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Biomedical subjects

P Vernia

Publications and source records attributed to P Vernia.

At least 19 recordsLinked to original sources
PubMed2003

Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis.

AIM: To determine the efficacy of infliximab in the treatment of chronic refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis. METHODS: This open study included seven patients (four females, three males) with chronic refractory pouchitis complicated by fistulae. Pouchitis was diagnosed by clinical, endoscopic and histological criteria. The sites of the fistulae were as follows: pouch-bladder in one, vaginal in three, perianal in two, and both vaginal and perianal in one. Extra-intestinal manifestations (erythema nodosum, arthralgia) were present in four patients. Crohn's disease was carefully excluded in all patients after re-evaluation of the history, re-examination of the original proctocolectomy specimen and examination of the proximal small bowel. All patients had been treated with antibiotics and three with steroids. Patients received infliximab, 5 mg/kg, at 0, 2 and 6 weeks. Azathioprine (2.5 mg/kg) was also started for all patients as bridge therapy. Clinical response was classified as complete, partial or no response. Fistulae closure was classified as complete (cessation of fistulae drainage and total closure of all fistulae), partial (a reduction in the number, size, drainage or discomfort associated with fistulae) or no closure. The pouchitis disease activity index and quality of life were also used as outcome measures. RESULTS: Clinically, all patients improved. At the 10-week follow-up, six of the seven patients had a complete clinical response, and five had complete fistulae closure. At the 10-week follow-up, the median pouchitis disease activity index decreased from 12 (baseline) (range, 10-15) to 5 (range, 3-8); the median quality of life decreased from 37 points (range, 33-40) to 14 (range, 9-18). Erythema nodosum and arthralgia showed complete remission soon after the first infusion of infliximab. CONCLUSIONS: These preliminary results indicate that infliximab may be recommended for the treatment of refractory pouchitis complicated by fistulae following ileal pouch-anal anastomosis for ulcerative colitis.

Adult↗
PubMed2003

Effect of predominant methanogenic flora on the outcome of lactose breath test in irritable bowel syndrome patients.

BACKGROUND: The relationship between hydrogen and methane production is a possible confounding factor in the interpretation of H(2) breath tests (HBT), but is usually disregarded for the interpretation of HBT and, in most instances, only H(2) excretion is measured. The present study was designed to evaluate the effect of predominant fasting methane CH(4) or H(2) production on the outcome of lactose HBT, in a large, homogeneous series of adult patients with irritable bowel syndrome (IBS). PATIENTS AND METHODS: A lactose HBT was performed in 237 IBS patients with predominant fasting methane production (CH(4)>H(2)), recording the outcome of the test, amount of gas excreted and occurrence of clinical symptoms. Data were compared to those of 237 age- and sex-matched IBS patients with low fasting CH(4) excretion. RESULTS: The test was positive in 124 predominant CH(4) producers (52.3%) (PMP), as compared to 201 (84.8%) low methane producers (LMP) (P<0.0001). Peak hydrogen concentration and area under the curve of H(2) were significantly (P<0.001) lower, and the occurrence of symptoms during the test less frequent, in PMP vs LMP patients. During the test, CH(4) excretion doubled in 57/113 (50.4%) patients with negative HBT, and in 49/124 (39.5%) with positive HBT. CONCLUSIONS: Patients with predominant fasting methane production excrete less H(2) than LMP, after an oral load of lactose. The lower prevalence of severe lactose intolerance in PMP, as well as lower incidence of symptoms during the test, is, indeed, related to lower and slower H(2) excretion. The assumption that H(2) excretion is an effective means of quantifying the amount of malabsorbed carbohydrates is questionable in PMP. Methane-producing patients likely have a higher 'false negative' rate as compared to LMP after an oral load of lactose. Nonetheless, as symptoms are related to the amount of gas produced in the colon, HBT identifies patients with 'lactose intolerance', irrespective of the presence of lactose malabsorption, and helps in predicting the effect of lactose-restricted diet.

Adolescent↗
PubMed2003

Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial.

