Summary On the assumption that bacteria in the gut may be a cause of symptoms and/or complications of Crohn’s disease, various antibiotics are efficaciously employed in some affected patients. However, we do not know exactly why and how they are helpful. A possible explanation is that one or several bacterial species may have a primary role in the aetiology of Crohn’s disease, but this is not supported by the data in our possession. Another hypothesis is that intestinal bacteria may cause flare-up of the disorder, either by inducing intestinal lesions or by an interaction with the immune system, but we know today that specific pathogens can cause flares only in a minority of cases. On the contrary, there is considerable evidence that the intestinal microflora and its products may amplify and perpetuate inflammation in Crohn’s disease. Despite the fact that few controlled trials have been conducted, and have shown inconclusive results, antibiotics are widely employed for improving symptoms and for inducing remission of active phases. At present, a combination of metronidazole and ciprofloxacin, active against many enteric bacteria, has proved to be effective in the treatment of Crohn’s disease complications. This therapy also seems to be effective in acute flares as an alternative to, or in combination with, corticosteroids.

OBJECTIVE: We sought to determine whether psychosocial factors influence the course of ulcerative colitis, hypothesizing that high perceived stress among patients with inactive disease will increase the risk of subsequent exacerbation. METHODS: Sixty-two patients with known ulcerative colitis were enrolled into a prospective cohort study while in clinical remission. Their perceived stress, depressive symptoms, and stressful life events were followed, along with potential confounders, for up to 45 months; exacerbation status was monitored for up to 68 months. RESULTS: The 27 patients who experienced an exacerbation were compared with those who remained in remission. Having a score in the upper tertile on the long-term (past 2 yr) baseline Perceived Stress Questionnaire significantly increased the actuarial risk of exacerbation (hazards ratio = 2.8, 95% confidence interval 1.1–7.2). At any given study visit, high long-term stress tripled the risk of exacerbation during the next 8 months (risk for the three tertiles, 8.3%, 16.7%, and 26.2%, p = 0.02). Shorter sleep time, briefer remission, histological activity, and use of nonsteroidal antiinflammatory drugs, antibiotics, or oral contraceptives also increased the medium- and/or long-term risk of exacerbation, but adjustment for these variables did not eliminate the associations with stress. Exacerbation was not associated with stressful life events, depressive symptoms, short-term (past month) perceived stress, smoking, disease extent or duration, or severity of recent course. CONCLUSIONS: Short-term stress does not trigger exacerbation in ulcerative colitis, but long-term perceived stress increases the risk of exacerbation over a period of months to years.

Levenstein, S; Varvo, V; Scribano, ML; Berto, E; Milite, G; Andreoli, A; Luzi, C; Prantera, C Author Information

BACKGROUND AND AIMS:The use of antibiotics in the treatment of active Crohn's disease has recently increased on the assumption that enteral flora may play a role in the origin of symptoms and/or complications of Crohn's disease. The aim of this study was to evaluate retrospectively the efficacy of metronidazole and/or ciprofloxacin in the treatment of acute phases of Crohn's disease.METHODS:The clinical records of 233 inpatients seen at our clinic for active Crohn's disease and treated with metronidazole and/or ciprofloxacin (1 g daily each) during the period 1984-1996 were reviewed; the patients were divided into three groups according to antibiotic therapy. The primary criterion of success was the achievement of a complete or partial remission evaluated on the basis of the Simple Index; a secondary criterion of success was the efficacy of therapy on individual symptoms and signs.RESULTS:Similar rates of success were obtained with the three schemes of treatment: 70.6% with antibiotic combination, 72.8% with metronidazole, 69.0% with ciprofloxacin. The most frequent symptoms and signs such as diarrhoea, abdominal pain, fever, abdominal mass and abscesses improved in about 60% of patients in the three groups. Remission time after antibiotic treatment was about one year. Side effects requiring discontinuation of therapy occurred in about 20% of patients.CONCLUSIONS:Metronidazole and ciprofloxacin seem to be useful in treating active phases of Crohn's disease. These results strongly support the important role of faecal flora in causing Crohn's disease symptoms.

