Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. METHODS: Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. RESULTS: We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. CONCLUSIONS: The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.

Detection of tubule boundaries based on circular shortest path and polar-transformation of arbitrary shapes.

In studies of germ cell transplantation, counting cells and measuring tubule diameters from different populations using labelled antibodies are important measurement processes. However, it is slow and sanity grinding to do these tasks manually. This paper proposes a way to accelerate these processes using a new image analysis framework based on several novel algorithms: centre points detection of tubules, tubule shape classification, skeleton-based polar-transformation, boundary weighting of polar-transformed image, and circular shortest path smoothing. The framework has been tested on a dataset consisting of 27 images which contain a total of 989 tubules. Experiments show that the detection results of our algorithm are very close to the results obtained manually and the novel approach can achieve a better performance than two existing methods.

Upper and lower body anaerobic performance of semi-elite Rugby League players.

AIM: The aim of this study was to measure the upper and lower body anaerobic performance of semi-elite Rugby League (RL) players. METHODS: Twenty-two semi-professional RL players and 24 physically active but untrained men completed two Wingate anaerobic tests (WAnT) on an electronic arm ergometer and a cycle ergometer separated by three days. Percent body fat was used determined from the sum of six skinfolds and upper and lower muscle cross-sectional area (CSA) was calculated from anthropometric data. RESULTS: Upper and lower body absolute peak (P=0.035, P=0.002) and mean (P=0.005, P=0.031) power were higher in the RL group compared to the control group. Upper and lower body relative peak power was higher (P=0.022, P=0.047) in the control group compared to the RL group. Peak and mean power (relative and absolute) were higher (P≤0.05) in the lower body compared to the upper body. Peak and mean power relative to upper and lower muscle CSA was higher (P≤0.001) in the upper body compared to the lower body for both groups. CONCLUSION: Semi-elite Rugby League players have well developed absolute anaerobic power, but relative to body weight upper and lower body anaerobic power is not well developed. The upper body is able to generate more power relative to body weight and muscle CSA compared to the lower body during the WAnT. Future studies should examine the upper body anaerobic performance of elite RL players and other sports that have similar upper body demands.

The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer.

BACKGROUND: Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches. METHODS: Cytotoxicity testing (MTT) and cell cycle blockade assessed drug responsiveness. Methylation specific PCR and pyrosequencing identified sites of promoter methylation in p57(Kip2). siRNA to p57(Kip2) was used to look at the changes in apoptosis of carboplatin treated EOC cells. EOC tissues (20 cases) were assessed for mRNA levels of p57(Kip2). RESULTS: Carboplatin resistance was reversed using 5-aza-cytidine in vitro. Promoter methylation sites and preferential sensitivity to seliciclib were seen in PEO1CarbR cells. Silencing p57(Kip)2 decreased the apoptotic response to the effects of platinum but produced sensitisation to seliciclib. EOC biopsies indicated an association of high levels of p57(Kip2)mRNA with complete responses to chemotherapy and improved outcome. CONCLUSION: We conclude that p57(Kip2) is a candidate biomarker of platinum sensitivity/resistance in EOC and such cases may show preferential response to the cyclin-dependent kinase inhibitor seliciclib.

Leg strength and the VO2 max of older men.

The purpose of the study was to determine if leg strength limits VO2 max and the ability to reach a plateau during VO2 max test in older men during cycle ergometry. Men aged 70-80 years were randomly selected into a strength training (ST, n=12) 3 times weekly for 16 weeks, followed by 4 weeks detraining or a non-training control group (C, n=12). Leg strength and VO2 max were assessed every 4 weeks for 20 weeks; body composition and cardiac function were assessed before and after 16 weeks training and after 4 weeks detraining. Leg strength, upper leg muscle mass (ULMM), arterial-venous O2 difference (a-v O2 difference) and VO2 max increased in the ST group (95±0.6%, 7±0.7%. 6.2±0.5% and 8±0.8%, respectively; P<0.05) after 16 weeks training. After 4 weeks detraining, gains in ULMM (50%) and strength (75%) were retained, but VO2 max and a-v O2 difference returned to pre-training levels. There was no change in the ability of the participants to reach a plateau during VO2 max testing over the 20-week study. These findings indicate that leg strength may not limit either VO2 max or the ability to plateau during VO2 max tests in older men during cycle ergometry.

Does upper body strength and power influence upper body Wingate performance in men and women?

