Search

Background: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA)., Aims: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD., Methods: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated., Results: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL., Conclusions: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL., Competing Interests: Conflict of interest The Authors have no conflict of interest to declare. No specific funding. This work was supported by the Italian Group for Inflammatory Bowel Diseases (IG-IBD); the Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia; and the University of Pavia, Pavia, Italy. No specific funding was obtained., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Histological mucosal healing has become a paramount target goal to achieve in the treatment of inflammatory bowel diseases. However, there is still a lack of agreement on the best way to reach this goal, since numerous histological scores are available worldwide., Aims: We investigated whether claudin-2, a member of claudin family involved in the regulation of intestinal tight junctions, might be useful to assess the presence of active disease in patients with inflammatory bowel diseases., Methods: Biopsies from 123 patients with ulcerative colitis, Crohn's disease, infectious colitides and irritable bowel syndrome patients where tested with immunohistochemistry for claudin-2., Results: Claudin-2 appeared to be a very sensitive marker of disease activity in inflammatory bowel diseases, but was negative in the other kinds of patients. In addition, immunohistochemistry for claudin-2 showed good reproducibility by different pathologists., Conclusions: Should these findings be confirmed in more numerous cohorts of patients, and especially in those with minimal or focal residual disease activity, this simple assessment could be useful in the routine daily practice to facilitate the task of pathologists and clinicians in the diagnosis and management of patients with inflammatory bowel diseases., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Clostridium difficile infection (CDI) causes nosocomial/antibiotic-associated diarrhea and pseudomembranous colitis, with dramatic incidence/mortality worldwide. C. difficile virulence factors are toxin A and toxin B (TcdB) which cause cytopathic/cytotoxic effects and inflammation. Until now studies were focused on molecular effects of C. difficile toxins (Tcds) on different cells while unexplored aspect is the status/fate of cells that survived their cytotoxicity. Recently we demonstrated that enteric glial cells (EGCs) are susceptible to TcdB cytotoxicity, but several EGCs survived and were irreversibly cell-cycle arrested and metabolically active, suggesting that EGCs could became senescent. This is important because allowed us to evaluate the not explored status/fate of cells surviving Tcds cytotoxicity, and particularly if TcdB induces senescence in EGCs. Rat-transformed EGCs were treated with 10 ng/ml TcdB for 6 h-48 h, or for 48 h, followed by incubation for additional 4 or 11 days in absence of TcdB (6 or 13 total days). Senescence markers/effectors were examined by specific assays. TcdB induces senescence in EGCs, as demonstrated by the senescence markers: irreversible cell-cycle arrest, senescence-associated-β‑galactosidase positivity, flat morphology, early and persistent DNA damage (ATM and H2AX phosphorylation), p27 overexpression, pRB hypophosphorylation, c‑Myc, cyclin B1, cdc2 and phosphorylated-cdc2 downregulation, Sirtuin‑2 and Sirtuin‑3 overexpression. TcdB-induced EGC senescence is dependent by JNK and AKT activation but independent by ROS, p16 and p53/p21 pathways. In conclusion, TcdB induces senescence in EGCs. The extrapolation of these results to CDI leads to hypothesize that EGCs that survived TcdB, once they have acquired a senescence state, could cause irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and tumors due to persistent inflammation, transfer of senescence status and stimulation of pre-neoplastic cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Enteric glial cells (EGCs) are components of the enteric nervous system, an organized structure that controls gut functions. EGCs may be vulnerable to different agents, such as bacterial infections that could alter the intestinal epithelial barrier, allowing bacterial toxins and/or other agents possessing intrinsic toxic effect to access cells. Palmitate, known to exhibit lipotoxicity, is released in the gut during the digestion process. In this study, we investigated the lipotoxic effect of palmitate in cultured EGCs, with particular emphasis on palmitate-dependent intracellular lipid remodeling. Palmitate but not linoleate altered mitochondrial and endoplasmic reticulum lipid composition. In particular, the levels of phosphatidic acid, key precursor of phospholipid synthesis, increased, whereas those of mitochondrial cardiolipin (CL) decreased; in parallel, phospholipid remodeling was induced. CL remodeling (chains shortening and saturation) together with palmitate-triggered mitochondrial burst, caused cytochrome c (cyt c) detachment from its CL anchor and accumulation in the intermembrane space as soluble pool. Palmitate decreased mitochondrial membrane potential and ATP levels, without mPTP opening. Mitochondrial ROS permeation into the cytosol and palmitate-induced ER stress activated JNK and p38, culminating in Bim and Bax overexpression, factors known to increase the outer mitochondrial membrane permeability. Overall, in EGCs palmitate produced weakening of cyt c-CL interactions and favoured the egress of the soluble cyt c pool outside mitochondria to trigger caspase-3-dependent viability loss. Elucidating the mechanisms of palmitate lipotoxicity in EGCs may be relevant in gut pathological conditions occurring in vivo such as those following an insult that may damage the intestinal epithelial barrier., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: It is generally thought that gallbladder motility plays a more or less important role in the pathogenesis of gallstones. Some studies have shown that some abnormalities of its intrinsic innervations, but