The treatment of functional dyspepsia with red pepper.

AIM: : To decrease the intensity of dyspeptic symptoms by impairing the visceral nociceptive C-type fibres with capsaicin, contained in red pepper powder. METHODS: : The study was performed on 30 patients with functional dyspepsia and without gastro-oesophageal reflux disease and irritable bowel syndrome. After a 2-week washout period, 15 patients received, before meals randomly and in a double-blind manner, 2.5 g/day of red pepper powder for 5 weeks, and 15 patients received placebo. A diary sheet was given to each patient to record, each day, the scores of individual and overall symptom intensity, which subsequently were averaged weekly and over the entire treatment duration. RESULTS: : The overall symptom score and the epigastric pain, fullness and nausea scores of the red pepper group were significantly lower than those of the placebo group, starting from the third week of treatment. The decrease reached about 60% at the end of treatment in the red pepper group, whilst placebo scores decreased by less than 30%. CONCLUSIONS: : Red pepper was more effective than placebo in decreasing the intensity of dyspeptic symptoms, probably through a desensitization of gastric nociceptive C-fibres induced by its content of capsaicin. It could represent a potential therapy for functional dyspepsia.

Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial.

BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.

Bone turnover in short-term and long-term home parenteral nutrition for benign disease.

6 mo afterward. Long-HPN was assessed only at baseline. In short-HPN, there was a hyperkinetic turnover at baseline. At follow-up, OC was similar to baseline, whereas cross-links, urinary calcium and magnesium decreased (P < 0.03), and parathyroid hormone increased (P < 0.001). The variation of urinary calcium correlated with that of cross-links (r = 0.73, P < 0.04). In long-HPN, OC was low or low-normal in almost all the patients, and cross-links were normal. Mean OC was lower than that of short-HPN both at baseline (P < 0. 003) and at follow-up (P < 0.002). The results suggest that in the early period of HPN bone metabolism improved from a hyperkinetic turnover to a positive balance. A low bone-formation rate appeared to be a characteristic feature of long-term HPN.

Oral rehydration solution containing rice maltodextrins in patients with total colectomy and high intestinal output.

Oral rehydration solutions containing rice maltodextrins (R-ORS) have been reported to be more effective than glucose-based ORS in reducing intestinal losses in infectious diarrhea. To evaluate the effect of R-ORS in patients with total colectomy and high intestinal output, a perspective open noncontrolled study was performed on 13 adult patients who consumed 1 l/day of R-ORS for 7 days. Body weight, daily ileal and urinary output, serum electrolytes, aldosterone and renin activity were measured the day before (day 0) and on the last day of the study (day 7). Net changes (mean +/- SE) from day 0-7 showed an increase of urine Na (40 +/- 16 mmol/day, p < 0.04) and K (24 +/- 8 mmol/day, p < 0.02). Body weight increased in seven patients. Serum renin activity decreased (-0.60 +/- 0.26 ng/ml/min) in these patients but not in the six patients in whom body weight remained unchanged (0.19 +/- 0.07 ng/ml/min; p < 0.03). Ileal and urinary volume remained stable. In patients with high ileal output, R-ORS supplementation improved Na and K balance. The association of increased body weight with decreased serum renin concentrations suggests that a positive water balance also occurred.

Effect of a mineral water on gastric emptying of patients with idiopathic dyspepsia.

The antidyspeptic property of mineral waters has for many years been based on empirical data. In the present paper we evaluated the effects of one type of mineral water, Tettuccio water from Montecatini, on gastric emptying in patients with idiopathic dyspepsia. Fourteen subjects, eight patients with idiopathic dyspepsia and delayed gastric emptying at scintigraphy and six healthy subjects with normal gastric emptying were studied. The gastric emptying of mineral water was studied with a scintigraphic method and compared with that of tap water. In patients with idiopathic dyspepsia, gastric emptying of both waters was slower than in controls but the gastric emptying of mineral water was significantly faster than that of tap water, both in dyspeptic patients and in healthy subjects. In conclusion, this mineral water stimulates gastric emptying. Further studies are needed on the possible role of this water in the management of chronic idiopathic dyspepsia.

[Changes caused by mineral water on gastrointestinal motility in patients with chronic idiopathic dyspepsia]. / Modificazioni indotte da un'acqua minerale sulla motilità gastrointestinale di pazienti con dispepsia cronica idiopatica.

BACKGROUND: The antidyspeptic property of mineral waters has been based for ages on empirical data. In the present paper the effects of one of them (Tettuccio, Montecatini) on gastrointestinal motility of patients with dyspepsia has been evaluated. METHODS: The study was carried out on 24 patients with idiopathic dyspepsia and delayed gastric emptying at scintigraphy and 18 healthy subjects with normal gastric emptying. The gastric emptying of this mineral water was studied with a scintigraphic method in comparison with tap water, while its effects on gastroduodenal contractions were evaluated by of manometry. RESULTS: The gastric emptying of this mineral water was significantly faster than that of tap water, both in dyspeptic patients and in normals. Manometric examination showed that the administration of mineral water induced a brief decrease of phasic motor activity, followed by a progressive increase, which in some cases ended in an activity front of the Migrating Motor Complex. CONCLUSIONS: This mineral water has a stimulating effect on both gastric emptying and interdigestive cyclic motor activity of the gastroduodenal tract. Both these effects could be useful in the treatment of chronic idiopathic dyspepsia and impaired gut clearing.

