Effect of probiotics (Lactobacillus plantarum 299 plus Bifidobacterium Cure21) in patients with poor ileal pouch function: a randomised controlled trial.

OBJECTIVE: Poor pouch function after restorative proctocolectomy for ulcerative colitis is a considerable problem. Pouchitis and functional disorders are the most common reasons. Probiotics seem to have a beneficial effect in pouchitis but have not been assessed in functional pouch disorders. The aim was to analyse the effects of probiotics in patients with poor pouch function. METHODS: Thirty-three patients were randomized to probiotics (Lactobacillus plantarum 299 and Bifidobacterium infantis Cure 21) or placebo in a double blinded, 1:1 fashion. The treatment effect was assessed by the pouch functional score (PFS; 0-15, 15 worst), pouchitis disease activity index (PDAI; 0-18, 18 worst), and levels of four faecal biomarkers of inflammation (calprotectin, lactoferrin, myeloperoxidase [MPO] and eosinophilic cationic protein [ECP]). RESULTS: Thirty-two patients were included (probiotics = 17, placebo = 16). There was no difference in change in the PFS from before to after treatment between the groups (median difference: -1.00, 95% C.I. -3.00 to 0.00, p = 0.119). Furthermore, probiotics had no effect on PDAI (median difference: 0.00, 95% C.I. 0.00-1.00, p = 0.786), or on faecal biomarkers. Significant correlations were observed between PDAI and each of the faecal biomarkers at study start. There were no correlations between PFS or PDAI symptom subscore and the biomarkers. PDAI endoscopic and histologic subscores correlated significantly to each of the biomarkers. CONCLUSION: The hypothesis that probiotics improves pouch-related dysfunction was not confirmed. Faecal biomarkers could play a future role in the management of pouch patients.

Long-term outcome after surgery for Crohn's anal fistula.

AIM: Treatment of Crohn's anal fistula remains challenging and little is known about factors associated with healing. The aim of this study was to assess the rate of healing after surgical treatment and analyse clinical variables related to healing. METHOD: A total of 119 patients [63 women, mean age 36 (±13.7) years] with histopathologically verified Crohn's disease underwent a surgical procedure for anal fistula at four main referral centres in Sweden, January 1998 to December 2009. Baseline and treatment-related variables were recorded and analysed for correlation with fistula healing at a final follow-up after a mean of 7.2 (median 7.1, 1.0-17.5) years. RESULTS: Of the 119 patients 62 (52%) were healed at final follow-up. Fourteen healed after one procedure and the remaining 48 healed after a further median of 4.0 (2-20) procedures. Ten (8%) patients were subjected to a proctectomy. Final healing was more common in patients operated with a procedure aiming at eradicating the fistula (P = 0.0001), without proctitis (P = 0.02) and a shorter duration of Crohn's disease (P = 0.0019). CONCLUSION: Long-term healing of a Crohn's anal fistula can be expected in about half of the patients, usually after repeated surgical treatment. The probability for cure was higher when a curative operation was performed in a patient without proctitis and with a shorter duration of Crohn's disease. An attempt to close a Crohn's anal fistula is thus often worthwhile.

Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation.

Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14(+)DR(int) MQs characterized inflamed intestinal mucosa while total CD141(+) or CD1c(+) DCs numbers were unchanged. However, CD103(+) DCs, including CD141(+)CD103(+) and CD1c(+)CD103(+) DCs, were reduced in inflamed intestine. In MLNs, two CD14(-) DC populations were identified: CD11c(int)HLADR(hi) and CD11c(hi)HLADR(int) cells. A marked increase of CD11c(hi)HLADR(int) DC, particularly DR(int)CD1c(+) DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH(+) cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.

Colectomy for patients with ulcerative colitis and primary sclerosing cholangitis - what next?

