Influence of the timing of administration of 300 mg ranitidine on 24-hour gastric pH in patients acute duodenal ulcer.

The 24-hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double-blind crossover trial involved 3 centres. Twenty-four-hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14-day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours-19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours-12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P less than 0.05). In contrast, during the whole night (19.00 hours-07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P less than 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy.

Fate of orally ingested enzymes in pancreatic insufficiency: comparison of two pancreatic enzyme preparations.

The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.

Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride.

BACKGROUND: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. AIM: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. METHODS: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below - 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 +/- 5.6% (n=29) and 3.2 +/- 3.8% (n=31) in the calcium-vitamin D-fluoride and calcium-vitamin D-placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit.

Amantadine for chronic hepatitis C: pilot study in 14 patients.

BACKGROUND: Amantadine, a widely available antiviral drug, has been previously reported to be effective in patients with chronic hepatitis C who failed to respond to interferon-alpha therapy. Nevertheless, its efficacy has not been fully studied, particularly in naive patients. OBJECTIVE AND DESIGN: We conducted a pilot study to determine the efficacy and the safety of amantadine as initial therapy in patients with chronic hepatitis C. METHODS AND PARTICIPANTS: Fourteen consecutive patients (mean age, 40 years; M/F ratio, 9/5) with chronic hepatitis C, elevated alanine aminotransferase (ALT) and without cirrhosis were treated with a 6-month course of amantadine, 100 mg orally twice daily. Main outcome measures were ALT concentrations and serum hepatitis C virus-RNA (HCV-RNA) levels at the end of therapy. RESULTS: All adverse events were mild or moderate and were not treatment limiting. At the end of treatment, all patients had detectable serum HCV-RNA and only one patient had a normal ALT level. The serum HCV-RNA median level and the ALT median level were not significantly different at the end of treatment as compared to baseline levels. CONCLUSIONS: Our results show that amantadine alone cannot be recommended as an alternative therapy in patients with chronic hepatitis C.

Placebo-controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives (GETAID).

OBJECTIVE: Endoscopic postoperative recurrences occur early after 'curative' surgery for Crohn's disease. Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn's disease. The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after 'curative' resection for ileal, colonic or ileocolonic Crohn's disease. We conducted a multicentre double-blind controlled trial comparing Claversal (1g tid) with placebo, starting within 15 days after surgery. The macroscopic normality of the two anastomotic segments was assessed at surgery. Patients were clinically and biologically evaluated twice (6-week interval), and colonoscopy was performed at 12 weeks. Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four-grade score. RESULTS: Between May 1989 and May 1991 12 centres included 126 patients, 70 women and 56 men, aged 33 +/- 12 years (range 16-70) in the study. Disease locations were ileal, colonic and ileocolonic in 45, 6 and 49%, respectively. Claversal and placebo groups were similar at inclusion, except for ESR (37 +/- 26 vs. 27 +/- 23 mm/h in the Claversal and placebo groups, respectively; P < 0.05). Nine patients were withdrawn from the study. Adverse reactions occurred only in six patients. Five patients were excluded for protocol violation. Finally, 106 patients could be evaluated at 12 weeks (55 Claversal and 51 placebo). An endoscopic relapse was observed in 50% and 63% of the Claversal and placebo groups, respectively (P = 0.16), with a similar grade distribution. Claversal was well tolerated. CONCLUSIONS: Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn's disease. There was a slight trend towards greater efficacy of Claversal; it could be worthwhile trying higher dosages and/or 5-ASA compounds with different intestinal release profiles.

Pituitary function after selective adenomectomy for Cushing's disease.

This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F:8 M, mean age 33.6 years) undergoing transsphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy; repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 15% and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery.

[Presence of anti-Yersinia pseudotuberculosis agglutinins during a flare-up of ileal Crohn's disease. Apropos of 3 cases]. / Présence d'agglutinines anti-"Yersinia pseudotuberculosis" lors d'une poussée de maladie de Crohn iléale. A propos de trois cas.

