4A). Under these experimental conditions, overexpression of VEGF for 4 weeks was associated with increased new vessel formation within the liver (Supporting Fig. 4B) and increased hepatic collagen deposition (Sirius red staining, Fig. 3A). In line with these changes, overexpression of VEGF also resulted in a time-dependent increase of hydroxyproline, a collagen-specific amino acid, and Col1a1 mRNA within the liver (Fig. 3B,C). AZD8055 purchase As depicted in Fig. 2E,F, overexpression of VEGF was also associated with altered hepatic levels of Cxc chemokines. As in CCl4-treated mice (Supporting Fig. 2), the angiogenic chemokine Cxcl1 (Supporting Fig. 4C) and the angiostatic

chemokine Cxcl9 (Fig. 3D) were highly abundant within the liver in response to VEGF overexpression. Because the in vivo results suggested a close association between VEGF pathways and the expression of chemokines, we next assessed the direct effects of the angiostatic chemokine Navitoclax nmr Cxcl9 on VEGF-mediated effects on endothelial cells and stellate cells in vitro. Both cell types are considered to be involved in neoangiogenesis within the liver 14 and express both Cxcl9 and its receptor Cxcr3 (Supporting Fig. 5A,B). As depicted in Fig. 4A,B, Cxcl9 significantly abrogated the proliferative and migratory response of VEGF on endothelial cells. We next assessed direct functional aspects of Cxcl9 on angiogenesis in a Matrigel assay. As

shown in Fig. 4C, Cxcl9 indeed strongly abrogated endothelial network formation, supporting its direct involvement in VEGF-induced vessel formation. Furthermore, Cxcl9 inhibited the scratch closure in a functional scratch assay, which is also considered as a combination of proliferation and migration of endothelial cells (Supporting Fig. 5C). Importantly, the inhibitory effects of Cxcl9 were also found in primary sinusoidal endothelial cells isolated from livers of medchemexpress CCl4 damaged animals (Fig. 5A,B), supporting the relevance of our findings for the injury model used in our study. On a molecular level, the effects of

Cxcl9 were associated with a reduced phosphorylation of VEGFR2 (KDR), its downstream mediator PLCγ, JNK, and ERK in primary endothelial cells (Fig. 5C), supporting earlier results of antiangiogenic chemokines on the VEGF signaling pathway. 17 Cxcl9 also reduced the VEGF-induced proliferation of stellate cells (Supporting Fig. 6A), which was also associated with a reduced phosphorylation of KDR, JNK, and ERK (Supporting Fig. 6B). As endothelial and stellate cells are both considered to play a pivotal role during liver neoangiogenesis, we also evaluated the direct interaction between these cell types with and without treatment of Cxcl9. Indeed, conditioned medium from VEGF stimulated endothelial cells induced the proliferation and migration of stellate cells in vitro, which was strongly reduced by concomitant treatment of endothelial cells with Cxcl9 (Supporting Fig. 6C).

5,25–29 Neutrophils are not normally present in normal colonic mucosa. The presence and infiltration of neutrophils into the lamina propria, crypt epithelium (cryptitis) and crypt lumen (crypt abscesses) is a sign of active disease, with the degree of neutrophilic inflammation an indication of disease activity. It is, however, also present in infectious

colitis and other colitides and is not pathognomonic of UC. A minority of UC patients may have cecal patch inflammation, rectal sparing (pediatric patients) or backwash ileitis. Level of agreement: a-82%, b-18%, c-0%, d-0%, e-0% Quality of evidence: II-2 Classification of recommendation: B Non-classical UC features which include cecal patch inflammation, rectal sparing and backwash ileitis have been observed Buparlisib manufacturer in a small proportion of patients. These features should not be PI3K Inhibitor Library confused with CD.30–42 Inflammation of the peri-appendiceal cecal mucosa (‘cecal patch’) is well described in western series, particularly those with left-sided

colitis.30–32 The clinical features and natural history of those with cecal patch inflammation appear to be similar to those with isolated left-sided disease.31 Similarly, cecal patch inflammation has also been described in Asian UC patients, being seen more frequently in those with less extensive disease.33–36 In one study from Japan, it has been shown to better respond to medical therapy but this observation will require confirmation in large controlled MCE公司 studies.35 Endoscopic and histologic rectal sparing has been observed in a small proportion of pediatric UC patients at the time of initial presentation37–39 while in adults, it may be seen after topical or systemic therapy for UC.20–23 On the other hand, ‘relative’ rectal sparing has been reported in adult UC patients at presentation.43,44 Inflammation of the distal terminal ileum, termed ‘backwash ileitis’ is seen in up to 20%

