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In this pilot study, we assessed the role of autophagy in Crohn's Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management., (© 2024. The Author(s).)

Background: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients., Research Design and Methods: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF., Results: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment ( p  = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded., Conclusions: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 10 10 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy ( n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition ( p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).

Background: Videocapsule endoscopy (VCE) is considered the gold standard for overt and obscure gastrointestinal bleeding (OGIB), after negative upper and lower endoscopy. Nonetheless, VCE's diagnostic yield is suboptimal, and it represents a costly, time-consuming, and often not easily available technique. In order to evaluate bleeding risk in patients with atrial fibrillation, several scoring systems have been proposed, but their utilization outside the original clinical setting has rarely been explored. The aim of the study is to evaluate potential role of bleeding risk scoring systems in predicting the occurrence of positive findings at VCE examination, and therefore in increasing VCE diagnostic yield., Methods: Data from consecutive patients undergoing VCE between April 2015 and June 2020 were retrospectively retrieved, and clinical and demographic characteristics were collected. HAS-BLED, ATRIA, and ORBIT scores were calculated, and patients were considered at low or high risk of bleeding accordingly. Discriminative ability of the scores for positive VCE findings has been evaluated by area under receiver operator characteristic curve (AUC) calculation. Diagnostic yield of scores in high- and low-risk patients was calculated., Results: A total of 413 patients underwent VCE examination, among which 368 (89%) for OGIB. Positive findings were observed in 246 patients (67%), with angiodysplasias being the most frequent lesion (92%). The three scores displayed similar consistent discriminative ability for positive VCE findings (mean AUC = 0.69), and identified high-risk group of patients in which VCE has a higher diagnostic yield., Conclusions: In the present retrospective study, bleeding scores accurately discriminated patients with higher probability of positive findings at VCE examination. Bleeding scores utilization may help in the management of patients with OGIB, with a potential consistent resource optimization and cost-saving., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ., Research Design and Methods: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints., Results: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6 th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6 th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016)., Conclusion: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology and immunomediated pathogenesis. In the last years, the comprehension of the complex mechanisms involved in the intestinal mucosal homeostasis, and the analysis of the alterations potentially leading to inflammatory pathologic states, has consistently increased. Specifically, the extraordinary impulse in the field of research of the intestinal microbiome has opened the door to the investigation of possible novel approaches to the diagnosis, management and therapeutic applications in IBD. In line with that, administration of probiotic bacteria has been intensely evaluated, leading to much more exciting results in experimental models than in clinical practice. Considering the consistent heterogeneity of the available studies on probiotics, the increased knowledge of the properties of the single bacterial species would ideally lead to unravel potential mechanisms of action that may bring therapeutic applications in specific pathologic condition. Among the relevant molecular pathways for mucosal homeostasis maintenance, the vitamin D/vitamin D receptor (VDR) pathway has been intensely studied in the very last years. In fact, besides osteometabolic functions, the vitamin D exerts important homeostatic effects in the organism at multiple levels, such as immunomodulation, inflammation control, and microbiota regulation, which are likely to play a relevant role in intestinal mucosa protection. In the present review, recent findings about probiotic applications in IBD and mechanisms of action linking vitamin D/VDR pathway to IBD are reported. Available evidence for probiotic effect on vitamin D/VDR are reviewed and potential future application in IBD patients are discussed. At present, many aspects of IBD pathogenesis are still obscure, and current therapeutic options for IBD treatment are at best suboptimal. The increasing comprehension of the different pathways involved in IBD pathogenesis will lead to novel findings ideally leading to potential clinical applications. Microbiota manipulation and vitamin/VDR pathway appear a promising field for future research and therapeutic developments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pagnini, Di Paolo, Graziani and Delle Fave.)