Sera of 19 patients who had been admitted with an attack of Crohn's disease were tested for agglutinins against Yersinia. The localization and the extent of the disease were highly variable. Only three patients with a subacute obstruction syndrome due to ileitis had a high circulating antibody titer directed against Yersinia pseudotuberculosis type IV (greater than or equal to 1/500). Culture of the stools did not isolate any pathogenic organisms; particularly, Yersinia pseudotuberculosis failed to grow even though specific methods were used. In one case, a strain of Yersinia enterocolitica was identified which did not prove to be pathogenic. Under corticoid and antibiotic treatment, the course was favorable in every patient. Agglutinin titers progressively decreased and serology became negative within seven to ten months. A patient had a relapse of ileitis but agglutinin titers failed to rise again. In these three patients with unquestionable Crohn's disease, it may be concluded that there was serological evidence of superinfection with Yersinia pseudotuberculosis type IV. This organism might be responsible for acute ileitis mimicking an attack of Crohn's disease.

[Sensitivity of gastric parietal cells to histamine after administration of enprostil and ranitidine during 4 weeks in healthy subjects]. / Sensibilité des cellules pariétales gastriques à l'histamine après administration pendant 4 semaines d'enprostil et de ranitidine chez le sujet sain.

Parietal cell sensitivity is increased in patients with active duodenal ulcer. It has been shown to increase in healthy volunteers after a 4-week treatment with H2-receptor blockers. Metaanalyses of therapeutic trials have indicated that time to first relapse was longer after ulcer healing with prostaglandins (PG) than after healing with H2-receptor blockers, which might be due to a different effect of the two treatments on parietal cell sensitivity. OBJECTIVES--To study, in healthy volunteers, basal gastric acid secretion, acid secretory responses and parietal cell sensitivity to histamine before and after a 4-week treatment with enprostil (E) and ranitidine (R). METHODS--This was a randomized double-blind double-dummy crossover study. Twelve male healthy volunteers (22-44 years) were randomly assigned to receive a 4-week treatment with either E (35 micrograms bid) or R (150 mg bid). After a 2-month washout period, they were crossed to the alternate treatment. Basal acid output (BAO), acid secretory responses to low-dose histamine infusion (histamine dihydrochloride 2.5 micrograms/kg/h) (LDAO), to a high-dose histamine infusion (25 micrograms/kg/h) (HDAO) and parietal cell sensitivity (PCS = LDAO/HDAO x 100) were measured 24 hours before the first administration and 72 hours after the last administration of each medication. RESULTS--All secretory parameters were similar before treatment with E and R. As compared to pretreatment values: a) HDAO tended to increase after both treatments (NS); b) LDAO (m +/- sem) slightly increased after R (18.4 +/- 2.6 vs 13.9 +/- 3.3 mEq) (NS) but not after E (12.5 +/- 1.8 vs 13.2 +/- 1.9 mEq); c) PCS (m +/- sem) was unchanged after R (36 +/- 4 vs 33 +/- 6) but decreased after R (30 +/- 6 vs 36 +/- 0.5; P < 0.02). When secretory parameters after treatment with R and treatment with E were compared, the difference was significant for LDAO (P < 0.02) and PCS (P < 0.05). CONCLUSIONS--If also found in patients with duodenal ulcer disease, these results might, at least partly, explain the lesser propensity of the ulcers to relapse early after healing with PG than after healing with H2-receptor blockers. However enprostil has been with-drawn from the market and it is now well established that one factor influencing the relapse rate is the efficiency of the treatment given to achieve ulcer healing in eradicating Helicobacter pylori. Consequently, the interest of our results is presently mostly physiological.

[Toxic megacolon with colonic perforation complicating Campylobacter jejuni ileo-colitis]. / Colectasie avec perforation colique compliquant une iléo-colite à Campylobacter jejuni.

Campylobacter jejuni is an enteropathogen with invasive ability which may be responsible for acute colitis. We report the case of a 38-year-old woman who was hospitalized for severe acute colitis. Stool specimen examination revealed Campylobacter jejuni. A laparotomy was performed due to clinical deterioration and toxic megacolon. Colic perforations were observed. The examination of the colectomy specimen revealed ulcerative pancolitis. This is the first published case of Campylobacter jejuni infection complicated by toxic megacolon and perforation.