BACKGROUND: The treatment of distal ulcerative colitis, refractory to conventional 5-ASA/steroid treatment, is still a matter of debate. The present study aimed at confirming, with adequate statistical power, previous data indicating the usefulness of topical butyrate and 5-ASA in the treatment of this condition. DESIGN: Double-blind, placebo-controlled, multicentre study. A total of 51 patients with distal (< 65 cm) ulcerative colitis, refractory to topical 5-ASA/cortisone, were randomly allocated to receive topical 5-ASA 2 g and 80 mM L-1 sodium-butyrate bid (Group A; 24 patients) or 5-ASA 2 g and 80 mL saline bid (Group B; 27 patients) for 6 weeks. Sigmoidoscopy with biopsies, as well as clinical and laboratory evaluations, were carried out at enrollment and at the end of the trial. Primary endpoints: remission or marked improvement in endoscopic, histologic and clinical findings. RESULTS: Most parameters showed a significant improvement vs. baseline in both groups. Remission in six patients and improvement in 12 patients in Group A vs. one remission and 13 with improvement in Group B (P < 0.05). A significant difference in favour of Group A was recorded regarding the number of bowel movements (P < 0.01), urgency (P < 0.05) and the patients' self evaluation (P < 0.01). DISCUSSION: The combined treatment with topical butyrate and 5-ASA is significantly more effective than 5-ASA alone in the management of refractory distal colitis. Further improvements in the treatment of refractory distal ulcerative colitis may be feasible based on the identification of patient subgroups and the association of two or more active drugs. Butyrate may well be one of them.

Adult↗
PubMed2001

Lactose malabsorption, irritable bowel syndrome and self-reported milk intolerance.

BACKGROUND: The relationship between lactose malabsorption, irritable bowel syndrome and development of intestinal symptoms is unclear, especially when the ingested dose of milk is small. Thus, the role of hydrogen breath testing in the diagnostic work-up of patients with nonspecific intestinal symptoms is still debated. AIMS: To establish the relationship between lactose malabsorption, severe self-reported milk intolerance, irritable bowel syndrome and related symptoms. METHODS: The prevalence of lactose malabsorption was prospectively assessed by means of a hydrogen breath test in 839 patients (503 with irritable bowel syndrome, based on the Rome criteria, regularly consuming milk, and 336 subjects who identified themself as milk intolerant, after an oral load of 25 g lactose). The test was considered "positive" when a hydrogen peak exceeding 20 ppm over baseline values was observed in two or more samples. Attempts were also made to establish whether the predominant presenting symptom (diarrhoea, constipation, alternating diarrhoea and constipation, pain and gaseousness) might be helpful in predicting the outcome of the breath test. RESULTS: The prevalence of a positive breath test was comparable in the two groups (337 patients with irritable bowel syndrome (66.9%) vs 240 patients with milk intolerance (71.4%)). The same holds true for the first peak of hydrogen excretion, total hydrogen output and prevalence of symptoms during, and in the four hours after, the test. The predominant presenting symptom was not useful for predicting outcome of the test either in regular milk users or in milk intolerant subjects. CONCLUSIONS: The almost identical results of the lactose breath test of patients with irritable bowel syndrome and subjects with self-reported milk intolerance suggests that the two conditions overlap to such an extent that the clinical approach should be the same. A lactose breath test should always be included in the diagnostic work-up for irritable bowel syndrome, as fermentation of malabsorbed lactose is likely responsible for triggering symptoms. Conversely, lactase deficiency is probably irrelevant in most subjects not affected by irritable bowel syndrome, within a moderate milk consumption.

Adolescent↗
PubMed2000

Topical butyrate for acute radiation proctitis: randomised, crossover trial.

BACKGROUND: No available therapy has, as yet, proven effective to treat acute radiation proctitis (ARP) following radiation therapy for malignant pelvic disease. We assessed whether sodium butyrate enemas, at a dose of 80 mmol/L (80 mL/24 h), might offer effective treatment for this condition. METHODS: 20 patients presenting with ARP after completing a cycle of 35-52 Gy external-beam radiation therapy for pelvic malignant disease, were treated for 3 weeks with topical sodium butyrate and saline enemas according to a randomised, double-blind, crossover protocol. Clinical, endoscopic, and histological findings were assessed at enrollment, at week 3, and then at the end of the study. Data were analysed by two-tailed t test for paired data (continuous variables) and a logistic-regression model with variable multiple response for ordered categorical data. FINDINGS: Topical butyrate, but not saline, led to remission of symptoms (clinical score from 8.2 [SE 1.6] to 1.5 [0.7] vs 7.9 [1.8] to 8.1 [3.4]). When the treatment regimen was switched, eight out of nine of the previously placebo-treated patients went into remission, whereas three patients relapsed when switched to saline. The advantage of butyrate over placebo, expressed as CI, odds ratio, and p value was significant for almost all the clinical, endoscopic and histological factors taken into consideration. INTERPRETATION: Topical sodium butyrate, unlike other therapeutic regimens used so far, proved effective in the treatment of ARP.

