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Background: The etiology of Crohn's disease remains unknown. A putative mycobacterial cause of the disease is still controversial., Aims: To assess the mycobacterial hypothesis in Crohn's disease using a polymerase chain reaction technique., Patients and Methods: Nested polymerase chain reaction with primers on the 16S-rRNA coding region (16S-rDNA) and with primers specific both to the insertion sequences (IS) 900, and IS 901/902 were used to amplify Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum DNA in frozen endoscopic intestinal biopsies or surgical resection specimens from patients with Crohn's disease (n = 47: 25 endoscopic biopsies and 22 surgical resection samples, +/- lymph nodes), ulcerative colitis (n = 27), and non inflammatory bowel diseases (n = 20: colonic tumors and diverticulitis). Positive as well as negative controls were used throughout the study., Results: All strains of Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum tested were positive for both primer systems. Of the 94 biopsies tested, 5 (2 Crohn's disease, 1 ulcerative colitis and 2 controls) were positive with the 16S-rDNA primers but did not correspond to Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum. None of the specimens was positive with the IS primers., Conclusion: These results do not support the hypothesis that Mycobacterium paratuberculosis, or Mycobacterium avium subsp. silvaticum play a role in Crohn's disease.

We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.

Objectives: Depending its frequency, the association in the same subject of Crohn's disease and another pathology can be fortuitous or the expression of genetic or environmental interrelationships. The aim of our study was to identify among a series of patients with Crohn's disease preliminary data which would be suggestive of a significant association between Crohn's disease and other pathologies., Patients and Methods: Personal and familial histories were collected in 832 patients with Crohn's disease who were seen consecutively in the same hospital clinic from 1974 to 1994., Results: We found 4 cases (0.5%) of associated Crohn's disease-multiple sclerosis and Crohn's disease-rheumatoid purpura in the same patient. Each of the following genetic diseases was associated with Crohn's disease in one patient (0.1%): Charcot-Marie-Tooth disease, deuteroanopia, multiple exostosis, familial ichthyosis, periodic disease., Conclusion: We describe for the first time sporadic cases of associated Crohn's disease and another rare disease, Charcot-Marie-Tooth disease, familial ichthyosis and periodic disease. We suggest that there is a significant interrelationship between personal and familial histories of Crohn's disease and multiple sclerosis which should be verified in prospective studies.

Background & Aims: In Crohn's disease, smoking increases the risk for surgical procedures. The influence of smoking on the overall severity of the disease remains controversial. The purpose of the study was to examine the effects of smoking on the long-term course of Crohn's disease and the relationship between smoking and therapy., Methods: The medical charts of 400 consecutive patients whose smoking habits were specified by direct interview were reviewed., Results: Frequency and extent of excisional surgery were not significantly different in smokers and nonsmokers, but smokers required more glucocorticoids and immunosuppressive drugs. The effect of smoking on the need for immunosuppressive drugs was dose-dependent and was significant in women but not in men. For female smokers, the 10-year risk of immunosuppressive therapy was 52% +/- 11% compared with 24% +/- 10% for nonsmokers (P < 0.001). The risk of surgery increased only in patients who smoked and did not take immunosuppressive drugs. The surgical rate increased significantly during smoking in 19 patients who started smoking after diagnosis and decreased significantly in 34 patients who stopped compared with matched controls., Conclusions: Patients who smoke, particularly women and heavy smokers, run a high risk of developing severe disease. Immunosuppressive therapy neutralizes the influence of smoking on surgical rates.