[Colonic lymphoma simulating cryptogenetic colitis associated with common variable hypogammaglobulinemia]. / Lymphome colique simulant une colite cryptogénétique et associé à une hypogammaglobulinémie commune variable.

We report the case of a 72 year-old woman with late-onset common variable immunoglobulin deficiency who was hospitalized for diarrhoea and fever. Colonoscopy showed aphtoïd and deep ulcerations in the rectum, the sigmoid and transverse colon, suggestive of Crohn's disease. Histologic and immunohistochemical study revealed a low grade B cell mucosa-associated lymphoid tissue (MALT) lymphoma. This is an unusual presentation for colonic lymphoma, and the second case of colonic lymphoma associated with late-onset common variable immunoglobulin deficiency.

[Pathogenesis of cholelithiasis in chronic pancreatitis]. / Pathogénie de la lithiase biliaire au cours de la pancréatite chronique.

The prevalence and the pathogenesis of gallstones in patients with chronic pancreatitis have never been studied prospectively. The aim of this study was to evaluate prospectively the prevalence of gallstones with ultrasonography and to look for markers of pigment or cholesterol stone formation in gallbladder bile. Ultrasonography was performed in 39 patients and detected gallstones in 7 patients and sludge in 3. Common bile duct and intrahepatic bile duct dilatation were observed in 16 and 13 patients, respectively. Liver biopsies were obtained in 31 patients and cirrhosis was found in 4. There were calcium bilirubinate granules in 7 of the 27 bile samples examined. Cholesterol crystals were not found in any case. The nucleation time (median: 21 days) was higher in patients with chronic pancreatitis than in patients with cholesterol stones (median: 2 days) (P < 0.001) but was not different from nucleation time in patients either free of stones (median: 21 days) or with pigment stones (median: 21 days). The cholesterol saturation index was similar in patients with chronic pancreatitis and in controls. The 2 patients with chronic pancreatitis who underwent cholecystectomy had pigment stones. Calcium bilirubinate granules were more frequent in patients with intrahepatic bile ducts dilatation (P < 0.02). In conclusion, this study demonstrates a high prevalence of cholelithiasis in chronic pancreatitis patients. Pigment stone formation could be favored by cholestasis.

[Clinical course of symptomatic duodeno-jejunal Crohn's disease]. / Aspects cliniques et évolutifs de la maladie de Crohn duodéno-jéjunale symptomatique.

AIMS: To describe retrospectively the characteristics of inaugural, symptomatic Crohn's disease of the upper gastrointestinal tract. METHODS: Eighteen patients (12 male and 6 female) with symptomatic Crohn's disease of the upper intestinal tract and without previous distal localisation were studied. RESULTS: Mean age of patients at diagnosis (21.3 years) was less than that usually reported in Crohn's disease. The time elapsed from first symptoms to diagnosis (mean = 29.8 months) was remarkably long for some patients, mainly as a result of an unusual clinical presentation. Abdominal pain and weight loss were the most common presenting features; diarrhea was rarely the main symptom. Persistent anorexia and weight loss without digestive symptoms had led to a diagnosis of anorexia nervosa in 4 patients. Zollinger-Ellison syndrome was the initial diagnosis in 3 other patients. Sixteen patients were followed during at least 2 years. All were treated with steroids for their first attack and 75 % required immunosuppressive therapy for steroid dependence. At the end of follow-up, 6 patients only were in remission without treatment or under mesalamine. CONCLUSION: Crohn's disease with initial symptomatic lesions of the upper gastrointestinal tract occurs mainly in young male patients. The clinical presentation may be very unusual, leading to misdiagnosis. The clinical course is close to that of diffuse jejunoileitis.

[Collagenous colitis, IgA deficiency, Basedow's disease and atrophic gastritis]. / Colite collagène, déficit en IgA, maladie de Basedow et gastrite atrophique.

