Danilo Badiali

Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation

The present multicenter double-blind placebo-controlled trial evaluates the therapeutic effectiveness of small-volume daily doses of an isosmotic polyethylene glycol (PEG) electrolyte solution in the treatment of chronic nonorganic constipation. After a complete diagnostic investigation, patients still constipated at the end of a four-week placebo-treatment run-in period were enrolled and randomized to receive either placebo or PEG solution 250 ml twice a day for the following eight weeks. Patients were assessed at four and eight weeks of treatment, and they reported frequency and modality of evacuation, use of laxatives, and relevant symptoms daily on a diary card. Oroanal and segmental large-bowel transit times were assessed with radiopaque markers during the fourth week of the run-in period and the last week of the treatment period. During the study period, dietary fiber and liquids were standardized and laxatives were allowed only after five consecutive days without a bowel movement. Of the 55 patients enrolled, five dropped out, three because of adverse events and two for reasons unrelated to therapy; another two were excluded from the efficacy analysis because of protocol violation. Of the remaining 48 patients (37 women, age 42±15 years, mean±sd), 23 were assigned to placebo and 25 to PEG treatment. In comparison to placebo, PEG solution induced a statistically significant increase in weekly bowel frequency at four weeks and at the end of the study (PEG: 4.8±2.3 vs placebo: 2.8±1.6;P<0.002) and a significant decrease in straining at defecation (P<0.01), stool consistency (P<0.02), and use of laxatives (P<0.03). Oroanal, left colon, and rectal transit times were significantly shortened by PEG treatment. There was no difference between controls and PEG-treated patients as far as abdominal symptoms and side effects were concerned. In conclusion, PEG solution at 250 ml twice a day is effective in increasing bowel frequency, accelerating colorectal transit times, and improving difficult evacuation in patients with chronic nonorganic constipation and is devoid of significant side effects.

Effect of wheat bran in treatment of chronic nonorganic constipation : a double-blind controlled trial

After a two-week basal period, 24 patients were randomly allocated to receive, with a crossover double-blind design, for two consecutive four-week periods, bran (20 g/24 hr) or placebo. The daily intake of water and dietary fibers was standardized. Symptomatology, oroanal transit time, bowel frequency, and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment. Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period. Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit. During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit. Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments.

Anorectal function in multiple system atrophy and Parkinson's disease

This study was designed to investigate anorectal function in Parkinsons disease and multiple system atrophy (MSA). After a standardized interview, 17 patients with Parkinsons disease (PD) and 16 patients with multiple system atrophy (MSA) underwent anorectal manometry with a continuously perfused multi‐lumen catheter, located to record pressures from the anal canal, and a balloon for rectal distension. Data were analyzed by observers blind to the neurologic diagnosis. Disease duration was shorter in the MSA than in the PD group (6 + 4 versus 10 + 5 yrs, p <0.05). Most patients reported a bowel frequency of less than three evacuations per week and some patients had fecal incontinence. Most manometric recordings disclosed an abnormal pattern during straining (a paradoxic contraction or lack of inhibition) in 13 patients with MSA and 11 patients with PD. Mean anal pressures and rectal sensitivity threshold were not significantly higher in the MSA group, whereas the inhibitory anal reflex and rectal compliance thresholds were within the normal range in both groups. Manometric patterns did not differentiate patients with MSA from patients with PD. Most patients in both groups showed an abnormal straining pattern, decreased anal tone, or both dysfunctions. In conclusion, our findings suggest that although bowel and anorectal dysfunctions do not differentiate MSA from PD, both abnormalities occur earlier and develop faster in MSA than in PD.

Age‐dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene

Abstract  Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio‐pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti‐inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.

Psychopathological features of irritable bowel syndrome patients with and without functional dyspepsia: a cross sectional study

BackgroundIrritable bowel syndrome (IBS) and functional dyspepsia (FD) show considerable overlap and are both associated with psychiatric comorbidity. The present study aimed to investigate whether IBS patients with FD show higher levels of psychopathology than those without FD. As a preliminary analysis, it also evaluated the psychopathological differences, if any, between IBS patients featuring the two Rome III-defined FD subtypes, i.e. postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).MethodsConsecutive outpatients (n = 82, F = 67, mean age 41.6 ± 12.7 years) referred to our third level gastroenterological centre, matching the Rome III criteria for IBS and, if present, for concurrent FD, were recruited. They were asked to complete a 90-item self-rating questionnaire, the Symptom Checklist 90 Revised (SCL-90-R), in order to assess the psychological status. Comparisons between groups were carried out using the non-parametric Mann-Whitney U test.ResultsPatients with IBS only were 56 (68.3%, F = 43, mean age 41.6 ± 13.3 years) and patients with both IBS and FD were 26 (31.7%, F = 24, mean age 41.8 ± 11.5 years), 17 of whom had PDS and 9 EPS. Patients with both IBS and FD scored significantly higher on the SCL-90-R GSI and on eight out of the nine subscales than patients with IBS only (P ranging from 0.000 to 0.03). No difference was found between IBS patients with PDS and IBS patients with EPS (P ranging from 0.07 to 0.97), but this result has to be considered provisional, given the small sample size of the two subgroups.ConclusionsIBS-FD overlap is associated with an increased severity of psychopathological features. This finding suggests that a substantial subset of patients of a third level gastroenterological centre with both IBS and FD may benefit from psychological assessment and treatment.

