Higher Endotoxin Levels Research Articles

Community structure of bacteria and fungi in aerosols of a pig confinement building

Modern intensive husbandry practices can create poor indoor air quality, with high levels of airborne dust, endotoxins, ammonia, and microorganisms. Air in a sow breeding barn was investigated to determine the biomass composition of bioaerosols using molecular methods supplemented with microscopic and cultivation-dependent approaches. A total of 2.7±0.7×10(7) bacterial cellsm(-3) air and 1.2±0.3×10(6) fungi sporesm(-3) were detected, corresponding to the fungal biovolume constituted 98% of the total microbial biovolume (fungal and bacterial). Fifty-two percent of all 4',6-diamidino-2-phenyl indole-stained cells were detectable with fluorescence in situ hybridization (FISH) with a general bacterial probe mixture. Quantitative FISH of the bacterial consortium revealed Firmicutes as the dominant group with Streptococcus as the major genus, while Actinobacteria constituted 10% of the detectable bacteria. Additionally, the study revealed an abundant and diverse fungal community including species not previously found in similar environments. The most abundant fungal 18S rRNA gene clone sequences identified affiliated with the Aspergillus-Eurotium cluster, but among others, species of Wallemia, Mucorales, and Russulales were detected. For both fungi and anaerobic bacteria, a hitherto undescribed diversity was found in bioaerosols from a modern sow breeding barn, which potentially could create poor indoor air quality, although their effect on the health of farmworkers and stock still is not resolved.

Colonic microbiome is altered in alcoholism.

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.

Effect of oxidative stress and endotoxin on human serum albumin in brain-dead organ donors

Albumin, among other molecules, binds and detoxifies endotoxin in healthy people. Oxidative stress leads to protein oxidation and thus to the impaired binding properties of albumin. This property, in combination with increased gut permeability, leads to the appearance of endotoxin in the systemic circulation and to impaired organ function. We hypothesize that these processes occur in the serum of brain-dead organ donors. Endotoxin was determined with an adapted Limulus amoebocyte lysate assay. The albumin fractions and binding capacity were determined by high-performance liquid chromatography (HPLC). FlowCytomix (eBioscience, San Diego, Calif) was used to determine the cytokine levels. Carbonylated proteins (CPs) and myeloperoxidase (MPO) were measured by an enzyme-linked immunosorbent assay (ELISA). Eighty-four brain-dead organ donors were enrolled and categorized by the duration of intensive care unit (ICU) stay. The albumin-binding capacity for dansylsarcosine was reduced in brain-dead patients compared with controls. Endotoxin positivity in 16.7% of donors was associated with decreased binding capacity in donors and worse survival of recipients. The CP and MPO levels of organ donors were significantly higher than in healthy controls. The durations of ICU stay increased albumin oxidation. In addition, interleukin-6 (IL-6), IL-8, IL-10, and IL-1β levels were increased in patients, whereas the interferon-γ (IFN-γ) levels were within the normal range. We conclude that oxidative stress and systemic endotoxemia are present in brain-dead organ donors, which might affect recipient survival. High endotoxin levels might be caused by increased gut permeability and decreased binding capacity of albumin influenced not just by higher albumin oxidation.

Traffic-Related Pollutants and Wheezing in Children

Background and aims. Traffic related air pollutants from diesel engine exhaust are found in fine and ultrafine particulates. The Cincinnati Childrens Allergy and Air Pollution Birth Cohort Study was initiated to determine if early exposure to these pollutants increased risk for development of early atopic sensitization and allergic respiratory disease phenotypes in children. Materials and methods. Over 700 infants born to at least one atopic parent were recruited to participate in a birth cohort study. Participants received annual medical evaluations and skin testing to two foods and 15 aeroallergens from ages 1-4 and again at age seven. Indoor home assessments were conducted at age one. Outdoor traffic related air pollutant exposure was estimated using proximity and land use regression (LUR) modeling. Clinical outcomes were based upon case definitions for wheezing at ages one and three and allergic rhinitis at age three. Results. At age 1 exposure to stop and go traffic was associated with wheezing during infancy and recurrent wheezing was twice more likely among African-American infants. Exposure to high levels of elemental carbon attributable to traffic (ECAT) estimated with a LUR model predicted recurrent wheezing at age 1 as well as multiple wheezing phenotypes at age 3. Exposure to high levels of endotoxin combined with multiple dogs during the first year reduced risk for recurrent wheezing during the first year of life. Early sensitization to tree pollen aeroallergens in foods (egg white, milk) in infancy increased likelihood of allergic rhinitis during age 3. Conclusion. High exposure to traffic related air pollutants represent independent risk factors for wheezing during infancy and early childhood. Further studies are needed to explore long-term effects of traffic exposure on development of asthma in childhood. Scientific significance. Reduction and mitigation of exposure to traffic related air pollutants could reduce risk of respiratory illnesses during childhood.

