men drove for two hours in the afternoon, in an instrumented car on a simulated motorway. In a repeated measures, counterbalanced design, they were given alcohol or placebo under conditions of normal sleep or prior sleep restriction. Measurements were: driving impairment (lane drifting), subjective sleepiness, and EEG measures of sleepiness.

Results:Whereas sleep restriction and alcohol each caused a significant deterioration in all indices, the combined alcohol and sleep restriction further and significantly worsened lane drifting (which typifies sleep related crashes). This combined effect was also reflected to a significant extent in the EEG, but not with subjective sleepiness. That is, alcohol did not significantly increase subjective sleepiness in combination with sleep loss when compared with sleep loss alone.

Conclusions:Modest, and apparently “safe” levels of alcohol intake exacerbate driving impairment due to sleepiness. The sleepy drivers seemed not to have realised that alcohol had increased their sleepiness to an extent that was clearly reflected by a greater driving impairment and in the EEG.
Monitoring of umbilical cord blood lead levels and sources assessment among the Inuit: Table 1
Authors: Lévesque B , Duchesne J-F , Gariépy C , Rhainds M , Dumas P , Scheuhammer A M , Proulx J-F , Déry S , Muckle G , Dallaire F , Dewailly É
Published: August 2003

Analyses completed on samples collected between 1993 and 1996 showed that about 7% of 475 Inuit newborns from northern Quebec (Canada) had a cord blood lead concentration equal to or greater than 0.48 μmol/l, an intervention level adopted by many governmental agencies. A comparison between the cord blood lead isotope ratios of Inuit and southern Quebec newborns showed that lead sources for these populations were different. Our investigation suggests that lead shots used for game hunting were an important source of lead exposure in the Inuit population. A cohort study conducted in three Inuit communities shows a significant decrease of cord blood lead concentrations after a public health intervention to reduce the use of lead shot. Lead shot ammunition can be a major and preventable source of human exposure to lead.
Can salivary lead be used for biological monitoring of lead exposed individuals?: Figure 1
Authors: Koh D , Ng V , Chua L H , Yang Y , Ong H Y , Chia S E
Published: August 2003

Background:Measurement of blood lead (BPb) is the usual method for biomonitoring of persons exposed to inorganic lead.

Aim:To explore the use of salivary lead (SPb) as an alternative.

Methods:BPb and SPb levels were measured in a group of 82 lead exposed adults.

Results:The mean BPb of the workers was 26.6 μg/dl (SD 8.6, range 10–48) and the mean SPb level 0.77 μg/dl, or 3% of the BPb level. As the SPb distribution was skewed, logarithmic transformation was performed to normalise the distribution. A bivariate scattergram of BPb and logSPb (r= 0.41, p = 0.00) had a line of best fit expressed as BPb = 29.7 + 8.95logSPb. The relation of logSPb and BPb was stronger among non-smokers (r= 0.42) compared to smokers (r= 0.3); and among those without a medical condition (r= 0.44). Multiple linear regression analysis (fitting smoking and medical condition into the model) yielded an R of 0.54, and an adjusted R2of 0.26.

Conclusion:The study findings do not support the use of SPb for biomonitoring at BPb levels ranging from 10 to 50 μg/dl.
Do junior doctors take sick leave?: Table 1
Authors: Perkin M R , Higton A , Witcomb M
Published: August 2003

Nosocomial infections place a heavy burden on overstretched health services. An audit of junior doctors’ sick leave behaviour was undertaken in 1993 and again in 2001. The object was to ascertain the level of common infectious illness and to investigate whether junior doctors were remaining at work inappropriately. The doctors were asked if any factors had influenced their decision to take sick leave or not. Between the two audits several initiatives have been introduced to improve the working conditions of junior doctors, including the New Deal to reduce hours of work. Eighty one junior doctors in a large teaching hospital participated in 1993 and 110 in 2001. The number reporting an infectious illness in the previous six months was similar (61.7% in 1993, 68.2% in 2001). There had been a significant increase in the percentage of infectious illness episodes for which the doctors took sick leave (15.1% in 1993, 36.8% in 2001, p < 0.001). The most common reason for taking less sick leave than was felt necessary was concern about colleagues having to do extra work (72% in 1993, 68% in 2001). Consultant pressure was cited by 26% (1993) and 20% (2001). Use of the staff occupational health unit was minimal, with none of the ill doctors contacting the department in 1993 and only three in 2001. Overall, despite the reduction in the number of infectious doctors not taking sick leave, the majority remained at work. Fundamental changes are needed if potentially infected doctors are not to present a risk of iatrogenic infection.
Occupational asthma due to IgE mediated allergy to the flowerMolucella laevis(Bells of Ireland): Figure 1
Authors: Miesen W M A J , van der Heide S , Kerstjens H A M , Dubois A E J , de Monchy J G R
Published: August 2003

Background:About 25% of greenhouse flower and/or ornamental plant growers sensitised to workplace flowers or moulds have occupational asthma, a disease that is suffered by 8% of the growers who cultivate these crops.

Aim:To document a case of occupational asthma due to IgE mediated allergy to the flowerMolucella laevis.