In a 37-year-old woman with chronic watery diarrhea of three years duration, the diagnostic of collagenous colitis was established by optical and ultrastructural examination of rectal and colonic biopsies. No other cause of diarrhea could be found. Moreover, this patient had also selective IgA deficiency, Grave's disease and chronic atrophic gastritis of auto-immune type. Sequential treatments with loperamide, cholestyramine and antibiotics did not modified diarrhea which improved with salazosulfapyridine and betamethasone enemas. These observations suggest that collagenous colitis might be a part of the spectrum of enteropathies associated with immunoglobulin deficiencies.

[Bronchogenic cyst of the right hemidiaphragm mimicking a hydatic cyst of the liver].

Ectopic subdiaphragmatic development of a bronchogenic cyst is rare. We report the case of a 28-year-old woman with a symptomatic bronchogenic cyst of the right hemidiaphragm simulating a hydatic cyst of the liver on ultrasonography and CT scan. Diagnosis of a diaphragmatic lesion was made during laparotomy, and complete resection was successful. Final diagnosis was done on pathology.

[Treatment of duodenal ulcer outbreak with omeprazole. Results of a multicenter non-controlled study]. / Traitement de l'ulcère duodénal en poussée par l'oméprazole. Résultats d'une étude non contrôlée multicentrique.

Sixty-one patients with symptomatic endoscopically confirmed duodenal ulcer, 5 mm or more in diameter, were treated with omeprazole 30 mg once daily in the morning for 4 weeks. Complete ulcer healing was assessed by endoscopy performed after 15 and, if necessary, 29 days of treatment. The healing rate as 83 p. 100 (49/59 patients) after 2 weeks, and 98 p. 100 (58/59 patients) after 4 weeks. Only 5 patients remained symptomatic on day 15. Fifty-six patients did not take any antacid during the course of treatment. There were few adverse effects. No clinically significant changes in laboratory parameters were observed. These results confirm: the remarkable efficiency of omeprazole in short-term treatment of duodenal ulcer, the good tolerance to this drug, at least in short duration treatment.

[Functional, morphological and biochemical study of the jejunal mucosa in cryptogenetic colitis]. / Etude fonctionnelle, morphologique et biochimique de la muqueuse jéjunale dans les colites cryptogénétiques.

The function of the jejunum has been assessed in patients with ulcerative colitis (n = 23) and Crohn's disease of the colon (n = 20) by measurement of serum folate levels, oral folic acid and D-xylose absorption. Forty-six normal subjects served as controls. The mean serum folate level was 4.5 +/- 2.0 ng/ml in patients with the disease and 7.8 +/- 1.7 ng/ml in controls (p less than 0.001) and was similarly decreased in both ulcerative colitis and Crohn's disease patients. It was lower in patients under sulphasalazine therapy (n = 15) than in those untreated: 3.5 +/- 1.5 vs. 4.8 +/- 2.1 ng/ml (p less than 0.05). Serum folate correlated with disease activity in the latter only. The peak serum folate obtained during the oral absorption test was decreased in patients: 38.9 +/- 12.9 vs. 60.8 +/- 19.3 ng/ml in controls (p less than 0.001); this decrease was similar in ulcerative colitis and Crohn's disease, in treated and untreated patients and was independent of disease activity. Basal serum folate did not correlate with peak serum folate in any patient group. D-xylose absorption was normal in every case. Jejunal biopsies were performed in 23 patients, 13 of whom had folic acid malabsorption (13 with ulcerative colitis, 10 with Crohn's disease of the colon). The crypt height/villus height ratio was abnormal (greater than 0.6) in only 2 patients and borderline in 9 others. The fragility of enterocyte brush-borders and lysosomes, as assessed by biochemical methods, was normal in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevention of duodenal ulcer recurrence. A new prospect]. / Prévention de la récidive de l'ulcère duodénal. Une nouvelle perspective.

