Evaluation of soil intake by growing Creole young bulls in common grazing systems in humid tropical conditions.

Soil is the main matrix which contributes to the transfer of environmental pollutants to animals and consequently into the food chain. In the French West Indies, chlordecone, a very persistent organochlorine pesticide, has been widely used on banana growing areas and this process has resulted in a long-term pollution of the corresponding soils. Domestic outside-reared herbivores are exposed to involuntary soil intake, and tethered grazing commonly used in West Indian systems can potentially favour their exposure to chlordecone. Thus, it appears necessary to quantify to what extent grazing conditions will influence soil intake. This experiment consisted of a cross-over design with two daily herbage allowance (DHA) grazed alternatively. Six young Creole bulls were distributed into two groups (G1 and G2) according to their BW. The animals were individually tethered and grazed on a restrictive (RES) or non-restrictive (NRES) levels of DHA during two successive 10-days periods. Each bull progressed on a new circular area every day. The two contrasting levels of DHA (P0.05) due to the lower DMI of RES compared with NRES treatment.

A critical review of clinical trials in systemic lupus erythematosus.

One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs.

Fatigue, patient reported outcomes, and objective measurement of physical activity in systemic lupus erythematosus.

OBJECTIVE: Fatigue is a common symptom in systemic lupus erythematosus (SLE), and engaging in physical activity may reduce fatigue. We aimed to characterize relationships between fatigue, other health status measures assessed with the Patient Reported Outcomes Measurement Information System (PROMIS) instruments, and accelerometer-based physical activity measurements in patients with SLE. The internal consistency of each PROMIS measure in our SLE sample was also evaluated. METHODS: This cross-sectional study analyzed 123 adults with SLE. The primary fatigue outcome was Fatigue Severity Scale score. Secondary outcomes were PROMIS standardized T-scores in seven health status domains. Accelerometers were worn for seven days, and mean daily minutes of light, moderate/vigorous, and bouted (10 minutes) moderate/vigorous physical activity were estimated. Cronbach's alpha was determined for each PROMIS measure to assess internal consistency. Relationships between Fatigue Severity Scale, PROMIS, and physical activity were summarized with Spearman partial correlation coefficients (r), adjusted for average daily accelerometer wear time. RESULTS: Mean Fatigue Severity Scale score (4.3, SD 1.6) was consistent with clinically relevant levels of fatigue. Greater daily and bouted moderate/vigorous physical activity minutes correlated with lower Mean Fatigue Severity Scale score (r = -0.20, p = 0.03 and r = -0.30, p = 0.0007, respectively). For PROMIS, bouted moderate/vigorous physical activity minutes correlated with less fatigue (r = -0.20, p = 0.03). PROMIS internal consistency was excellent, with Cronbach's alpha > 0.90 for each domain. Mean PROMIS T-scores for fatigue, pain interference, anxiety, sleep disturbance, sleep-related impairment, and physical function were worse than reported for the general US population. More moderate/vigorous physical activity minutes were associated with less pain interference (r = -0.22, p = 0.01). Both light physical activity and moderate/vigorous physical activity minutes correlated with better physical function (r = 0.19, p = 0.04 and r = 0.25, p = 0.006, respectively). CONCLUSION: More time spent in moderate/vigorous physical activity was associated with less fatigue (Fatigue Severity Scale and PROMIS), less pain interference, and better physical function (PROMIS). PROMIS had excellent internal consistency in our SLE sample, and six of seven PROMIS measures indicated poorer average health status in SLE patients compared with the general US population.

Impact of the post-weaning parasitism history on an experimental Haemonchus contortus infection in Creole goat kids.