Airborne Microorganisms, Endotoxin, and Dust Concentration in Wood Factories in Italy

Exposure to biological agents and dusts occurs in homes and occupational environments and it is known to cause adverse health effects. There is limited information concerning the occupational exposure levels of airborne biohazard during wood processing, but this exposure is associated with a range of adverse health effects. Control of exposure to microbiological hazards and dust in woodworking is not easy. In fact, various types of wood are commonly used and they generate complex mixtures of dusts and biological agents with various health risks. The aim of this study was to investigate the concentration of dust, bacteria, and endotoxins encountered in six different wood factories. These people were exposed to between 0.05 and 12.00 mg inhalable dust m(-3) and between 0.40 and 6.93 ng inhalable endotoxins m(-3). Total bacteria concentrations in the air of the factories examined were within a range of 130-2000 CFU m(-3), the value of Gram negative was within a 0-164 CFU m(-3), and the concentration of Gram positive was within 1-104 CFU m(-3). In conclusion, people working in wood factories may be exposed to high levels of inhalable dust and endotoxins.

Endotoxin levels in house dust samples and juvenile inflammatory bowel disease — a case–control study

Background and aims Animal contact may reduce the risk not only for allergic diseases but also for inflammatory bowel diseases (IBD). We aimed to clarify the association between endotoxin levels in the home environment and IBD. Methods A case–control study including 85 IBD cases (aged: 8–29 years) and 91 controls undergoing strabismus surgery (aged: 11–23 years) was conducted in Southern Germany. A questionnaire and a dust sampling sock were mailed to the parents (Response: 71% among cases, 58% among controls). Endotoxin levels were determined using Limulus Amoebocyte Lysate assay tests. Logistic regression models adjusting for age, sex, high parental school education, family history of IBD, environmental factors in the first year of life (urban place of living, farm animal or pet contact), and presence of cats or dogs in the room were performed. Results Geometric mean levels of endotoxin were lower among cases (50.67 Endotoxin Units (EU)/mg; geometric standard deviation (GSD); 2.32) than controls (60.25 EU/mg; GSD: 2.22). Endotoxin levels were inversely, but not statistically significantly, related to case status in the multivariate logistic regression analysis (OR for the interquartile range increase: 0.70; 95%CI: 0.46–1.04). Conclusion In our study sample, high endotoxin levels were inversely related to case status. Whether endotoxin is a marker of hygiene or causal needs further investigation.

Examining Associations of Circulating Endotoxin With Nutritional Status, Inflammation, and Mortality in Hemodialysis Patients

Lipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram-negative bacteria. Subclinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis (HD) patients. Endotoxin level and clinical effect are determined by its soluble receptor sCD14 and high-density lipoprotein. We examine the hypothesis that endotoxin level correlates with mortality. In this cohort study, endotoxin levels were measured in 306 long-term HD patients who were then followed up for a maximum of 42 months. Soluble CD14 and cytokines levels were also measured. The mean (±SD) endotoxin level was 2.31 ± 3.10 EU/mL (minimum: 0.26 EU/mL, maximum: 22.94 EU/mL, interquartile range: 1.33 EU/mL, median: 1.27 EU/mL). Endotoxin correlated with C-reactive protein (r= 0.11, P< .04). On multivariate logistic regression analysis, high body mass index and low high-density lipoprotein (HDL) cholesterol levels were associated with higher endotoxemia (endotoxin below or above of median). In multivariate Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the third quartile versus first quartile were associated with a trend toward increased hazard ratio for death (hazard ratio: 1.83, 95% confidence interval: 0.93 to 3.6, P = .08). In this HD cohort, we found associations between endotoxemia and C-reactive protein, body composition, and HDL. Moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to assess the effect of endotoxemia on mortality in dialysis population.

