Differential inflammatory potential of particulate matter (PM) size fractions from Imperial Valley, CA.

Particulate matter (PM) in Imperial Valley originates from a variety of sources such as agriculture, traffic at the border crossing, emissions from the cross-border city of Mexicali, and the drying lakebed of the Salton Sea. Dust storms in Imperial Valley, California regularly lead to exceedances of the federal air quality standards for PM10 (diameter less than 10 microns). To determine if there are differences in the composition and biological response to Imperial County PM by size, ambient PM samples were collected from a sampling unit stationed in the northern-most part of the valley, South of the Salton Sea. Ultrafine, fine, and coarse PM samples were collected and extracted separately. Chemical composition of each size fraction was obtained after extraction by using several analytical techniques, and biological response was measured by exposing a cell line of macrophages to particles and quantifying subsequent gene expression. Biological measurements demonstrated coarse PM induced an inflammatory response in macrophages measured in increases of inflammatory markers IL-1ß, IL-6, IL-8 and CXCL2 expression, whereas ultrafine and fine PM only demonstrated significant increases in expression of CYP1a1. These differential responses were due not only to particle size, but to the distinct chemical profiles of each size faction as well. Community groups in Imperial Valley have already completed several projects to learn more about local air quality, giving residents access to data that provides real-time levels of PM2.5 and PM10 as well as recommendations on health-based practices dependent on the current AQI (air quality index). However, to date there is no information on the composition or toxicity of ambient PM from the region. The data presented here could provide more definitive information on the toxicity of PM by size, and further inform the community on local air quality.

Whole egg consumption and cortical bone in healthy children.

Eggs contain bioactive compounds thought to benefit pediatric bone. This cross-sectional study shows a positive link between childhood egg intake and radius cortical bone. If randomized trials confirm our findings, incorporating eggs into children's diets could have a significant impact in preventing childhood fractures and reducing the risk of osteoporosis. INTRODUCTION: This study examined the relationships between egg consumption and cortical bone in children. METHODS: The cross-sectional study design included 294 9-13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical bone. Body composition and biomarkers of bone turnover were assessed using dual-energy X-ray absorptiometry and ELISA, respectively. RESULTS: Egg intake was positively correlated with radius and tibia cortical bone mineral content (Ct.BMC), total bone area, cortical area, cortical thickness, periosteal circumference, and polar strength strain index in unadjusted models (r = 0.144-0.224, all P < 0.050). After adjusting for differences in race, sex, maturation, fat-free soft tissue mass (FFST), and protein intakes, tibia relationships were nullified; however, egg intake remained positively correlated with radius Ct.BMC (r = 0.138, P = 0.031). Egg intake positively correlated with total body bone mineral density, BMC, and bone area in the unadjusted models only (r = 0.119-0.224; all P < 0.050). After adjusting for covariates, egg intake was a positive predictor of radius FFST (ß = 0.113, P < 0.050) and FFST was a positive predictor of Ct.BMC (ß = 0.556, P < 0.050) in path analyses. There was a direct influence of egg on radius Ct.BMC (ß = 0.099, P = 0.035), even after adjusting for the mediator, FFST (ß = 0.137, P = 0.020). Egg intake was positively correlated with osteocalcin in both the unadjusted (P = 0.005) and adjusted (P = 0.049) models. CONCLUSION: If the positive influence of eggs on Ct.BMC observed in this study is confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to promote pediatric bone development and prevent fractures.

Insulin Resistance Negatively Influences the Muscle-Dependent IGF-1-Bone Mass Relationship in Premenarcheal Girls.

CONTEXT: IGF-1 promotes bone growth directly and indirectly through its effects on skeletal muscle. Insulin and IGF-1 share a common cellular signaling process; thus, insulin resistance may influence the IGF-1-muscle-bone relationship. OBJECTIVE: We sought to determine the effect of insulin resistance on the muscle-dependent relationship between IGF-1 and bone mass in premenarcheal girls. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted at a university research center involving 147 girls ages 9 to 11 years. MAIN OUTCOME MEASURES: Glucose, insulin, and IGF-1 were measured from fasting blood samples. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin. Fat-free soft tissue (FFST) mass and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry. Our primary outcome was BMC/height. RESULTS: In our path model, IGF-1 predicted FFST mass (b = 0.018; P = .001), which in turn predicted BMC/height (b = 0.960; P < .001). IGF-1 predicted BMC/height (b = 0.001; P = .002), but not after accounting for the mediator of this relationship, FFST mass. The HOMA-IR by IGF-1 interaction negatively predicted FFST mass (b = -0.044; P = .034). HOMA-IR had a significant and negative effect on the muscle-dependent relationship between IGF-1 and BMC/height (b = -0.151; P = .047). CONCLUSIONS: Lean body mass is an important intermediary factor in the IGF-1-bone relationship. For this reason, bone development may be compromised indirectly via suboptimal IGF-1-dependent muscle development in insulin-resistant children.