Unlabelled: Artificial nutrition prior to bowel resection has not been evaluated fully. The aim of the present study was to assess the effects of preoperative artificial nutrition upon postoperative complications, length of resected bowel and relapses of Crohn disease., Results: Between 1990 and 1994, 108 consecutive patients underwent bowel resection for Crohn disease. Thirty nine patients had received exclusive enteral nutrition (n = 14) or parenteral nutrition (n = 25) for 19 +/- 10 days. Patients who had received artificial nutrition were more malnourished and had complicated Crohn disease (fistulae, abscesses) more often than patients operated without artificial nutrition. After 19 days of artificial nutrition, the nutritional state of patients was not significantly improved. Postoperative complication rate was higher in patients operated after artificial nutrition (33 vs. 16%; P = 0.03). Using multivariate prognosis analysis, the extent of colic resection was significantly associated with postoperative complications (P = 0.0003). Length of resected bowel and relapse rates were similar in patients with or without preoperative nutrition., Conclusion: Artificial nutrition prior to bowel resection for Crohn's disease is indicated in patients with the most severe form of the disease. A preoperative nutrition of 19 days does not seem to reduce postoperative complications nor the length of resected bowel.

The aim of this study was to look for seasonal fluctuations in the clinical course of Crohn's disease. Eighty-three patients residing in the Paris area were included in the study and they had all undergone continuous clinical monitoring throughout the first three years of the disease. During this period, the clinical activity of the disease was ranked monthly on a semi-qualitative scale ranging from 0 to 4. The dates of corticosteroid treatment and of resection surgery carried out during the first three years of the disease were also recorded. The mean clinical score varied significantly (P < 0.0001) for different months of the year, the three highest scores being recorded during the three months of Spring-time (April, May and June). The number of months of corticosteroid treatment differed significantly (P < 0.05) for the various seasons, the six highest values being reported during Spring and Summer months. The number of intestinal resections differed significantly (p < 0.05) during different seasons, the highest incidence again being reported during Spring. This study demonstrates seasonal variations in the clinical course of Crohn' disease in the Paris area, with a peak occurring in the Spring.

A postoperative handicap index designed to predict diarrhoea and malnutrition following bowel resection in patients with Crohn's disease is proposed. The index takes into account the location and extent of resection, and its value can be calculated from operative records. Retrospective (n = 218) and prospective (n = 68) series of patients were studied. Diarrhoea and malnutrition developed in 102 patients (47 per cent) and 13 patients (6 per cent) respectively in the retrospective series, and in 40 (59 per cent) and one (1 per cent) of those in the prospective series. The handicap index correlated with faecal weight and faecal fat in 112 patients tested. Positive and negative predictive values of an index score greater than 20 for the development of diarrhoea, and over 50 for the development of malnutrition, were 0.64 and 0.90, and 0.60 and 0.99 respectively in the retrospective series; values were 0.80 and 0.71, and 0.25 and 1.00 in the prospective series. The postoperative handicap index is a useful tool for predicting the functional consequences of bowel resection for Crohn's disease.

Corticosteroids are an efficient treatment for active Crohn's disease. The treatment has to be undertaken with a daily intake equivalent to 1 mg/kg per day of prednisolone for a 3 to 7 week period. Immunosuppressive agents are indicated in case of corticodependency or in case of large intestinal resection. Artificial nutrition (enteral or parenteral) is proposed in corticoresistant forms, and is usually followed by an immunosuppressive therapy. Surgical management is reserved for complications, including resistance to all medical therapy. Surgical resection has to be limited in order to avoid a short bowel syndrome. Surgery should not be considered as the ideal therapy as it has been demonstrated that recurrence after surgery increases at distance. 5-aminosalycilates compounds are an alternative therapy in mild attacks. Mesalazine may reduce the recurrence and could be considered as a possible maintenance treatment.