Methods and Results:There was a history of work related seasonal asthmatic and rhinoconjunctivitis symptoms in aMolucella laevisgrower. Bronchial obstruction following exposure toMolucella laeviswas documented by a fall in FEV1from 89% to 73% of predicted during seasonal exposure toMolucella laevis.Daily PEF measurements showed a fall from 500 to 250 l/min during this period following withdrawal of inhaled steroids. Bronchial reactivity to inhaled methacholine was increased (PC201.45 mg/ml). Confirmation of sensitisation toMolucella laevisflower pollen extract was done using an SPT and by demonstration ofMolucella laevisspecific serum IgE (18 IU/ml; class 4). Specific inhalation challenge withMolucella laevisextract provoked an early and late asthmatic reaction (EAR and LAR) with a fall in FEV1compared with control day of 40% and 53% respectively, with associated 5.1-fold increase in absolute sputum eosinophil cell counts and 2.9-fold increase in neutrophil cell counts.
Age related differences in work injuries and permanent impairment: a comparison of workers’ compensation claims among adolescents, young adults, and adults
Authors: Breslin C , Koehoorn M , Smith P , Manno M
Published: August 2003

Background:There is growing evidence that adolescent workers are at greater risk for work injury.

Aims:To investigate the severity of work injuries across age groups.

Methods:Workers’ compensation records were used to examine work related injuries among adolescents (15–19 years old), young adults (20–24 years old), and adults (25+ years old) between 1993 and 2000. The incidence of compensated injuries was calculated for each age group and compared by gender, industry, and type of injury. The presence and degree of permanent impairment in each age group was also examined.

Results:For males, adolescents and young adults had higher claim rates than adults. For females, adults had the highest claim rates and young adults the lowest. Rates of permanent impairment indicated that age was positively associated with severity of injury.

Conclusions:Indicators of health consequences, in particular presence of permanent impairment, provide preliminary evidence that compensated work injuries sustained by youth are not as serious as injuries sustained by adults. Nevertheless, there was evidence that some young workers sustain injuries that have long term consequences. Documenting the consequences of the injuries that young workers sustain has implications for secondary prevention efforts and health services policy.
Integrative assessment of multiple pesticides as risk factors for non-Hodgkin’s lymphoma among men
Authors: De Roos A J , Zahm S H , Cantor K P , Weisenburger D D , Holmes F F , Burmeister L F , Blair A
Published: August 2003

Background:An increased rate of non-Hodgkin’s lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult.

Methods:During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable.

Results:Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these “potentially carcinogenic” pesticides suggested a positive trend of risk with exposure to increasing numbers.

Conclusion:Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios.
Shift work and subfecundity: a causal link or an artefact?
Authors: Zhu J L , Hjollund N H , Boggild H , Olsen J
Published: August 2003

Aims:The Danish National Birth Cohort (DNBC) was used to examine whether shift work is associated with reduced fecundity as estimated by time to pregnancy (TTP).

Methods:From 1 March 1998 to 1 May 2000, 39 913 pregnant women were enrolled in the DNBC. Data on job characteristics and TTP (0–2, 3–5, 6–12, and >12 months) were used for 17 531 daytime workers and 3907 shift workers who had planned the pregnancy. Fecundity odds ratios (ORs) were calculated with 95% confidence intervals using the discrete time survival analysis techniques performed by logistic regression. An OR above 1 expresses a shorter TTP and then a higher fecundity. Potential confounders, such as age at conception, gravidity, prepregnant body mass index, smoking, and alcohol consumption, as well as occupational characteristics, were also included in the model.

Results:Fixed evening workers and fixed night workers had a longer TTP. Compared with daytime workers, the adjusted ORs were 0.80 (95% CI 0.70 to 0.92) for fixed evening workers, 0.80 (95% CI 0.63 to 1.00) for fixed night workers, 0.99 (95% CI 0.91 to 1.07) for rotating shift (without night) workers, and 1.05 (95% CI 0.97 to 1.14) for rotating shift (with night) workers. When analysis was restricted to nulliparous women, the estimates remained unchanged. The proportions of unplanned pregnancies and contraceptive failures were higher among fixed evening and fixed night workers.

Conclusions:There was no unequivocal evidence of a causal association between shift work and subfecundity. The slightly reduced fecundity among fixed evening workers and fixed night workers may be mediated by pregnancy planning bias or differential options for sexual contacts.
Mortality and cancer incidence in a cohort of meatworkers
Authors: Fritschi L , Fenwick S , Bulsara M
Published: August 2003

Aims:To determine the risk of all cause mortality, cause specific mortality, and incident cancer in meatworkers.

Methods:In a retrospective cohort study, a list of members of a meatworkers union in Australia was matched with the national death and cancer registries. Standardised mortality ratios (SMR) and standardised incidence ratios (SIR) were calculated using Australian population rates. Exposure to animal viruses, animal blood, animal faeces, and plastic pyrolysis products was assigned according to job title. A nested case control analysis examined the risk of mortality and cancer incidence by each exposure.

Results:There were approximately 20 000 subjects available for analysis. Male workers had increased risk of mortality from all causes (SMR 116, 95% CI 105 to 128) and from injury (SMR 131, 95% CI 108 to 157). Risk of incident lung cancer in males was non-significantly increased (SIR 164, 95% CI 97 to 259) and males had a raised risk of head and neck cancer (SIR 188, 95% CI 103 to 315). There were no significant associations with specific exposures.

Conclusions:Compared to the general Australian population, meatworkers have increased risk of death from all causes, death from injury, and incident lung and head and neck cancer. Analysis by occupational exposures did not disclose any strong evidence of specific occupational risk factors, although this analysis was limited by small numbers of some outcomes and exposure assessment which was based on job titles only.