Endotoxin removal by hemoperfusion in septic shock

Many symptoms of septic shock are due to the presence of endotoxin in the bloodstream. The biological activity of endotoxins is associated with lipopolysaccharide (LPS). LPS induces systemic inflammatory response and a high level of endotoxin in blood is associated with worse clinical outcome. Reduction of the level of circulating endotoxins with hemoperfusion through the filter with high affinity for LPS could potentially interrupt the biological cascade of sepsis. The aim of the study was to evaluate the efficiency of extracorporeal endotoxin elimination in patients with Gram-negative septic shock.

Do Other Components of Bedding Dust Affect Sensitisation to House Dust Mites?

Bedding dust is a mixture of many components, of which the house dust mite (HDM) allergen, Der p 1, is the most allergenic. There has been little work to investigate the effect of other bedding dust components on HDM sensitisation. The objective of the study was to determine the effect of endotoxin in bedding dust on the allergic response in HDM-sensitised individuals. Twenty-nine house dust mite-sensitised adults were skin prick and allergen patch tested against a sterile solution of their own bedding dust and against a solution containing the same concentration of Der p 1 as the bedding solution for comparison. There was no significant difference in wheal size between the diluted house dust mite solution and the bedding dust in spite of their high levels of endotoxin. Symptomatic subjects had larger, but not statistically significant, responses to commercial house dust mite solution than asymptomatic subjects. Allergen patch test responses were negative in 22/29 of subjects using either bedding dust solutions or comparable diluted house dust mite solutions. An individual's own bedding dust does not appear to contain factors that enhance skin prick test or atopy patch test responses to house dust mites.

COMMENTARY: Acceptable Levels of Endotoxin in Vaccine Formulations During Preclinical Research

This brief commentary reviews endotoxin levels of commercial vaccines and puts them into context for the preclinical researcher working in vaccines. Vaccines are not required to adhere to endotoxin levels as outlined in the United States Pharmacopoeia. Vaccine manufacturers have to show that the vaccine is safe and efficacious in clinical trials. Endotoxin limits are typically lot release specifications for most vaccines, but these values are not available to most researchers designing preclinical experiments. The limits outlined are calculated from endotoxin levels found in a variety of vaccine types such as gene vectors, recombinant subunits, polysaccharide, live attenuated, inactivated and toxoid vaccines. It is clear that certain families of vaccines such as toxoids contain much higher levels of endotoxin, where others such as purified recombinant subunits and gene vectors may contain very low levels.

Endotoxemia related to cardiopulmonary bypass is associated with increased risk of infection after cardiac surgery: a prospective observational study

IntroductionPrevious studies have documented a high frequency of endotoxemia associated with cardiopulmonary bypass (CPB). Endotoxemia may be responsible for some of the complications associated with cardiac surgery. The purpose of the study was to examine the prevalence of endotoxemia during cardiopulmonary bypass supported aortocoronary bypass grafting surgery (ACB) using a new assay, the Endotoxin Activity Assay (EAA), and explore the association between endotoxemia and post-operative infection.MethodsThe study was a single center prospective observational study measuring EAA during the perioperative period for elective ACB. Blood samples were drawn at induction of anesthesia (T1), immediately prior to release of the aortic cross-clamp (T2), and on the first post-operative morning (T3). The primary outcome was the prevalence of endotoxemia. Secondary outcomes assessed included infection rates, intensive care unit (ICU) and hospital length of stay. An EAA of < 0.40 units was interpreted as "low", 0.41 to 0.59 units as "intermediate", and ≥0.60 units as "high".ResultsA total of 57 patients were enrolled and 54 patients were analyzable. The mean EAA at T1 was 0.38 +/- 0.14, at T2 0.39 +/- 0.18, and at T3 0.33 +/- 0.18. At T2 only 13.5% (7/52) of patients had an EAA in the high range. There was a positive correlation between EAA and duration of surgery (P = 0.02). In patients with EAA ≥0.40 at T2, 26.1% (6/23) of patients developed post-operative infections compared to 3.5% (1/29) of those that had a normal EAA (P = 0.0354). Maximum EAA over the first 24 hours was also strongly correlated with risk of post-operative infection (P = 0.0276).ConclusionsHigh levels of endotoxin occur less frequently during ACB than previously documented. However, endotoxemia is associated with a significantly increased risk of the development of post-operative infection. Measuring endotoxin levels during ACB may provide a mechanism to identify and target a high risk patient population.