Gastrointestinal nematode (GIN) infections have an important negative impact on small ruminant production. The selection of genotypes resistant to these parasitic infections is a promising alternative control strategy. Thus, resistance against GIN is an important component of small ruminant breeding schemes, based on phenotypic measurements of resistance in immune mature infected animals. In this study we evaluated both the impact of the post-weaning parasitism history on the response to an experimental Haemonchus contortus infection of resistant and susceptible Creole kids chosen on the basis of their estimated breeding value, and the interaction with the kid's genetic status. During the post-weaning period (from 3 months until 7 months of age) Creole kids were reared at pasture according to four different levels of a mixed rotational stocking system with Creole cattle: 100% (control), 75% (GG75), 50% (GG50), and 25% (GG25) of the total stocking rate of the pasture. The level of infection of the kids decreased significantly at 50% and 25% of the total stocking rate. After the post-weaning period at pasture, at 11 months of age kids were experimentally infected with H. contortus. The faecal egg counts (FEC) were significantly lower in the groups showing the highest FEC at pasture. This result suggests that a degree of protection against an experimental H. contortus infection occurred during the post-weaning period and was dependant on the level of parasitism. Interestingly, no interaction was observed between this level of protection and the genetic status. In conclusion, the level of post-weaning natural parasitism history at pasture would not influence the genetic status evaluation. More generally our results suggest that it would be better to expose kids to a high level of gastrointestinal parasitism during the post-weaning period in order to increase the basal level of resistance thereafter.

Relative bioavailability of soil-bound chlordecone in growing lambs.

The pollution of soil with the pesticide chlordecone (CLD) is a problem for the use of agricultural surfaces even years after its use has been forbidden. Therefore, the exposure of free-ranged animals such as ruminants needs to be investigated in order to assess the risk of contamination of the food chain. Indeed, measured concentrations could be integrated in a lowered extent if the soil binding would reduce the bioavailability of the pesticide. This bioavailability of soil-bound CLD in a heavily polluted andosol has been investigated relatively of CLD given via spiked oil. Twenty-four weaned lambs were exposed to graded doses of 2, 4 or 6 µg CLD/kg body weight during 15 days via the contaminated soil in comparison to spiked oil. The concentration of this pesticide has been determined in two target tissues: blood serum and kidney fat. The relative bioavailability (RBA) corresponds to the slope ratio between the test matrix-contaminated soil- in comparison to the reference matrix oil. The RBA of the soil-bound CLD was not found to significantly differ from the reference matrix oil in lambs meaning that the pesticide ingested by grazing ruminants would not be sequestered by soil binding. Therefore, CLD from soil gets bioavailable within the intestinal level and exposure to contaminated soil has to be integrated in risk assessments.

Cross-infection between tropical goats and heifers with Haemonchus contortus.

Developing effective biological control without the systematic use of anthelmintics is necessary to reduce the impact of gastrointestinal nematodes on small ruminants. Therefore, grazing management systems that use different host species to dilute nematodes in pasture appear to be promising for worm control. A trial was carried out to investigate the specificity of Haemonchus contortus for goats and cattle and to evaluate cross-infection between ruminant species. The effect of an experimental infection of 12 heifers by the free-living stages of H. contortus collected from goats (500 larvae per kg liveweight) was evaluated and compared to uninfected controls. After 28 and 35 days, egg excretion was measured. The experimental infection of heifers by H. contortus was not significant, with no egg excretion. These results, i.e., the lack of cross-infection of GIN between goats and cattle, suggest that integrated grazing using such animals could be employed for pasture dilution and decontamination.

Effect of dietary supplementation on resistance to experimental infection with Haemonchus contortus in Creole kids.

The aim of the present study was to test the effect of dietary supplementation on resistance to experimental infection with Haemonchus contortus in Creole kids. One trial with three replicates involved a total of 154 female kids that were chosen from three successive cohorts of the Creole flock of INRA-Gardel in 2007. The kids were placed into four treatments according to the amount of concentrate they received: G0 (no concentrate and a quality Dichantium spp. hay ad libitum, HAY), G1 (HAY+100g commercial concentrate d(-1)), G2 (HAY+200 g commercial concentrate d(-1)), G3 (HAY+300 g commercial concentrate d(-1)). The G0-G3 groups were infected with a single dose of 10,000 H. contortus third stage larvae (L(3)) at Day 0 (D0). Each infected group was comprised of one half resistant and one half susceptible genetically indexed kids. The average breeding values on egg excretion at 11 months of age were distant of 0.70, 0.65, 0.61 and 0.61 genetic standard deviations in G0, G1, G2 and G3, respectively. The faecal egg count (FEC), packed cell volume (PCV), eosinophilia (EOSI) and dry matter intake (DMI) indices were monitored weekly until 42 days post-infection. Enzyme-linked immunosorbent assay was carried out on serum samples to determine the level of IgA anti-H. contortus L(3) crude extracts and adult excretion/secretion products (ESP). The 10,000 L(3) dose received by the kids induced a severe infection: 8000 eggs per gram at the FEC peak, a PCV less than 15% and mortality. Interestingly, the supplemented animals in G3 showed a higher level of EOSI but a lower level of IgA anti-L3 and IgA anti-ESP than non-supplemented animals (G0). Resistant and susceptible kids had significantly different FEC variations within the groups. Susceptible kids had a 1.6 times higher egg output than resistant kids in G0. This difference was not found in the supplemented groups. The results of this study showed that supplementary feeding improved resistance of Creole kids to H. contortus experimental infection.