Inflammatory Bowel Diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the '50s, are still the mainstay of treatment for moderate to severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on the long-term natural history of the disease, the steroid-sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so-called "low bioavailability" steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and a more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding., Aims: To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality., Methods: In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score., Results: Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3)., Conclusions: The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: Complementary and alternative medicines (CAM) are being used increasingly by patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and usage of CAM in different geographical areas of Italy and possible predictors of their use., Methods and Materials: A structured questionnaire, administered to outpatients, attending 8 general hospitals and 9 tertiary referral centres, was completed by 2011 patients (909 CD, 1087 UC and 15 indeterminate colitis). 583 patients lived in the North, 659 in Central Italy and 769 in the South., Results: CAM users were 475 (23.6%) with no regional differences in their distribution. Usage correlated significantly with female gender (p=0.030), higher education (p=0.021), hospitalization rates (p=0.000), extra-intestinal complications (p=0.000), non-adherence to conventional treatments (p=0.054), adverse reactions to conventional treatments (p=0.000), and active disease (p=0.007); 5-ASA usage was associated with a more limited use of CAM (p=0.005). Dietary changes or supplements and prayer were significantly more frequently reported in South, while Northern Italian patients more frequently used homeopathy, herbal medicines and physical exercises. Patients in Central Italy adopted an intermediate behavior. CAM use ameliorated the patient's general well-being according to two thirds of the users. Costs were higher for Northern patients than in Central or Southern Italy., Conclusion: One in four IBD patients in Italy use CAM. More money is spent on CAM in Northern Italy. Regional differences emerged as regards the type of CAM but not in terms of disease features, frequency of and reasons for CAM use, or perceived effects., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate in a prospective study whether a simplified clinical score prior to endoscopy in upper gastrointestinal bleeding (UGIB) patients was able to predict endoscopic findings at urgent endoscopy., Methods: All consecutive UGIB patients referred to a single endoscopic center during a 16 mo period were enrolled. Before endoscopy patients were stratified according to a simple clinical score (T-score), including T1 (high-risk), T2 (intermediate-risk) and T3 (low-risk). Endoscopy was performed in all cases within 2 h, and high-risk stigmata were considered for further analysis., Results: Out of the 436 patients included into the study, 126 (29%) resulted to be T1, 135 (31%) T2, and 175 (40%) T3. Overall, stigmata of recent haemorrhage (SRH) were detected in 118 cases (27%). SRH occurred more frequently in T1 patients than in T2/T3 cases (85% vs 3.2%; c2 = 304.5309, P < 0.001). Older age (t = 3.311; P < 0.01) and presence of comorbidities (c2 = 14.7458; P < 0.01) were more frequently detected in T1 than in T2/T3 patients., Conclusion: Our simplified clinical score appeared to be associated with the detection of endoscopic findings which may deserve urgent endoscopy. A further, randomised study is needed to assess its accuracy in safely scheduling endoscopy in UGIB patients.

Objective: To validate an Italian version of the Impact of Event Scale (IES) in patients addressing the emotional impact of a recent road accident., Methods: Seventy-nine subjects were examined within 1-34 weeks after an accident by means of (1). an Italian version of the IES, (2). a free description of the accident, and (3). a questionnaire assessing subjects' behaviour and feelings., Results: IES data were analysed by means of the principal component analysis (PCA) method, followed by a quartimax rotation, obtaining a two-factor solution interpreted as intrusion (Factor 1) and avoidance (Factor 2). Furthermore, the scores to the two subscales were considered in order to assess their predictive value on some variables linked to the traumatic event. Intrusion significantly discriminated the emotional intensity and fear level of subjects as a consequence of the accident., Conclusions: The IES is a two-dimensional test capable of evaluating posttraumatic stress. The intrusion and avoidance factors explained 40% of the total variance. The two-factor solution has a psychological counterpart and is similar to the findings of earlier studies conducted on a larger number of subjects in other countries.

Background: Use of sulphasalazine in ulcerative colitis patients is hampered by a variety of side-effects, including male infertility. 5-aminosalicylic acid is better tolerated and has been increasingly used to treat patients intolerant/allergic to sulphasalazine but it may also be associated with side-effects., Aim: To evaluate tolerance of long-term treatment with sulphasalazine and 5-aminosalicylic acid in ulcerative colitis., Methods: Side-effects to sulphasalazine (2-3 g/day) and 5-aminosalicylic acid (1.2-2.4 g/day) were recorded in 685 patients: 410 patients received only sulphasalazine, 130 only 5-aminosalicylic acid, and 145 both drugs. In patients with side-effects to sulphasalazine, a desensitisation protocol (rechallenge) was attempted to improve tolerance, and patients still presenting side-effects after desensitisation were switched to 5-aminosalicylic acid. Male fertility was also assessed in 42 males on sulphasalazine and on 5-aminosalicylic acid., Results: Side-effects were observed in 110/555 patients (20%) on sulphasalazine and in 18/275 patients (6.5%) on 5-aminosalicylic acid during a median period of follow-up of 7 and 5 years, respectively. Desensitisation was achieved in 40% of patients intolerant to sulphasalazine. 5-aminosalicylic acid intake induced side-effects in 2/130 patients (1.5%) who had not taken sulphasalazine before versus 4/91 patients (4%) tolerating sulphasalazine and 12/54 patients (22%) intolerant/allergic to sulphasalazine, the difference in incidence of side-effects in the two latter groups being statistically significant (4.4% vs 20.8%, p=0. 001). Fertility was found to be affected in all patients on sulphasalazine but improved when put onto 5-aminosalicylic acid., Conclusions: 5-aminosalicylic acid should be considered the drug of choice in the treatment of ulcerative colitis bearing in mind that intolerance or allergy may occur in a few patients also on this drug.