these studies were usually limited to one cell component., Aims: We investigated the main cell components of gallbladder intrinsic innervation in patients with and without gallstones., Methods: Archival gallbladder specimens from 39 patients, 27 with gallstones (age range 45-69 yrs) and 12 patients without gallstones (age range 39-71 yrs) were obtained. Full thickness sections were obtained from the gallbladder neck and immunohistochemistry was carried out for enteric neurons (neuron-specific enolase and calretinin), enteric glia (S100) and interstitial cells of Cajal (CD117 and CD34); tryptase staining was also done to distinguish the latter from mast cells., Results: Apart from calretinin-positive neurons, patients with gallstones featured a significant decrease of neurons, enteric glial cells (EGC) and mast cells compared to those without gallstones; interstitial cells of Cajal were extremely few and only found in two patients, one for each group., Conclusions: The intrinsic innervations of the gallbladder is abnormal in gallstone patients, and this may contribute to gallstone formation in these subjects., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: To date, there is still uncertainty on the role of specialized intestinal metaplasia in the carcinogenic process of Barrett's oesophagus (BE); this fact seems of importance for planning adequate surveillance programs., Aims: To predict the risk of progression towards dysplasia/cancer based on typical morphological features by evaluating the importance of intestinal metaplasia in BE patients., Methods: 647 cases with a histological diagnosis of BE, referred to the Endoscopy Unit of a tertiary centre between 2000 and 2012 were retrospectively identified, and divided into two groups according to the presence/absence of intestinal metaplasia. For each patient, all histological reports performed during a follow-up of 4-8 years were analyzed., Results: Overall, 537 cases (83%) with intestinal metaplasia and 110 cases (17%) without intestinal metaplasia were included. During the follow-up period, none of the patients without intestinal metaplasia developed dysplasia/cancer nor progressed to metaplasia, whereas 72 patients with intestinal metaplasia (13.4%) showed histological progression of the disease., Conclusion: The histological identification of intestinal metaplasia seems to be an essential factor for the progression towards dysplasia and cancer in BE patients., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The accuracy and effectiveness of targeted oesophageal biopsies in Barrett's oesophagus to detect dysplasia using new magnification techniques are unknown. Aim of this study was to investigate whether the combined use of acetic acid, magnification and electronic filters allows the same accuracy as the four-quadrant random biopsies pattern; pathologist interobserver agreement both in low grade and high grade dysplasia was also assessed., Methods: Fifty-four consecutive patients newly diagnosed with Barrett's oesophagus were enrolled in a prospective study from a single endoscopy unit. Biopsies were evaluated by the local pathologist and by an expert pathologist from another pathology unit., Main Outcome Measurement: Dysplasia detection rate and interobserver agreement for the histologic diagnosis of dysplasia., Results: The use of acetic acid, magnification and electronic filters showed an unacceptably low dysplasia detection rate by the two pathologists (9.2% and 5.5% for targeted biopsies, respectively). The interobserver agreement for low grade dysplasia between pathologists was low (Cohen's K weighted=0.45)., Conclusions: In an average setting, the standard four-quadrant method should still be preferred, along with the implementation of a routine second evaluation by an expert pathologist., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Since the introduction of biological therapy, endoscopic and histological remission, i.e. mucosal healing, has become an important therapeutic goal in Crohn's Disease and Ulcerative Colitis. Mucosal healing is associated with lower rates of hospitalization and surgery, although its role in preventing progression and changing the natural history of the disease has not been clearly demonstrated. A precise definition of mucosal healing has not yet been established, although the concept used in clinical trials is the "complete absence of all inflammatory and ulcerative lesions in all segments of gut" at endoscopy. This definition does not include mucosal improvement and does not distinguish among grades of mucosal healing. In both Crohn's Disease and Ulcerative Colitis trials, several qualitative and quantitative numeric endoscopic indices have been proposed to measure and distinguish endoscopic changes. In addition, the microscopic features associated with inflammatory bowel diseases are considerably modified by the course of the disease and the treatments adopted. However, it is not yet clear whether microscopic healing should be a primary endpoint in clinical trials. In this paper we discuss endoscopic and histological findings and the limitations of the endoscopic and histological indices as a basis for a standardised diagnosis of mucosal healing., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Complications following gastrointestinal surgery may require re-intervention, can lead to prolonged hospitalization, and significantly increase health costs. Some complications, such as anastomotic leakage, fistula, and stricture require a multidisciplinary approach. Therapeutic endoscopy may play a pivotal role in these conditions, allowing minimally invasive treatment. Different endoscopic approaches, including fibrin glue injection, endoclips, self-expanding stents, and endoscopic vacuum-assisted devices have been introduced for both anastomotic leakage and fistula treatment. Similarly endoscopic treatments, such as endoscopic dilation, incisional therapy, and self-expanding stents have been used for anastomotic strictures. All these techniques can be safely performed by skilled endoscopists, and may achieve a high technical success rate in both the upper and lower gastrointestinal tract. Here