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) occurs in 2%-8% of patients who suffer from ulcerative colitis (UC). For patients who require colectomy, ileal pouch-anal anastomosis (IPAA) or ileorectal anastomosis (IRA) is employed to preserve continence.We evaluated the outcomes after IPAA and IRA for patients with UC-PSC, using patients with UC but without PSC as controls (UC-only group). PATIENTS: In a case-control study conducted at Sahlgrenska University Hospital, Sweden, patients with UC-PSC (N=48; 31 IPAA and 17 IRA) were compared to patients with UC only (N=113; 62 IPAA and 51 IRA). Functional outcomes (Öresland score), pouchitis, surgical complications, and failure were evaluated. RESULTS: For patients with IPAA, the median Öresland scores were similar for the two groups: 5 (range, 0-13) for the UC-PSC group and 5 for the UC-only group (range, 0-12; p>0.05). However, the IRA scores were significantly different at 7 (range, 2-11) and 3 (range, 0-11) for the respective groups (p=0.005). Pouchitis was more frequent in patients with UC-PSC. Complication rates did not differ. For patients with IPAA, the failure rate was 16% for those in the UC-PSC group versus 6% for those in the UC-only group (p>0.05); the corresponding results for IRA were 53% versus 22% (p=0.03). CONCLUSIONS: For cases of IPAA, pouchitis seems to be more common in patients with UC-PSC. However, the functional outcomes and failure rates are unaffected by concurrent PSC. For patients with UC-PSC, functional outcome is poor and the failure rate is high after IRA.

Pouch design and long-term functional outcome after ileal pouch-anal anastomosis.

BACKGROUND: Functional outcome is of utmost importance after ileal pouch-anal anastomosis. Although pouch design and construction of the anastomosis are known technical determinants of function, there are few long-term results. This retrospective study evaluated functional outcome for two different pouch designs, and for handsewn versus stapled pouch-anal anastomoses. METHODS: The analysis included 412 patients who had either a J or K pouch (double-folded J pouch), of whom 123 had a J pouch (96 handsewn and 27 stapled) and 289 had a K pouch (95 handsewn and 194 stapled). Functional outcome was evaluated by a mailed questionnaire to achieve an Oresland score (0 to 15; 15 worst). RESULTS: Mean functional scores were 6.1 for J pouches and 4.9 for K pouches (P < 0.001). Regression analysis showed that reservoir design and age at surgery were predictors of functional outcome (P < 0.001). A higher proportion of patients with a J pouch and handsewn anastomosis than with a K pouch and stapled anastomosis had a score of 8 or more, a level previously demonstrated to impact negatively on quality of life (32 versus 16 per cent; P = 0.006). CONCLUSION: The K pouch was associated with a better long-term functional outcome than the J pouch in this patient population.

Can a failed ileal pouch anal anastomosis be left in situ?

OBJECTIVE: Failure after ileal pouch-anal anastomosis (IPAA) is reported with a frequency of 10-20%. The failed IPAA can be excised or defunctioned. Indications for excision and further management of an indefinitely diverted pouch are poorly described. The aim of the present investigation was to investigate pouch-related problems and the histopathological pattern of the pouch mucosa in this group of patients. METHOD: In a cohort of 620 patients having IPAA with a median follow-up of 14 years, 56 patients with failure were identified. The patients with defunctioned pouches were assessed with regard to pouch-related problems and endoscopy with biopsies was performed. Biopsies were stained with haematoxylin-eosin, PAS for neutral mucins and Alcian blue/high iron diamine for sialomucins/sulphomucins. Morphological changes were grouped into three types modified according to Veress and assessed for dysplasia. RESULTS: Twenty-two patients with an indefinitely diverted pouch were found. The follow-up time after surgery for failure was 10 years. Thirteen patients completed the follow-up. Except for two patients with pelvic/perineal pain, there were no clinical problems. The majority of patients displayed mild to moderate macroscopic signs of inflammation. Morphologically, findings ranged from a preserved mucosal pattern to intense inflammatory reaction. No case of dysplasia or carcinoma was found. CONCLUSION: Most patients with an indefinitely diverted pouch had no complaints regarding the pouch. There was no case of dysplasia. Indefinite diversion may be preferable to pouch excision, especially given the associated morbidity.

