ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19.

BACKGROUND: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. OBJECTIVE: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. METHODS: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point. RESULTS: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality. CONCLUSION: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

A novel processed food classification system applied to Australian food composition databases.

BACKGROUND: The extent of food processing can affect the nutritional quality of foodstuffs. Categorising foods by the level of processing emphasises the differences in nutritional quality between foods within the same food group and is likely useful for determining dietary processed food consumption. The present study aimed to categorise foods within Australian food composition databases according to the level of food processing using a processed food classification system, as well as assess the variation in the levels of processing within food groups. METHODS: A processed foods classification system was applied to food and beverage items contained within Australian Food and Nutrient (AUSNUT) 2007 (n = 3874) and AUSNUT 2011-13 (n = 5740). The proportion of Minimally Processed (MP), Processed Culinary Ingredients (PCI) Processed (P) and Ultra Processed (ULP) by AUSNUT food group and the overall proportion of the four processed food categories across AUSNUT 2007 and AUSNUT 2011-13 were calculated. RESULTS: Across the food composition databases, the overall proportions of foods classified as MP, PCI, P and ULP were 27%, 3%, 26% and 44% for AUSNUT 2007 and 38%, 2%, 24% and 36% for AUSNUT 2011-13. Although there was wide variation in the classifications of food processing within the food groups, approximately one-third of foodstuffs were classified as ULP food items across both the 2007 and 2011-13 AUSNUT databases. CONCLUSIONS: This Australian processed food classification system will allow researchers to easily quantify the contribution of processed foods within the Australian food supply to assist in assessing the nutritional quality of the dietary intake of population groups.

FIT for the future: a case for risk-based colorectal cancer screening using the faecal immunochemical test.

Worldwide, the guaiac faecal occult blood test (gFOBT) is being replaced with the more accurate faecal immunochemical test (FIT) for colorectal cancer (CRC) screening. From January 2016, the National Screening Committee in the UK has recommended a change from the gFOBT to the FIT following a successful Bowel Cancer Screening Programme pilot study with over 40 000 participants. Although the test has shown improved uptake and the ability to detect significantly more colorectal cancers and advanced adenomas, the higher uptake and test positivity will challenge the capacity of colonoscopy services. One of the main advantages of the FIT is that it provides a quantitative haemoglobin concentration which has been shown to relate to the risk of CRC. Risk scoring systems which combine the FIT concentration with risk factor assessment have been shown to improve the sensitivity of the test. This individualized approach to screening could enable those at greatest risk to be referred for colonoscopy, optimizing resource use and ultimately patient outcomes.

Predictors of repeat participation in the NHS bowel cancer screening programme.

OBJECTIVES: Most types of population-based cancer screening require repeat participation to be effective. This study investigated predictors of repeat participation in the NHS Bowel Cancer Screening Programme (BCSP). METHODS: The BCSP in England offers biennial colorectal cancer screening using a guaiac fecal occult blood test (gFOBt) from age 60-74 years. This analysis included 62,081 individuals aged 60-64 years at the time of the first invitation (R1). The main outcome was repeat participation at their second (R2) or third (R3) invitation. Behavioural measures derived from screening records included late return of the gFOBt kit, compliance with follow-up investigations and previous screening participation. Other potential predictors of repeat participation included results of individual test kit analysis (normal, weak positive, strong positive, spoilt) and the definitive result of the gFOBt screening episode (normal or abnormal). Age, sex and socioeconomic deprivation were also recorded. RESULTS: Overall repeat uptake was 86.6% in R2 and 88.6% in R3. Late return of the test kit was consistently associated with lower uptake (R2: 82.3% vs 88.6%, P<0.001; R3: 84.5% vs 90.5%, P<0.001). A definitive abnormal gFOBt result in the previous screening episode was a negative predictor of repeat uptake (R2: 61.4% vs 86.8%, P<0.001; R3: 65.7% vs 88.8%, P<0.001). Weak positive (R2: 76.9% vs 86.8%, P<0.001; R3: 81.7% vs 88.8%, P<0.05) and spoilt test kits (R2: 79.0% vs 86.6%, NS; R3: 84.2% vs 92.2%, P<0.05) were associated with lower repeat uptake, but were not consistently independent predictors in all invitation rounds or subgroups. Among those with a definitive abnormal gFOBt result, noncompliance with follow-up in a previous screening episode was also associated with lower repeat uptake (R2: 24.3% vs 67.1%, P<0.001; R3: 43.2% vs 69.9%, P<0.001). CONCLUSIONS: Behavioural markers and test results from previous screening episodes have been implicated in subsequent gFOBt uptake.