The aim of this study was to analyze the pattern of mortality among patients with ulcerative colitis (UC) and compare it with mortality in the general population of the same age and sex. All patients with UC admitted to one of the Inflammatory Bowel Disease Clinics in Rome, from January 1970 to December 31, 1989 were enrolled. Vital status was ascertained through the Registry Office of the last municipality of residence as of July 1, 1990. Cause of death was ascertained through record linkage with the national or regional mortality file and coded using the ninth revision of the International Classification of Diseases. Standardized Mortality Ratios (SMRs) were computed to compare mortality among UC patients with mortality in the general population of the same age and sex. Out of a total of 508 UC patients admitted during the study period, 27 deaths were observed, compared with 27.6 expected (SMR = 98). After excluding prevalent cases, an excess risk of death was observed among newly diagnosed cases in the first year after diagnosis (SMR = 644; p < 0.001); ulcerative colitis was the main reason for this excess mortality. Mortality for other diseases was close to that expected. In conclusion, ulcerative colitis impairs life expectancy in the first year after diagnosis, while no excess mortality seems to be present afterwards.

On the assumption that bacteria in the gut may be a cause of symptoms and/or complications of Crohn's disease, various antibiotics are efficaciously employed in some affected patients. However, we do not know exactly why and how they are helpful. A possible explanation is that one or several bacterial species may have a primary role in the aetiology of Crohn's disease, but this is not supported by the data in our possession. Another hypothesis is that intestinal bacteria may cause flare-up of the disorder, either by inducing intestinal lesions or by an interaction with the immune system, but we know today that specific pathogens can cause flares only in a minority of cases. On the contrary, there is considerable evidence that the intestinal microflora and its products may amplify and perpetuate inflammation in Crohn's disease. Despite the fact that few controlled trials have been conducted, and have shown inconclusive results, antibiotics are widely employed for improving symptoms and for inducing remission of active phases. At present, a combination of metronidazole and ciprofloxacin, active against many enteric bacteria, has proved to be effective in the treatment of Crohn's disease complications. This therapy also seems to be effective in acute flares as an alternative to, or in combination with, corticosteroids.

We investigated psychologic influences on duodenal ulcer by examining the effect of personality, stress, and mood, measured at diagnosis, on subsequent ulcer healing. Stressful life events, psychopathology (assessed using the Minnesota Multiphasic Personality Inventory), anxiety, depression, smoking, alcohol consumption, nonsteroidal antiinflammatory drug use, and serum pepsinogen I levels were determined immediately after endoscopy showed duodenal ulcer craters in 70 patients with recent onset of symptoms. Endoscopy was repeated following 6 weeks of ranitidine therapy. Six ulcers (8.6%) persisted, and the duodenum remained inflamed in an additional five cases, for a total of 16% with incomplete healing. The only baseline characteristic significantly associated with poor healing was anxiety (p = 0.03 for ulcer persistence, p = 0.02 for incomplete healing). Being in the highest anxiety tertile was associated with a more than fourfold elevation in the risk of incomplete healing (p = 0.02). The association between anxiety and poor healing was not changed by modification of the anxiety score to eliminate gastrointestinal symptom items or by adjustment for serum pepsinogen, sex, or cigarette smoking. Anxiety inhibits the healing of duodenal ulcers treated with adequate antisecretory therapy.

Seventy-five patients with recent-onset dyspepsia and endoscopically visible duodenal ulcer underwent psychological evaluation. Following ranitidine treatment, they were reinterviewed periodically for 12 to 76 months (mean 38.6). Ulcer symptoms were present during a mean of 14.9% of follow-up months. Patients did significantly worse if they had a low-status occupation, low education, depression, stressful life events, or abnormal Minnesota Multiphasic Personality Inventory at baseline. Of patients recalling premorbid life stress, those with a normal MMPI had a particularly benign course, whereas those with an abnormal MMPI did particularly poorly (6% versus 29% of months symptomatic: p < 0.04). Age, gender, smoking, drinking, antiinflammatory drugs, pepsinogen, Helicobacter pylori titers, and initial healing had no prognostic effect. Low socioeconomic status, life stress, depression, and psychopathology each predict a relatively poor symptom outcome for duodenal ulcer treated with antisecretory therapy, but psychologically stable individuals who develop an ulcer under stress have an excellent long-term prognosis.