Long-term function and manovolumetric characteristics after ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: Long-term pouch function and physiological characteristics after ileal pouch-anal anastomosis (IPAA) are poorly described. The aim of this study was to undertake a prospective investigation of long-term pouch function and manovolumetric characteristics. METHODS: Forty-two patients with a median follow-up of 16 years after IPAA were included. Function was assessed using a questionnaire and a score was calculated ranging from 0 to 15 (15 being the worst). Manovolumetry was performed and pouchitis recorded. A paired analysis was conducted, as the results were compared with previous data for each patient. RESULTS: The median functional score was 3.5 (range 0-10) at 2 years and 5 (range 1-11) at 16 years (P = 0.013). Resting anal canal pressures were higher (P < 0.001) and squeeze pressures lower (P = 0.008) at long-term follow-up. Ileal pouch volumes at distension pressures of 10, 20 and 40 cm H(2)O were diminished at 16 years (P < 0.001, P = 0.005 and P = 0.058 respectively). The volume and pressure for first sensation and urge to defaecate were reduced. Increased age correlated positively with a poor functional score. A history of pouchitis did not affect functional or physiological characteristics. CONCLUSION: Ileal pouch function declines in the long term. The reasons are unclear, but the ageing process may have an impact.

The place for colectomy and ileorectal anastomosis: a valid surgical option for ulcerative colitis?

BACKGROUND: Conflicting views regarding the use of ileorectal anastomosis (IRA) in ulcerative colitis (UC) exist and this controversy prompted us to review our experience, especially against the background of the current tendency to choose the ileal pouch-anal procedure (IPAA). METHODS: Thirty-two consecutive patients with IRA were studied. Complications, failure rate, reasons for failure and functional results were assessed. The median follow-up time was 3.5 years. RESULTS: The overall complication rate was 28%. The rectum was excised in 4 patients, indicating a failure rate of 12%. The mean daily evacuation frequency was 5.6. Despite urgency occurring in one-third of the patients, continence function was well preserved. CONCLUSIONS: Employed on a selective basis, IRA is a safe procedure with low mortality and morbidity and good prospects for success in many patients with UC. The patients must be prepared to submit to life-long rectoscopy surveillance.

Ileal pouch anal anastomosis for ulcerative colitis is feasible for septuagenarians.

OBJECTIVE: Proctocolectomy and ileal pouch anal anastomosis (IPAA) has become the standard surgery for patients with mucosal ulcerative colitis (MUC). Although there is no absolute age limitation, there are concerns as to its use in elderly patients due to the risks of potential complications and poor function. The aim of this study was to assess the complications and outcome of patients over the age of 70 years with MUC who underwent IPAA. Results in these patients were compared to the results in a group of patients aged less than 70 years who had IPAA. METHODS: After Institutional Review Board approval, a retrospective review of the medical records of patients with MUC who underwent IPAA was undertaken. These patients were divided into four age groups: <30 years of age, 30-49 years, 50-69 years, >or=70 years. RESULTS: From 1989 to 2001, 330 patients underwent IPAA for preoperative clinical and histopathological and postoperative histopathologically confirmed MUC; 17 were aged>or=70 years. The mean hospital stay was 5.8 (SEM 0.7) days in the patients aged<70 years and 6.0 (SEM 0.4) days in the patients aged>or=70 years (P=0.911). Postoperative complications occurred in 39% of patients>or=70 years and in 40% in the <70 years group (P=0.08). Pouch failure occurred in two (11.8%) patients>or=70 years and in 6 (1.9%)<70 (P=0.2). CONCLUSION: IPAA is a safe and feasible option in MUC patients over the age of 70 with functional results similar to results seen in younger patients.

Diffusive solvent dynamics in a polymer gel electrolyte studied by quasielastic neutron scattering.