of UC patients, typically in those with pancolitis although rarely ileal erosions may occur in those without cecal involvement.40–42 Serological tests (ASCA, pANCA) are not required for the diagnosis of UC but may occasionally be helpful in differentiation of UC from CD. Level of agreement: a-65%, b-23%, c-12%, d-0%, e-0% Quality of evidence: II-1 Classification of recommendation: B Serological markers perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been extensively studied in the Caucasian IBD population45 but less data exists for Asian IBD patients.46–55 Although pANCA and ASCA are more specific for UC and CD, respectively, their usefulness is limited by their low sensitivity and not required for the diagnosis of UC in clinical practice. In a meta-analysis, pANCA positivity alone has a 55.3% sensitivity and 88.5% specificity for UC.

5,25–29 Neutrophils are not normally present in normal colonic mucosa. The presence and infiltration of neutrophils into the lamina propria, crypt epithelium (cryptitis) and crypt lumen (crypt abscesses) is a sign of active disease, with the degree of neutrophilic inflammation an indication of disease activity. It is, however, also present in infectious

colitis and other colitides and is not pathognomonic of UC. A minority of UC patients may have cecal patch inflammation, rectal sparing (pediatric patients) or backwash ileitis. Level of agreement: a-82%, b-18%, c-0%, d-0%, e-0% Quality of evidence: II-2 Classification of recommendation: B Non-classical UC features which include cecal patch inflammation, rectal sparing and backwash ileitis have been observed Selleckchem Nutlin 3 in a small proportion of patients. These features should not be PCI-32765 purchase confused with CD.30–42 Inflammation of the peri-appendiceal cecal mucosa (‘cecal patch’) is well described in western series, particularly those with left-sided

colitis.30–32 The clinical features and natural history of those with cecal patch inflammation appear to be similar to those with isolated left-sided disease.31 Similarly, cecal patch inflammation has also been described in Asian UC patients, being seen more frequently in those with less extensive disease.33–36 In one study from Japan, it has been shown to better respond to medical therapy but this observation will require confirmation in large controlled medchemexpress studies.35 Endoscopic and histologic rectal sparing has been observed in a small proportion of pediatric UC patients at the time of initial presentation37–39 while in adults, it may be seen after topical or systemic therapy for UC.20–23 On the other hand, ‘relative’ rectal sparing has been reported in adult UC patients at presentation.43,44 Inflammation of the distal terminal ileum, termed ‘backwash ileitis’ is seen in up to 20%

of UC patients, typically in those with pancolitis although rarely ileal erosions may occur in those without cecal involvement.40–42 Serological tests (ASCA, pANCA) are not required for the diagnosis of UC but may occasionally be helpful in differentiation of UC from CD. Level of agreement: a-65%, b-23%, c-12%, d-0%, e-0% Quality of evidence: II-1 Classification of recommendation: B Serological markers perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been extensively studied in the Caucasian IBD population45 but less data exists for Asian IBD patients.46–55 Although pANCA and ASCA are more specific for UC and CD, respectively, their usefulness is limited by their low sensitivity and not required for the diagnosis of UC in clinical practice. In a meta-analysis, pANCA positivity alone has a 55.3% sensitivity and 88.5% specificity for UC.

NAFLD starts with over-nutrition, imbalance between energy input and output for which the roles of genetic predisposition and environmental factors (diet, physical activity) are being redefined. Regulation of energy balance operates at both central nervous system and peripheral selleck chemicals sites, including adipose and liver. For example, the endocannabinoid

system could potentially be modulated to provide effective pharmacotherapy of NAFLD. The more profound the metabolic abnormalities complicating over-nutrition (glucose intolerance, hypoadiponectinemia, metabolic syndrome), the more likely is NAFLD to take on its progressive guise of non-alcoholic steatohepatitis (NASH). Interactions between steatosis and insulin resistance, visceral adipose Dabrafenib mouse expansion and subcutaneous adipose failure (with insulin resistance, inflammation and hypoadiponectinemia) trigger amplifying mechanisms for liver disease. Thus, transition from simple steatosis to NASH could be explained by unmitigated hepatic lipid partitioning with failure of local adaptive mechanisms leading to lipotoxicity. In part one of this review, we discuss newer concepts of appetite and metabolic regulation, bodily lipid distribution, hepatic lipid turnover, insulin resistance and adipose failure affecting adiponectin secretion. We review evidence