Objectives: Bacteria in the gut lumen may play a role in the etiology and/or the symptoms of Crohn's disease (CD). Although various antibacterial drugs have been employed in clinical practice, few controlled trials have been conducted, and those had conflicting results. The aim of this study was to investigate the efficacy and the safety of a combination of metronidazole and ciprofloxacin, compared with methylprednisolone, in treating 41 consecutive patients with active CD. Methods: Eligible patients, 13 men and 28 women, mean age 38 yr, were randomly allocated to receive, for 12 wk, ciprofloxacin 500 mg twice daily plus metronidazole 250 mg four times daily or methylprednisolone 0.7-1 mg/kg/day, with variable tapering to 40 mg, followed by tapering of 4 mg weekly. Results: Ten of the 22 antibiotic patients (45.5%) and 12 of the 19 steroid patients (63 %) obtained clinical remission (Crohn's Disease Activity Index less than or equal to 150) at the end of the 12-wk study (p = NS). Five patients on antibiotics (22.7%) and five patients on steroids (26.3%) were considered treatment failures because of deterioration or persistent symptoms. Six patients receiving antibiotics (27.3%) and two on steroids (10.6%) were withdrawn from the trial because of side effects. One patient on antibiotics was not compliant. Conclusions: metronidazole and ciprofloxacin could be an alternative to steroids in treating the acute phase of CD.

BACKGROUND/AIMS:Recurrence of lesions of Crohn's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93% of cases. This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery.METHODS:In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five-point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was performed.RESULTS:Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (chi 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesalamine group and 56% in the placebo group (chi 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1.CONCLUSIONS:This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's disease.

To clarify whether and how psychologic factors might contribute to peptic ulcer, in this study we addressed the relations between psychologic characteristics and known biologic risk factors among ulcer patients. In 75 patients with recent-onset, symptomatic duodenal ulcer, an index of three potential psychologic risk factors (stressful life events, abnormal Minnesota Multiphasic Personality Inventory, mood disturbance) was examined in relation to historical risk factors (sex, age, seasonality, family history, smoking, alcohol use, coffee consumption, nonsteroidal antiinflammatory drug use), and to blood type, serum pepsinogen I, and Helicobacter pylori antibody titers. The more risk factors in a patient's history, the less likely he or she was to have psychopathology or stress (r = -0.45, p = 0.0007). The mean number of conventional risk factors was 2.7 in patients with all three psychologic risk factors and 4.4 in patients with none; conversely, the mean number of psychologic factors was 0.9 among patients with five or more biologic risk factors and 2.1 among patients with fewer than three risk factors. This negative association was strongest among patients with no previous ulcer history. The psychologic factors also tended to vary inversely with H. pylori antibody titers but not with blood type O or pepsinogen. Duodenal ulcer patients who are atypical in terms of their conventional risk factors are likely to be emotionally fragile, under stress, or both, especially at the time of their first ulcer symptoms. A clinician diagnosing an ulcer in an individual who does not match the usual patient profile should be on the lookout for psychologic factors.

OBJECTIVES:It is not known whether any link exists between life stress and disease activity in ulcerative colitis; attempts to demonstrate one have been complicated by recall bias, distressing psychological consequences of disease, psychogenic symptom exaggeration, and an irritable bowel component of inflammatory bowel disease symptoms. We therefore studied the relationship between psychological measures and two different aspects of ulcerative colitis activity.METHODS:The relation of perceived stress, depression, state anxiety, trait anxiety, and life events with endoscopic appearance of the rectal mucosa was studied "blind" in 46 asymptomatic outpatients with known ulcerative colitis. The same measures were then examined in relation to subjective activity, comparing the group in clinical remission with 32 ulcerative colitis outpatients who reported symptoms.RESULTS:Among asymptomatic patients, the level of stress over the past 2 yr on the General Perceived Stress Questionnaire was higher in the 11 with mucosal abnormalities than in the 35 with a normal rectal mucosa (p = 0.004). Among the entire population, symptomatic patients were more likely to recall major life events in the previous 6 months than the asymptomatic group (p = .02). Adjustment for smoking and for duration of remission did not substantially alter these findings.CONCLUSIONS:Life stress is associated with both objective and subjective aspects of activity in ulcerative colitis. Although the association of life events with reported symptoms may be subject to recall bias, the association of perceived stress with rectal mucosal abnormalities in asymptomatic patients is strongly suggestive of a true link between psychological factors and ulcerative colitis activity.