In vitro effects of Tabernaemontana citrifolia extracts on Haemonchus contortus.

Tabernaemontana citrifolia (Apocynaceae) is traditionally used as an anthelmintic preparation for ruminants in Guadeloupe (French West Indies). This study was carried out to evaluate the in vitro effect of this plant against the parasitic nematode of small ruminants Haemonchus contortus. Three extracts (aqueous, methanolic and dichloromethane) of T. citrifolia fruit, leaf and root were tested on four developmental stages of the parasite, using egg hatch assay (EHA), larval development assay (LDA), L3 migration inhibition assay (LMI), and adult worm motility assay (AWM). Compared to the negative control, significant effects were observed for the different parts of T. citrifolia but with differences depending on the parasitic stage; efficacies on the larval development of H. contortus from 88.9% to 99.8% for fruit, from 72.1% to 83.8% for root and from 33.5% to 85% for leaf with dose-dependent effect for the methanolic extract. The root gave the best result on EHA (22.7% efficacy for dichloromethane extract) and AWM (56% efficacy, with dose-dependent effect for dichloromethane extract) and the leaf on LMI (49.4% efficacy). These results suggest that T. citrifolia possess anthelmintic activity against H. contortus. The active ingredients responsible for the activity could be the alkaloid compounds present in the plant parts of the plant.

Production systems of Creole goat and their implications for a breeding programme.

The Creole goat is a local meat breed well adapted to the tropical environment of Guadeloupe, a French island in the Caribbean. A survey of 47 goat farmers was conducted in May 2008 to describe the Guadeloupean goat farming systems. It was the preliminary step for the implementation of a breeding programme for Creole goats. Farmers had 31 does on average. A small number (4%) kept only Creole goats. Most of them (62%) had a mixed herd of Creole and crossbreds. One-third of them (34%) reared only crossbred goats. Farmers appreciate the rusticity and resistance of the Creole goat but consider its growth as too slow. The most desired traits for goat selection were conformation and growth for males (77% of the answers). These traits were also important for females (30% of the answers). Maternal qualities were also frequently cited (maternal behaviour 23%, reproduction 20% and milk production 17%). Disease resistance was not seen as an important trait (10% and 7% of the answers for bucks and does, respectively). A typology constituted of five groups of farmers was also created. Farmers of three groups were retained to participate at a selection programme. They kept Creole goats and have expressed a strong willingness to join a selection programme. The results of the survey suggest that a breeding programme should mostly focus on the Creole goat as a maternal breed. Real consideration should be given to disease resistance. The Creole goat has indeed a key role to play in the sustainability of local farming systems.

Influence of earthworms on development of the free-living stages of gastrointestinal nematodes in goat faeces.

With the important infection of small ruminants by gastrointestinal nematodes, and in the face of reduced efficacy of anthelminthic treatments, a search for other biological options is necessary. The effect of earthworms on the free-living stages of Haemonchus contortus and Trichostrongylus colubriformis in faeces from goats naturally infected in tropical pastures was evaluated. Two levels (0 vs 14 individuals per container) of indigenous earthworms (50% Pontoscolex corethrus and 50% Perionyx excavatus) were added to containers filled with soil and faeces collected from 20 grazing goats. After 1 week, the numbers of free-living stages of each infective larvae species was measured. The addition of earthworms reduced by 34% (P<0.006) the number of infective larvae recovered in the faeces of goats. The reduction was significant for both larvae species, 29% and 33% for H. contortus and T. colubriformis, respectively. The ratio of the two species of larvae, without or with earthworms, did not vary significantly (P>0.21). These results must be confirmed in experiments on pasture, with other ratios and combinations of earthworms.