The aim of this study was to determine the influence of muscular strength and power on upper body Wingate performance in men and women. Muscular strength (1 repetition maximum bench press), muscular power (bench throws) and upper body anaerobic performance (Wingate Anaerobic Test (WAnT)) was assessed in 24 men and 16 women. Men had significantly ( P<0.001) higher absolute and relative peak and mean power and blood lactate concentration during the WAnT compared to their female counterparts. Men also produced significantly ( P<0.001) higher strength and absolute and relative peak and mean power during the bench press and throw, respectively, compared to the female participants. For men body mass and mean power produced during the bench throw explained approximately 84% and 87% of the variance in Wingate peak ( P<0.001 and P=0.039, respectively) and mean ( P<0.001 and P=0.028, respectively) power. For women mean power produced during the bench throw explained approximately 72% and 52% of the variance in Wingate peak ( P=0.002) and mean ( P=0.017) power, respectively. For men body mass and to a lesser extent muscular power best predicts upper body Wingate performance while for women only muscular power predicts upper body Wingate performance.

Analysis of historical negative control group data from the rat in vivo micronucleus assay.

A database of micronuclei counts for historical negative control data from rat in vivo micronuclei tests performed in 10 different laboratories was established. Data were available from over 4000 negative control rats from 10 laboratories. The mean frequency of micronucleated cells (MN)/1000 cells ranged from 0.44 to 2.22, a 5-fold range. Overall there were no major sex or strain differences in frequency, although there were some small but statistically significant differences within laboratories. There was appreciable variability between experiments compared with variability within experiments in some laboratories. No specific factor was identified which could explain this variability although it was noted that many different vehicles were used in the experiments. It is hoped that these data will help laboratories beginning studies with the rat micronucleus assay and those involved in the assessment of micronucleus assay results.

Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases.

OBJECTIVES: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population. METHODS: This analysis included 19,041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization. RESULTS: Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population. CONCLUSIONS: Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit-risk profile.

Development of a log-quadratic model to describe microbial inactivation, illustrated by thermal inactivation of Clostridium botulinum.

In the commercial food industry, demonstration of microbiological safety and thermal process equivalence often involves a mathematical framework that assumes log-linear inactivation kinetics and invokes concepts of decimal reduction time (D(T)), z values, and accumulated lethality. However, many microbes, particularly spores, exhibit inactivation kinetics that are not log linear. This has led to alternative modeling approaches, such as the biphasic and Weibull models, that relax strong log-linear assumptions. Using a statistical framework, we developed a novel log-quadratic model, which approximates the biphasic and Weibull models and provides additional physiological interpretability. As a statistical linear model, the log-quadratic model is relatively simple to fit and straightforwardly provides confidence intervals for its fitted values. It allows a D(T)-like value to be derived, even from data that exhibit obvious "tailing." We also showed how existing models of non-log-linear microbial inactivation, such as the Weibull model, can fit into a statistical linear model framework that dramatically simplifies their solution. We applied the log-quadratic model to thermal inactivation data for the spore-forming bacterium Clostridium botulinum and evaluated its merits compared with those of popular previously described approaches. The log-quadratic model was used as the basis of a secondary model that can capture the dependence of microbial inactivation kinetics on temperature. This model, in turn, was linked to models of spore inactivation of Sapru et al. and Rodriguez et al. that posit different physiological states for spores within a population. We believe that the log-quadratic model provides a useful framework in which to test vitalistic and mechanistic hypotheses of inactivation by thermal and other processes.

Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis.

OBJECTIVE: To describe the distribution and severity of muscle weakness using manual muscle testing (MMT) in 172 patients with PM, DM and juvenile DM (JDM). The secondary objectives included characterizing individual muscle group weakness and determining associations of weakness with functional status and myositis characteristics in this large cohort of patients with myositis. METHODS: Strength was assessed for 13 muscle groups using the 10-point MMT and expressed as a total score, subscores based on functional and anatomical regions, and grades for individual muscle groups. Patient characteristics and secondary outcomes, such as clinical course, muscle enzymes, corticosteroid dosage and functional status were evaluated for association with strength using univariate and multivariate analyses. RESULTS: A gradient of proximal weakness was seen, with PM weakest, DM intermediate and JDM strongest among the three myositis clinical groups (P < or = 0.05). Hip flexors, hip extensors, hip abductors, neck flexors and shoulder abductors were the muscle groups with the greatest weakness among all three clinical groups. Muscle groups were affected symmetrically. CONCLUSIONS: Axial and proximal muscle impairment was reflected in the five weakest muscles shared by our cohort of myositis patients. However, differences in the pattern of weakness were observed among all three clinical groups. Our findings suggest a greater severity of proximal weakness in PM in comparison with DM.

