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Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days. The median ± IQR difference in final versus starting weight was 696 ± 425g in the DHA-ALT® group compared to 132 ± 278g in the controls (p=.08). Within 12 hours, median ± IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT® vs. control group (4.1 ± 0.3 vs 2.5 ± 0.5, p=0.009; 0.7 ± 0.3 vs 0.2 ± 0.005, p=0.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® versus the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (p=0.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA.

Objectives Nasal potential difference (NPD) measurement is part of the diagnostic criteria for cystic fibrosis (CF) and now used routinely as an endpoint in clinical trials of correcting the basic defect in CF. Intestinal current measurement (ICM), measured ex vivo on a rectal biopsy, has been used to study cystic fibrosis transmembrane conductance regulator (CFTR) function but has not been compared to NPD in the same subject in adults and children. The aim of the study is to evaluate the potential usefulness of ICM as a marker of CFTR function for treatment studies compared NPD in patients with CF and in healthy control subjects. Methods ICM and NPD were performed on healthy controls and patients with CF. The healthy adults were individuals undergoing routine screening colonoscopy at the Beth Israel Deaconess Medical Center. The healthy children were undergoing colonoscopy for suspicion of inflammation in Hadassah Hebrew University Medical Center. The CF adults were recruited from Boston Children's Hospital CF Center and CF Center Worcester Mass, the children with CF from Hadassah CF Center. Results ICM measurements in healthy control subjects (n = 16) demonstrated a mean (±SE) carbachol response of 16.0 (2.2) μA/cm, histamine response of 13.2 (2.1) μA/cm and a forskolin response of 6.3 (2.0) μA/cm. Basal NPD of -15.9 (1.9) and response to Cl free + isoproterenol of -13.8 (2.0). These responses were inverted in CF subjects (n = 12) for ICM parameters with carbachol response of -3.0 (0.5) μA/cm, histamine -1.0 (0.8) μA/cm and a forskolin response of 0.5 (0.3) and also for NPD parameters; basal NPD of -42.2 (4.3) and response to Cl free + isoproterenol of 4.3 (0.7). Pearson correlation test showed the comparability of ICM and NPD in assessing CFTR function. Conclusions ICM is equivalent to NPD in the ability to distinguish patients with CF from controls and could be used as surrogate markers of CFTR activity in treatment protocols.

Aliment Pharmacol Ther 2012; 35: 255–265 Summary Background Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. Aim To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. Methods We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. Results A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P

Cystic fibrosis (CF) is associated with fatty acid alterations characterized by low linoleic and docosahexaenoic acid. It is not clear whether these fatty acid alterations are directly linked to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction or result from nutrient malabsorption. We hypothesized that if fatty acid alterations are a result of CFTR dysfunction, those alterations should be demonstrable in CF cell culture models. Two CF airway epithelial cell lines were used: 16HBE, sense and antisense CFTR cells, and C38/IB3-1 cells. Wild-type (WT) and CF cells were cultured in 10% fetal bovine serum (FBS) or 10% horse serum. Fatty acid levels were analyzed by GC-MS. Culture of both WT and CF cells in FBS resulted in very low linoleic acid levels. When cells were cultured in horse serum containing concentrations of linoleic acid matching those found in human plasma, physiological levels of linoleic acid were obtained and fatty acid alterations characteristic of CF tissues were then evident in CF compared with WT cells. Kinetic studies with radiolabeled linoleic acid demonstrated in CF cells increased conversion to longer and more-desaturated fatty acids such as arachidonic acid. In conclusion, these data demonstrate that CFTR dysfunction is associated with altered fatty acid metabolism in cultured airway epithelial cells.