Prevention of recurrence is now the main therapeutic problem in the management of duodenal ulcer disease. It has been shown that in the absence of maintenance treatment the mean recurrence rate within 6 to 12 months from healing obtained with drugs other than H2-receptor antagonists (H2A) is lower than when healing is obtained with H2A. Possible reasons for this discrepancy are examined. When the recurrence rates observed with each of the non-H2A drugs were compared individually with those observed with H2A, the only important and constant difference was in favour of colloidal bismuth subcitrate (CBS). This beneficial effect of CBS is due to its bactericidal action on Helicobacter pylori. Unlike healing, prevention of recurrent ulcer is primarily, if not exclusively, related to eradication of this organism. Although the ideal treatment providing both healing of duodenal ulcers and eradication of Helicobacter pylori has not yet been determined (CBS administered alone eradicates this organism in only 10 to 25 percent of cases), it will soon be possible to modify dramatically the natural course of duodenal ulcer disease and even to obtain its cure.

[Gastroesophageal reflux (II). Major medical therapeutics: efficacy and risks]. / Reflux gastro-oesophagien (II). Les thérapeutiques médicales majeures: efficacité et risques.

REFERENCE DATA FOR THE THERAPEUTIC MANAGEMENT OF GASTROESOPHAGEAL REFLUX (GOR): The natural history of the disease; the short- and long-term efficiency of the various therapies and their potential risks; patient-related factors (age, associated disorders, personal preference, duration and severity of his reflux disease). First line therapy will be medical in all cases. POTENTIAL CANDIDATES FOR SURGERY: Only patients with proven GOR, with or without esophagitis but who have required proton-pump inhibitors (PPI) are potential candidates for surgery; if their esophagitis is not healed after a 8-week PPI regimen, especially, if they remain symptomatic; if they relapse shortly after treatment withdrawal and require either frequent intermittent courses or long-term continuous treatment with PPI; moreover if they relapse while continuously taking PPI at usual dosage. LONG-TERM TREATMENT WITH PPI: It looks safe. However there still is some concern about the complete safety of extremely prolonged treatments started in young patients.

[Gastroesophageal reflux (II). Surgical interventions: results and indications]. / Reflux gastro-oesophagien (II). Les interventions chirurgicales: résultats et indications.

ANTIREFLUX SURGERY: Peri and postoperative morbidity is higher with Nissen fundoplication than with a 180 degrees posterior fundoplasty (Toupet procedure) which carries the risk of a compromised result with time. Although a 270 degrees posterior gastric valve may be the best technique, the surgeon's skill looks more important than the procedure used, especially for laparoscopic surgery. Its advantages include reduced postoperative pain, shorter hospital stay and convalescent time. INDICATIONS FOR SURGERY: Surgery must only be entertained in patients with severe GOR disease, especially those who require continuous PPI treatment. Excluding cases of esophagitis with deep ulcers and/or stenosis, severity criteria to be taken into account are mainly symptomatic and not anatomical. Age is an important decision-making factor. IN CLINICAL PRACTICE: Patients over 60 years of age or with any surgical risk and patients with associated severe motor disorders such as sclerodermia should be given drug therapy unless high-dose PPI are unsuccessful. Conversely, laparoscopic surgery performed by a skilled surgeon should be preferred in younger subjects, especially under 40. In the intermediate age range, patients should be informed about the advantages and drawbacks of the various methods as patient participation is essential in the decision making process.

[Dermatitis herpetiformis (author's transl)]. / Dermatite herpétiforme. A propos de 9 cas.

Detailed investigations of 9 patients with dermatitis herpetiformis are presented. In all cases cutaneous lesions were controlled by dapsone alone or by dapsone and gluten free diet. Granular IgA deposits were found in 7 patients, linear IgA deposits in one, and C3 component of complement in one. 3 patients out of 8 tested, carried the specific HLA-B8 antigen. Despite an extensive investigation, no malabsorption was detected. Jejunal biopsies were performed in 8 cases. Jejunal villous flattening was observed in one patient. It improved after a 2 months gluten free diet on subsequent jejunal biopsies. D. H. seems peculiar in France as compared with case reports from other countries: low prevalence of gluten sensitive enteropathy; rare occurrence of the specific HLA-B8 antigen; incidence of D. H. seems to be low in France. It is noticeable that french incidence of coeliac disease is low as well. This suggests a genetic difference in the investigated population (low prevalence of HLA-B8 antigen) and/or different alimentary habits, particularly a low dietary gluten amount.