Association of adenovirus 36 infection with adiposity and inflammatory-related markers in children.

CONTEXT: Although animal studies suggest that adenovirus 36 (Ad36) infection is linked to obesity and systemic inflammation, human data are scant and equivocal. OBJECTIVE: Associations of Ad36 infection with total body adiposity and inflammatory-related markers were determined in 291 children aged 9-13 years (50% female, 49% black). DESIGN: Fasting blood samples were measured for presence of Ad36-specific antibodies and TNF-α, IL-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). Fat mass and fat-free soft tissue mass were measured by dual-energy X-ray absorptiometry. RESULTS: The overall prevalence of Ad36 seropositivity [Ad36(+)] was 42%. There was a higher percentage of Ad36(+) children in the highest tertiles of TNF-α and IL-6 compared with their respective middle and lowest tertiles (both P < .03). There was also a trend toward a higher prevalence of Ad36(+) children in the highest tertile of VEGF compared with tertiles 1 and 2 (P = .05). Multinomial logistic regression, adjusting for age, race, sex, and fat-free soft tissue mass, revealed that compared with children with the lowest TNF-α, IL-6, and VEGF levels (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 [95% confidence interval (CI) 1.2-4.0], 2.4 (95% CI 1.4-4.0), and 1.8 (95% CI 1.0-3.3), respectively, for those in the highest TNF-α, IL-6, and VEGF levels (tertile 3). No association was observed between Ad36(+) and greater levels of fat mass or MCP-1 (all P > .05). CONCLUSIONS: In children, our data suggest that Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass.

A randomized trial of vitamin D3 supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption.

CONTEXT: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. OBJECTIVE: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. DESIGN: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. RESULTS: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. CONCLUSION: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.

Racial differences in cortical bone and their relationship to biochemical variables in Black and White children in the early stages of puberty.

UNLABELLED: Osteoporotic fracture rates differ according to race with Blacks having up to half the rate of Whites. The current study demonstrates that racial divergence in cortical bone properties develops in early childhood despite lower serum 25-hydroxyvitamin D in Blacks. INTRODUCTION: Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of Black and White children in the early stages of puberty and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. METHODS: A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n = 155 males; n = 164 Blacks) in the early stages of puberty. RESULTS: Blacks had greater cortical volumetric bone mineral density, mass, and size compared to Whites (all p < 0.01), contributing to Blacks having 17.0 % greater tibial strength (polar strength-strain index (SSIP)) (p < 0.001). Turnover markers indicated that Blacks had higher bone formation (osteocalcin (OC) and bone-specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than Whites (all p < 0.01). Blacks also had lower 25-hydroxyvitamin D (25(OH)D) and higher 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) (all p < 0.05). There were no correlations between tibial bone properties and 25(OH)D and PTH in Whites (all p ≥ 0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in Blacks, respectively (all p ≤ 0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH, and OC. CONCLUSIONS: Divergence in tibial cortical bone properties between Blacks and Whites is established by the early stages of puberty with the enhanced cortical bone properties in Black children possibly being explained by higher PTH and OC.

25-hydroxyvitamin D, insulin-like growth factor-I, and bone mineral accrual during growth.

CONTEXT: The extent to which 25-hydroxyvitamin D [25(OH)D] and IGF-I influence bone mineral content (BMC) accrual from early to mid-puberty is unclear. OBJECTIVE, SETTING, AND PARTICIPANTS: This study sought to determine relationships among 25(OH)D, IGF-I, and BMC in community-dwelling prepubertal females (n = 76; aged 4-8 yr at baseline) over a period of up to 9 yr. DESIGN: The hypothesis that changes in IGF-I vs. 25(OH)D are more strongly associated with BMC accrual was formulated after data collection. 25(OH)D and IGF-I were log-transformed and further adjusted using two-way ANOVA for differences in season and race. Linear mixed modeling (including a random subject-specific intercept and a random subject-specific slope on age) was employed to analyze the proportion of variance the transformed 25(OH)D and IGF-I variables explained for the bone outcomes. RESULTS: IGF-I was more strongly associated with BMC accrual than 25(OH)D at the total body (R(2) = 0.874 vs. 0.809), proximal femur (R(2) = 0.847 vs. 0.771), radius (R(2) = 0.812 vs. 0.759), and lumbar spine (R(2) = 0.759 vs. 0.698). The rate of BMC accrual was positively associated with changes in IGF-I but negatively associated with 25(OH)D. When IGF-I and 25(OH)D were included in the same regression equation, 25(OH)D did not have a significant predictive effect on BMC accrual above and beyond that of IGF-I. CONCLUSIONS: These prospective data in early adolescent females indicate that both 25(OH)D and IGF-I have a significant impact on bone mineral accrual; however, the positive association of IGF-I and BMC accrual is greater than the negative association of 25(OH)D and BMC accrual.