Background Cystic fibrosis (CF) is characterized by an excessive inflammatory response in epithelial cells and macrophages. In CF mice, lung inflammation can be abrogated by oral treatment with docosahexaenoic acid (DHA). Since PPARs and LXRs are important regulators of inflammation and fatty acid metabolism in macrophages, we hypothesized that these pathways are dysregulated in CF macrophages and are corrected with DHA treatment. Methods Peritoneal macrophages were obtained from wild type and cftr −/− mice. LPS induced cytokine secretion and NFκB activity were analyzed with and without oral DHA treatment. The expression and activity of PPARα,γ, δ and LXRα were analyzed by RT-PCR and EMSA. Results LPS induced TNFα and IL-6 secretion and NFκB p65 activity were increased in CF macrophages. This was associated with low basal PPARγ expression and attenuated LPS induced induction of PPARδ, LXRα and ABCA1. DHA pretreatment in vivo decreased TNFα secretion and p65 activity, and increased PPARα and γ expression and function. The effects of DHA could be reproduced by PPAR agonists and blocked by a PPARα antagonist. Conclusion Impaired regulation of nuclear receptors may contribute to the abnormal LPS induced signaling in CF macrophages and is reversed by DHA.

The aim of the present study was to quantify absorption coefficients of specific fatty acids in preterm infants as a function of diet, formula or breast milk (BM), and postnatal age; to identify the fatty acid structural characteristics that determine optimal fatty acid absorption.Fatty acids from dietary and fecal samples were extracted and quantified by gas chromatography-mass spectroscopy. Fatty acid absorption coefficients (FA-CFAs) were calculated by comparing the total amount of fatty acids supplied by the diet to the amount quantified in the total fecal output during a 3-day period.A total of 18 infants (BM 8, formula 10) were studied at 2 weeks of age, and 20 infants (BM 10, formula 10) were studied at 6 weeks of age. FA-CFAs decreased with increasing carbon length in formula-fed infants at 2 and 6 weeks. Results were similar but less in magnitude in BM-fed infants at 2 weeks with no difference at 6 weeks.Preterm infants fed formula demonstrated lower FA-CFAs as a function of increasing carbon length. This is consistent with limited pancreatic lipase production and with lipase being present in BM but not in formula. The fact that this pattern was seen in BM-fed infants at 2 weeks but not 6 weeks of age suggests that intestinal immaturity may also play a role in impaired fatty acid absorption. These data highlight principles that need to be considered to optimize delivery and absorption of dietary long-chain polyunsaturated fatty acids in preterm infants.

Background: Feeding intolerance (FI), defined as delayed advancement to full enteral feedings, in the preterm infant leads to growth failure and may play a role in the pathogenesis of necrotizing enterocolitis, the leading gastrointestinal cause of death in the NICU. Methods: Serum gut hormone (GH) levels in 64 preterm infants born at < 30 weeks gestational age (GA) were measured on day of birth and at postnatal day 7 (Millipore, USA). Univariate linear regression was performed between GH levels and GA and between GH levels and days to full feedings. Results: Mean GA was 28.1 ± 1.3 wks and birthweight 1038.6 ± 276.6 gms. Leptin and gastrointestinal inhibitory peptide (GIP) on the day of birth (p=.04; p=.006) and leptin and pancreatic polypeptide (PP) at day 7 (p=.004; p=.01) were positively correlated with GA. Higher PP levels on the day of birth (p=.02) were correlated with FI while lower levels of GIP, polypeptide YY (PYY) and glucagon-like peptide 2 (GLP-2) at day 7 (p=.001; p=.0001; p=.03) were associ...

Background: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites shown to produce toxic effects in the liver and pancreas in vivo and in vitro. Because alcohol-induced chronic pancreatitis is associated with mutations in the gene responsible for cystic fibrosis (CFTR), we hypothesized that CFTR dysfunction leads to increased levels of these toxic nonoxidative ethanol metabolites following alcohol administration. Methods: Cystic fibrosis (CF) and wild-type (WT) mice were injected intraperitoneally with 1, 2, or 3 g/kg of 50% ethanol. Mice were sacrificed and the liver and pancreas removed for FAEE analysis. Results: The mean FAEE concentration (pmol/g) detected in the liver of cftr−/− mice following injection with 2 g/kg of ethanol was significantly greater than the amount detected in WT (p < 0.005). A similar trend in FAEE concentration was seen in the pancreas, but the difference was not statistically different. In both the liver and pancreas, analysis of individual FAEE species demonstrated a selective increase in ethyl oleate. Conclusion: These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure.