we will review the endoscopic management of post-surgical complications; these techniques should be considered as first-line approach in selected patients, allowing to avoid re-operation, reduce hospital stay, and decrease costs., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The existence of mild forms of celiac disease (CD) can make the histology-based diagnosis difficult to reach. Since anti-endomysium (EMA) and anti-tissue transglutaminase (anti-tTG) are detectable in culture supernatants of duodenal biopsies from CD patients, our aim was to assess if this system can support the histology in the diagnostic work-up. A total of 559 suspected CD patients underwent serum EMA/anti-tTG detection, upper endoscopy with duodenal biopsy sampling, histologic analysis, and organ culture to detect EMA/anti-tTG in supernatants. A subgroup of 30 patients with organ culture positive results were put on a gluten-free diet (GFD). Their gluten-dependency was evaluated by the psychological general well-being and beck depression inventory indexes. Statistical analysis was performed by Cohen k inter-test, Friedman test, and Dunn multiple comparison. Two hundred forty-one out of 559 (43.1%) patients showed intestinal villous atrophy, whereas serum and organ culture EMA/anti-tTG were positive in 293/559 (52.4%) and 334/559 (59.7%) patients, respectively. The strength of agreement resulted good for serology vs histology (k = 0.730), good for organ culture vs histology (k = 0.662), and very good for serology vs organ culture (k = 0.852). After 12 months of GFD, psychological general well-being index significantly increased, and beck depression inventory index significantly decreased (P < 0.001 for each one). Data highlight the organ culture system as a useful tool to assist the histology in diagnosing CD, mainly in cases without villous atrophy or in seronegative patients. The marked improvement in quality of life after a GFD further supports the reliability of this system in diagnosing CD., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Bowel ultrasound has been shown to be a useful tool to evaluate patients with inflammatory bowel disease, especially Crohn's disease. However, such data are still scarce in ulcerative colitis patients., Aims: To establish the value of bowel ultrasound in moderate to severe ulcerative colitis patients, and compare these data with endoscopic findings., Patients and Methods: Endoscopic, ultrasound and C-reactive protein data from 51 patients with moderate to severe ulcerative colitis observed during a 3-year period were retrospectively obtained and analysed., Results: All patients displayed pathological thickness (>4 mm) of the colon wall. This value strongly correlated with C-reactive protein values (p=0.0001) and the endoscopic score (p<0.0001). Also, a strong correlation (p<0.0001) was found between CRP values and endoscopic score., Conclusions: Bowel ultrasound, in expert hands, may represent a useful adjunctive (or first line) tool for the evaluation of patients with moderate to severe ulcerative colitis., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: There is at present a relative lack of knowledge concerning drug-related colitides, although these may be not infrequent entities in clinical practice., Aims: To assess the frequency and the clinical-pathological subtypes of drug-related colitides in a gastrointestinal pathology referral centre., Methods: All charts of endoscopic biopsy samples referred for colitis in a eight-year period were reviewed. To be classified as drug related colitis, patients' charts should report the use of any drug in a two month period before colonoscopy and no other obvious cases of colitis be present. For analysis, we considered only patients taking one drug in this period., Results: We found 122 cases of drug-related colitis out of 3877 charts reviewed (3% of the overall colitis group). These cases were represented by microscopic colitis (50%), eosinophil rich infiltrate of the left colon (34%), ischemic colitis (11%), pseudomembranous colitis (3%), apoptotic colopathy (2%). The drugs most frequently associated with these colitides were represented by non-steroidal anti-inflammatory drugs., Conclusion: It is important to raise awareness concerning drug-related colitides, to avoid diagnostic errors and provide a better therapeutic approach to patients with these conditions., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: It is unclear whether questionnaires and diary cards, which are widely used to collect data on bowel habits, provide analogous information., Aims: We verified the concordance between the data provided by a daily diary and a retrospective questionnaire., Methods: A 4-week diary (DIARY) concerning bowel habits was compiled by 221 subjects. They were also asked to fill out a questionnaire on their bowel habits before (BEF) and after (AFT) the diary period., Results: Concerning bowel movements, no significant difference was detected in the concordance between BEF and DIARY (rho: 0.80), AFT and DIARY (rho: 0.84), or BEF and AFT (rho: 0.84). The mean concordance in the other defecation-related parameters between BEF and DIARY (K: 0.62) and between DIARY and AFT (K: 0.63) were both significantly lower than that seen between BEF and AFT (K: 0.80; p<0.01)., Conclusion: A considerable discrepancy between the two methods of assessment was found. The higher concordance between BEF and AFT than between DIARY and AFT regarding defecation-related parameters suggests that when a subject recalls events, even those from the recent past, he/she tends to generalize, reporting more or less the same data for different periods of time. These two instruments cannot be viewed as interchangeable, and their inherent differences must be taken into account when deciding which one to employ in different settings., (Copyright (c) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting., Aims: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls., Methods: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers., Results: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores., Conclusions: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.