that NASH only occurs when over-nutrition is complicated by insulin resistance and a highly disordered metabolic milieu, the same ‘metabolic movers’ that 上海皓元医药股份有限公司 promote type 2 diabetes and atheromatous cardiovascular disease. The net effect is accumulation of lipid molecules in the liver. Which lipids and how they cause injury, inflammation and fibrosis will be discussed in part two. It is more than 30 years since alcoholic hepatitis-like lesions were

recognized among over-weight or diabetic non-drinkers, for which Ludwig, in 1980, coined the term non-alcoholic steatohepatitis (NASH).1 Interest in this disorder has burgeoned recently.2–6 A decade ago it was known that fatty liver had many causes,2 and the present convention is to label cases with definable single etiologies as such, e.g. drug-induced steatohepatitis, fatty liver associated with parenteral nutrition, rather than ‘secondary NASH’. The term non-alcoholic fatty liver disease (NAFLD) should be reserved for those cases in which there is not one single cause. The latter are nearly always associated with overweight, particularly central obesity and insulin resistance, and often glucose intolerance/type 2 diabetes (T2D), dyslipidemia, hypertension and other features of the metabolic syndrome.2–5 For this reason, we proposed the term metabolic steatohepatitis,2 but the simpler term NAFLD infers an inextricable relationship between this type of fatty liver and the metabolic complications of over-nutrition.

The dingo differs from the domestic dog C. familiaris and its hybrids by restriction

of pelage colours to combinations of yellow, black and white, and in skull measurements including relatively INCB018424 datasheet larger palatal width (Fig. 5a,c,g,j, Table 5), relatively longer rostrum (Fig. 5e,f,i,k, Table 5), relatively shorter skull height (Fig. 5b,d, Table 5) and relatively wider top ridge of skull (Fig. 5h, Table 5). Note that owing to the enormous variation in dog phenotypes, dog breeds used in the analysis were restricted to those of similar size and structure to dingoes. Note that the following canids are considered by some authors as actual dingoes with some geographical variation (Corbett, 1985, 1995). Others recognized them as separate forms (Gollan, 1982). 1 Different from the New Guinea singing dog Canis hallstromi by its greater height at the withers (Koler-Matznick et al., 2003). It resembles the New Guinea singing dog in most other morphological characteristics (Koler-Matznick et al., 2003). 2 Different from LDE225 order Thai pariah dogs, as defined by Corbett (1985), by being larger in cranial (total skull length of pre-20th century dingoes 189.0 mm ± 1.8; Thai pariah dog male = 179.5 mm ± 3.1, female = 173.2 mm ± 3.6) and external measurements (Corbett, 1985). Dingoes are dog-like and possess a fairly broad head, tapered muzzle, erect ears and a bushy tail (Kerr,

1792; Fig. 6). Relative to similar-sized domestic dogs, dingoes have longer and more slender muzzles. The 19th century dingoes we examined, like wolves but unlike many dogs, do not possess dewclaws on the hind legs (Ciucci et al., 2003). Dingoes can have five basic pelage colours: yellow, brown, ginger/red, black and white (Cairns, Wilton & Ballard, 2011). These colours occur in various combinations and 19th century skin specimens included animals that 上海皓元医药股份有限公司 are entirely

white (Fig. 6), entirely yellow/brown (Fig. 6), entirely black, yellow with white patches (Fig. 6), particularly at the tip of the tail and ankles (Fig. 6), and yellow with black fur along the dorsal parts of the body (sable, Fig. 6). The original specimen of C. dingo (Fig. 1) illustrated in Mazell & Phillip (1789) was uniformly brown on its dorsal surface, with the face, underparts and feet being white (Kerr, 1792). Other pre-1800 paintings included colours such as dark brown, reddish brown, and sandy with sabling (Supporting Information Figure S1). The specimen of C. macdonnellensis (Matschie, 1915) ZMB 22418 at the Museum für Naturkunde, Berlin, and the specimen of C. familiaris australasiae (Desmarest, 1820) at the Muséum National d’Histoire Naturelle, Paris, were both predominantly yellow with some dark fur along the dorsum (sabling). Historical records describing dingo colours are scant, and mostly not detailed (Elledge et al., 2006).