Bone and fat relationships in postadolescent black females: a pQCT study.

UNLABELLED: Despite adolescent black females experiencing the highest rates of obesity, the effect of excess fat mass on bone structure and strength in this population is unknown. Our findings in postadolescent black females suggest that excess weight in the form of fat mass may adversely influence cortical bone structure and strength. INTRODUCTION: Although adolescent obesity has been associated with reduced bone structure and strength in white females, this relationship has not been studied in adolescent black females, a population experiencing the highest rates of obesity. Our objective was to compare bone structure and strength between postadolescent black females with normal and high levels of adiposity. METHODS: Black females with ≤ 32% body fat were classified as normal body fat (NF; n = 33, aged 19.3 ± 1.3 years); females exceeding this cutoff were classified as high body fat (HF; n = 15, aged 19.0 ± 1.1 years). Using peripheral quantitative computed tomography, tibial and radial bones were scanned at the 4% (trabecular) and 20% (cortical) sites from the distal metaphyses. Fat-free soft-tissue mass (FFST) and %body fat were assessed by dual-energy X-ray absorptiometry. RESULTS: After controlling for either FFST or body weight, the HF vs. NF group had lower total cross-sectional area (CSA; 9-17%), cortical CSA (6-15%), and strength-strain index (SSI; 13-24%) at the cortical site of the tibia (all p < 0.05). At the cortical site of the radius, the HF vs. NF group had lower total CSA (14%, p = 0.03), cortical CSA (9%, p = 0.04), and SSI (15%, p = 0.07) after control for body weight. There were no group differences in either the FFST-adjusted cortical bone values at the radius or in the trabecular bone parameters (body weight- or FFST-adjusted) at the tibia and radius. CONCLUSIONS: Consistent with our adiposity and bone data in late-adolescent white females, our findings in black females entering adulthood also suggest that obesity may adversely influence cortical bone strength.

A national study of cross infection control: 'are we clean enough?'.

OBJECTIVE: To establish what cross infection control policies and procedures are in place within UK orthodontic departments and how they compare with recommended guidelines. DESIGN: A hospital-based cross-sectional study investigating UK orthodontic departments between March 2007 and January 2008. SUBJECTS AND METHODS: The main outcome measure was a questionnaire constructed for the study, based on current cross infection control guidelines. All orthodontic departments within district general hospitals were invited to participate via email and the response rate was 48%. RESULTS: Five key areas were explored, which included a) training, education and personal protection, b) the clinical environment, c) decontamination of instruments, d) decontamination of appliances and impressions and e) disposal of waste. Ninety-eight percent of departments provided training in cross infection control and 98% also had a policy to check staff immunisation status. With respect to the clinical environment, 97% of the departments surveyed had separate 'clean' and 'dirty' zones. Half of all departments used central sterile services departments (CSSD) for instrument sterilisation. Seventy-eight percent of departments had a policy to decontaminate impressions/appliances at the chairside and all departments used 'yellow bags' for clinical waste and puncture-proof containers for sharps waste. CONCLUSIONS: UK orthodontic departments have implemented policies and procedures which would ensure a high standard of cross infection control. In particular, this related to the decontamination of surfaces and instruments, the use of personal protection and disposal of clinical waste. Most departments had policies and procedures in place for staff education and training in cross infection control and personal protection.

A gene expression profiling approach assessing celecoxib in a randomized controlled trial in prostate cancer.

