Background & Aims: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's ...disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator–activated receptor γ (PPARγ) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators.
Methods: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARγ and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry.
Results: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARγ and tumor necrosis factor (TNF)-α, synthesized, at least in part, by adipocytes.
Conclusions: These results suggest that confined increased PPARγ mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-α in the inflammatory response.
GASTROENTEROLOGY 1999;117:73-81
Crohn's disease is a chronic inflammatory disorder of the bowel whose cause is unknown. During the acute phase of the disease, glucocorticoids such as prednisolone and prednisone are commonly used.
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...,
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However, this treatment is often associated with clinically important side effects, such as moon face, hirsutism, and acne.
Budesonide is a glucocorticoid that is a highly potent topical antiinflammatory agent with lower systemic activity than conventional glucocorticoids,
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because it is nearly 90 percent metabolized during its first pass through the liver to forms with minimal or no steroidal activity.
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Budesonide capsules contain granules that allow the slow release of . . .
The aim of this work was to assess the quality of life (QoL) of patients with Crohn's disease (CD) prospectively over 1 yr and to determine factors of influence.
A total of 231 CD patients were ...included. At month 0 (M0), M3, M6, M9, and M12, patients were given a validated QoL questionnaire (self-administered) to fill in and a clinical form referring to the period of 3 months before the visit. The QoL questionnaire was made up of the Short-Form-36 and the Rating Form of Inflammatory Bowel Disease Patients Concerns. The impact on QoL of the following factors was analyzed: age, gender, CD duration and localization, presence of extradigestive manifestations or concomitant disease, disease course, medical treatments, and surgery. We studied the correlations between QoL and disease activity assessed by both patients and investigators by a visual analog scale.
At M0, all the scores of the Short-Form-36 were significantly lower than those of a standard population, nevertheless improving between M0 and M12. Patients' main worries were first "having an ostomy bag" followed by "uncertain nature of the disease," "energy level." and finally "having surgery." QoL was better correlated with assessment of disease course by the patient than by the investigator. Significant factors of impairment in QoL were female gender, tobacco, active CD, involvement of the colon, hospitalization, corticoid treatment, and surgery in the past 3 months. Conversely, intake of immunosuppressors improved QoL.
Patients' QoL is impaired by CD and is underestimated by doctors. Tobacco, hospitalization, and use of corticoids have a negative impact on QoL. Conversely, the use of immunosuppressors is associated with a better QoL.
Background/Aims
Infectious agents have long been suspected of playing a role in the initiation of Crohn's disease. The objective of this study was to search for likely microbial agents in diseased ...tissues using immunocytochemical techniques.
Methods
Intestines and mesenteric lymph node specimens of 21 patients from two French families with a high frequency of Crohn's disease and from Connecticut were studied. The microbial agents searched for included
Bacteroides vulgatus, Borrelia burgdorferi, Escherichia coil, Listeria monocytogenes, Streptococcus spp., bovine viral diarrhea virus, influenza A virus, measles virus, parainfluenza virus, and respiratory syncytial virus.
Results
Seventy-five percent of the patients with Crohn's disease (12 of 16) were positively labeled with the antibody to
Listeria. Macrophages and giant cells immunolabeled for this antigen were distributed underneath ulcers, along fissures, around abscesses, within the lamina propria, in granulomas, and in the germinal centers of mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the
E. coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The immunolabeling for the latter two agents also occurred within macrophages and giant cells, distributed in a pattern similar to that of
Listeria antigen.
Conclusions
The results suggest that
Listeria spp.,
E. coli, and streptococci, but not measles virus, play a role in the pathogenesis of Crohn's disease.
Background & Aims Some women with inflammatory bowel disease require therapy with tumor necrosis factor (TNF) antagonists during pregnancy. It is not clear whether these drugs are transferred to the ...fetus via the placenta and then cleared, or whether structurally different TNF antagonists have different rates of transfer. Methods We studied 31 pregnant women with inflammatory bowel disease receiving infliximab (IFX, n = 11), adalimumab (ADA, n = 10), or certolizumab (CZP, n = 10). Serum concentrations of the drugs were measured at birth in the mother, infant, and in cord blood, and then monthly in the infant until the drugs were undetectable. Drug concentrations in the cord and the infant at birth were compared with those of the mother. Results Concentrations of IFX and ADA, but not CZP, were higher in infants at birth and their cords than in their mothers. The levels of CZP in infants and their cords were less than 2 μg/mL. The median level of IFX in the cord was 160% that of the mother, the median level of ADA in the cord was 153% that of the mother, and the median level of CZP in the cord was 3.9% that of the mother. IFX and ADA could be detected in the infants for as long as 6 months. No congenital anomalies or serious complications were reported. Conclusions The TNF antagonists IFX and ADA are transferred across the placenta and can be detected in infants at birth; the drugs were detected in infants up to 6 months after birth. CZP has the lowest level of placental transfer, based on levels measured in cords and infants at birth, of the drugs tested.