Optimising faecal occult blood screening:retrospective analysis of NHS Bowel Cancer Screening data to improve the screening algorithm.

BACKGROUND: Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or 'spots') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed 'abnormal' and the subject is referred for further investigation, usually colonoscopy. If 1-4 windows are positive, the result is initially 'unclear' and up to two further kits are submitted, further positivity leads to colonoscopy ('weak positive'). If no further blood is detected, the test is deemed 'normal' and subjects are tested again in 2 years' time. We studied the association between spot positivity % (SP%) and neoplasia. METHODS: Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named 'SP%'. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored.The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2. RESULTS: During Episode 2, 284,261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result.The proportion of cancers detected was positively correlated with SP%, with an R(2) correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ~4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%. CONCLUSIONS: This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern.Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ~4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Faecal occult blood testing.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The chapter on faecal occult blood testing includes 21 graded recommendations. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of screening programmes and services.

Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme.

BACKGROUND: Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region. METHODS: Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years. RESULTS: Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9-89.1%), quintiles of poor self-assessed health (87.5-89.5%), non-white ethnicity (84.6-90.6%) and population density (87.9-89.3%), and geographical regions (86.4-90%). CONCLUSION: Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.

The impact of media coverage of the Flexible Sigmoidoscopy Trial on English colorectal screening uptake.

OBJECTIVE: To assess the impact of media coverage of the UK Flexible Sigmoidoscopy Trial on colorectal screening uptake in England. SETTING: In April 2010, publication of the UK Flexible Sigmoidoscopy (FS) Trial results generated considerable media interest in both FS and colorectal cancer (CRC) generally. METHODS: We used routinely collected data from the south of England (excluding London) to analyse return of faecal occult blood test (FOBt) kits within 28 days of the invitation (early uptake) among 60-69 year olds, before (T1, n = 31,229), around the time of (T2, n = 39,571), and one month after (T3, n = 33,430) the FS publicity. RESULTS: FOBt uptake over the whole period was 58.2%, with 38.4% of the kits returned within 28 days (early uptake). Across the three time periods, early uptake was 35.8% at T1, 39.4% at T2, and 39.7% at T3. Multivariate regression controlling for age, gender and socioeconomic status confirmed that uptake was higher if people received the FOBt kit around the time of the media coverage (T2: odds ratio [OR] = 1.17, 95% CI = 1.13-1.20), or one month after (T3: OR = 1.18, 95% CI = 1.15-1.22) than before (T1). Sub-group analyses demonstrated that the impact was stronger among previous non-responders than among first-time invitees or previous responders (P < 0.001). CONCLUSION: Media coverage of the FS Trial appeared to have a small but positive impact on FOBt screening uptake, especially among people who had previously abstained from screening.

Reappraisal of the options for colorectal cancer screening in England.

AIM: The aim was to use newly available data to estimate the cost effectiveness and endoscopy requirements of screening options for colorectal cancer (CRC) to inform screening policy in England. METHODS: A state transition model simulated the life experience of a cohort of individuals in the general population of England with normal colon/rectal epithelium through to the development of adenomas and CRC and subsequent death. CRC natural history model parameters and screening test characteristics were estimated simultaneously by a process of model calibration. This process was fitted to observed data on CRC incidence in the absence of screening, data from existing screening programmes, and data from the UK flexible sigmoidoscopy (FS) screening trial. The costs, effects and resource impact were evaluated for a range of screening options involving the guaiac or immunochemical faecal occult blood test (gFOBT/iFOBT) and FS. RESULTS: The model suggests that screening strategies involving FS or iFOBT may produce additional benefits compared with the current policy of biennial gFOBT for 60-74-year-olds. The age at which a single FS screen results in the greatest quality-adjusted life year gain was 55, with similar gains for ages between 52 and 58. Strategies which combined FS and iFOBT showed further benefits and improved economic outcomes. CONCLUSIONS: Strategies which combine different screening modalities may provide greater clinical and economic benefits. The collection of comprehensive screening data using a uniform format will enable comparative analysis across screening programmes in different countries, will improve our understanding of the disease and will allow identification of optimal screening modalities.

Primary care endorsement letter and a patient leaflet to improve participation in colorectal cancer screening: results of a factorial randomised trial.