BACKGROUND: We performed a pilot study, looking at the COX-2 inhibitor celecoxib, on newly diagnosed prostate cancer patients in the neo-adjuvant setting using DNA microarray analysis. PATIENTS AND METHODS: This was a single-blinded, randomized controlled phase II presurgical (radical prostatectomy) 28-day trial of celecoxib versus no drug in patients with localized T1-2 N0 M0 prostate cancer. cDNA microarray analysis was carried out on prostate cancer biopsies taken from freshly obtained radical prostatectomy samples. Results were confirmed by qPCR analysis of a selection of genes. RESULTS: Multiple genes were differentially expressed in response to celecoxib treatment. Statistical analysis of microarray data indicated 24 genes were up-regulated and 4 genes down-regulated as a consequence of celecoxib treatment. Gene changes e.g. survivin, SRP72kDa, were associated with promoting apoptotic cell death, enhancement of antioxidant processes and tumour suppressor function (p73 and cyclin B1 up-regulation). CONCLUSION: Celecoxib at 400 mg b.i.d. for 4 weeks perioperatively gave rise to changes in gene expression in prostate cancer tissue consistent with enhancement of apoptosis and tumour suppressor function. Given the short time interval for the duration of this study, the data are encouraging and provide a good rationale for conducting further trials of celecoxib in prostate cancer.

Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage.

The adaptation of the tubercle bacillus to the host environment is likely to involve a complex set of gene regulatory events and physiological switches in response to environmental signals. In order to deconstruct the physiological state of Mycobacterium tuberculosis in vivo, we used a chemostat model to study a single aspect of the organism's in vivo state, slow growth. Mycobacterium bovis BCG was cultivated at high and low growth rates in a carbon-limited chemostat, and transcriptomic analysis was performed to identify the gene regulation events associated with slow growth. The results demonstrated that slow growth was associated with the induction of expression of several genes of the dormancy survival regulon. There was also a striking overlap between the transcriptomic profile of BCG in the chemostat model and the response of M. tuberculosis to growth in the macrophage, implying that a significant component of the response of the pathogen to the macrophage environment is the response to slow growth in carbon-limited conditions. This demonstrated the importance of adaptation to a low growth rate to the virulence strategy of M. tuberculosis and also the value of the chemostat model for deconstructing components of the in vivo state of this important pathogen.

Former college artistic gymnasts maintain higher BMD: a nine-year follow-up.

INTRODUCTION: If higher bone gains acquired from weight-bearing sports during growth persist into old age, the residual benefits could delay or even prevent osteoporotic fractures. The purpose of this study was to determine if the higher areal bone mineral density (aBMD) observed 15 years after competitive training and competition in former female college artistic gymnasts (GYM) compared with controls (CON) is maintained nine years later in this same cohort approaching menopause. In this 9-year follow-up, aBMD changes were also compared between GYM (n=16; aged 45.3+/-3.3 years) and CON (n=13; aged 45.4+/-3.8 years). METHODS: Total body, lumbar spine, proximal femur, femoral neck, leg, and arm aBMD were assessed at baseline and follow-up using dual-energy X-ray absorptiometry (DXA), (Hologic QDR-1000W). GYM had higher aBMD at all sites at follow-up (P<0.05; eta (2)>0.14). RESULTS: While there were no significant differences between groups for percent changes in aBMD at the total body, lumbar spine, total proximal femur, femoral neck, and arm, the change in leg aBMD was significantly different between GYM and CON (P=0.05; eta (2)=0.14). CONCLUSIONS: Former female college artistic gymnasts maintained significantly higher aBMD than controls 24 years after retirement from gymnastics training and competition. This study provides greater insight into the effects of past athletic participation on skeletal health in women approaching menopause.

Damped Bernstein modes in a weakly relativistic pair plasma.

Relativistic Bernstein modes are not totally undamped, but have a small, negative definite imaginary frequency component that peaks where the frequency is closest to the rest cyclotron harmonic.

Bernstein modes in a weakly relativistic electron-positron plasma.

The form of the propagating electrostatic Bernstein mode in a relativistic electron-positron plasma is markedly different from that in the classical plasma, once the momentum-dependent cyclotron frequency is accounted for in full inside the integrations. Given that particles in different parts of momentum space "see" a different cyclotron frequency, there is no simple global singularity which reproduces the classical dispersion features.

Learning to read in Williams syndrome: looking beneath the surface of atypical reading development.

In this paper, we make a fundamental distinction between literacy attainment scores and the actual process of learning to read, and examine these two aspects of reading in atypical development. Reading skills in a group of children and adults with the genetic disorder Williams syndrome (WS) were compared to a group of typically developing children matched for reading age and receptive vocabulary scores. Study 1 focused on the product of reading and explored the relationship between reading, general cognition, and phonological skills. Phonological skills were shown to be related to individual differences in reading attainment in both groups, although more weakly in the WS group. Experiment 2 examined the process of learning to read. The two groups were taught to associate abbreviated spellings (cues) with spoken words. The cues differed in their phonetic closeness to the target words, whereas the target words differed on the semantic variable of imageability. Compared to controls, the WS group showed slower learning, less sensitivity to the phonetic quality of the cue, and reduced influence from the imageability of words. The results support the hypothesis that although reading levels in WS depend on phonological skills, the full development of their reading is compromised by weak semantics. The studies highlight the importance in atypical populations of examining both reading levels and the actual process of learning to read.