Unlabelled: The efficacy of clofazimine (Lamprene) was analysed retrospectively in twenty one patients with anoperineal lesions (APL) of Crohn's disease. Clofazimine is known for its antimycobacterial, antiinflammatory and immunomodifier properties. It is used with success in leprosy and certain dermatological disorders. A number of clinical and laboratory arguments suggest the probability of a role of mycobacteria in the etiology of Crohn's disease., Methods: twenty one patients with ileo-colono-anal or bucco-colono-anal Crohn's disease formed the basis of this study. They had been treated in various ways for APL, without success. They had APL of varying degrees of advancement (primary lesions: seven cases; secondary lesions: ten cases; major advanced lesions: four cases). Treatment with Lamprene was given for three to 38 months (mean: 12 months), the mean cumulative dose being 40 grams (4 to 146). Other therapeutic measures were started simultaneously in twelve patients: medical in six cases, medico-surgical in four cases and surgical only in two cases. The aim of treatment in fourteen cases was to obtain the healing of ulcerated lesions and/or fistulas, in three patients to delay dilatation sessions and in four patients to avoid proctectomy in the short-term., Results: ten patients showed no improvement while eleven were improved (with regression of primary lesions in ten cases). Taking combined treatment into consideration, the link between the result obtained and Lamprene was considered probable in five cases, possible in four cases and uncertain in one case. Lamprene was well tolerated in general. It was not possible to evaluate the efficacy of treatment regarding intestinal disease., Conclusion: the efficacy of Lamprene in ano-perineal lesions of Crohn's disease is possible and is worthy of evaluation in a controlled trial.

One hundred and two patients with Crohn's colitis present on average for 8 years, were studied retrospectively in order to determine whether or not a group of patients existed in whom the disease remained limited to the colon, and if such a group could be identified early on in the course of the disorder. At the time of the diagnosis of Crohn's disease, 34 patients had a concomitant anoperineal lesion, while 68 had disease affecting the colon only. In the latter, at the end of the follow-up period, the disease remained exclusively limited to the colon in 39 cases (57 p. cent). The actuarial rate of non-extra-colonic spread was 75, 40 and 35 p. cent at 5, 10 and 15 years respectively. Spread involved above all the anoperineal region (55 p. cent at 10 years), and less often the ileum (20 p. cent at 10 years). In patients monitored for at least 6 years, there was no significant difference between those in whom disease had spread and those in whom it remained limited to the colon, regarding the main initial clinical findings by history and examination, the same applying after the disease had been present for 3 years. These results would go against the existence of a specific entity of "Crohn's disease affecting the colon as an organ" and support the opinion that coloproctectomy with a pouch should be avoided in colitis due to Crohn's disease.

Psoas abscess were found in 6 cases among 166 patients with Crohn's disease between 1985 and 1989; in one case, it was the first sign of Crohn's disease. Diagnosis was usually difficult and should be suspected on the following signs: lower abdominal quadrant pain, psoitis, abdominal mass, sciatica or pain along the course of the femoral nerve. Diagnosis was confirmed in nearly all cases by computerized axial tomography. Effective therapy combines drainage and bowel resection.

To determine whether an elemental diet or a polymeric defined formula diet would be more effective for treating active Crohn's disease, we conducted a prospective randomised clinical trial in 30 patients with active Crohn's disease unresponsive to steroids and/or complicated by malnutrition. They received a four to six week enteral nutrition course with either an elemental diet or a polymeric diet. Clinical remission occurred in 10 of the 15 patients on elemental diet compared with 11 of the 15 patients assigned to polymeric diet. Both groups showed similar improvements in nutritional status, biological inflammation, alpha 1 antitrypsin clearance, and colonoscopic lesions (diminished in 17 out of 24 patients). Most patients relapsed during the year after discharge. We conclude that enteral nutrition, whatever the diet, is an efficient primary therapy for active Crohn's disease but does not influence the long term outcome.