In vitro effects of Cucurbita moschata seed extracts on Haemonchus contortus.

This study was carried out to evaluate the in vitro effect of Cucurbita moschata seed against the parasitic nematode of small ruminants Haemonchus contortus. Three extracts (aqueous, methanolic and dichloromethane) of C. moschata seed were tested in vitro on four developmental stages of H. contortus using egg hatch assay (EHA), larval development assay (LDA), L3 migration inhibition (LMI) assay and adult worm motility (AWM) assay. The highly significant (P<0.001) ability to stop larval development (inhibition>90% for each extract) and the negative effect of the dichloromethane and methanolic extracts on adult worm motility (inhibition of motility >59.2% after 24h of incubation) compared to the negative controls, suggest anthelmintic properties of C. moschata seed against H. contortus. The active principles responsible for the activity could be secondary metabolites such as amino acid compounds or terpenoid compounds present in the extracts.

Impact on productivity of peri-parturient rise in fecal egg counts in Creole goats in the humid tropics.

The control of gastrointestinal nematodes requires an understanding of their epidemiology so that particular parasite stages can be targeted. Dam infection during early lactation is one example of this in ruminant nematode infections. The existence of the peri-parturient relaxation in immunity and its impact on productivity were examined in a Creole goat flock from Guadeloupe, exposed to mixed natural infection (predominantly Haemonchus contortus and Trichostrongylus colubriformis). A total of 1,511 l were obtained from 909 does resulting from 463 dams and 150 sires. Fecal and blood samples were collected at kidding before anthelmintic drenching, 4 and 6 weeks after kidding. The traits analyzed were logarithm transformed fecal egg counts (FEC), packed cell volume (PCV), and logarithm transformed blood eosinophilia counts (EOS) for does at each sampling point and changes in these during the postpartum period. With the exception of the PCV values measured at kidding, lactating does had significantly higher FEC and lower PCV than control dry does at every sampling point. Geometric means of FEC in lactating does were 819 +/- 174, 677 +/- 146 and, 699 +/- 160 eggs per gram (EPG) at kidding, 4 and 6 weeks after kidding respectively. Geometric means of FEC in dry does were 187 +/- 57, 89 +/- 28, 133 +/- 43 at these time points, respectively. EOS differences were not consistent between groups and probably not specific enough for variations in Creole goats' peri-parturient rise to be discussed. As does aged, their egg output decreased and primiparous does always had greater egg output than multiparous ones. Overall, does' FEC at 4 weeks after kidding decreased by 1.3% each year. The higher the litter size, the higher the FEC at kidding and inverse applied for PCV measurements. Does that stopped lactating had significantly lower FEC and higher PCV values than lactating does with low milk yields. Higher infection rates during early lactation in Creole goats were recorded in does with lower maternal ability assessed by the average daily weight gain of kids between 10 and 30 days of age. Kids from dams with higher FEC (i.e. >600 EPG higher than corresponding does) had 17% lower average daily weight gain between 30 and 70 days postpartum and were approximately 1 kg lighter at weaning than kids from dams with lower FEC. Thus, it is clear that a peri-parturient rise in FEC exists in Creole goats. By controlling the intensity of this peri-parturient rise in FEC, herd health and productivity could be substantially improved.

Preweaning productivity of suckling goats and sheep in Guadeloupe (FWI) under intensive reproductive rate and grazing management.