It is unknown why some patients with inflammatory bowel disease develop primary sclerosing cholangitis. We have recently shown that patients with primary sclerosing cholangitis have an increased prevalence of mutations in the gene responsible for cystic fibrosis (CFTR) compared with individuals with inflammatory bowel disease alone. Our aim was to examine whether induction of colitis by oral dextran leads to bile duct injury in mice heterozygous or homozygous for mutations in CFTR. The effect of oral administration of docosahexaenoic acid to correct a fatty acid imbalance associated with cystic fibrosis was also examined to determine whether this would prevent bile duct inflammation. Wild-type mice and mice heterozygous and homozygous for CFTR mutations were given dextran orally for 14 days to induce colitis. Bile duct injury was quantitated by blinded histological scoring and measurement of serum alkaline phosphatase activity. The effect of pretreatment with docosahexaenoic acid for 7 days was examined. Treatment of mice with 100 mg dextran/day for 9 days followed by 85 mg/day for 5 days resulted in a significant increase in bile duct injury as determined by histological scoring in homozygous cystic fibrosis mice compared with wild-type mice ( P = 0.005). The bile duct injury seen in cystic fibrosis mice was reflected in a threefold increase in serum alkaline phosphatase ( P = 0.0006). Pretreatment with oral docosahexaenoic acid decreased both histological evidence of bile duct injury and serum alkaline phosphatase levels. In the setting of colitis, loss of CFTR function leads to bile duct injury.

Some of the pathological manifestations of cystic fibrosis are in accordance with an impaired expression and/or activity of PPARgamma. We hypothesized that PPARgamma expression is altered in tissues lacking the normal cystic fibrosis transmembrane regulator protein (CFTR). PPARgamma mRNA levels were measured in colonic mucosa, ileal mucosa, adipose tissue, lung, and liver from wild-type and cftr-/- mice by quantitative RT-PCR. PPARgamma expression was decreased twofold in CFTR-regulated tissues (colon, ileum, and lung) from cftr-/- mice compared to wild-type littermates. In contrast, no differences were found in fat and liver. Immunohistochemical analysis of PPARgamma in ileum and colon revealed a predominantly nuclear localization in wild-type mucosal epithelial cells while tissues from cftr-/- mice showed a more diffuse, lower intensity labeling. A significant decrease in PPARgamma expression was confirmed in nuclear extracts of colon mucosa by Western blot analysis. In addition, binding of the PPARgamma/RXR heterodimer to an oligonucletotide containing a peroxisome proliferator responsive element (PPRE) was also decreased in colonic mucosa extracts from cftr-/- mice. Treatment of cftr-/- mice with the PPARgamma ligand rosiglitazone restored both the nuclear localization and binding to DNA, but did not increase RNA levels. We conclude that PPARgamma expression in cftr-/- mice is downregulated at the RNA and protein levels and its function diminished. These changes may be related to the loss of function of CFTR and may be relevant to the pathogenesis of metabolic abnormalities associated with cystic fibrosis in humans.

Background Morbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet. Objective The aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease. Methods 130 infants

The mechanism by which Pseudomonas causes excessive inflammation in the cystic fibrosis lung is unclear. We have reported that arachidonic acid is increased and docosahexaenoic acid (DHA) decreased in lung, pancreas, and ileum from cftr−/−mice. Oral DHA corrected this defect and reversed the pathology. To determine which mediators regulate inflammation in lungs from cftr−/−mice and whether inhibition occurs with DHA, cftr−/−and wild-type (WT) mice were exposed to aerosolized Pseudomonas lipopolysaccharide (LPS). After 2 days of LPS, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2, and KC levels in bronchoalveolar lavage fluid were increased in cftr−/−compared with WT mice and not suppressed by pretreatment with oral DHA. Neutrophil levels were not different between cftr−/−and WT mice. After 3 days of aerosolized LPS, neutrophil concentration, TNF-α, and the eicosanoids 6-keto-PGF1α, PGF2α, PGE2, and thromboxane B2were all increased in bronchoalveolar lavage fluid from cftr−/−mice compared with WT controls. Oral DHA had no significant effect on TNF-α levels in cftr−/−mice. In contrast, neutrophils and eicosanoids were decreased in cftr−/−but not in WT mice treated with DHA, indicating that the effects of DHA on these inflammatory parameters may be related to correction of the membrane lipid defect.

Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o−sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/−transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2αsecretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/−Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators.