The nutritional development with three types of enteral diets during 28 days, was compared in 45 patients with malnutrition presenting an active Crohn's disease. Enteral feeding consisted of a polymeric mixture (Realmentyl) administered in addition to a normal oral diet in 11 patients; the same mixture was administered alone exclusively to 9 patients, and an elemental diet (Vivonex HN) administered exclusively to 25 patients. The total caloric intake reached, in the three groups, the mean values of 60.2, 36.9 and 33.8 kcal/kg of ideal weight/day, respectively. 33 patients also received steroids. At the end of 28 days of enteral diet, the improvement in the weight and the anthropometric measurements (muscle circumference, triceps skinfold) was significantly more marked (gain of 6.5 kg) with the supplemental polymeric mixture than with exclusive enteral diet, polymeric diet (+/- 2.0 kg) or basic (+1.2 kg). Transferrin and albumin plasma levels increased in all 3 groups, but much faster with the exclusive elemental feeding, in spite of a higher urinary urea excretion in these patients. The overall nutritional development was significantly better with supplemental polymeric feeding, and was identical in the two other groups. These results confirm that the supplemental polymeric enteral feeding is more effective, from the nutrition standpoint. With an exclusive enteral feeding, the nutritional result is appreciably the same, whether the mixture consists of polymers or basic elements.

Total parenteral nutrition may be responsible for gallbladder sludge and lithiasis which might possibly be related to gallbladder bile stasis. Gallbladder motility has not yet been studied during constant-rate enteral nutrition. We performed serial ultrasonographic studies of gallbladder volume and contents in ten patients receiving constant-rate enteral nutrition during 35 +/- 17 days. Each patient had two weekly examinations at 9 AM and 2 PM on the same day. None of the patients developed gallbladder sludge or lithiasis. The gallbladder was frequently seen to be contracted. Mean gallbladder volume during constant-rate enteral nutrition was not significantly different from mean gallbladder volume after Bladex. Individual gallbladder volume changed significantly from one measurement to another. This study showed that gallbladder motility is preserved during constant-rate enteral nutrition. The persistence of gallbladder contractions may prevent the development of biliary sludge ad lithiasis.

Using clustering analysis, we sought to identify groups of patients on the basis of the disease course among a population of 177 patients with Crohn's disease and followed for 3 years or more, starting from the first frank exacerbation of the disease. The first 36 values of a monthly clinical score represented the active variables of the clustering analysis. This method yielded 2 course groups, A and B, of 95 and 82 patients respectively. The unfavorable course in group A was characterized by the persistence of the clinically active disease at 3 years, whereas group B individuals achieved complete clinical remission within 2 years of onset on the average. Among the initially known clinical data which could explain the course, only the incidence of an occlusive syndrome was higher in group B, which showed a more favorable course. Although we applied clustering analysis to a patient sample over a period of only 3 years, our results do suggest the existence or 2 primary course groups within the population of patients with Crohn's disease. It would appear that the disease course cannot be predicted from the clinical parameters present at the time of onset, but rather becomes apparent during the course of the first 2 years.

203 patients suffering from Crohn's disease were interviewed by questionnaire about the repercussion of the disease in their school, professional, and familial life. This study, conducted in 3 centers, shows that these patients usually experience little difficulty during their school attendance, and that they succeed, in the majority of the cases, in adjusting to their professional life. This adjustment appears, however, more problematical as far their leisures are concerned.

To re-evaluate the relationship between Crohn's disease and sarcoidosis, we compared the numbers and types of cells recovered by bronchoalveolar lavage from normal volunteers and patients with Crohn's disease, with other forms of inflammatory bowel disease, and with sarcoidosis. Patients with Crohn's disease, but not patients with other inflammatory bowel disorders, had an increase in the number of T lymphocytes on the surface of the lower respiratory tract similar to that seen in patients with sarcoidosis. As in sarcoidosis, this lymphocytosis results from an expansion of the T4+ T-lymphocyte subset, is characteristic of patients with active disease only, and is not associated with similar abnormalities in the peripheral blood. Thus, patients with apparently localized Crohn's disease have sarcoid-like lymphocytosis of the lower respiratory tract, a finding that emphasizes the systemic nature of Crohn's disease and the disorder's close relationship to sarcoidosis.

The aim of this study was to investigate the value of elemental diet in steroid-resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid-dependent Crohn's disease. However, elemental diet does not prevent relapse.