The association between endotoxin and lung function among children and adolescents living in a rural area.

BACKGROUND⁄ Knowledge of the effects of domestic endotoxin on children's lung function is limited. The association between domestic endotoxin and asthma or wheeze and lung function among school-age children (six to 18 years of age) was examined. The interaction between endotoxin and other personal and environmental characteristics and lung function was also assessed. A case-control study was conducted in and around the rural community of Humboldt, Saskatchewan, between 2005 and 2007. Parents of cases reported either doctor-diagnosed asthma or wheeze in the previous year. Controls were randomly selected from those not reporting these conditions. Data were collected by questionnaire to ascertain symptoms and conditions, while spirometry was used to measure lung function including forced vital capacity and forced expiratory volume in 1 s. Dust collected from the child's play area floor and the child's mattress was used to quantify endotoxin, and saliva was collected to quantify cotinine levels and assess tobacco smoke exposure. There were 102 cases and 207 controls included in the present study. Lower forced expiratory volume in 1 s was associated with higher mattress endotoxin load among female cases (beta=-0.25, SE=0.07 [P<0.01]). There was a trend toward lower forced vital capacity, which was associated with higher play area endotoxin load among cases with high tobacco smoke exposure (beta=-0.17, SE=0.09 [P<0.10]). Findings indicated that high endotoxin levels present in common household areas of rural children with asthma or wheeze may also affect their lung function. These associations may be potentiated by tobacco smoke exposure and female sex.

Workers’ exposure to dust, endotoxin and β-(1–3) glucan at four large-scale composting facilities

Objectives To characterise compost workers’ exposure to dust, endotoxin and β-(1–3) glucan during various operational practices and investigate whether dust concentrations are a useful indicator of endotoxin exposure in compost workers. Methods This study assessed inhalable dust fractions, bacterial endotoxin and β-(1–3) glucan in 117 personal samples and 88 ambient samples from four large-scale composting facilities. Results Employees’ exposures to inhalable dust, endotoxin and β-(1–3) glucan exhibited a large range. Inhalable dust was found to be generally low (GM 0.99 mg/m 3, GSD 2.99 mg/m 3). Analysis of the biological component of the dust showed that employees’ exposures to endotoxin were elevated (GM 35.10 EU/m 3, GSD 9.97 EU/m 3). Employees’ exposure to β-(1–3) glucan was low (GM 0.98 ng/m 3, GSD 13.39 ng/m 3). Dust levels were elevated during manual sorting and screening of waste and high levels of endotoxin and β-(1–3) glucan were observed during all practices involving the movement of waste. A significant correlation was observed between the personal dust levels and personal endotoxin concentrations ( r = 0.783, p < 0.05) and that personal inhalable dust concentration may be a valuable predictor for personal endotoxin concentration in the sites studied. Conclusions Workers at composting sites are exposed to high levels of bacterial endotoxin consistent with adverse respiratory outcomes even though in most cases, their personal dust exposure is below the suggested regulatory levels. Dose–response data for the biological components present in the dust encountered at composting sites are not well established at this time and site operators should adopt precautionary measures when assessing and managing these potential risks.

Health implications of lipopolysaccharide endotoxins in domestic container water used by rural households in South Africa

This study assessed the occurrence of endotoxins, cyanobacteria and enterobacteria in untreated drinking water stored in domestic water containers by rural households in South Africa. Endotoxins, cyanobacteria, total coliforms and Escherichia coli were measured in the following numbers and ranges in container-water samples: 4-54 microg l(-1), 69-64,505 cells ml(-1), 9,000-280,000 CFU/100 ml and 90-1,100 CFU/100 ml, respectively, in source water and 0.23-24.7 microg l(-1), 1-501,187 cells ml(-1), 25-1,584,893 CFU/100 ml and 1-25,118 CFU/100 ml, respectively, in water from containers. The concentrations of these contaminants in water often exceeded guidelines. Container type, especially those that permit light into the vessel, played a significant role in the occurrence of these contaminants. Limited guidelines, as well as the absence of health evidence, make it uncertain whether the high levels of endotoxins in the containerised drinking water could cause a health effect in healthy persons. Most importantly, in the context of exposure to endotoxins potentially derived from high levels of cyanobacteria and enterobacteria such as coliforms in the water, a case is made for possible health effects in immune-compromised individuals exposed to water containing endotoxins and the bacteria that potentially produce it.