The usefulness of 99mTc-HMPAO scintigraphy in the early detection of postoperative recurrence of Crohn's disease was evaluated in 17 patients undergoing ileocecal resection and prospectively followed up for one year. Scintigraphy was performed 6 and 12 months after surgery and recurrence assessed by colonoscopy within two weeks. As controls, four patients with ileocecal resection for cecal carcinoma were studied. To perform scintigraphy, autologous granulocytes were labeled with 99mTc-HMPAO, injected, and tau-camera images acquired after 30 min and 3 hr. Six months after surgery, 4/8 Crohn's disease patients showed endoscopic recurrence, and 30-min scintigraphy was positive only in these four patients (four true positives, four true negatives). At 12 months, endoscopic recurrence was detected in 10/14 Crohn's disease patients, and 30-min scintigraphy was positive in 9/14 patients (eight true positives, three true negatives, two false negatives, one false positive). Scintigraphy at 3 hr showed a lower specificity in detecting CD recurrence both at 6 and 12 months. The endoscopic and 30-min scintigraphic score were significantly correlated both at 6 and 12 months (P = 0.007; P = 0.04). Scintigraphy was negative in 4/4 controls at 30 min (four true negatives) and positive in 1/4 (one false positive) at 3 hr. We conclude that 99mTc-HMPAO scintigraphy at 30 min is a sensitive technique for the early detection of Crohn's disease recurrence in patients under regular follow-up after surgery.

Gamma interferon (IFN gamma) impairs epithelial barrier function and induces HLA-DR expression on colonic cancer cell lines. Salicylates have been shown to reduce IFN gamma induced HLA-DR expression. The effect of 5-aminosalicylic acid (5-ASA) on IFN gamma induced changes in transepithelial resistance and permeability was investigated in HT29 clone 19A and Caco 2 monolayers. Monolayers were incubated with different concentrations of IFN gamma (100, 500, 1000, and 3000 U/ml) and 5-ASA. IFN gamma induced class II expression in a time and dose dependent manner in HT29:19A but not Caco 2 cells. HT29:19A monolayers incubated with both IFN gamma and 5-ASA showed lower HLA-DR expression compared with monolayers incubated with IFN gamma alone. Electrical resistance and 14C-mannitol flux across HT29:19A monolayers were significantly changed by IFN gamma. Addition of both IFN gamma and 5-ASA to the basolateral surface of the monolayers significantly reduced paracellular permeability compared with addition of IFN gamma alone. These data show that IFN gamma is able to induce HLA-DR expression and to impair the barrier function of HT29:19A monolayers, and that 5-ASA reduces IFN gamma induced HLA-DR expression and inhibits the effects of IFN gamma on epithelial barrier function.

Background: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis., Methods: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study., Results: Fourteen patients on SCFA improved (overall score 11.3 +/- 2.0 vs. 7.4 +/- 3.5) as compared to five in the placebo group (overall score 10.0 +/- 1.9 vs. 8.9 +/- 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pretrial differences between the two groups., Conclusion: The present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.