Pleural effusion accompanying liver cirrhosis is usually right sided (66%), but may be bilateral (17%) or left-sided (17%).8 Although the pathogenesis of hepatic hydrothorax is not fully understood, peritoneo-pleural

communication is suggested as one of the significant causes.9 Hepatic hydrothorax can be seen in the absence of ascites due to the negative intrathoracic pressure during breathing, drawing the peritoneal fluid through diaphragmatic defects into the pleural cavity. Radioisotopes3,4 and indocyanine green5 are useful for Nutlin-3a in vitro detecting the transdiaphragmatic passage of ascitic fluid into the pleural cavity. Direct demonstration of a diaphragmatic defect with non-invasive imaging techniques, such as magnetic resonance imaging, is extremely CP-868596 solubility dmso difficult, as the defect itself is usually quite small.10

A method allowing direct observation of the diaphragm by thoracoscopy has been reported,11 but is not generally performed because of the highly invasive nature of the procedure. Ultrasonography contrast agent is used mainly for intravascular signal enhancement, but can also be used for non-vascular imaging of body cavities, such as the urinary bladder,12 uterine cavity13 or peritoneal cavity.14 Sonazoid is a second-generation microbubble agent for ultrasonography, comprising perfluorobutane microbubbles with a median diameter of 2–3 µm. Sonazoid is reconstituted with 2 mL sterile water for injection.15 In the present study, we tried to detect the movement of ascitic fluid into the pleural space by ultrasonography with Sonazoid. The appropriate dosage for an intraperitoneal injection of Sonazoid has not been determined, so we used the

dosage applied in intravenous infusion. As a result, the passage of the contrast agent from the peritoneal cavity to the pleural space was clearly demonstrated only several seconds to 10 min after Sonazoid injection in five patients. These five patients were all diagnosed with hepatic hydrothorax. Moreover, movement of ascitic fluid into the pleural cavity was observed in real time. Ultrasonography contrast agent injected into the abdominal cavity reportedly spreads uniformly in approximately 8 min.14 Enhancement of the pleural cavity was observed within 1 min after Sonazoid MCE公司 injection in four of five patients in this study because the injection point was near the right diaphragm. Velocity of ascitic fluid movement into the pleural cavity is reportedly proportional to the pressure difference between the pleural and peritoneal cavities.16 We therefore supposed the following from the results of this study. In three of the five patients diagnosed with hepatic hydrothorax and showing turbinated enhancement, a large pressure difference between the pleural and peritoneal cavities caused a large volume of Sonazoid to move into the pleural cavity. A small pressure difference probably caused slower diffusion of Sonazoid in the two patients with enhancement spots.

Previous studies have emphasized the behavioural plasticity of successful urban wildlife species. In this study,

we emphasize the importance of disturbance monitoring by successful urban exploiters, Metformin cell line allowing them to vary their behavioural responses according to the level of risk to which they are exposed. Cities are challenging environments for many species of wildlife, presenting a loss of natural resources (i.e. habitat and food) and high levels of anthropogenic disturbance, that is pedestrian traffic, vehicular traffic and industrial noise (Lowry, Lill & Wong, 2012). Despite this, some species do extremely well in urban environments. Successful ‘urban adapters’ (sensu McKinney, 2006) are generally species that show high levels of opportunistic behaviour (i.e. are habitat or trophic generalists and can exploit novel niches; Bateman & Fleming, 2012, Lowry et al., 2012), or, in the case of birds, are also more gregarious or sedentary (Kark et al., 2007) or have large breeding ranges, high fecundity, dispersal and survival (Møller, 2008). Behavioural flexibility

and adaptive adjustments are therefore identified as a feature of successful urban species and are likely to be important in facilitating resource use, avoiding disturbance and enhancing communication (Slabbekoorn & Peet, 2003; Patricelli Napabucasin mouse & Blickley, 2006; Baker et al., 2007; Evans, Boudreau & Hyman, 2010; Lowry et al., 2012; Sol, Lapiedra & Gonzalez-Lagos, 2013). A major aspect of behavioural flexibility in urban adapters is how such animals are able to modify their antipredator medchemexpress behaviour towards humans, which may be regarded as ‘predation-free predators’ (Beale & Monaghan, 2004). Models of optimal escape theory predict that individuals should flee when costs of staying outweigh costs of flight, based on the variables of risk posed by the predator,

the cost of fleeing, the potential to rely on other defensive tactics, and the size of the prey group (i.e. increased vigilance and predator dilution) (Ydenberg & Dill, 1986; Cooper & Frederick, 2007). Animals should, therefore, assess the degree of risk represented and dynamically adjust their antipredator behaviour accordingly. In urban environments, where there is a high level of background disturbance, the success of urban wildlife may rely on their abilities to clearly distinguish between genuinely threatening and non-threatening stimuli and become habituated to some human activity. Although animals still need to be sensitive to the level of threat because of human presence, living without fear in the vicinity of humans is identified as a key behavioural trait of urban adapters (Kark et al., 2007).