A quasielastic neutron scattering study has been performed on a polymer gel electrolyte consisting of lithium perchlorate dissolved in ethylene carbonate/propylene carbonate and stabilized with poly(methyl methacrylate). The dynamics of the solvent, which is crucial for the ion conduction in this system, was probed using the hydrogen/deuterium contrast variation method with nondeuterated solvent and a deuterated polymer matrix. Two relaxation processes of the solvent were studied in the 10-400 microeV range at different temperatures. From analysis of the momentum transfer dependence of the processes we conclude that the faster process ( approximately 100 microeV) is related to rotational diffusion of the solvent and the slower process ( approximately 10 microeV) to translational diffusion of the solvent. The translational diffusion is found to be similar to the diffusion in the corresponding liquid electrolyte at short distances, but geometrically constrained by the polymer matrix at distances beyond approximately 5 A. The study indicates that the hindered diffusion of the solvent on a length scale of the polymer network interchain distance ( approximately 5-20 A) is sufficient to explain the reduced macroscopic diffusivity and ion conductivity of the gel electrolyte compared to the liquid electrolyte.

Development of an immunoassay for the determination of polyaromatic hydrocarbons in plasma samples from oiled seabirds.

External exposure assessment of oiled seabirds is undertaken by assessment of the percentage oil coverage of the plumage. Nondestructive monitoring of the toxic fraction of petroleum oils and diesels (polyaromatic hydrocarbons, PAHs) which enters the general circulation (internal exposure burden) of oiled seabirds is rarely undertaken. This is because the traditionally used chromatographic methods for plasma PAH analysis require larger sample volumes than those that can be safely collected from smaller species, such as guillemots (Uria aalge). Furthermore, these methods are not a cost-effective or practical approach for analysis of large numbers of birds in a short time period as part of an oil spill response in wildlife rehabilitation centers. This study describes the modification and validation of a commercially available PAH immunoassay (cRaPID PAH) to enable high-throughput, cost-effective, simple, and rapid determination of total PAH concentrations in 50 microL volumes of plasma. The limit of detection of the assay was 0.1 ng/mL as benzo-apyrene (BaP) equivalents with a working range of 0.120 ng/mL. As further validation of the immunoassay, PAHs were determined by GC-MS. GC-MS data were significantly positively correlated with corresponding immunoassay data for the same birds (r2 = 0.976, p < 0.001). The plasma PAH concentrations of 40 oiled guillemots stranded on U.K. shores were determined using the assay to demonstrate its usefulness for biomonitoring studies. The mean ,PAH concentration observed was 1.05 +/- 0.67 ppm (range 0.02-2.40 ppm as BaP equivalents). The modifications to the cRaPID PAH kit in this study enable nondestructive, high-throughput, semiquantitative determination of PAH concentrations in plasma samples suitable for exposure assessment of oiled seabirds during oil spill response and rehabilitation.

Influence of chain length on the alpha-beta bifurcation in oligomeric glass formers.

A series of oligo(propylene glycol) dimethyl ethers has been investigated using dielectric spectroscopy in order to relate features of the glass transition dynamics to the number of monomer units N in the chain. The results show that (i) when scaled with the glass transition temperature, the beta relaxations systematically become faster for larger N whereas the alpha relaxations display nearly identical temperature evolutions, i.e., the alpha-beta bifurcation shifts towards shorter times for larger N, (ii) the bifurcation scenario displays a crossover in behavior at N approximately 10 monomer units, signaling the transition from oligomeric to polymeric behavior, and (iii) the beta relaxation has a cooperative nature.

Crystal-like nature of acoustic excitations in glassy ethanol.

We report on inelastic x-ray scattering experiments on crystalline and glassy phases of ethanol in order to directly compare the influence of disorder on high frequency acoustic excitations. We find that both the dispersion and the line-width of the longitudinal acoustic excitations in the glass are the same as in the polycrystal in the reciprocal space portion covering the 1st and 2nd Brillouin zones. The structural disorder is found to play little role apart from an intrinsic angular averaging, and the nature of these excitations must essentially be the same in both glass and poly crystal.

The risk of dysplasia and cancer in the ileal pouch mucosa after restorative proctocolectomy for ulcerative proctocolitis is low: a long-term term follow-up study.