BACKGROUND: The trial aimed to investigate whether a general practitioner's (GP) letter encouraging participation and a more explicit leaflet explaining how to complete faecal occult blood test (FOBT) included with the England Bowel Cancer Screening Programme invitation materials would improve uptake. METHODS: A randomised controlled 2 × 2 factorial trial was conducted in the south of England. Overall, 1288 patients registered with 20 GPs invited for screening in October 2009 participated in the trial. Participants were randomised to either a GP's endorsement letter and/or an enhanced information leaflet with their FOBT kit. The primary outcome was verified with return of the test kit within 20 weeks. RESULTS: Both the GP's endorsement letter and the enhanced procedural leaflet, each increased participation by ∼6% - the GP's letter by 5.8% (95% CI: 4.1-7.8%) and the leaflet by 6.0% (95% CI: 4.3-8.1%). On the basis of the intention-to-treat analysis, the random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP's letter and 1.12 (P=0.029) for the leaflet. In the absence of an interaction, an additive effect for receiving both the GP's letter and leaflet (11.8%, 95% CI: 8.5-16%) was confirmed. The per-protocol analysis indicated that the insertion of an electronic GP's signature on the endorsement letter was associated with increased participation (P=0.039). CONCLUSION: Including both an endorsement letter from each patient's GP and a more explicit procedural leaflet could increase participation in the English Bowel Cancer Screening Programme by ∼10%, a relative improvement of 20% on current performance.

Estimation of infant dose and exposure to pethidine and norpethidine via breast milk following patient-controlled epidural pethidine for analgesia post caesarean delivery.

BACKGROUND: There is no information about the distribution of pethidine into breast milk and/or exposure of the breastfed infant during pethidine patient-controlled epidural analgesia after caesarean delivery. METHODS: We conducted an observational study among 20 women. The mean (95% confidence interval) pethidine dose administered was 670 (346-818) mg over 41 (35-46) h. Maternal plasma and milk and neonatal plasma were collected near the time of pethidine cessation and 6h later. Absolute and relative infant doses via milk and infant exposure were calculated. Infant behaviour was assessed using the Neurologic and Adaptive Capacity Score. RESULTS: At first and second sampling times, mean absolute infant doses for pethidine were 20 (14-27) µg/kg/day and 10 (7-13) µg/kg/day, while mean relative infant doses were 0.7 (0.1-1.4)% and 0.3 (0.1-0.5)% respectively. Similar values for norpethidine (expressed as pethidine equivalents) were 21 (16-26) µg/kg/day and 22 (12-32) µg/kg/day; and 0.7 (0.3-1)% and 0.6 (0.2-1)% respectively. Mean pethidine and norpethidine concentrations in neonatal plasma were 3 (0-6.1) µg/L and 0.6 (0.2-1) µg/L. Compared with a time-matched maternal sample, the infant's exposure was 1.4 (0.2-2.8)% for pethidine and 0.4 (0.2-0.6)% for norpethidine. The mean (95% confidence interval) neurologic and adaptive capacity score was 33.6 (32.2-34.9). CONCLUSION: The combined absolute infant dose of pethidine and norpethidine received via milk was 1.8% of the neonatal therapeutic dose and the combined relative infant dose was below the 10% recommended safety level. Breastfed infants are at low risk of drug exposure when mothers self-administer epidural pethidine after caesarean delivery.

256-channel magnetic imaging system.

We present the design and fabrication of a magnetoresistive imaging system capable of scanning 256 channels simultaneously along linear ranges of either 4 or 13 mm. High speed electronics read the channels and transfer the data to a computer that builds and displays the images. The system was successfully used to image magnetic tapes for real-time forensic validation purposes and can also be applied in other noninvasive imaging applications.

Expression system for synthesis and purification of recombinant human growth hormone in Pichia pastoris and structural analysis by MALDI-ToF Mass Spectrometry.

An expression system in Pichia pastoris for the production and purification of recombinant human growth hormone (rHGH) was designed and implemented. hGH cDNA sequence was cloned into pPICZalphaA vector under the control of AOX1 promoter, which included a polyhistidine-tag on the amino terminal end to enable affinity purification and a target site for Factor Xa protease such that protease cleavage in vitro would produce rhGH without any non-native N- and C-termini. Analyses of the affinity-purified rhGH product by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) showed a spectral peak at m/z 23699. Purified product digested with Factor Xa protease had a molecular mass of 22132 kDa. The molecular mass difference before and after Factor Xa protease digestion expectedly corresponds to the 12 amino acids in the rhGH amino terminus, which includes the EcoRI digestion site (Glu-Phe), the 6xHis tag for affinity purification, and the Factor Xa protease recognition sequence (Ile-Glu-Gly-Arg), a result that also indicates that the signal peptide was properly processed by P. pastoris. N-Terminal sequence analysis of the Factor Xa protease trimmed recombinant product confirmed the mature hGH sequence. Thus, the system designed functioned with its intended purpose effectively in expression, cleavage, and purification of the recombinant product.