Intestinal bacteria play a key role in inflammatory bowel disease. Probiotics attempt to modify disease by favourably altering bacterial composition, immune status, and inflammation. Until recently, ...probiotic therapy was considered ‘folk’ medicine, but there now is emerging interest on the part of the general public and scientific communities in the use of probiotics in human disease. This practical, evidence-based review examines probiotics as therapy for inflammatory bowel disease in humans. There are very few such published randomized clinical trials, but some data exist that possibly show an efficacy of probiotics as maintenance therapy in chronic relapsing pouchitis. Obstacles to providing probiotic therapy include selection of appropriate strains, poorly regulated probiotic quality standardization, processing and human biologic factors which impair probiotic viability, difficulty in maintaining new bacterial populations in the gut, and local product unavailability. Studies have focused on specific inflammatory bowel disease subgroups, limiting general applicability for the practitioner. Basic research highlights the importance of bacteria in these conditions, and the possibility that probiotics will modify physiological parameters. Well-designed, randomized clinical studies are still required to define the role of probiotics as therapeutic agents in inflammatory bowel disease.
Abstract Most data regarding the natural history of inflammatory bowel diseases and their therapeutic management are from tertiary referral-centres. However, the patients followed in these centres ...represent a selected sample and extrapolation of these data to the general population is disputable. The EPIMAD Registry covers a large area of Northern France with almost 6 million inhabitants representing 9.3% of the entire French population. From 1988 to 2008, 18,170 incident patients were recorded in the registry including 8071 incident Crohn's disease, 5113 incident ulcerative colitis and 591 unclassified inflammatory bowel disease cases. The aim of this study was to review some of the most recent information obtained from this large population-based registry since its launch in 1988.
Background. Although diosmectite has demonstrated efficacy in the treatment of acute watery diarrhoea in children, its efficacy in adults still needs to be assessed. The objective of this study was ...therefore to assess the efficacy of diosmectite on the time to recovery in adults with acute diarrhoea. Methods. A total of 346 adults with at least three watery stools per day over a period of less than 48 hours were prospectively randomized to diosmectite (6 g tid) or placebo during four days. The primary endpoint was time to diarrhoea recovery. Results. In the intention-to-treat population, median time to recovery was 53.8 hours (range 3.7–167.3) with diosmectite (n=166) versus 69.0 hours 2.2–165.2 with placebo, (n=163; P=.029), which corresponds to a difference of 15.2 hours. Diosmectite was well tolerated. Conclusion. Diosmectite at 6 g tid was well tolerated and reduced the time to recovery of acute watery diarrhoea episode in a clinically relevant manner.
Parenteral nutrition (PN) is still widely preferred to enteral nutrition (EN) in malnourished patients undergoing allogeneic stem-cell transplantation (allo-SCT) after myeloablative conditioning ...(MAC). The purpose was to determine whether EN improves early outcome after MAC allo-SCT.
Early outcome was prospectively assessed in patients undergoing MAC allo-SCT. A total of 121 consecutive patients undergoing a first MAC allo-SCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative syndrome were included. Patients who received cord blood were excluded. Enteral nutrition was systematically offered, although PN was provided when EN had been refused or was poorly tolerated. Among the patients, 94 received EN (EN group) and 27 did not (non-EN group). Overall survival (OS), cumulative incidence of engraftment and acute graft-versus-host disease (aGVHD) within the first 100 days after transplantation were studied. Because EN and PN treatment assignments were not random, propensity score adjustments were performed on patient outcomes.
Outcome was better in the EN group than in the non-EN group for OS (hazard ratio HR, 0.12; 95% confidence interval CI, 0.04-0.42; P=0.0008), neutrophil (HR, 2.07; 95% CI, 1.26-3.39; P=0.004), and platelet (HR, 1.93; 95% CI, 1.004-3.70; P=0.049) engraftments and aGVHD development (HR, 0.12; 95% CI, 0.04-0.39; P=0.0004). In Cox model analysis, EN demonstrated a protective effect (HR, 0.20; 95% CI, 0.05-0.77; P=0.019) on OS, whereas demonstrated a detrimental impact (HR, 4.18; 95% CI, 1.02-17.12; P=0.047). Enteral nutrition was found to be an independent factor in neutrophil engraftment (HR, 2.17; 95% CI, 1.24-3.81; P=0.007), whereas PN delayed platelet engraftment (HR, 0.57; 95% CI, 0.33-0.99; P=0.046). Enteral nutrition was the only factor that was protective against grades 3 to 4 aGVHD development (HR, 0.19; 95% CI, 0.05-0.72; P=0.01).
Routine use of EN is preferable to upfront PN in these patients.
5-aminosalicylic acid (5-ASA) is an antiinflammatory drug widely used in the treatment of inflammatory bowel diseases. It is known to inhibit the production of cytokines and inflammatory mediators, ...but the mechanism underlying the intestinal effects of 5-ASA remains unknown. Based on the common activities of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands and 5-ASA, we hypothesized that this nuclear receptor mediates 5-ASA therapeutic action. To test this possibility, colitis was induced in heterozygous PPAR-gamma(+/-) mice and their wild-type littermates, which were then treated with 5-ASA. 5-ASA treatment had a beneficial effect on colitis only in wild-type and not in heterozygous mice. In epithelial cells, 5-ASA increased PPAR-gamma expression, promoted its translocation from the cytoplasm to the nucleus, and induced a modification of its conformation permitting the recruitment of coactivators and the activation of a peroxisome-proliferator response element-driven gene. Validation of these results was obtained with organ cultures of human colonic biopsies. These data identify PPAR-gamma as a target of 5-ASA underlying antiinflammatory effects in the colon.
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