Lipid peroxidation and antioxidant status in adults receiving lipid-based home parenteral nutrition.

BACKGROUND: Infusion of lipid emulsions rich in polyunsaturated fatty acids (PUFAs) may increase lipid peroxidation, which is counteracted mainly by superoxide dismutase (SOD) (a zinc-, copper-, and manganese-dependent enzyme), selenium-dependent glutathione peroxidase (Se-GSHPx), and alpha-tocopherol. OBJECTIVE: We investigated lipid peroxidation and antioxidant status in patients receiving home parenteral nutrition (HPN) providing variable amounts of a lipid emulsion rich in PUFAs, and alpha-tocopherol, zinc, copper, and manganese as recommended by the American Medical Association, and no selenium. DESIGN: Serum malondialdehyde, plasma alpha-tocopherol, selenium, Se-GSHPx, PUFAs, and red blood cell Se-GSHPx and SOD were evaluated in 12 patients and in 25 healthy control subjects. Malondialdehyde was also assessed in a group of 40 healthy control subjects. RESULTS: Patients had significantly higher concentrations of malondialdehyde and SOD and lower alpha-tocopherol concentrations and selenium nutritional status. Linear regression analysis showed that malondialdehyde was associated with the daily PUFA load (r=0.69, P< 0.03) and with plasma alpha-tocopherol (r=-0.59, P< 0.05), but stepwise multiple regression analysis confirmed only the association between malondialdehyde and alpha-tocopherol; plasma alpha-tocopherol was associated with the daily PUFA load (r=-0.65, P< 0.04) and with the duration of HPN (r=-0.74, P< 0.02). CONCLUSIONS: In HPN patients, the peroxidative stress due to lipid emulsions rich in PUFAs is counteracted primarily by alpha-tocopherol. The dosages of alpha-tocopherol, zinc, copper, and manganese recommended by the American Medical Association appear sufficient to sustain SOD activity but inadequate to maintain alpha-tocopherol nutritional status. HPN formulations should be supplemented with selenium.

Long-term efficacy of bismuth carbomer enemas in patients with treatment-resistant chronic pouchitis.

BACKGROUND: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease. AIM: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis. METHODS: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. RESULTS: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9-15) to 6 (4-15) (P < 0.002), and were continued on bismuth carbomer enemas administered every third night for 12 months. Patients were monitored clinically, sigmoidoscopically and histologically every 2 months for evidence of recurrence (increase > or = 2 in the clinical symptom portion of the PDAI). Six of 10 patients (60%) were able to maintain remission throughout the 12-month trial; 4/10 had an exacerbation, two of which occurred soon after discontinuing daily treatment. Serum bismuth levels were negligible in all patients and no side-effects were registered. CONCLUSIONS: Our findings suggest that bismuth carbomer enemas are safe and effective in achieving and maintaining remission in patients with treatment-resistant chronic pouchitis.

Retrograde colonic spread of a new mesalazine rectal enema in patients with distal ulcerative colitis.

BACKGROUND: Rectal treatment with mesalazine enemas is the first-line therapy for distal ulcerative colitis. In order to improve the benefits of rectal therapy, a new 60 mL 5-ASA rectal gel enema preparation has been developed using a device which excludes direct contact of the inert propellant gas with the active drug. The purpose of the present study was to assess by scintigraphy the colonic distribution of this new mesalazine rectal gel enema. METHODS: Twelve patients with active ulcerative colitis were administered 4 g of the mesalazine rectal enema labelled with 100 MBq technetium sulphur colloid (99mTc-SC). Anterior scans of the abdomen were acquired at intervals for 4 h. Scans were analysed to evaluate the extent of retrograde flow and homogeneity of distribution of the radiolabelled enema in the rectum, sigmoid, descending and transverse colon. In addition, plasma levels of 5-ASA and Ac-5-ASA were measured for 6 h. RESULTS: All patients retained the entire rectal gel throughout the course of the study without reporting adverse events. In 11 out of 12 patients (92%) the gel had spread homogeneously beyond the sigmoid colon and had reached the upper limit of disease in all cases. The maximum spread (splenic flexure) was observed in 6 out of 12 patients (50%) within the first 2 h. The systemic absorption of mesalazine and its metabolite Ac-5-ASA was low. CONCLUSIONS: The new mesalazine enema represents an adequate alternative and a further technological improvement in the topical treatment of distal ulcerative colitis.

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.

BACKGROUND: Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects. METHODS: We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes. RESULTS: Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7). CONCLUSIONS: In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients.