Background: Immunohistochemical changes associated with development of cancer in Barrett's esophagus offer potential areas of intervention to prevent and manage esophageal cancer., Aims: To assess the role of cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2/cyclin-dependent kinase 1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence., Patients and Methods: Specimens from 46 patients with Barrett's esophagus (39% without dysplasia, 33% with dysplasia and 28% with adenocarcinoma) were stained for cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2., Results: Cyclooxygenase 2: No expression differences between groups were found, except for adenocarcinomas (p=0.04). Caudal-type homeobox transcription factor 2: Nuclear positivity decreased from Barrett's esophagus without dysplasia (71.6%), to Barrett's esophagus with low grade dysplasia (35.3%), to Barrett's esophagus with high grade dysplasia (17.14%); in adenocarcinoma these percentages were intermediate between high and low grade dysplasia (30.5%). Cell division cycle 2: Expression on deeper glandular structures was 40% in Barrett's esophagus without dysplasia, 55.47% in Barrett's esophagus with dysplasia, and 63.84% in adenocarcinoma, with no statistical differences between groups. Concerning cells of the superficial layer, Barrett's esophagus with low grade dysplasia expressed focal positivity (p=0.0001 vs. no dysplasia); Barrett's esophagus with high grade dysplasia displayed diffuse positivity (p=0.0001 vs. no dysplasia and low grade dysplasia). A diffuse positivity was found in Barrett's esophagus with adenocarcinoma (p=0.0001 vs. no dysplasia and low grade dysplasia)., Conclusions: Further evaluation of cyclooxygenase 2, cell division cycle 2 and caudal-type homeobox transcription factor 2, in association with morphology, might help to improve the accuracy of diagnosis and be useful for the clinical-pathological assessment of patients with Barrett's esophagus.