Development of a Thin Film Magnetic Moment Reference Material.

In this paper we present the development of a magnetic moment reference material for low moment magnetic samples. We first conducted an inter-laboratory comparison to determine the most useful sample dimensions and magnetic properties for common instruments such as vibrating sample magnetometers (VSM), SQUIDs, and alternating gradient field magnetometers. The samples were fabricated and then measured using a vibrating sample magnetometer. Their magnetic moments were calibrated by tracing back to the NIST YIG sphere, SRM 2853.

Production of recombinant human erythropoietin from Pichia pastoris and its structural analysis.

AIMS: To design and investigate a recombinant expression system producing a therapeutically important glycoprotein, human erythropoietin (rHuEPO), by Pichia pastoris. METHODS AND RESULTS: EPO cDNA was cloned into pPICZalphaA for expression under control of AOX1 promoter and fused, on the amino-terminal end, with a polyhistidine tag for rapid purification. A target site for factor Xa protease was also introduced, such that cleavage in vitro produced a mature form of rHuEPO having the native N- and C-termini. RHuEPO was characterized as to the extent and nature of N-linked glycosylation using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and western blotting. The rHuEPO produced was approximately 30 kDa. All three N-linked glycosylation sites were occupied dominantly by Man(17)(GlcNAc)(2). N-glycanase-treated rHuEPO purified but not digested with factor-Xa-protease, showed a spectral peak centered about m/z 20400 Da. CONCLUSIONS: The native polypeptide form of human EPO (c. 18 kDa) was obtained for the first time in P. pastoris expression system, after affinity purification, deglycosylation and factor-Xa-protease digestion. The amount of sodium dodecyl sulfate used prior to deglycosylation was found to be crucial in determining the dominant form of glycan in glycoproteins. SIGNIFICANCE AND IMPACT OF THE STUDY: The novel approaches to protein expression and purification system and structural analysis presented, would be important especially for therapeutic proteins expressed in P. pastoris.

Probiotics: an emerging therapy.

There is considerable clinical interest in the utility of probiotic therapy--the feeding of (live) non-pathogenic bacteria, originally derived from the alimentary tract, for disease treatment or health promotion. The microflora of the gastrointestinal tract is essential for mucosal protection, for immune education and for metabolism of fecal residue. Physiological disturbances of these processes, when they occur, result from: i) alteration of a microbial ecosystem, originally conserved by evolution; ii) reduced consumption of microorganisms; iii) invasion of pathogens; or iv) modern interventions. Recent data support the use of proven probiotic organisms in prevention and treatment of flora-related gastrointestinal disorders including inflammatory bowel disease, infectious and antibiotic related diarrheas, and post-resection disorders including pouchitis. Therapeutic activity of probiotic bacteria can be due to competition with pathogens for nutrients and mucosal adherence, production of antimicrobial substances, and modulation of mucosal immune functions. Although a promising treatment, controlled clinical trials are necessary to validate the benefit of probiotics.

Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs.

Mesenchymal stromal cells (MSCs) have the potential to treat many myocardial diseases. We investigated whether these multipotent stem cells derived from bone marrow could be administered safely into the coronary circulation of healthy dogs. We injected about 0.5 million cells per kg bodyweight of early passage autologous MSCs into the left circumflex coronary artery of anaesthetised dogs. During administration, we noted ST segment elevation and T wave changes characteristic of acute myocardial ischaemia. 7 days later, macroscopic and microscopic evidence of myocardial infarction was noted. Histological sections of myocardium showed several scattered regions of dense fibroplasia accompanied by macrophage infiltrates only in areas where the MSCs were observed. We also noted raised plasma concentrations of cardiac troponin I and collagen fibril deposition in the lesions. These findings show acute myocardial ischaemia and subacute myocardial microinfarction after intracoronary arterial injection of MSCs into dogs.

Hearing loss due to mannosidosis and otitis media with effusion. A case report and review of audiological assessments in children with otitis media with effusion.

A case of a child with mannosidosis and bilateral otitis media with effusion (OME) is reported here along with some discussion of relevant literature to emphasize the need for age appropriate audiometric assessment before and after insertion of grommets for glue ear (OME). There is a need for multidisciplinary teamwork in the management of children with hearing loss. If OME is treated surgically, age-appropriate hearing assessment is required before and after insertion of grommets. The need for audiological assessments will be relevant even if children had passed the newborn hearing screening test.

Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice.

BACKGROUND: The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL-10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL-10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118. AIM: To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL-10 knockout mice. METHODS: Twenty IL-10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed. RESULTS: L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice. CONCLUSION: In this placebo controlled trial, modification of enteric flora in IL-10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.