AIM: Some of the rare complications reported in patients with an ileopouch anal anastomosis (IPAA) after coloectomy for chronic ulcerative colitis are dysplasia and carcinoma. The supposed pathway is for the ileal pouch mucosa to go through adaptational changes then is to progress through the phases of chronic pouchitis, dysplasia and subsequently to adenocarcinoma. In many of these studies however, the dysplasia-cancer sequence is inconclusive since the carcinoma might have developed from the ileal mucosa itself or from residual viable rectal mucosa left behind. The purpose of this study was therefore to study the long-term ileal mucosal adaptation patterns and the incidence and grading of dysplasia in the ileal pouch mucosa in patients previously operated on for ulcerative proctocolitis. PATIENTS AND METHODS: Forty-five patients who had been operated on with an IPAA (25 males/20 females), with a median age of 54 years (range 34-76), were invited for clinical examination and pouch endoscopy including mucosal biopsies. The duration of their colitis until surgery was median 6 years (range 1-28) and the time median interval from start of disease until time of follow up 24.8 years (range 17-46). Three independent pathologists from two different centres reviewed sequential mucosal biopsies taken from separate sites of the pouch for dysplasia and mucosal adaptation patterns. RESULTS: The type C pattern with a severe inflammation in lamina propria together with severe atrophy of villi, sometimes with ulceration and granulation tissue, was observed by the two pathologists from one centre in 15 of 45 (33.3%) patients and in 11 (24.4%) of 45 by the third pathologist, respectively. As regards dysplasia one pathologist group evaluated 2/45 (4.4%) cases as low-grade dysplasia while the third pathologist considered one of these cases as indefinite for dysplasia and one as reactive. There was in this respect full agreement between the two centres in 43 (95.6%) of 45 cases. Neither high-grade dysplasia nor invasive carcinoma was diagnosed. CONCLUSION: Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.

The failed pelvic pouch: conversion to a continent ileostomy.

BACKGROUND: Excision of the ileal pouch-anal anastomosis (IPAA) with construction of a conventional ileostomy is in general the ultimate procedure after unsuccessful salvage surgery. Conversion of the IPAA to a continent ileostomy (CI) is an alternative. METHODS: The clinical outcome of 13 patients operated with conversion of IPAA into CI was evaluated. Median follow-up was 6 years. One patient was lost to follow-up. RESULTS: There were two failures with pouch excision. At follow-up, ten patients with intact CI were fully continent and none needed to use a stoma appliance. Revisional surgery had been required in 8 patients. CONCLUSIONS: Conversion of a failed IPAA into CI is a feasible procedure that may be considered an alternative to Brooke's ileostomy in motivated patients. The operation should ideally be done in specialized units.

The effect of diverticular disease on the colonic J pouch.

OBJECTIVE: The aim of this study was to assess the impact of the diverticular disease (DD) on function and on postoperative complications of the colonic J-pouch (CJP) with pouch-anal anastomosis. METHODS: Patients who underwent a CJP between December 1990 and August 2001, were retrospectively reviewed. The presence of DD in the CJP was assessed on pouchogram prior to ileostomy closure. A questionnaire designed to evaluate the degree of continence (total incontinence score (IS): 0 = worst, 20 = best) and pouch evacuation (total evacuation score (ES): 0 = worst, 28 = best) was used for comparison between patients with DD and those without DD (NDD). RESULTS: Sixty-six patients (47 males; 19 females) with a median age of 68 years (range 28-87 years) were included. The median follow-up period was 22 months (range 2-106 months). Twenty-four patients comprised the DD group and 42 were in the NDD group. The two groups were comparable for age, gender and time from ileostomy closure; all patients with postoperative chemoradiation therapy were in the NDD group. The total ES and IS total did not significantly differ between the two groups with a P-value of 0.11 and 0.09 respectively. Furthermore, there was no significant difference in the total incidence of pouch complications between the two groups (3 strictures, 1 leak, 1 fistula in the NDD group vs. 1 pelvic sepsis in the DD group; P = 0.4). CONCLUSIONS: The presence of DD in a CJP does not seem to impact pouch function or the postoperative complication rate.