Background: Available information on normal bowel habits was mainly gathered by means of telephone interviews or mailed questionnaires., Aims: We undertook a prospective study to evaluate the defecatory habits in subjects perceiving themselves as normal concerning this function., Subjects and Methods: A questionnaire (4-week diary with "yes-no" daily answers to six questions concerning bowel habits) was distributed to 204 subjects perceiving their defecation behaviour as normal., Results: The completed questionnaire was returned by 140 subjects. No significant differences were found between sexes or age groups for any variable, even though straining at stool and feeling of incomplete and/or difficult evacuation showed a trend to increase with age. No subject had less than three bowel movements per week or more than three per day. The percentage of symptoms linked to an abnormal defecatory behaviour was well below 10%. Fifty-five percent of subjects reported at least one parameter of abnormal functioning; the most frequent was straining at stool and the rarer was the manual manoeuvres to help defecation., Conclusions: In normal subjects the prevalence of symptoms considered in Rome II criteria as part of an abnormal defecatory behaviour (in more than 25% of defecations) is well below 10%, manual manoeuvres are almost never used to help defecation, and the frequency of defecations is at least three per week.

Anterior resection of the rectum is a frequent surgical procedure. However, abnormal bowel habits following this procedure are frequently reported. The functional evaluation of these patients is usually limited to the anorectal area. By means of colonic manometry, we have evaluated a patient with frequent urge for defecation and increased bowel frequency following anterior resection of the rectum with straight coloanal anastomosis and almost normal anorectal function. Analysis of the tracing revealed a reduction of contractile segmental activity and much more high-amplitude propagated contractions than which occur in healthy subjects. These high-amplitude propagated contractions, representing the manometric equivalent of mass movements, were always in association with urge for defecation and, sometimes, with loose stools. High-amplitude simultaneous contractions were also observed. We feel that the surgical resection of a potential physiological brake may be responsible for these observations.

Selective serotonin reuptake inhibitors are frequently employed to treat depression. However, although rarely, coagulation abnormalities have been described following the use of these compounds, and these effects appear to be enhanced by simultaneous use of nonsteroidal anti-inflammatory drugs. We describe a case of reversible symptomatic duodenal compression caused by a retroperitoneal hematoma after ingestion of sertraline and nimesulide.

Background and Aims: Functional gastrointestinal disorders are diagnosed by the presence of a characteristic set of symptoms. Aims of this study were to validate the Rome symptom criteria by factor analysis and to determine whether symptoms cluster in the same way in different cultures., Methods: One thousand forty-one gastroenterology clinic patients in the US (response rate 53%) and 228 family members accompanying clinic patients in Italy (84%) completed a previously validated symptom questionnaire. Factor analysis identified clusters of symptoms which are highly correlated with each other, and these were compared to the Rome diagnostic criteria., Results: In the US, 13 factors were identified. The irritable bowel factor was composed of three core symptoms corresponding to the Rome II classification system. Two dyspepsia factors were identified which correspond to the ulcer- and motility-like subtypes proposed in the Rome I classification system. All symptoms of constipation formed a single cluster as proposed in the Rome II classification system. Symptom clusters in the US agreed well with symptom clusters identified in Italian subjects., Conclusions: Empirically derived symptom clusters agree in most respects with the Rome II classification system and support their validity. These symptom clusters are independent of cultural differences in diet and behaviour.

Background: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones., Aims: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients., Patients: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction., Methods: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments., Results: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed., Conclusions: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.

Background: The dopamine D2 receptor antagonist levosulpiride is a substituted benzamide derivative, whose gastrokinetic properties are exploited clinically for the management of functional dyspepsia. However, for other benzamide derivatives, such as cisapride and mosapride, agonism towards serotonin 5-HT4 receptors is considered the main mechanism leading to gastrointestinal prokinesia., Aims: To assess whether levosulpiride is able to activate 5-HT4 receptors in the guinea-pig isolated gastrointestinal tract., Materials and Methods: Circular muscle strips from gastric antrum, and colonic longitudinal muscle strips were used to detect electrically stimulated neurogenic contractions. The effect of levosulpiride was assessed in the absence and presence of GR125487, a selective 5-HT4 receptor antagonist. Furthermore, potential interaction of levosulpiride with 5-HT3 receptors and tissue cholinesterases was assessed in unstimulated ileal longitudinal muscle-myenteric plexus preparations., Results: Antral and colonic strip contractions were cholinergic/tachykinergic in nature. Micromolar concentrations of levosulpiride potentiated submaximal responses, through a mechanism competitively antagonized by GR125487 (pKB=9.4). In LMMPs, levosulpiride slightly affected contractions caused by the 5-HT, receptor agonist 2-methyl-5-HT, and had no effect on contractions to exogenous acetylcholine., Conclusions: Our results indicate that levosulpiride acts as a moderate agonist at the 5-HT4 receptor. This property, together with antagonism at D2 receptors, may contribute to its gastrointestinal prokinetic effect.