In Guadeloupe, small ruminants are reared for meat production under pasture conditions. Intensive rotative grazing systems (irrigated, fertilized and high-stocked tropical pastures) allow satisfactory levels of production but generate high post-grazing residues. Experiments were designed to control these. A system in which residuals were mown (RM) was tested in comparison to the control system (residuals remained, RR). The same design was carried out over two years with Creole goats and Martinik sheep. An accelerated reproductive rate (3 parturitions over 2 years) was carried out. Systems were compared at three parturition seasons per year (dry, intermediate and rainy seasons). Each group was composed of 20 goats (36.0+/-2.5 kg) or 20 ewes (46.8+/-2.4 kg). The systems exhibited high levels of productivity in both species compared to other results in the tropics: more than 50 and 30 offspring born alive per hectare and per reproductive season for the goat and ewe flocks, respectively. The annual production at birth was 110 kg kids/ha per year and 133 kg lambs/ha per year (i.e. 21% more). Corresponding values at weaning were 630 kg kids/ha per year and 785 kg lambs/ha per year (i.e. 25% more). The RM system produced 10% more than the RR system in Creole goats, while it produced 35% more in Martinik sheep. Seasonal effects and other factors of variation are discussed.

Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation.

The development of genetically modified adenoviral vectors capable of specifically transducing a given cell population requires the addition and functional presentation of particular tropism determinants within the virus capsid, together with the abrogation of the molecular determinants that dictate their natural tropism in vivo. The human adenovirus serotype 5 (Ad5) first attaches to the cell surface following high-affinity binding of the C-terminal knob of the fiber capsid protein to the coxsackie and adenovirus receptor (CAR). Here we have assessed whether genetic shortening of the fiber shaft (virus BS1), or replacing the Ad5 fiber shaft and knob with their Ad3 counterparts (virus DB6), could cripple this interaction in vitro and in vivo. A 10-fold decrease in the binding of the modified capsids to soluble CAR was evidenced, which correlated with a similar reduction of their ability to transduce CAR-positive cells in vitro. The ability of BS1 to interact with cellular integrins was also impaired, suggesting that the penton base and the short-shafted fiber when embedded in the capsid preclude each other from efficiently interacting with their cognate cell surface receptors (CAR and integrins respectively). BS1 and DB6 intravenous injections in mice further supported a profound impairment of the ability of the capsid-modified viruses to transduce the liver as demonstrated by a 10-fold reduction of intracellular viral DNA and transgene expression. Interestingly enough, the host humoral response was also specifically weakened in BS1- and DB6-inoculated animals. Taken together, these observations indicate that (i) fiber shortening and (ii) pseudo-typing of Ad5-based vectors with the shaft and knob from non-CAR-binding serotypes constitute two promising strategies to successfully attenuate their native tropism in vitro and most importantly in vivo.

Controlled transgene expression by E1-E4-defective adenovirus vectors harbouring a "tet-on" switch system.

BACKGROUND: The "tet switch system" was originally described under the tet-off configuration with its components encoded by two separate plasmids. Since then, many virus vectors harbouring tet-off components have been designed and their regulation by tetracycline is widely reported. On the contrary, tet-on regulation by viral vectors is poorly documented. METHODS: E1-E4-defective adenoviruses harbouring either rtTA or the luciferase gene under a minimal inducible promoter (TK* or CMV*) or both components in a single genome were produced. Using either a double or a single virus strategy, induction of luciferase expression was investigated in various cell lines, in mice muscle and in rat brain. RESULTS: Over 400-fold induction can be reached with PC12 and NHA cells using a double virus strategy. Comparison of the background activity of different minimal inducible promoters revealed a significant difference between TK* and CMV* promoters both with the cell culture and the in vivo experiments. Interestingly, a single virus strategy permitted an induction exceeding 600-fold with human astrocyte primary cells. Moreover, the E1-E4-defective adenovirus-mediated tet-on system can be quickly switched off and turned back on again. Depending on the cell line, the level of rtTA derived by the single virus strategy differed, resulting in different efficiencies. Experiments performed in rat striatum and mouse muscle confirmed the importance of rtTA expression and minimal promoter used on both doxycycline-independent expression and induction efficiency. Under appropriated rtTA expression, a 32-fold induction is observed in mouse muscle. CONCLUSIONS: In the recombinant adenovirus context, the CMV* but not the TK* promoter is sensitive to transcriptional interference resulting in high doxycycline-independent expression. By paying attention to the rtTA expression, moderate and high induction can be obtained in vivo and in vitro accordingly.

Pharmacological profile of (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301), an orally and centrally active neurokinin-1 receptor antagonist.