Immune Dysregulation in Patients with Severe Acute Pancreatitis

To investigate patients with severe acute pancreatitis (SAP) by dynamic levels of pro-/anti-inflammatory cytokines and endotoxin (ET) in plasma and the relationship between immunity and infection, organ dysfunction. Seventy-two patients with SAP were recruited. The ET, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-4 (IL-4) were determined on admission and days 3, 7, and 14. For comparison, patients were analyzed through infection group versus non-infection group, multiple organ dysfunction syndrome (MODS) group versus non-MODS group. There were sixteen patients with secondary infection, twenty-two with MODS, and nine deaths. The infection group had higher levels of ET than the non-infection group on days 3 and 7. The dynamic cytokine levels of patients in the MODS group were unanimous with those outcomes in the infection group. The levels of cytokines in the infection group were different from the non-infection group, with more levels of TNF-α, IL-6 on days 3 and 7 and less on days 14, and more levels of IL-10, IL-4 on days 7 and 14. The levels of TNF-α, IL-6 in the MODS group were different from the non-MODS group, with more levels on days 3 and 7, and less levels on days 14. Immune dysregulation may play an important role in infection and organ dysfunction for patients with SAP.

Abstract 5736: Household endotoxin levels and risk of non-Hodgkin lymphoma

Abstract Subclinical variation in immune response may be a risk factor for non-Hodgkin lymphoma (NHL). Endotoxin is a substance located in the cell wall of gram-negative bacteria that elicits a strong innate and inflammatory immune response. It is present in large amounts in animal and human fecal material, other organic material, and cigarette smoke. We hypothesized that higher endotoxin exposure might be a risk factor for NHL because of its effect on B-cell activation. Using a population based, multi-center (Detroit, Iowa, Los Angeles and Seattle) case-control study, we evaluated the association between endotoxin levels in carpet dust and NHL risk. During an in-person interview, we collected used vacuum cleaner bags from participants who had used their vacuum within the past year and had owned at least half of their carpets or rugs for 5 years or more. Dust samples were analyzed using the kinetic chromogenic Limulus amebocyte lysate assay in the Pulmonary Toxicology Facility, University of Iowa. Endotoxin measurements from 629 cases and 467 controls were log-transformed and evaluated as both continuous and categorical variables. In order to examine a possible threshold effect, endotoxin levels among controls were categorized into tertiles, with the highest tertile further split into two equal groups based on a preliminary model search. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for sex, age, race, education, study center, and last change of vacuum bag. The highest category of household endotoxin level in dust was associated with a 35% significantly decreased risk of NHL relative to the lowest category (95% confidence interval [CI] = 0.44, 0.96). The effect was stronger for the diffuse large B-cell lymphoma (DLBCL) subtype (Odds Ratio [OR]= 0.49; 95% CI= 0.26,0.91). In conclusion, contrary to our initial hypothesis, our results suggest an inverse association between high levels of household endotoxin and NHL risk. Further studies are needed to validate this finding, ideally with endotoxin measurements prior to diagnosis. Possible mechanisms of action will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5736.

SCD14 in Bronchoalveolar Lavage 18, 42 and 162 Hours After Segmental Allergen Provocation