Fish oil has been recently proposed as a possible effective treatment in inflammatory bowel disease (IBD); however, a lot of annoying side effects (ie, belching, halitosis, diarrhea, etc) affect patient compliance. We carried out a study of patient tolerance in a group of Crohn's disease (CD) patients with a new fish oil derivative consisting of 500-mg capsules of eicosapentaenoic-docosahexaenoic (EPA 40%-DHA 20%), a free fatty acid mixture (Purepa), and we also evaluated its incorporation into phospholipids, both in plasma and in red cell membranes. Five groups of 10 CD patients in remission received nine Purepa capsules daily in four different preparations (A: uncoated, B: coated, pH 5.5; C: coated, pH 5.5, 60 min time release; D: coated, pH 6.9) and 12 x 1-g capsules daily of a triglyceride preparation (Max-EPA, EPA 18%-DHA 10%), respectively. We coated three of the four Purepa preparations in order to delay the release of contents in an attempt to minimize the side effects. After six weeks of treatment, the group taking Purepa capsules, coated, pH 5.5, 60 min time release (group C) showed the best incorporation of EPA and DHA in red blood cell phospholipid membranes (EPA from 0.2 to 4.4%, DHA from 3.7 to 6.3%), and no side effects were registered, whereas in all other groups side effects were experienced in 50% or more of subjects. This new preparation will make it possible to treat patients for long periods.

Short report: zinc sulphate supplementation corrects abnormal erythrocyte membrane long-chain fatty acid composition in patients with Crohn's disease.

Patients with Crohn's disease may become zinc-deficient and, in such patients, an altered metabolism of radiolabelled long-chain fatty acids has been reported. We have investigated the possible reversal by zinc supplementation of altered long-chain fatty acid profiles of red cells in Crohn's disease. Twenty patients with long-standing Crohn's disease in clinical remission received 200 mg of zinc sulphate daily for 6 weeks. Phospholipid fatty acid profiles of washed red cells were analysed before and after zinc treatment and compared to those of 20 unsupplemented healthy controls. Plasma zinc levels in Crohn's were 72 +/- 8 micrograms/dL before zinc treatment and increased to 114 +/- 10 micrograms/dl after the therapy. Prior to zinc supplementation, the percentage of palmitic, stearic and oleic acids was significantly higher in Crohn's disease, while linoleic, arachidonic and n-3 fatty acids were reduced in Crohn's disease compared to healthy controls. Zinc supplementation abolished these pre-treatment differences in red-cell long-chain fatty acid profiles but did not affect plasma fatty acid values. Further studies are needed to clarify whether these fatty acid changes can be related to the clinical course of the disease.

Spread and distribution of 5-ASA colonic foam and 5-ASA enema in patients with ulcerative colitis.

Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc]sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. The foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis.

Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas.

Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity.

Optimum dosage of 5-aminosalicylic acid as rectal enemas in patients with active ulcerative colitis.

5-Aminosalicylic acid (5-ASA), the active moiety of sulphasalazine (SASP), was given as a rectal enema to patients with mild to moderate distal ulcerative colitis to determine the minimum effective dosage. A double blind study was carried out using enemas containing 1, 2, or 4 g or 5-ASA or placebo for a one month treatment period. One hundred and thirteen patients with ulcerative colitis attending our outpatient clinic volunteered to participate. Clinical, sigmoidoscopic, and histological assessments were carried out at the beginning of the study and after 15 and 30 days of treatment. All patients who received 5-ASA enemas showed significantly better results than those who received a placebo enema (p less than 0.001) but no difference was detected among the patients receiving differing concentrations of 5-ASA. This study suggests that 1 g 5-ASA (in a 100 ml enema) is a sufficient dosage for patients with a mild to moderate attack of ulcerative colitis.

Role of rectal formulations: enemas.

Clinical experience with mesalazine enemas in the treatment of ulcerative colitis is reviewed. After rectal administration, plasma mesalazine levels remain low, and 15% of the administered dose is recovered in the urine. Enemas containing 2 and 4 g of mesalazine have been shown to be effective, safe, and well tolerated by patients with mild and moderate ulcerative colitis. Patients who cannot tolerate sulfasalazine and patients who do not respond to other treatments have been successfully treated with mesalazine enemas. Suppositories of mesalazine are more suitable for patients with disease confined to the distal region of the colon, whereas mesalazine enemas should be used in patients with more extensive disease. Mesalazine enemas have also been used for maintenance therapy in ulcerative colitis.

5-Aminosalicylic acid in patients with ulcerative colitis in remission: plasma levels after administration of a new rectal enema.

Plasma levels of total 5-aminosalicylic acid (5-ASA) were determined after a single administration of 2 g and 4 g 5-ASA enemas to 6 patients with ulcerative colitis. The mean plasma levels and AUC values confirmed that the active substance is poorly absorbed by rectal route.

5-Aminosalicylic acid as enemas or suppositories in distal ulcerative colitis?

Thirty-nine patients with documented active distal proctitis (less than 20 cm) received either 5-aminosalicylic acid (5-ASA) enemas (2 g in 100 ml) or suppositories 1 g b.i.d., in a controlled study. Twenty patients received enemas, while 19 patients received suppositories, for 30 days. No difference could be observed in terms of efficacy; however, it was the patients' opinion that treatment with suppositories was easier than that with enemas (p less than 0.01).