In comparison with a series of reference compounds, (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301) was characterized as a specific, orally, and centrally active neurokinin-1 (NK(1)) receptor antagonist with subnanomolar affinity for the human NK(1) receptor (K(i): 0.45 nM) and over 200-fold selectivity toward NK(2) and NK(3) receptors. R116301 inhibited substance P (SP)-induced peripheral effects (skin reactions and plasma extravasation in guinea pigs) and a central effect (thumping in gerbils) at low doses (0.08-0.16 mg/kg, s.c. or i.p.), reflecting its high potency as an NK(1) receptor antagonist and excellent brain disposition. Higher doses blocked various emetic stimuli in ferrets, cats, and dogs (ED(50) values: 3.2 mg/kg, s.c.; 0.72-2.5 mg/kg, p.o.). Even higher doses (11-25 mg/kg, s.c.) were required in mice (capsaicin-induced ear edema) and rats (SP-induced extravasation and salivation), consistent with lower affinity for the rodent NK(1) receptor and known species differences in NK(1) receptor interactions. R116301 inhibited the ocular discharge (0.034 mg/kg) but not the dyspnoea, lethality, or cough (>40 mg/kg, s.c.) induced by [betaALA(8)]-neurokinin A (NKA) (4-10) in guinea pigs, attesting to NK(1) over NK(2) selectivity. R116301 did not affect senktide-induced miosis (>5 mg/kg, s.c.) in rabbits, confirming the absence of an interaction with the NK(3) receptor. R116301 was inactive in guinea pigs against skin reactions induced by histamine, platelet-aggregating factor, bradykinin, or Ascaris allergens (>10 mg/kg, s.c.). In all species, R116301 showed excellent oral over parenteral activity (ratio, 0.22-2.7) and a relatively long duration (6.5-16 h, p.o.). The data attest to the specificity and sensitivity of the animal models and support a role of NK(1) receptors in various diseases.

[Iron overload and myelodysplastic syndromes]. / Surcharge martiale et syndromes myélodysplasiques (SMD).

Transfusion of RBC units, the only current treatment for many myelodysplastic syndromes, and excess intestinal absorption of Fe related to dyserythopoiesis often result in iron overload. This condition is associated with high rates of morbidity and mortality. High-risk patients include those with refractory anemia, sideroblastic anemia, 5q-syndrome, patients with a good prognosis (low or lower intermediate international prognosis score), patients having received over 100 RBC units, and patients under the age of 70. Deferoxamine, while it can prevent iron overload, is a strenuous treatment requiring 8-to-12 hour-overnight subcutaneous injections. When patients comply with the regimen, it efficiently prevents mortality due to iron overload, but must be implemented early in the disorder, usually before transfusing 20 RBC concentrates. A simple way of monitoring iron overload is to measure seric ferritin levels and record the number of RBC concentrates. The chelating treatment should be modulated according to age, MDS type, international prognosis score, number of RBC units received, ferritin levels, and most of all, patient tolerance. The direct subcutaneous approach is currently being evaluated by the French Group for Myelodysplasias for its efficiency to prevent disorders, but seems to be both efficient and well complied with (a national protocol is under way). The recent findings on the proteins implied in iron recycling by macrophages after destruction of RBCs, may in the long term, enable us to manage patients with less burdensome treatments and more effective new oral chelates.

Optimization of debris removal during bladder irrigation.

Debris build-up within the bladder is one of the main problems encountered by patients undergoing long term catheterization. One of the methods of ameliorating this is to wash out the bladder at regular intervals. In this paper, an alternative method of bladder irrigation is investigated experimentally. The effectiveness of several possible catheter designs has been examined, together with other relevant variables such as the proximity and alignment of the tube tip to the debris and the irrigation flow rate. Results show that debris removal is very sensitive to tube design, with best designs achieving almost complete removal and the worst practically none. The proprietary continuous irrigation catheter used was particularly poor for the type of debris used. Removal is insensitive to the distance of the tube tip from the bladder base up to a limiting value, above which it reduces rapidly. Where misalignment causes the inlet jet to miss the debris, removal rates are very low. Increasing flow rate increases removal up to a limiting value, above which it remains constant. Although the results show the general trends, to optimize the system requires further understanding of the detailed flow patterns within the bladder. A theoretical study using computational fluid dynamics is thus being undertaken.