Prevalence of tuberculosis in cattle in the Dangme-West district of Ghana, public health implications.

Bovine tuberculosis due to Mycobacterium bovis is a major cause of human gastrointestinal tuberculosis in developing countries where bovine milk is often not pasteurised before use. Little information is available on the prevalence of the disease in African cattle and its zoonotic impact. The Ghanaian Government, through its peri-urban dairy cattle development project, is promoting the use of milk and dairy products from local cows in selected districts of the country, including the Dangme-West district of the Greater Accra region. A survey was, therefore, undertaken to determine the prevalence of tuberculosis infection in cattle in this district and to assess the level of awareness with regard to the risks through milk consumption. The standard single intradermal comparative tuberculin test (SCITT) using purified protein derivative (PPD) of M. bovis and M. avium was used to detect cattle infected with M. bovis. The study established the prevalence of a 13.8% infection in cattle in the district although the prevalence was as high as 50% in some kraals. Prevalence was highest in the Ningo sub-district (19.0%), followed by Dodowa, the district capital (14.0%), while the other two sub-districts, Prampram and Osudoku had lower rates of 11.3 and 10. 8%, respectively. Cattle of all ages and both sexes were affected, but the prevalence in cows was twice as high as that in heifers or bulls. The study also established that there is a considerable lack of knowledge about bovine tuberculosis among cattle owners and herdsmen in the community and that milk is often used untreated, thus increasing the risk of human infection.

Detection and management of zoonotic diseases at the Kumasi slaughterhouse in Ghana.

Slaughterhouse surveys are important in the detection and management of zoonotic diseases. Routine reports from the Kumasi slaughterhouse, in the Ashanti region of Ghana, include cases of zoonotic diseases. Due to its location and size, Kumasi is the major cattle market and an important transit point for cattle trade from places within and outside Ghana. This present study was designed to examine slaughterhouse reports and to explore the nature of the knowledge, attitude and practices of butchers who operate at this slaughterhouse, in relation to zoonoses. The study was largely descriptive, employing qualitative methods and tools. Butchers were interviewed and their practices along the production line observed. The study indicates that zoonotic diseases are frequently detected at the Kumasi slaughterhouse. However the knowledge, attitudes, practices and beliefs of the butchers are largely inadequate for their profession in view of the important public health role that butchers play. The butchers have never received any form of training. It is recommended that the butchers receive training on a regular basis and that laws be formulated and implemented to protect the health of the butchers and the general public.

Phonological and semantic processes influence beginning readers' ability to learn to read words.

Children (4 to 6 years of age) were taught to associate printed 3- or 4-letter abbreviations, or cues, with spoken words (e.g., bfr for beaver). All but 1 of the letters in the cue corresponded to phonemes in the spoken target word. Two types of cues were constructed: phonetic cues, in which the medial letter was phonetically similar to the target word, and control cues, in which the central phoneme was phonetically dissimilar. In Experiment 1, children learned the phonetic cues better than the control cues, and learning correlated with measures of phonological skill and knowledge of the meanings of the words taught. In Experiment 2, the target words differed on a semantic variable-imageability-and learning was influenced by both the phonetic properties of the cue and the imageability of the words used.

Pathology of canine bladder and urethral cancer and correlation with tumour progression and survival.

Biopsy and necropsy specimens, comprising 107 primary carcinomas and three mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder, urethra, or both. Histological classifications developed for the assessment of human bladder cancer were found to be readily applicable to the dog. These classifications are based on histological features, including the pattern of growth, the cell type, the grade of transitional tumour and the depth of invasion of the bladder wall. Features associated with localized disease in canine transitional cell carcinoma included papillary architecture, "in-situ" tumour, low tumour grade and a strong peritumoral lymphoid cell reaction. Features of tumours with metastasis included infiltrating and non-papillary architecture, increasing tumour grade, depth of invasion, vascular invasion and presence of peritumoral fibrosing reaction. Wide variability was found within single tissue samples, indicating that multiple sample sites are necessary for the adequate characterization of a given lesion. Statistically significant correlations were found between: tumour grade and depth of invasion (P < 0.0001); tumour grade and presence of metastases (P < 0.029); and peritumoral desmoplasia and metastases (P < 0.029). It was concluded that canine bladder cancer could be classified for the purpose of clinical management with a modified World Health Organization system as developed for human tumours.