Development of a provisional core set of response measures for clinical trials of systemic sclerosis.

OBJECTIVE: To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc). METHODS: The Scleroderma Clinical Trials Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains (skin, musculoskeletal, cardiac, pulmonary, cardio-pulmonary, gastrointestinal, renal, Raynaud phenomenon and digital ulcers, health-related quality of life and function, global health, and biomarkers) for SSc clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting, during which the Steering Committee discussed the feasibility, reliability, redundancy and validity of the items. Round 3 sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility but lacked data on reliability and validity, but may still be useful research outcome measures for future trials. RESULTS: A total of 50 SCTC investigators participated in round 1, providing 212 unique items for the 11 domains. In all, 46 (92%) participants responded in round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged to be appropriate for inclusion in a 1-year multi-centre clinical trial. In total, 40 SCTC investigators completed round 3 and ranked 30 of 31 items as acceptable for inclusion in the core set. The Steering Committee also proposed 14 items for a research agenda. CONCLUSION: Using a Delphi exercise, we have developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc.

Reduced adhesion formation following laparoscopic versus open colorectal surgery.

BACKGROUND: Adhesion formation is common after abdominal surgery. This study aimed to compare the extent of adhesion formation following laparoscopic and open colorectal surgery. METHODS: An observational study was undertaken to identify adhesions in patients undergoing laparoscopy after previous laparoscopic or open colectomy. Adhesions were scored according to a system validated for interobserver (median kappa = 0.80) and intraobserver (kappa = 0.82) agreement. The primary endpoint was the overall adhesion score (0-10); a secondary endpoint was the adhesion score at the main incision site (0-6). RESULTS: Forty-six patients were recruited (13 laparoscopic and 33 open colectomy). In most patients (n = 29), laparoscopy was performed for tumour staging before liver resection. The median (interquartile range) overall adhesion score was 7 (5-8) in the open group and 0 (0-3) in the laparoscopic group (P < 0.001). A similar difference was found for the main incision score: 6 (4-6) versus 0 (0-0) (P < 0.001). CONCLUSION: There may be a reduction in adhesion formation following laparoscopic compared with open colectomy, although the small sample size limits this conclusion.

Management of equine skull fractures using fixation with polydioxanone sutures.

Ten horses presented with severe distortion of the facial contour, crepitus on palpation and mild to moderate epistaxis. Individual horses also showed ocular damage, ptosis, severe dyspnoea and movement of the facial bones concurrent with respiration. The fracture fragments were exposed using a large curvilinear incision and elevated using a retractor, periosteal elevator, chisel or Steinmann pin. The fracture fragments were unstable following reduction and fixation was necessary. Stabilisation was achieved with polydioxanone sutures placed through holes drilled in opposing sides of the fracture lines. Polydioxanone sutures provided good stability and had better handling properties than wire. There was good apposition of fracture edges and minimal complications. Use of polydioxanone sutures can also avoid the expense and complexity of plate fixation in selected cases, and should be considered as an alternative to fixation with stainless steel wire in any facial fracture that adjoins stable bone.

Systemic features and early prognostic factors in Hispanic and non-Hispanic children from the United States of America and Mexico with systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate if the persistence of systemic features is longer in Hispanic children with systemic juvenile idiopathic arthritis (S-JIA) than in non-Hispanic children with S-JIA and to determine early predictors of systemic and articular disease. METHODS: We performed a multi-center retrospective chart review of patients followed in six pediatric rheumatology centers with onset of S-JIA from 1974 to 2004. Patients were included in the study if they had been followed for > or = 1 year after disease onset. Information collected included demographic, clinical, laboratory and treatment data. Systemic features included fever, rash, lymphadenopathy, hepatosplenomegaly, pericarditis, and pleuritis. RESULTS: Of the 159 S-JIA patients screened, 120 (75%) met our inclusion criteria. There were 65 boys and 55 girls. The mean follow-up period for Hispanic patients was 5.7 years (SD 4.0) and for non-Hispanic patients was 8.6 years (SD 7.2). There was no significant difference in the presence of systemic features between Hispanic and non-Hispanic patients at 0.5, 1, 2, 4, 6, 8, and 10 years of follow-up. Polyarthritis at the 6-month visit was predictive of systemic features (OR 9.7, 95% CI 1.16-81.35, p = 0.036) and polyarthritis (OR 5.6, 95% CI 1.42-21.8, p = 0.014) at last follow-up. CONCLUSION: In children with S-JIA, Hispanics did not demonstrate longer persistence of systemic features than non-Hispanics. Polyarthritis at 6 months strongly predicted the development of persistent systemic features and chronic polyarticular disease.