Primary sclerosing cholangitis (PSC) is associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As proof of concept that CFTR dysfunction plays a role in PSC, induction of colitis in cftr mice results in bile duct injury that can be prevented by pretreatment with docosahexaenoic acid (DHA).Determine whether 1) CFTR dysfunction in cftr mice through a reduction in peroxisome proliferator activated receptor (PPAR)alpha or gamma leads to bile duct injury and 2) whether DHA prevents bile duct injury through an increase in PPAR.Cftr and wild-type (WT) mice were treated with dextran sodium sulfate (DSS) to induce colitis with or without pretreatment with oral DHA. PPARalpha and gamma as well as tumor necrosis factor (TNF)alpha were analyzed in liver tissue. PPARalpha mice were also treated with DSS and histology examined.PPARgamma mRNA levels were low, with DSS suppressing mRNA levels equally in WT and cftr mice. PPARalpha levels were no different between cftr and WT litter mates by reverse-transcription polymerase chain reaction. After DSS, WT mice showed a 9.3-fold increase in PPARalpha mRNA levels and increased nuclear localization compared with no DSS (P0.05), with no increase seen in cftr mice. This was not caused by changes in TNFalpha. DHA treatment led to 7.0-fold increase in PPARalpha mRNA levels in cftr mice (P0.01). PPARalpha mice treated with DSS did not develop bile duct injury, indicating that PPARalpha alone is not sufficient to cause bile duct inflammation.DSS induced bile duct injury in cftr mice is associated with a defect in PPARalpha expression, which is reversed by DHA.

BACKGROUND Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P

Background The critical fatty acids Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) decline in preterm infants within the first postnatal week and are associated with neonatal morbidities, including bronchopulmonary dysplasia (BPD). DHA and AA are precursors to downstream metabolites that terminate the inflammatory response. We hypothesized that treatment with Resolvin D1 and/or Lipoxin A4 would prevent lung injury in a murine model of BPD. Objective To determine the effect of Resolvin D1 and/or Lipoxin A4 on hyperoxia-induced lung injury. Methods C57/BL6 pups were randomized at birth to Room Air, Hyperoxia (>90% oxygen), Hyperoxia + Resolvin D1, Hyperoxia + Lipoxin A4, or Hyperoxia + Resolvin D1/Lipoxin A4. Resolvin D1 and/or Lipoxin A4 (2 ng/g) were given IP on days 0, 3, 6, and 9. On day 10, mice were sacrificed and lungs collected for morphometric analyses including Mean Linear Intercept (MLI), Radial Alveolar Count (RAC), and Septal Thickness (ST); RT-PCR analyses of biomarkers of lung development and inflammation; and ELISA for TGFβ1 and TGFβ2. Result The increased ST observed with hyperoxia exposure was normalized by both Resolvin D1 and Lipoxin A4; while, hyperoxia-induced alveolar simplification was attenuated by Lipoxin A4. Relative to hyperoxia, Resolvin D1 reduced the gene expression of CXCL2 (2.9 fold), TIMP1 (6.7 fold), and PPARγ (4.8 fold). Treatment with Lipoxin A4 also led to a reduction of CXCL2 (2.4 fold) while selectively increasing TGFβ2 (2.1 fold) and Smad3 (1.58 fold). Conclusion The histologic and biochemical changes seen in hyperoxia-induced lung injury in this murine model can be reversed by the addition of DHA and AA fatty acid downstream metabolites that terminate the inflammatory pathways and modulate growth factors. These fatty acids or their metabolites may be novel therapies to prevent or treat lung injury in preterm infants.

We previously showed that endocytosis at the apical plasma membrane (APM) of the pancreatic acinar cell is activated by the cleavage of GP2, a GPI-linked protein, from the apical cell surface. This endocytic process, as measured by horseradish peroxidase uptake into pancreatic acinar cells, is blocked by the tyrosine kinase inhibitors genistein and tyrphostin B42 as well as by disruption of actin filaments with cytochalasin. This suggests that the cleavage of GP2 from the cell membrane may activate endocytosis through a tyrosine kinase-regulated pathway. However, the mechanism by which GP2 and tyrosine kinases act together to activate endocytosis at the APM remains unknown. In this study, we demonstrate that pp60, p62yes, caveolin, and annexin, which have previously been implicated in endocytosis in other cell lines, were present in high abundance in GPI-enriched membranes by Western blot analysis. pp60, p62yes, and caveolin all co-immunoprecipitated with GP2 except annexin. An 85-kDa protein whose tyrosine-dependent phosphorylation is correlated with the activation of endocytosis in intact acinar cells also was present in these immunoprecipitates. This suggests that in pancreatic acini, GP2 may exist in a complex with src kinases, caveolin, and an 85-kDa phosphorylated substrate to regulate endocytosis at the APM.