Background: Human colonic motility is still poorly understood, especially as far as concerns its propulsive function. Available data refer almost exclusively to the forceful propulsive activity, which is recognized as high-amplitude propagated contractions, the manometric equivalent of mass movements. By contrast, information on less vigorous propulsive contractions is still lacking., Aims: To investigate the presence and behaviour of low-amplitude propagated contractile waves (less than 50 mmHg in amplitude) in the colon of healthy humans during a 24-hour study period., Subjects and Methods: A series of 16 healthy volunteers of both sexes entered the study, and were investigated by a standard technique involving a colonoscopically-positioned manometric catheter. During the study, two standard 1,000 kcal mixed meal and a 450 kcal breakfast were served. The recordings were, therefore, scanned for the presence of low-amplitude propagated contractile waves (waves of less than 50 mmHg in amplitude, propagated over at least three consecutive recording ports), their daily distribution, and their relationship with physiological events., Results: Low-amplitude propagated contractile waves were constantly present in all the tracings, with an average of about 61 events/subject/day and a mean amplitude of about 20 mmHg. More than 80% of these events appeared during the day, with a significant (p<0.05) increase after meals and after morning awakening. In 25% of subjects, these waves were accompanied by emission of flatus., Conclusions: In the human colon, low-amplitude propagated contractile waves are a constant physiological propulsive pattern, which is generally related to sleep-wake cycles and meal ingestion.

Background: Chronic anal fissure is a frequent and troubling condition, that may need surgical sphincterotomy for relief of symptoms. However, this approach may yield minor incontinence in up to 30% of cases. Interest has, therefore, recently increased in "chemical sphincterotomy" by using topical glyceryl trinitrate ointment. Unfortunately, there is, to date, no specific pharmaceutical preparation of such compound., Aims: To compare, according to a randomized double-blind crossover study, the effects of a pharmaceutical preparation of a specific 0.2% glyceryl trinitrate ointment (PMF 303) and of the common preparation reported in the literature on the anal resting pressure in patients with anal fissure., Patients and Methods: Twelve patients with chronic anal fissure (6 males and 6 females, age range 23-60 years] were recruited for the study. Two paired manometric studies were carried out at one-week intervals. After the basal anal pressure had been assessed, the patients were randomized to receive either one of the two preparations, and manometric measurements were repeated at 20, 40 and 60 minutes., Results: No differences were found between anal resting pressure in the basal study. Both preparations were able to significantly decrease (p=0.001) anal pressure throughout the study period. No significant differences were found between the two preparations., Conclusions: PMF 303 is able to decrease anal pressure in patients with anal fissure, to a similar extent to the widely tested (galenic) literature preparation. Availability of a specific formulation for the treatment of this condition may be clinically useful.

Manometric criteria for diffuse esophageal spasm have recently been restated. In this study, a cohort of 358 subjects was evaluated in a gastrointestinal motility laboratory for dysphagia and/or chest pain. Applying the recently proposed criteria of Richter and Castell, 18 subjects (5%) were diagnosed as having DES. Dysphagia was the major complaint (89%), while 44% of patients complained of chest pain and 33% of both symptoms. All patients shared more than 30% simultaneous contractions after wet swallows interspersed with normal peristaltic sequences. Associated manometric findings were repetitive (greater than 3 peaks) contractions (67%), high-amplitude contractions (33%), spontaneous activity (22%), prolonged duration (11%), and lower esophageal sphincter abnormalities (5%). Radiology disclosed significant abnormalities in only 27% of DES patients.

In linear pharmacokinetics, the time course of the plasma concentration of a drug, Ct, is expressed by the sum of exponential terms, (formula; see text) This article proposes a new statistical criterion for discriminating between alternate polyexponential models. According to this new criterion, the model that best interprets a set of experimental data points is that which minimizes the area between the approximate confidence limits of Ct.