Report of an Expert Panel on the reanalysis by of a 90-day study conducted by Monsanto in support of the safety of a genetically modified corn variety (MON 863).

MON 863, a genetically engineered corn variety that contains the gene for modified Bacillus thuringiensis Cry3Bb1 protein to protect against corn rootworm, was tested in a 90-day toxicity study as part of the process to gain regulatory approval. This study was reanalyzed by Séralini et al. who contended that the study showed possible hepatorenal effects of MON 863. An Expert Panel was convened to assess the original study results as analyzed by the Monsanto Company and the reanalysis conducted by Séralini et al. The Expert Panel concludes that the Séralini et al. reanalysis provided no evidence to indicate that MON 863 was associated with adverse effects in the 90-day rat study. In each case, statistical findings reported by both Monsanto and Séralini et al. were considered to be unrelated to treatment or of no biological or clinical importance because they failed to demonstrate a dose-response relationship, reproducibility over time, association with other relevant changes (e.g., histopathology), occurrence in both sexes, difference outside the normal range of variation, or biological plausibility with respect to cause-and-effect. The Séralini et al. reanalysis does not advance any new scientific data to indicate that MON 863 caused adverse effects in the 90-day rat study.

Calcified tumours of the paranasal sinuses in three horses.

Three horses, a 10-year-old Thoroughbred mare, a 9-year-old Thoroughbred gelding and a 6-year-old Arab gelding, with calcified tumours of the paranasal sinuses, are described. All horses presented with purulent nasal discharges and facial distortion. Exophthalmos, blepharospasm and ocular discharge were also a feature in individual horses. A presumptive diagnosis of a calcified tumour was made on the basis of clinical signs and radiographic and endoscopic findings. The tumours ranged from 15 to 25 cm in diameter. A large frontonasal bone flap was used to expose the tumours, which were cleaved into several pieces with an osteotome and removed. Histological examination of the masses identified cementomas in two cases and an osteoma in the third. Long term follow up from 18 months to 5 years after surgery indicated that there was no recurrence. This case series demonstrates that, although calcified tumours of the paranasal sinuses are rare in horses, they should be considered in the differential diagnosis of purulent nasal discharge, facial swelling and ocular distortion, and are amenable to surgical treatment.

What more can we learn from muscle histopathology in children with dermatomyositis/polymyositis?

OBJECTIVE: To correlate disease course and complications in children with juvenile dermatomyositis (JDM) and polymyositis (JPM) with specific features of muscle pathology on biopsy. METHODS: This is a retrospective cohort analysis of 59 children diagnosed with JDM or JPM between 1965 and 1998 and followed at the Cincinnati Children's Hospital Medical Center (CCHMC) for a mean duration of 7.3 years (range 1.1-24.5 years). Disease course was characterized as limited, chronic non-ulcerative or chronic ulcerative, similar to previously defined disease course subtypes reported by Crowe et al.(1). All subjects had diagnostic muscle biopsies performed at CCHMC and had disease for at least two years' duration in order to classify their disease course as either limited or chronic. Features of muscle histopathology that were evaluated included loss of the intramuscular capillary bed, infarct, perifascicular myopathy, direct immunofluorescence (DIF) staining of the intramuscular vasculature and specifically, the locale of DIF staining, i.e., small arteries or capillaries. Disease complications that were assessed included calcinosis, contractures, muscle atrophy, lipodystrophy, gastrointestinal ulceration, cutaneous ulceration and death. Data analysis was completed using Chi-square or Fisher's exact tests and logistic regression modeling. RESULTS: Twenty-two children (37%) had limited disease, 24 (41%) had chronic non-ulcerative disease and 13 (22%) had chronic ulcerative disease. Neither loss of the intramuscular capillary bed nor perifascicular myopathy on muscle biopsy significantly correlated with disease course or the various complications evaluated in this study. DIF staining of intramuscular vessels overall was not significantly associated with clinical disease course, but the localization of DIF staining to intramuscular arteries (rather than to capillaries) was significantly associated with the outcome of chronic ulcerative disease. Nine of the 13 children with chronic ulcerative disease had DIF-arterial staining on muscle biopsy (69%), significantly greater than DIF-arterial staining in children with limited disease (32% had DIF-arterial staining) (p = 0.04), chronic non-ulcerative disease (8% had DIF-arterial staining) (p = 0.0002), and non-ulcerative disease overall (limited + chronic non-ulcerative disease groups combined) (20% had DIF-arterial staining), with p = 0.001. Additionally, lack of DIF-arterial staining on biopsy was significantly correlated with patients not having gastrointestinal ulceration (p = 0.002), cutaneous ulceration (p = 0.004) and/or death (p = 0.02) as disease-related complications. Infarct on muscle biopsy was significantly associated with the development of chronic ulcerative disease (p = 0.02), being present on biopsy in 23% of children with chronic ulcerative disease compared with none of the patients with chronic non-ulcerative disease and 4% of those with limited disease. Infarct on muscle biopsy correlated with the outcomes of death (p = 0.01) and gastrointestinal ulceration (p = 0.03), but not with the development of cutaneous ulceration (p = 0.18). CONCLUSION: DIF-arterial staining and infarct on muscle biopsy are significantly associated with the development of chronic ulcerative disease in JDM and JPM, while perifascicular myopathy and loss of the intramuscular capillary network are not associated with disease course. The presence of DIF-arterial staining and infarct on biopsy should suggest early use of second-line therapeutic agents to more quickly bring disease activity under control.

Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO phase IV post marketing surveillance study.

OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.

Interstitial low dose rate brachytherapy for prostate cancer--a focus on intermediate- and high-risk disease.

AIMS: To investigate the role of brachytherapy in intermediate- and high-risk prostate cancer. We report our results and a review of published studies. MATERIALS AND METHODS: Between March 1999 and April 2003, 300 patients were treated with low dose rate 1-125 interstitial prostate brachytherapy and followed prospectively. The patients were stratified into low-, intermediate- and high-risk groups and received brachytherapy alone or in combination with external beam radiotherapy (EBRT) and/or neoadjuvant androgen deprivation (NAAD). One hundred and forty-six patients were classified as low risk, 111 as intermediate risk and 43 as high risk. Biochemical freedom from disease and prostate-specific antigen (PSA) nadirs were analysed for risk groups and for treatment received in each risk group. RESULTS: The median follow-up was 45 months (range 33-82 months) with a mean age of 63 years. Actuarial 5-year biochemical relapse-free survival for the low-risk group was 96%, 89% for the intermediate-risk group and 93% for the high-risk group. When stratified by treatment group, low-risk patients had a 5-year actuarial biochemical relapse-free survival of 94% for brachytherapy alone (n=77), 92% for NAAD and brachytherapy (n=66) and 100% for NAAD, EBRT and brachytherapy (n=3). In the intermediate-risk patients, biochemical relapse-free survival was 93% for brachytherapy alone (n=15), 94% for NAAD and brachytherapy (n=67), 75% for EBRT and brachytherapy (n=4) and 92% for NAAD, EBRT and brachytherapy (n=25). In the high-risk group, biochemical relapse-free survival was 100% for brachytherapy alone (n=2), 88% for NAAD and brachytherapy (n=7), 80% for EBRT and brachytherapy (n=5) and 96% for NAAD, EBRT and brachytherapy (n=29). Overall 3- and 4-year PSA = 0.5 ng/ml were achieved by 71 and 86%, respectively, and a 4-year PSA = 0.2 ng/ml was achieved by 63%. CONCLUSION: Although the role of combination treatment with pelvic EBRT and androgen therapy is not clear, our early results show that many patients with intermediate- and high-risk disease have excellent results with brachytherapy.

Placement of a long term tracheal cannula in a Thoroughbred racehorse with bilateral laryngeal dysfunction.

A Thoroughbred horse with bilateral laryngeal dysfunction was treated by placement of a long term tracheal cannula in order to restore full athletic function. The horse initially presented with right-sided arytenoid dysfunction that was considered to be due to a congenital malformation of the laryngeal cartilage. This was corrected by a right-sided laryngoplasty and ventriculectomy. The horse re-presented 1 year later with idiopathic left laryngeal hemiplegia. The decision was made to place a long-term tracheal cannula due to the low success rate and high complication rate associated with other surgeries used to correct bilateral arytenoid dysfunction. A three-piece tracheotomy cannula and stopper were positioned under general anaesthesia. The horse rapidly adjusted to the tracheal cannula and no post-surgical complications were encountered. The horse resumed training 4 weeks postoperatively. Due to the rules governing racing in Australia the horse was exported to New Zealand where he continued his racing career. It was concluded that tracheotomy is a straightforward technique associated with minimal complications and can provide an excellent prognosis for return of full airway function in racing horses. It is recognised that many issues need to be considered prior to more general acceptance of this technique, including assessment of animal welfare issues and public perception. In appropriate cases consideration should be given to using long term placement of a tracheotomy cannula as a treatment option to restore maximal airflow in horses with upper airway obstruction.