To measure the changes in whole blood fatty acid levels in premature infants and evaluate associations between these changes and neonatal morbidities.This was a retrospective cohort study of 88 infants born at30 weeks' gestation. Serial fatty acid profiles during the first postnatal month and infant outcomes, including chronic lung disease (CLD), retinopathy of prematurity, and late-onset sepsis, were analyzed. Regression modeling was applied to determine the association between fatty acid levels and neonatal morbidities.Docosahexaenoic acid (DHA) and arachidonic acid levels declined rapidly in the first postnatal week, with a concomitant increase in linoleic acid levels. Decreased DHA level was associated with an increased risk of CLD (OR, 2.5; 95% CI, 1.3-5.0). Decreased arachidonic acid level was associated with an increased risk of late-onset sepsis (hazard ratio, 1.4; 95% CI, 1.1-1.7). The balance of fatty acids was also a predictor of CLD and late-onset sepsis. An increased linoleic acid:DHA ratio was associated with an increased risk of CLD (OR, 8.6; 95% CI, 1.4-53.1) and late-onset sepsis (hazard ratio, 4.6; 95% CI, 1.5-14.1).Altered postnatal fatty acid levels in premature infants are associated with an increased risk of CLD and late-onset sepsis.

Introduction Intragastru balloon systems have been used tot weight loss m obese patients. Because of a high complication rate this method was abandoned in the 1980s. Recently, a new generation of intragastric balloon system has been introduced in clinical use. We report the eNciency and tolerance of the Bioenterics lntragastric Balloon System (BIB). Methods Obese patients willing to reduce weight wetv oticred the possibility of weight reduction assistance by the BIB Initially a questionnaire was completed by all patients, inquiring about medical history, comorbidiv, dietary' habits and previous treatment t0r obesity. BIB placement was pertormed during upper endoscopy on an outpatient basis under intravenous sedation. The system was tilled with 500ml saline, coloured with methyienblue to identity, any leakage, A dieticians consultation was pertomled every month. lhe BIB was removed endoscopically aher 6 months Weight loss was a s se~d each month and alter removal ot the BIB. Results From July 2001 to November 2002, 60 Patients (19 male, 49 iemale, mean age 44.2 years (range 26 67)) underwent BIB iruplacement. Mean initial BMi was 38.6 kg/ru 2 (range 2952) witil a mean imtial excess weight of 41.8 kg (range 13-80) and nman initial %excess wright ot 3 5 8 (133-549) Iniual upper endoscopy was normal in 43 and abnormal in 17 patients (9 esophagitis, 3 small hiatal hernia, 4 gastritis, 3 duodenal ulcers, 2 patienl:s with double pattmlognes). In all 60 patients the insertion procedure was uneventful, in 2 patients the BIB had to be removed within the first week due to intolerance, in the retraining 58 patients the mean intmgastric residing time of tbe BIB was 6 6 months (range 4.5-9.0). There was no spomaneons loss ot the device. The mean weight loss was l l .2kg (range 035~ corresponding to a %excess weight loss of 30% (0-116.7). In the first week of treatment 48 patients (82%) suffered t~rom vomiting over a mean time of 3 7 days, heartburn occurred in 13 patients (22%) and hospitalisation was necessary m 2 patients Vomiting and heartburn requinng PPi-therapy lasted longer than one week in 8 (13%) and 14 (24%) patients, respectively No major complications like pertoration or obstruction were observed. Conclusion "[he insertion of BIB offers a highly efhcient method tot rapid weight reduction in obese patients Vomiting and retlux s}~nptoms are common within the tirst 4 days alter placement, but can be controlled by drug therapy Overall, the therapy is well tolerated, sate and associated with a low complication rate.