Colectomy with ileo-rectal anastomosis (IRA) was introduced in the 'fifties as an alternative to proctocolectomy with ileostomy in patients with ulcerative colitis (UC). Seventy-four patients affected by UC and submitted to IRA were followed up with clinical, endoscopic and histological controls for a median follow-up period of 9.5 years (range: 3-25 years). The long-term outcome was assessed by evaluating the course of the proctitis, the need for medical therapy, functional results, the need for rectal excision, and mortality during the follow-up. The patients were classified in three groups according to the type of the outcome (success: low-relapsing proctitis, rare or no need for medical therapy, good functional results; partial failure: relapsing proctitis with frequent need for medical therapy and/or poor functional results; failure: necessity of proctectomy). In order to define the prognostic value the clinical characteristics at surgery (age, gender, duration of disease, rectal inflammation, and type of surgery) were compared in the three groups. The long-term outcome was judged as a success in 46 patients (62%), partial failure in 19 patients (26%) and failure in 9 patients (12%). Only one patient developed cancer in the rectal stump (incidence: 1.3%). None of the clinical parameters at surgery except rectal inflammation influenced the outcome: patients showing moderate or severe inflammation in the rectum at surgery had a higher failure rate than those with mild or no inflammation (p < 0.02). These data confirm that colectomy with IRA is a safe surgical procedure with good functional results in most cases and with a low risk of cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy, tolerability and patient acceptance of a new flavoured PEG solution for gut lavage was compared with a standard preparation for bowel cleansing in a randomized controlled trial of patients undergoing colonoscopy. One hundred and sixty patients were randomly allocated either to a standard preparation (2-day semi-liquid diet, laxatives and cleansing enemas) or to gut lavage (fractionalized ingestion of lavage solution, two litres in the afternoon before and a third litre the morning of the examination). Adequacy of colon cleansing was scored evaluating residual stool in each colonic segment and overall mucosal visibility. Tolerability of methods was assessed by evaluating the incidence and severity of side-effects. Patient acceptance was graded (good, fair to good, poor) according to the patient's judgement about the ease of execution and interference with sleep and working activity. Less residual stool (p < 0.05) and better visualization of colonic mucosa (p < 0.05) were obtained with gut lavage than with standard preparation. Both methods were well-tolerated and a low incidence of side effects was recorded in both groups. Patient acceptance was good in more than 80% of patients in both groups. We conclude that gut lavage is a rapid, effective and well-tolerated method for bowel cleansing. The use of a flavoured solution in a fractionalized schedule seems to improve the tolerability and the patient acceptance of this method.

Whether inflammatory bowel diseases (IBD) can be classified as autoimmune disorders is not established. Since circulating acid-labile interferon-alpha (IFN-alpha) is believed to reflect autoimmune reactions, we tested sera from two groups of IBD patients for the presence of circulating IFN. No detectable IFN was found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic lupus erythematosus patients. These observations provide evidence that IBD differs from systemic autoimmune disorders, at least for the presence of circulating IFN.

Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds. To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis. Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM). Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms. Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.

Lamina propria mononuclear cells can be isolated from mucosal specimens of human colon. In the present study, we have explored whether both the phenotypes and functional properties can be studied in lamina propria mononuclear cell suspensions isolated from the same set of endoscopic biopsies in patients with ulcerative colitis. The counts of CD11b+ lamina propria mononuclear cells in mild active ulcerative colitis were significantly higher than those of both quiescent ulcerative colitis and controls. Similarly, the CD16+ and the CD19+ lamina propria mononuclear cells were significantly increased in mild ulcerative colitis patients in comparison to both quiescent ulcerative colitis and control lamina propria mononuclear cells. Lamina propria mononuclear cells from all the biopsy samples appeared to produce detectable amounts of immunoglobulins of the three classes. The production of IgG in mild ulcerative colitis cultures was significantly higher than that observed in quiescent ulcerative colitis and controls. In contrast, the production of IgA in active ulcerative colitis lamina propria mononuclear cell cultures appeared to be significantly lower than that of both quiescent ulcerative colitis and controls. This study shows that morphology, phenotypes, and functional properties can be assessed in lamina propria mononuclear cell suspensions obtained from the same set of endoscopic biopsy samples. We have also shown that changes in phenotypes and functional status of lamina propria mononuclear cells occurred in mild active ulcerative colitis while no significant abnormality of these parameters was found in quiescent ulcerative colitis. This indicates that a normalization of mucosal immune functions occurs in ulcerative colitis patients when complete clinical and histological remission is achieved.

A 14 month old girl was found to have a deletion of the whole of band 5q23. By comparing 19 other cases monosomic for a part of the 5q13-q31 segment, the constitutional 5q interstitial deletions fall into two groups: adult patients with Gardner-like symptoms and mental retardation associated with deletion 5q21-q22, and patients (mostly children) with unspecific signs and symptoms and different deletions.