Comparative outcome of stapled trans-anal rectal resection and macrogol in the treatment of defecation disorders

AIM To prospectively assess the efficacy and safety of stapled trans-anal rectal resection (STARR) compared to standard conservative treatment, and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR. METHODS Thirty patients (Female, 28; age: 51 ± 9 years) with rectocele or rectal intussusception, a defecation disorder, and functional constipation were submitted for STARR. Thirty comparable patients (Female, 30; age 53 ± 13 years), who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol, were assessed. Patients were interviewed with a standardized questionnaire at study enrollment and 38 ± 18 mo after the STARR procedure or during macrogol treatment. A responder was defined as an absence of the Rome III diagnostic criteria for functional constipation. Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients, respectively. RESULTS After STARR, 53% of patients were responders; during conservative treatment, 75% were responders. After STARR, 30% of the patients reported the use of laxatives, 17% had intermittent anal pain, 13% had anal leakage, 13% required digital facilitation, 6% experienced defecatory urgency, 6% experienced fecal incontinence, and 6% required re-intervention. During macrogol therapy, 23% of the patients complained of abdominal bloating and 13% of borborygmi, and 3% required digital facilitation. No preoperative symptom, defecographic, or manometric finding predicted the outcome of STARR. Post-operative defecography showed a statistically significant reduction (P < 0.05) of the rectal diameter and rectocele. The post-operative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified, and that rectal compliance was reduced (P = 0.01). CONCLUSION STARR is not better and is less safe than macrogol in the treatment of defecation disorders. It could be considered as an alternative therapy in patients unresponsive to macrogol.

Role of body position, gender, and age on pelvic floor location and mobility

The location and mobility of pelvic floor in different body positions and their relation to age and gender was assessed in 117 patients (19 men, 98 women, age range 10–77 years) with chronic nonorganic constipation (defined as less than three bowel movements per week for at least three years) by means of defecography. Eleven females (age range 16–69 years), without gastrointestinal symptoms, affected by noninvasive carcinoma of the cervix represented a control group. Pelvic floor location was measured as the distance in centimeters of the anorectal junction from the pubococcygeal line; pelvic floor mobility was measured during squeezing, straining, and defecation assuming the pelvic location at rest as zero reference. Pelvic floor location and mobility did not differ between controls and constipated patients. In both groups pelvic floor location at rest was significantly higher (P=0.001) with patients lying down than sitting up, whereas pelvic floor mobility during squeezing was greater with the patients sitting up than lying down (P=0.003). In both positions, pelvic floor location at rest was significantly lower (P=0.01) in females than in males. Pelvic floor mobility during squeezing was significantly different between gender. Parity and hysterectomy did not appear to affect pelvic floor location. Data emerging from this study indicate that body position is one of the major determinants of the pelvic floor location.

Functional magnetic resonance in the evaluation of oesophageal motility disorders.

Functional magnetic resonance imaging (fMRI) has been recently proposed for the evaluation of the esophagus. Our aim is to assess the role of fMRI as a technique to assess morphological and functional parameters of the esophagus in patients with esophageal motor disorders and in healthy controls. Subsequently, we assessed the diagnostic efficiency of fMRI in comparison to videofluoroscopic and manometric findings in the investigation of patients with esophageal motor disorders. Considering that fMRI was shown to offer valuable information on bolus transit and on the caliber of the esophagus, variations of these two parameters in the different types of esophageal motor alterations have been assessed. fMRI, compared to manometry and videofluoroscopy, showed that a deranged or absent peristalsis is significantly associated with slower transit time and with increased esophageal diameter. Although further studies are needed, fMRI represents a promising noninvasive technique for the integrated functional and morphological evaluation of esophageal motility disorders.

A Double-Blind Controlled Trial on the Effect of Cisapride in the Treatment of Constipation in Paraplegic Patients

The present double‐blind controlled study compared with a crossover design, the efficacy of cisapride with that of placebo in the treatment of constipation in 10 paraplegic patients. The trial consisted of a 5‐week run‐in period and two 12‐week test periods, separated by a 4‐week washout period. Total and segmental large‐bowel transit times were assessed by means of radiopaque markers during the last week of the run‐in and of the two test periods. Bowel frequency during run‐in, placebo, and cisapride periods was, respectively, 2.9 · 2, 4.1 · 3, and 3.6 · 2.7 evacuations per week (NS). Neither the use of laxatives nor the modality of evacuation changed among the study periods. Oro‐anal transit time during run‐in, placebo, and cisapride periods was, respectively, 146 · 45, 93 · 49 (p < 0.01 vs. run‐in), and 103 · 53 h (p < 0.02 vs. run‐in; NS vs. placebo). The measurement of the large‐bowel segmental transit times showed that transit through the right colon, left colon, and rectum did not differ during the three study periods. In conclusion, cisapride at the dosage of 10 mg four times a day was no more effective than placebo in improving bowel frequency and oro‐anal or segmental large‐bowel transit times in paraplegic patients.

Effect of endogenous cholecystokinin on postprandial gallbladder refilling. Ultrasonographic study in healthy subjects and in gallstone patients.

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB “contractor” patients with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P<0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.