Conventional evolutionary wisdom is that new vertebrate

species normally arise either via a splitting of lineages (cladogenesis) or by gradual transformations through time in ancestral-descendant series of populations (anagenesis). However, all known vertebrate taxa that are constitutively clonal clearly arose via interspecific hybridization events between progenitor species with standard sexuality. The basic suspicion is that normal meiotic and sexual operations became disrupted in hybrid offspring in ways that Akt inhibitor precipitated each evolutionary transition to ameiotic asexual reproduction. For several clonal vertebrate taxa, researchers have used molecular markers to help clarify some of the detailed cytogenetic mechanics Selleckchem Palbociclib of unisexual origins (Uzzell, 1970; Dawley & Bogart, 1989; Quattro, Avise & Vrijenhoek, 1992a). Molecular markers have also been used to pinpoint the sexual species and the direction(s) of the original cross(es) that produced each unisexual biotype (e.g. Avise et al., 1991). To pick just a few examples, the diploid parthenogenetic rock lizard Darevskia rostombekovi of central Europe apparently arose via a single cross between a sexual D. raddei female and a sexual D. portschinskii male (Moritz, Wright & Brown, 1992; MacCulloch et al., 1997), whereas some other unisexual

taxa such as parthenogenetic lizards Menetia greyii (Adams et al., 2003) and hybridogenetic fishes named Poeciliopsis monacha-lucida (Quattro, Avise & Vrijenhoek, 1991) each encompass multiple evolutionary lineages that originated via separate hybridization events. In the Poeciliopsis case, the hybridizations that give rise to unisexual biotypes 上海皓元医药股份有限公司 appear to be ongoing. For these unisexual fish, the interpretation is that each such

event genetically ‘freezes’ a new clonal genotype (Vrijenhoek, 1984), which if lucky might happen to fill an open ecological niche. Thus, overall, many biotypes are generated but probably only a few persist for very long. Another revelation about unisexual origins is that the sexual progenitors that hybridized to produce each clonal lineage usually are not sister species but instead belong to different branches of the phylogenetic tree for that taxonomic genus. Two hypotheses (not mutually excusive) have been advanced for this observation. Under the balance hypothesis, parthenogenesis can arise only when the genomes of parental species are divergent enough to disrupt meiosis in hybrids yet not so divergent as to seriously compromise hybrid viability or fertility. By contrast, the phylogenetic constraint hypothesis posits that genetic peculiarities predispose particular parental species to produce unisexual lineages following hybridization.

The stimulant laxative (sodium picosulphate, SPS) is also effective clearing the bowel in 81% [2] and is a liquid easily taken by children. PEG and a stimulant are commonly combined for cleansing the colon for colonoscopy [3]. Aim: ZD1839 mw determine how much stool is produced by combined PEG and SPS in patients with palpable fecaloma requiring disimpaction. Materials and Methods: The study was performed on 17 participants (8 males and 9 females, Mean age 9.1 ± 1.0 yrs, range 4–17 yrs) recruited from the a tertiary teaching

hospital. Inclusion criteria: 2 years chronic constipation, palpable fecaloma on presentation confirmed by presence of enlarged stool-filled rectum on x-ray. Participants were taught to fill in a daily PCI-32765 diary recording stool volume produced and laxative dose taken. Laxatives were given according to a predetermined dosage regimen taking high concentrations (4–8 sachets) of Movicol (PEG + electrolytes) on day 1 and 2. Each sachet of Movicol contained 14.7 g of PEG plus electrolytes and was made up

with 125 ml water per sachet plus an equal volume of juice or milk and 10–20 drops of SPS (Dulcolax SP) was added. Patients drank 125–250 ml per half hour using a fun approach (MOTIVATE). They continued to take 1 sachet of Movicol plus 10 drops of SPS for 14 days. Three subjects were excluded from analysis due to lack of data. Results: Over day 2–4, all subjects produced between 0.5 to 4.0 liters of stool (over the first 4 days). They continued to produce at least 250 ml of stool per day in the following 2 weeks (table 1). Mean total stool produced over 14 days was 4.2 ± 0.6 L. The subject’s