Administration, Topical↗
PubMed2000

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis: randomized, double-blind, placebo-controlled pilot study.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availability/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 +/- 2.02 to 2.58 +/- 2.19 (P < 0.05) in the combined treatment group and from 6.07 +/-1.60 to 3.46 +/- 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (delta9.58 +/- 4.19 vs 5.92 +/- 3.48) and the UCDAI score (delta4.67 +/- 2.19 vs 2.54 +/- 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

Administration, Oral↗
PubMed2000

Multiple organ dysfunction in ulcerative colitis.

OBJECTIVE: The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. METHODS: The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976-1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. RESULTS: Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called "impending megacolon" in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. CONCLUSIONS: These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.

Adolescent↗
PubMed1999

Circulating soluble factor-inhibiting natural killer (NK) activity of fresh peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients.

This study was performed in order to assess the cytotoxic activity, both natural (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it with their clinical features. Cytotoxicity assays were performed using sensitive target cells for NK and ADCC activities. In some experiments, highly purified NK cells, obtained both by Percoll density gradient and by co-culturing non-adherent PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we evaluated NK cell parameters such as number, surface expression of adhesion molecules (CD11a/CD18, CD49d and CD54) and response to different stimuli. We observed a decreased NK cytotoxicity of PBMC from IBD patients, both in ulcerative colitis (UC) and Crohn's disease (CD), independently of the clinical activity of disease. In contrast, the ADCC lytic activity was within normal range. The lower NK cytotoxic activity observed in our IBD patients cannot be related to a decreased number of NK cells, surface expression of adhesion molecules, defective response to IL-2 and maturative defect. Decreased NK activity was induced in PBMC of controls when serum of patients was added and this was unrelated to monocyte-derived modulating factor(s). Our data show a decreased natural killing by fresh PBMC from IBD patients. This lower activity seems to be unrelated to a primary NK cell defect, since purified NK cells exhibited normal levels of killing. It might be hypothesized that serum factors, possibly derived from lymphocytes, with inhibitory properties on NK activity, might be functionally active in the blood of IBD patients, thus modulating NK activity.

Adolescent↗
PubMed1998

Serum levels of soluble CD30 are increased in ulcerative colitis (UC) but not in Crohn's disease (CD).

Imbalance in Th1 and Th2 subsets and their derived cytokines seems to be involved in the immune abnormalities underlying UC and CD. CD30 is a member of the tumour necrosis factor/nerve growth receptor superfamily expressed on T cells producing Th2 cytokines and released as a soluble form. In this study high levels of soluble CD30 were found in sera of UC patients independently of disease activity. Furthermore, increased titres of soluble CD30 molecule were shown, in the same patients, by mitogen-stimulated cultures of peripheral blood mononuclear cells. Our data seem to indicate that an activation of Th2 immune response is involved in the pathogenesis of UC, but not of CD. Furthermore, this finding indicates that serum soluble CD30 measurement may be helpful for differentiating these two forms of inflammatory bowel disease.

Adolescent↗
PubMed1998

Quantitative analysis of stool losses in adult celiac disease: use of near-infrared analysis reconsidered.

BACKGROUND: An attempt has been made to establish whether near-infrared stool analysis is more suitable for quantifying malabsorption than the traditional stool fat analysis. A group of celiac disease (CD) patients was used as index population. METHODS: Stool fat, nitrogen, and water were measured with near-infrared analysis of 1- and 3-day stool collections in 96 celiac disease patients on a free diet (in 39 also on gluten-free diet) and in 96 matched controls and 14 patients with latent CD. RESULTS: The fecal output of fat, nitrogen, and water was significantly increased in free-diet CD, whereas their percentage content was only slightly modified compared with controls. None of the variables under consideration differed significantly between the 24-h and 72-h stool specimens. CONCLUSION: Our data show that the high value of fecal fat, nitrogen, and water, in celiac disease, are mainly due to the fecal weight, whereas the percentage composition of stool does not offer additional diagnostic information. Furthermore, 3-day stool collection is not necessary to confirm or rule out malabsorption in most patients. Near infrared analysis of 24-h specimens is time- and cost-effective and may increase the use of stool analysis and be usefully employed to monitor the clinical follow-up of patients with chronic diarrhea.

Adult↗
PubMed1998

Doppler sonography of the superior mesenteric artery in Crohn's disease.