A 30-question Perceived Stress Questionnaire (PSQ) was validated, in Italian and English, among 230 subjects. Test-retest reliability was 0.82 for the General (past year or two) PSQ, while monthly Recent (past month) PSQs varied by a mean factor of 1.9 over 6 months; coefficient alpha > 0.9. General and/or Recent PSQ scores were associated with trait anxiety (r = 0.75), Cohen's Perceived Stress Scale (r = 0.73), depression (r = 0.56), self-rated stress (r = 0.56), and stressful life events (p < 0.05). The General PSQ was higher in in-patients than in out-patients (p < 0.05); both forms were correlated with a somatic complaints scale in a non-patient population (r > 0.5), and were higher, among 27 asymptomatic ulcerative colitis patients, in the seven who had rectal inflammation than in those with normal proctoscopy (p = 0.03). Factor analysis yielded seven factors, of which those reflecting interpersonal conflict and tension were significantly associated with health outcomes. The Perceived Stress Questionnaire may be a valuable addition to the armamentarium of psychosomatic researchers.

A randomized, placebo-controlled multicenter trial was conducted to evaluate the efficacy and safety of a delayed-release formulation of 5-aminosalicylic acid (5-ASA) (Asacol; Giuliani & Bracco, Milan, Italy) for prevention of clinical relapse in 125 patients with inactive Crohn's disease. Patients in remission [Crohn's Disease Activity Index (CDAI) less than 150] between 3 months and 2 years were randomly allocated to receive either 800 mg 5-ASA three times daily (n = 64) or placebo (n = 61) for up to 12 months or until relapse of symptoms. Relapse was defined by a CDAI greater than 150, with a minimum increase of 100 points over the baseline value. The cumulative relapse rates were 12% in the 5-ASA group and 22% in the placebo group at 3 months [95% confidence interval (CI) for the difference, -4 to 24]; 28% and 41%, respectively, at 6 months (95% CI, -4 to 30); and 34% and 55%, respectively, at 12 months (95% CI, 3-39; P = 0.02, log rank test). Significant decrease in the risk of relapse was found in patients with ileitis, in those with previous bowel resection and, in those with prolonged prestudy remission. Eight patients (5 on 5-ASA, 3 on placebo) withdrew from the study because of adverse reactions, but no major clinical or laboratory adverse effect was observed. It is concluded that oral 5-ASA coated with Eudragit S (Rohn Pharma GmbH, Wieterstadt, Germany), 2.4 g daily, is safe and seems superior to placebo in preventing or delaying clinical relapse in Crohn's disease, especially in milder cases and in ileal disease.

Some recent studies have proposed a subclassification of Crohn's Disease (CD) on the basis of the pathological picture. In fact CD is a heterogeneous disease, and it is probable that the clinical and pathological disorders we now consider as CD may in the near future be divided into several conditions, probably with different causes as well, including environmental factors. Clinical and pathological similarities to mycobacterial disease, along with recent isolation of mycobacteria from tissues taken from patients with CD, and the recognition of atypical mycobacteria as causative agents of an enteritis pathologically similar to CD, all go to strengthen the hypothesis that these organisms are one of the above environmental factors. Researchers should therefore seek to identify and characterize this subgroup of CD patients who may have mycobacterial disease and to perform trials of antimycobacterial therapy. Analysis of the literature gives some suggestions for identifying this subgroup of patients: i) isolation of atypical mycobacteria from the tissues; ii) presence of high specific antibody levels and increase of same after antimycobacterial therapy; iii) presence of granulomas, and iv) strong suspicion of an environmental factor.

This study was designed to determine the individual fatty-acid pattern in plasma and in two adipose tissue sites of rats submitted to portacaval shunt (PCS) using the button technique. The animals were studied both in a fed state and after a 48-hour fast. Glucose, ketone bodies (KB), lactate and pyruvate levels were also measured. The results of the shunted animals were compared with pair-fed and freely fed control groups. In PCS rats, plasma free fatty-acid (FFA) levels were not significantly higher than in freely fed controls. beta-Hydroxybutyrate was significantly lower in PCS rats compared with both control groups. A 48-hour fast caused an elevation of plasma FFA and KB in all groups, but in PCS rats this increase was less pronounced. Lactate levels did not decrease during fasting in PCS rats, as they did in the control groups. PCS did not modify plasma FFA or the adipose tissue composition, neither in fed nor in fasted rats. We conclude that the PCS rats operated upon by using the button technique show mild modifications in lipid metabolism, affecting the fatty-acid composition neither in plasma FFA nor in adipose tissue.