age and total stool volume produced by Day 4, 7 and 14 were fitted to linear regressions. 上海皓元医药股份有限公司 There was little relationship between age and stool volume at Day 4 (r2 = 0.43, Gradient = 0.2), Day 7 (r2 = 0.40, Gradient = 0.27) and Day 14 (r2 = 0.30, Gradient = 0.36). Children were easily able to drink the large volume of PEG solution using the MOTIVATE method. Table 1 Number of patients and total stool volume produced Total Stool (L) 0.5–2.5 2.5–4.5 4.5–6.5 6.5–8.5 8.5–10.5 Day 1–4 12 (86%) 2 (14%) – – – Day 1–7 8 (57%) 5 (36%) 1 (7%) – – Day 1–14 5 (36%) 3 (21%) 4 (29%) 1 (7%) 1 (7%) Conclusion: For disimpaction in children with a palpable fecaloma and rectal enlargement, combined polyethylene glycol and sodium picosulphate given at high dose on day 1 and 2 are effective in producing large volumes of stool. The MOTIVATE method provided a fun way to drink the large volume of osmotic and stimulant laxatives and a successful and well tolerated method of disimpaction in children with chronic constipation and large solid stools in the rectum. 1. Candy, DC, et al, J Pediatr Gastroenterol Nutr, 2006. 43:65–70. 2. Atkin, WS, et al, BMJ, 2000. 320:1504–1508. 3.

The stimulant laxative (sodium picosulphate, SPS) is also effective clearing the bowel in 81% [2] and is a liquid easily taken by children. PEG and a stimulant are commonly combined for cleansing the colon for colonoscopy [3]. Aim: learn more determine how much stool is produced by combined PEG and SPS in patients with palpable fecaloma requiring disimpaction. Materials and Methods: The study was performed on 17 participants (8 males and 9 females, Mean age 9.1 ± 1.0 yrs, range 4–17 yrs) recruited from the a tertiary teaching

hospital. Inclusion criteria: 2 years chronic constipation, palpable fecaloma on presentation confirmed by presence of enlarged stool-filled rectum on x-ray. Participants were taught to fill in a daily Tanespimycin diary recording stool volume produced and laxative dose taken. Laxatives were given according to a predetermined dosage regimen taking high concentrations (4–8 sachets) of Movicol (PEG + electrolytes) on day 1 and 2. Each sachet of Movicol contained 14.7 g of PEG plus electrolytes and was made up

with 125 ml water per sachet plus an equal volume of juice or milk and 10–20 drops of SPS (Dulcolax SP) was added. Patients drank 125–250 ml per half hour using a fun approach (MOTIVATE). They continued to take 1 sachet of Movicol plus 10 drops of SPS for 14 days. Three subjects were excluded from analysis due to lack of data. Results: Over day 2–4, all subjects produced between 0.5 to 4.0 liters of stool (over the first 4 days). They continued to produce at least 250 ml of stool per day in the following 2 weeks (table 1). Mean total stool produced over 14 days was 4.2 ± 0.6 L. The subject’s

age and total stool volume produced by Day 4, 7 and 14 were fitted to linear regressions. medchemexpress There was little relationship between age and stool volume at Day 4 (r2 = 0.43, Gradient = 0.2), Day 7 (r2 = 0.40, Gradient = 0.27) and Day 14 (r2 = 0.30, Gradient = 0.36). Children were easily able to drink the large volume of PEG solution using the MOTIVATE method. Table 1 Number of patients and total stool volume produced Total Stool (L) 0.5–2.5 2.5–4.5 4.5–6.5 6.5–8.5 8.5–10.5 Day 1–4 12 (86%) 2 (14%) – – – Day 1–7 8 (57%) 5 (36%) 1 (7%) – – Day 1–14 5 (36%) 3 (21%) 4 (29%) 1 (7%) 1 (7%) Conclusion: For disimpaction in children with a palpable fecaloma and rectal enlargement, combined polyethylene glycol and sodium picosulphate given at high dose on day 1 and 2 are effective in producing large volumes of stool. The MOTIVATE method provided a fun way to drink the large volume of osmotic and stimulant laxatives and a successful and well tolerated method of disimpaction in children with chronic constipation and large solid stools in the rectum. 1. Candy, DC, et al, J Pediatr Gastroenterol Nutr, 2006. 43:65–70. 2. Atkin, WS, et al, BMJ, 2000. 320:1504–1508. 3.