Lipopolysaccharides (LPS) have been associated with a protective role in the development of asthma while higher levels of endotoxin have been linked with more severe asthma. LPS recruit neutrophils and eosinophils and activate macrophages via the CD14 receptor. The soluble CD 14 receptor (sCD14) has been found in bronchoalveolar lavage fluid in different diseases including allergic asthma. To elucidate the kinetics and the regulation of sCD14 concentrations in BAL in asthma, 18 patients with allergic asthma underwent segmental allergen challenge at different time points (10 min, 18, 42 and 162 h). In addition, CD14(+) peripheral blood mononuclear cell (PBMC-CD14(+)) cultures from seven allergic and seven non-allergic subjects were stimulated with LPS, leukotrien D(4) (LTD(4)), a combination of LPS and LTD(4), IL-17 and LTD(4) in presence of the leukotriene-receptor antagonist (LTRA) Montelukast for 6, 12 and 24 h. sCD14 concentrations in BAL and the supernatants were measured by ELISA. sCD14 concentrations in BAL were significantly increased 18 h after allergen challenge and peaked at 42 h. At 162 h, concentrations had returned to baseline levels. In PBMC-CD14(+) cultures, sCD14 levels increased significantly 24 h after stimulation with LTD(4) and Montelukast was able to block LTD(4)-induced stimulation. Allergen challenge leads to a significant increase in sCD14 concentrations in BAL and might modulate the allergen-induced inflammation. In addition, LTD(4) might play a role in the release of sCD14, and it could be speculated that sCD14 reduction by LTRA might contribute to the mechanisms of LTRA in the treatment of allergic asthma.

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers

ObjectiveTo examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins.MethodsRisk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case–cohort, and 2 case–control studies of cotton textile industry workers, and 15 cohort and 2 case–control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses.ResultsThe summary risk of lung cancer was 0.72 (95% CI, 0.57–0.90) for textile workers and 0.62 (0.52–0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose–dependent protective effect of endotoxins on lung cancer risk.ConclusionDespite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Increased bactericidal/permeability increasing protein in patients with cirrhosis

High levels of endotoxin in patients with cirrhosis are thought to be responsible for the activation of tumour necrosis factor-alpha (TNF)-alpha-mediated pro-inflammatory pathways involved in haemodynamic alterations. Bactericidal/permeability increasing protein (BPI) is a protein found in neutrophils with endotoxin-binding and neutralization capacity. It is not known whether defective BPI production or release is present in cirrhosis. We investigated the levels of BPI in cirrhotic patients and its relation to other endotoxin-binding proteins and inflammatory markers. Plasmatic levels of BPI, lipopolysaccharide-binding protein, soluble CD14, TNF-alpha and BPI mRNA expression in neutrophils were determined in 130 patients and 30 healthy controls. The capacity of patients' plasma to inhibit lipopolysaccharide (LPS)-mediated TNF-alpha production by monocytes from healthy donors was assessed in vitro. Patients with cirrhosis exhibited an increase in BPI mRNA and plasma level of BPI when compared with healthy controls (P<0.05). Child C group displayed the highest frequency of patients with a high concentration of BPI. A positive correlation was found between TNF-alpha and plasma levels of BPI (P<0.01). High levels of BPI in plasma were able to significantly reduce in vitro TNF-alpha release by monocytes after a challenge with LPS (8.54 +/- 1.04 vs. 10.44 +/- 0.85 pg/ml, P=0.028). BPI is increased in cirrhotic patients, especially in those with more severe liver disease. The amount of BPI in the plasma correlated with the TNF-alpha level and was able to reduce LPS-mediated TNF production by monocytes. BPI possibly plays a regulatory role by antagonizing the pro-inflammatory mechanisms mediated by TNF-alpha.

Cleaning efficacy of medical device washers in North American healthcare facilities

The objective of this study was to determine the worst case levels of organic soil on surgical instruments and whether the commercially available TOSI((R)) provided a clinically relevant organic challenge to an instrument washer. Our data showed that protein and haemoglobin levels (374 and 111microg/cm(2), respectively) from the instruments evaluated correlated with those on a TOSI that had a visual score of 2-3 (267 and 60microg/cm(2), respectively). However, the regular TOSI (without the plastic cover) and the TOSI Lum-Chek do not present difficult cleaning challenges; therefore, a visual TOSI score of 1-5 after processing in an automated washer represents a serious cleaning problem. Our results showed that surgical instruments may have high post-cleaning levels of carbohydrate (up to 352microg/cm(2)) and endotoxin (up to 25 373EU/cm(2)), suggesting unrecognised issues with the quality of water used for the final rinse. The average carbohydrate and endotoxin levels post procedure and before cleaning were 138.9microg/cm(2) and 18.14EU/cm(2), respectively. The average protein and haemoglobin levels both showed >99% reduction in levels post cleaning. Our data support the need to monitor the water quality used in instrument washers. In addition, there is an urgent need for establishment of standardised criteria for rapid cleaning indicators for instrument washers to ensure that they provide a clinically relevant method for monitoring washers used in healthcare facilities.