Structural investigations of polymer electrolyte poly(propylene oxide)-LiClO4 using diffraction experiments and reverse Monte Carlo simulation.

The structure of an amorphous polymer electrolyte, poly(propylene oxide) (PPO) complexed with LiClO4, has been studied using reverse Monte Carlo (RMC) simulations. The simulations require no force field but are based on experimental data only, in this case from x-ray and neutron diffraction experiments. Excellent agreement between the experimental data and the structures resulting from the RMC simulation is obtained. Samples with ether-oxygen to lithium concentrations (molar ratios) O:Li=16:1 and 5:1 were studied and compared to results of pure PPO from a previous study. We focus on the effects of the solvated salt on the structure of the polymer matrix, the spatial distribution of ions, and the correlations between the anions and the polymer chains. Analyzing the structures produced in the simulations, we find that for a concentration 16:1, the interchain distance is approximately the same as in pure PPO but more well defined. For a concentration 5:1, we find a larger and less well-defined interchain distance compared to the 16:1 concentration. This signifies that at the 16:1 salt concentration, there is enough free volume in the polymer host to accommodate the ions, and that the solvation of salt induces ordering of the polymer matrix. At the higher salt concentration 5:1, the polymer network must expand and become less ordered to host the ions. We also note, in accordance with previous studies, that the solvation of salt changes the conformation of the polymer chain towards more gauche states. The simulations furthermore reveal marked correlations between the polymer chains and the anions, which we suggest arise predominantly from an interaction mediated via cations, which can simultaneously coordinate both ether oxygens in the polymer chains and anions. Interanionic distances at 5 A, which are consistent with two or more anions being coordinated around the same cation, are also observed. On a larger scale, the RMC structure of PPO-LiClO4 16:1 clearly indicates the presence of salt-rich and salt-depleted domains having a length scale of <20 A. In view of such a heterogeneous structure of PPO-LiClO4 16:1, it is plausible that the increased ordering of the polymer matrix is due to rather well-defined structural arrangements within the salt-rich domains, and that the characteristic interchain distance in the salt-rich domains is similar to that of the pure polymer.

Chain-length-dependent relaxation scenarios in an oligomeric glass-forming system: from merged to well-separated alpha and beta loss peaks.

We have studied the relaxation dynamics of a homologous series of propylene glycol based dimethyl ethers in the supercooled regime by means of broadband dielectric spectroscopy. The system is chosen in order to minimize changes of the intermolecular interactions with varying molecular weight, M. A gradual transformation from a scenario of well-separated to one of merged alpha and beta loss peaks was observed with decreasing M. The results give strong evidence for the currently debated excess wing being due to an underlying beta relaxation. The study suggests that the main difference between glass formers with and without excess wings is the relaxation time at the merging temperature.

Using adhesion to probe viscoelasticity of polymer film surfaces: a quartz crystal microbalance study.

We have used a quartz crystal microbalance to monitor the adhesion of small particles to the surface of polystyrene films. This technique is shown to provide a signature of viscoelastic relaxation processes at the polymer surface. For M(n) values less than 10(4) and greater than 10(5), this signature occurs at a temperature approximately 12.5 K above the measured bulk glass transition temperature, T(g). For intermediate values of M(n) however, the relaxation signature occurs at temperatures as low as 7 K above the bulk T(g). This observation suggests a slight decrease in the T(g) value near the polymer surface. A model incorporating the effects of enrichment of polymer chain ends at the free surface was considered and found to provide a quantitative description of the data.

Sound wave scattering in network glasses.

The acoustic branch of two network glasses, (Li2O)xB2O3 ( x = 0.25 and 0.5), is followed over a large momentum transfer range 1-12 nm(-1), using inelastic x-ray scattering. We observe the transition from propagating modes to a region of strong scattering as the Ioffe-Regel limit is reached. A region of Rayleigh scattering of the acoustic modes precedes the strong scattering regime at larger Q, causing a rapid decrease of the mean-free path of the modes.