OBJECTIVE: The aim of this study was to evaluate blood flow in the superior mesenteric artery (SMA) in patients with active and inactive Crohn's disease (CD) using Doppler sonography to dynamically assess the changes of resistance in both fasting and postprandial states. SUBJECTS AND METHODS: Doppler sonography of the SMA was performed on 15 patients (mean age, 38 +/- 4 years) with active CD and on 15 patients (mean age, 41 +/- 5 years) with inactive CD. Imaging was performed at both fasting and 15 min after an 1890-kJ meal. A preliminary examination of 10 healthy volunteers with no signs of intestinal disease (mean age, 28 +/- 2 years) was necessary to define the parameters of normality. Because we wanted to express the postprandial resistive change in the SMA, we introduced a parameter called resistive difference (RD), defined as the mathematic difference between the resistive index measured at fasting (highest value) and measured at 15 min after the meal (lowest value). RESULTS: By evaluating the relationship between the RD and extension of disease, we found a direct correlation between progressive extension of disease and reduction of the RD in patients with active CD (correlation coefficient, .98) whereas we found no such correlation in patients with inactive CD (correlation coefficient, .05). CONCLUSION: We believe that Doppler sonography of the SMA is a promising noninvasive method to detect inflammatory disease of the small bowel, to evaluate its extension, and to document resolution of disease after therapy.

Adult↗
PubMed1995

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate.

Nine patients with distal ulcerative colitis refractory to standard therapy were treated with intrarectal instillation of a sodium butyrate solution and 5-ASA. A marked clinical, endoscopical and, to a smaller extent, histological improvement was observed in seven of nine patients. The clinical improvement usually occurred within the second week of therapy, and thus earlier than in previous cases treated with butyrate alone. This preliminary experience suggests that the combined butyrate-5-ASA treatment may prove a useful therapeutic tool in refractory distal ulcerative colitis and possibly increase the effectiveness of the individual therapeutic regimens.

Administration, Topical↗
PubMed1995

Sorbitol malabsorption and nonspecific abdominal symptoms in type II diabetes.

Some data suggest that sorbitol intake may be responsible for diarrhea in diabetic patients. One hundred thirteen hydrogen breath tests were performed in type II diabetics (72) and normal controls (41) after oral loads of sorbitol ranging from 2.5 to 20 g in iso-osmolar solutions to assess the role of malabsorption of this compound in the genesis of abdominal symptoms. The prevalence of sorbitol malabsorption and abdominal symptoms, peak (Cmax H2) and total (Ctot H2) hydrogen production, and mouth to cecum transit time (MCTT) did not differ in type II diabetics and controls. Malabsorption was observed more frequently with the highest doses of sorbitol (10% of patients at a dose of 2.5 g and approximately 75% at 20 g). Symptoms, usually consisting of mild discomfort and abdominal distension, were observed only after sorbitol loads of 10 and 20 g in 27.2% of the diabetics and in 36.3% of the controls. Diarrhea was present in three subjects (two diabetics and one control) only at a dose of 20 g. These data indicate that it is highly unlikely for sorbitol to play a role in inducing diabetes diarrhea. A moderate (up to 10 g) sorbitol intake is not contraindicated in type II diabetics.

Abdomen↗
PubMed1995

Short-chain fatty acid topical treatment in distal ulcerative colitis.

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.

Acetates↗
PubMed1995

Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactose-free diet.

Lactose malabsorption may induce abdominal symptoms indistinguishable from those of the irritable bowel syndrome (IBS), however the exact relationship between the two conditions and the optimal differential diagnostic workup are still to be defined. We prospectively studied the prevalence of lactose malabsorption (by means of a hydrogen breath test) and the clinical effect of a long-term lactose-free diet in 230 consecutive patients with a suggested diagnosis of irritable bowel syndrome, no organic disease of the GI tract, and no history of milk intolerance. Lactose malabsorption was diagnosed in 157 patients (68.2%). In 48 (43.6%) of the 110 patients who complied with the diet symptoms subsided, in 43 they were somewhat reduced and in 17 they remained unchanged. Symptoms never fully subsided in lactose malabsorbers non-compliant with the diet or in normal lactose absorbers who adhered to a lactose-free regimen. Partial improvement was observed in 20% of these subjects. No relation was demonstrated between pre-trial symptoms and the outcome of the diet. The occurrence of symptoms during the lactose breath test strongly suggested a favorable response to diet, but did not help in predicting whether symptoms would subside or be reduced. Conversely, their absence during the test was not associated with an acceptable negative predictive value. The high prevalence of lactose malabsorption in the patients under study suggests that in Italy IBS and lactose malabsorption are frequently associated. A test for diagnosing lactose malabsorption should always be included in the diagnostic workup for IBS and a long-term lactose-free regimen recommended if the test is positive.

Adult↗
PubMed1991

Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report.

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.

Acetates↗